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Showing 561–580 of 2058 publications.
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Lowres, Nicole; Freedman, Ben Ben[No abstract available]
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Kay, Sharon; Moore, Benjamin M.; Moore, Laura; Seco, Michael; Barnes, Christopher; Marshman, David; Grieve, Stuart M.; Celermajer, David S.Background: Prompted by a cluster of observations concerning ascending aortic pathology in elite rugby players, we assessed over 150 asymptomatic predominantly retired players with echocardiography, aiming to document the prevalence and severity of ascending aortic dilatation and/or anterior aortic effacement, both risk factors for potentially catastrophic aortic complications. Methods: Rugby players (at least 5 years of high level competitive rugby) were classified as elite (national, state or first grade representatives) or non-elite. A total of 152 asymptomatic players with a mean age of 45 13 years (range 2165) underwent transthoracic echocardiography. Z-scores (number of standard deviations from a population mean) were calculated for aortic root and ascending aortic size. Results: Regarding the aortic root, a Z-score of >2 was seen in 24% (expected prevalence 2.3%, p < 0.001) and a Z-score >3 was seen in 4% (expected prevalence 0. 1%, p < 0.001). Sixty-two (62) players (41%) had an aortic root greater than 40 mm diameter. Ascending aortic Z-scores were >2 in 53% of players and >3 in 22% (p < 0.001). Abnormal anterior aortic effacement at the sinotubular junction (STJ) was seen in 88 players (58%). Abnormal aortic dilatation and effacement were associated with a longer duration of competitive rugby participation and elite status, respectively. Conclusions: Ascending aortic dilatation with abnormal anterior effacement is exceedingly common in asymptomatic retired elite rugby players. This warrants increased surveillance in retired players until the clinical significance of these findings can be further investigated. 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand
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Zhao, Emma; Lowres, Nicole; Woolaston, Anna; Naismith, Sharon Linda; Gallagher, Robyn D.Background: Minimising risk factors through secondary prevention behaviour is challenging for patients following an acute coronary syndrome. Cognitive impairment can potentially make these changes more difficult. However, cognitive impairment prevalence in acute coronary syndrome patients is poorly understood. Design: This study was based on a systematic review. Methods: A systematic review was conducted of PubMed, Medline, PsycINFO and Cochrane databases up to March 2019, to identify studies reporting the prevalence of cognitive impairment in acute coronary syndrome patients. Predefined inclusion criteria were specified, including use of a validated cognitive impairment screening tool. Studies were excluded if patients had diagnosed dementia or coronary artery bypass graft surgery. Strengthening The Reporting of Observational Studies in Epidemiology and Cochrane Risk of Bias tools were used to assess quality. Results: From 747 potential studies, nine were included. The total sample size was 6457 (range 532174), mean age range was 51.377.4 years, and range of proportions of males was 57100%. Reported cognitive impairment prevalence rates varied substantially (985%) with no clear pattern over time. From the two studies which examined domains, verbal fluency, memory and language were affected the most. Meta-analysis could not be undertaken due to diverse screening tools (n = 9), cut-off scores and screening timepoints. Conclusions: Cognitive impairment in acute coronary syndrome patients is currently poorly described, and likely affects a substantial number of acute coronary syndrome patients who remain undetected and have the potential to develop to dementia in the future. As domains are most affected, this could impact understanding and retention of health education. Research is needed to accurately determine the prevalence of cognitive impairment in acute coronary syndrome patients and create suitable standardised measures and thresholds. The European Society of Cardiology 2019.
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Obeidy, Peyman; Ju, Lining Arnold; Oehlers, Stefan H.; Zulkhernain, Nursafwana Syazwani; Lee, Quintin; Galeano Ni, Jorge Luis; Kwan, Rain Y.Q.; Tikoo, Shweta; Cavanagh, Lois L.; Mrass, Paulus E.; Cook, Adam J.L.; Jackson, Shaun P.; Biro, Mat Roediger, Ben R.; Sixt, Michael; Weninger, Wolfgang PeterT lymphocytes utilize amoeboid migration to navigate effectively within complex microenvironments. The precise rearrangement of the actin cytoskeleton required for cellular forward propulsion is mediated by actin regulators, including the actin-related protein 2/3 (Arp2/3) complex, a macromolecular machine that nucleates branched actin filaments at the leading edge. The consequences of modulating Arp2/3 activity on the biophysical properties of the actomyosin cortex and downstream Tcell function are incompletely understood. We report that even a moderate decrease of Arp3 levels in T cells profoundly affects actin cortex integrity. Reduction in total F-actin content leads to reduced cortical tension and disrupted lamellipodia formation. Instead, in Arp3-knockdown cells, the motility mode is dominated by blebbing migration characterized by transient, balloon-like protrusions at the leading edge. Although this migration mode seems to be compatible with interstitial migration in three-dimensional environments, diminished locomotion kinetics and impaired cytotoxicity interfere with optimal Tcell function. These findings define the importance of finely tuned, Arp2/3-dependent mechanophysical membrane integrity in cytotoxic effector T lymphocyte activities. 2019 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
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Leung, K. L.; Fong, Winnie; Freedman, Ben Ben; Bajorek, Beata V.; Lee, Vivian Wing YanIntroduction: Studies of Caucasian populations have shown that beta-blockers may exacerbate weight gain, a risk factor for many chronic diseases. Still, beta-blockers are the most prescribed antihypertensives in the Chinese population in Hong Kong. We aimed to explore the association between beta-blocker use, hypertension, and weight status of this population. Methods: A post-hoc analysis regarding body mass index (BMI) and the use of beta-blockers was performed based on the medication profile of community-dwelling older adults. Participants BMI, hypertension diagnosis, name, dose, frequency, route of administration of beta-blockers, and other drugs that may alter body weight were recorded. Results: Of 1053 Chinese individuals aged ?65 years (mean age 76.97.2 years, 80% female) from 32 elderly centres in Hong Kong, 18% (185/1053) of them consumed beta-blockers. That group also had a significantly larger proportion of obese individuals (45.9% vs 32.1%, P=0.002). After adjusting for other weight-altering drugs, beta-blockers remained a significant predictor of overweight and obesity (P=0.001). As the hypertensive population had significantly higher BMI than the normotensive population (24.33.6 vs 22.93.5, P<0.001), a sub-analysis on those with hypertension diagnosis confirmed that only the hypertensive population taking atenolol had a significantly larger population of obese individuals (BMI ?25) compared with those who took metoprolol (58.9% vs 38.5%, P=0.03) and those who did not take any beta-blockers (58.9% vs 38.4%, P=0.007). Conclusions: Our findings taken together with other guideline reservations cast doubt on whether beta-blockers, particularly atenolol, should be the major drug prescribed to older adults with hypertension. 2020 Hong Kong Academy of Medicine.
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Cai, Xiaoping; Ahmad, Gulfam A.U.; Hossain, Farjaneh; Liu, Yuyang; Wang, Xiaosuo; Dennis, Joanne Marie; Freedman, Ben Ben; Witting, Paul KennethSerum amyloid A (SAA) promotes endothelial inflammation and dysfunction that is associated with cardiovascular disease and renal pathologies. SAA is an apoprotein for high-density lipoprotein (HDL) and its sequestration to HDL diminishes SAA bioactivity. Herein we investigated the effect of co-supplementing HDL on SAA-mediated changes to vascular and renal function in apolipoprotein E-deficient (ApoE?/?) mice in the absence of a high-fat diet. Male ApoE?/? mice received recombinant human SAA or vehicle (control) by intraperitoneal (i.p.) injection every three days for two weeks with or without freshly isolated human HDL supplemented by intravenous (i.v.) injection in the two weeks preceding SAA stimulation. Aorta and kidney were harvested 4 or 18 weeks after commencement of treatment. At 4 weeks after commencement of treatment, SAA increased aortic vascular cell adhesion molecule (VCAM)-1 expression and F<inf>2</inf>-isoprostane level and decreased cyclic guanosine monophosphate (cGMP), consistent with SAA stimulating endothelial dysfunction and promoting atherosclerosis. SAA also stimulated renal injury and inflammation that manifested as increased urinary protein, kidney injury molecule (KIM)-1, and renal tissue cytokine/chemokine levels as well as increased protein tyrosine chlorination and P38 MAPkinase activation and decreased in Bowmans space, confirming that SAA elicited a pro-inflammatory phenotype in the kidney. At 18 weeks, vascular lesions increased significantly in the cohort of ApoE?/? mice treated with SAA alone. By contrast, pretreatment of mice with HDL decreased SAA pro-inflammatory activity, inhibited SAA enhancement of aortic lesion size and renal function, and prevented changes to glomerular Bowmans space. Taken together, these data indicate that supplemented HDL reduces SAA-mediated endothelial and renal dysfunction in an atherosclerosis-prone mouse model. 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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Yang, Nianji; Tan, Richard P.; Chan, Alex H.P.; Lee, Bob S.L.; Santos, Miguel; Hung, Juichien; Liao, Yun; Bilek, Marcela M.M.; Fei, Jian; Wise, Steven G.; Bao, Shishan SanThe functionality and durability of implanted biomaterials are often compromised by an exaggerated foreign body reaction (FBR). M1/M2 polarization of macrophages is a critical regulator of scaffold-induced FBR. Macrophage colony-stimulating factor (M-CSF), a hematopoietic growth factor, induces macrophages into an M2-like polarized state, leading to immunoregulation and promoting tissue repair. In the present study, we explored the immunomodulatory effects of surface bound M-CSF on poly-l-lactic acid (PLLA)-induced FBR. M-CSF was immobilized on the surface of PLLA via plasma immersion ion implantation (PIII). M-CSF functionalized PLLA, PLLA-only, and PLLA+PIII were assessed in an IL-1? luciferase reporter mouse to detect real-time levels of IL-1? expression, reflecting acute inflammation in vivo. Additionally, these different treated scaffolds were implanted subcutaneously into wild-type mice to explore the effect of M-CSF in polarization of M2-like macrophages (CD68+/CD206+), related cytokines (pro-inflammatory: IL-1?, TNF and MCP-1; anti-inflammatory: IL-10 and TGF-?), and angiogenesis (CD31) by immunofluorescent staining. Our data demonstrated that IL-1? activity in M-CSF functionalized scaffolds was ?50% reduced compared to PLLA-only at day 1 (p < 0.01) and day 2 (p < 0.05) post-implantation. There were >2.6-fold more CD206+ macrophages in M-CSF functionalized PLLA compared to PLLA-only at day 7 (p < 0.001), along with higher levels of IL-10 at both day 7 (p < 0.05) and day 14 (p < 0.01), and TGF-? at day 3 (p < 0.05), day 7 (p < 0.05), and day 14 (p < 0.001). Lower levels of pro-inflammatory cytokines were also detected in M-CSF functionalized PLLA in the early phase of the immune response compared to PLLA-only: a ?58% decrease at day 3 in IL-1? a ?91% decrease at day 3 and a ?66% decrease at day 7 in TNF; and a ?60% decrease at day 7 in MCP-1. Moreover, enhanced angiogenesis inside and on/near the scaffold was observed in M-CSF functionalized PLLA compared to PLLA-only at day 3 (p < 0.05) and day 7 (p < 0.05), respectively. Overall, M-CSF functionalized PLLA enhanced CD206+ macrophage polarization and angiogenesis, consistent with lower levels of pro-inflammatory cytokines and higher levels of anti-inflammatory cytokines in early stages of the host response, indicating potential immunoregulatory functions on the local environment. 2020 American Chemical Society.
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MacEr-Wright, Jessica L.; Sileikaite-Morvaki, Inga; Rayner, Benjamin Saul; Hawkins, Clare L.The exposure of RNA and DNA nucleobases to the oxidant hypochlorous acid (HOCl) results in the generation of different stable chlorinated products. These chlorinated nucleobases are formed in vivo, particularly in chronic inflammatory pathologies, which are characterized by the overproduction of HOCl by myeloperoxidase. As such, chlorinated nucleosides are used as biomarkers of inflammation. However, these compounds have also attracted attention as potential chemotherapeutic agents with 8-chloro-adenosine (8ClA), for example, currently in clinical trials for the treatment of hematological cancers, including chronic lymphocytic leukemia. 8ClA has mainly RNA-directed effects in malignant cells, with exposure resulting in ATP depletion and apoptotic cell death. Whether 8ClA has significant reactivity with nonmalignant cells has not been widely studied. Here we show that prolonged incubation of J774A.1 macrophage-like cells with 8ClA results in the perturbation of cellular metabolism and apoptotic cell death. These effects are associated with an accumulation of 8-chloroadenosine triphosphate (8Cl-ATP), an effect not seen in experiments utilizing other chlorinated nucleosides. Exposure of the macrophages to 8ClA did not significantly change basal mitochondrial respiration or glycolysis but resulted in an increase in maximal mitochondrial respiration as well as spare respiratory capacity within these cells. Additionally, 8ClA exposure also altered the mRNA expression of a range of antioxidant and DNA damage repair genes in the macrophages in a manner consistent with a reduction in the capacity of the cells to cope with oxidative stress and repair DNA damage. Taken together, these results provide new insight into pathways by which the production of HOCl during chronic inflammation could perturb immune cell function and may also have implications for the use of 8ClA as a chemotherapeutic drug. 2019 American Chemical Society.
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Yavari, Saber Amin; Croes, Michiel; Akhavan, Behnam; Jahanmard, Fatemeh; Eigenhuis, C. C.; Dadbakhsh, Sasan; Vogely, Henri Charles; Bilek, Marcela M.M.; Fluit, Adriaan Camille; Boel, C. H.Edwin; van der Wal, Bart C.H.; Vermonden, Tina; Weinans, Harrie H.; Zadpoor, Amir A.Additive manufacturing has facilitated fabrication of complex and patient-specific metallic meta-biomaterials that offer an unprecedented collection of mechanical, mass transport, and biological properties as well as a fully interconnected porous structure. However, applying meta-biomaterials for addressing unmet clinical needs in orthopedic surgery requires additional surface functionalities that should be induced through tailor-made coatings. Here, we developed multi-functional layer-by-layer coatings to simultaneously prevent implant-associated infections and stimulate bone tissue regeneration. We applied multiple layers of gelatin- and chitosan-based coatings containing either bone morphogenetic protein (BMP)-2 or vancomycin on the surface of selective laser melted porous structures made from commercial pure Titanium (CP Ti) and designed using a triply periodic minimal surface (i.e., sheet gyroid). The additive manufacturing process resulted in a porous structure and met the the design values comparatively. X-ray photoelectron spectroscopy spectra confirmed the presence and composition of the coating layers. The release profiles showed a continued release of both vancomycin and BMP-2 for 23 weeks. Furthermore, the developed meta-biomaterials exhibited a very strong antibacterial behavior with up to 8 orders of magnitude reduction in both planktonic and implant-adherent bacteria and no signs of biofilm formation. The osteogenic differentiation of mesenchymal stem cells was enhanced, as shown by two-fold increase in the alkaline phosphatase activity and up to four-fold increase in the mineralization of all experimental groups containing BMP-2. Eight-week subcutaneous implantation in vivo showed no signs of a foreign body response, while connective tissue ingrowth was promoted by the layer-by-layer coating. These results unequivocally confirm the superior multi-functional performance of the developed biomaterials. 2019
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Gondoputro, William; Rajendran, Saissan; Celermajer, David S.; Qasabian, Raffi A.Acute limb ischemia in young adults warrants thorough investigation to determine the underlying cause. Here, we present a case of acute upper limb ischemia in a marathon runner secondary to paradoxical embolism. The patient had associated deep venous thrombosis of the lower limb with multiple pulmonary emboli and patent foramen ovale. This case report emphasizes the under-recognition of intense endurance exercise as a risk factor for venous thromboembolism and highlights the potentially debilitating embolic sequelae of venous thromboembolism in patients with patent foramen ovale. 2020 The Authors
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Wali, Jibran A.; Jarzebska, Natalia; Raubenheimer, David R.; Simpson, Stephen James; Rodionov, Roman Nikolaevich; OSullivan, John F.The majority of the epidemiological evidence over the past few decades has linked high intake of fats, especially saturated fats, to increased risk of diabetes and cardiovascular disease. However, findings of some recent studies (e.g., the PURE study) have contested this association. High saturated fat diets (HFD) have been widely used in rodent research to study the mechanism of insulin resistance and metabolic syndrome. Two separate but somewhat overlapping models the diacylglycerol (DAG) model and the ceramide modelhave emerged to explain the development of insulin resistance. Studies have shown that lipid deposition in tissues such as muscle and liver inhibit insulin signaling via the toxic molecules DAG and ceramide. DAGs activate protein kinase C that inhibit insulin-PI3K-Akt signaling by phosphorylating serine residues on insulin receptor substrate (IRS). Ceramides are sphingolipids with variable acyl group chain length and activate protein phosphatase 2A that dephosphorylates Akt to block insulin signaling. In adipose tissue, obesity leads to infiltration of macrophages that secrete pro-inflammatory cytokines that inhibit insulin signaling by phosphorylating serine residues of IRS proteins. For cardiovascular disease, studies in humans in the 1950s and 1960s linked high saturated fat intake with atherosclerosis and coronary artery disease. More recently, trials involving Mediterranean diet (e.g., PREDIMED study) have indicated that healthy monounsaturated fats are more effective in preventing cardiovascular mortality and coronary artery disease than are low-fat, low-cholesterol diets. Antioxidant and anti-inflammatory effects of Mediterranean diets are potential mediators of these benefits. 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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Welton, Thomas; Constantinescu, Cris S.; Auer, Dorothee P.; Dineen, Robert A.Research suggests that disruption of brain networks might explain cognitive deficits in multiple sclerosis (MS). The reliability and effectiveness of graph theoretic network metrics as measures of cognitive performance were tested in 37 people with MS and 23 controls. Specifically, relationships with cognitive performance (linear regression against the paced auditory serial addition test-3 seconds [PASAT-3], symbol digit modalities test [SDMT], and attention network test) and 1-month reliability (using the intraclass correlation coefficient [ICC]) of network metrics were measured using both resting-state functional and diffusion magnetic resonance imaging data. Cognitive impairment was directly related to measures of brain network segregation and inversely related to network integration (prediction of PASAT-3 by small worldness, modularity, characteristic path length, R2 = 0.55; prediction of SDMT by small worldness, global efficiency, and characteristic path length, R2 = 0.60). Reliability of the measures for 1 month in a subset of nine participants was mostly rated as good (ICC >0.6) for both controls and MS patients in both functional and diffusion data, but was highly dependent on the chosen parcellation and graph density, with the 0.2-0.5 density range being the most reliable. This suggests that disrupted network organization predicts cognitive impairment in MS and its measurement is reliable for a 1-month period. These new findings support the hypothesis of network disruption as a major determinant of cognitive deficits in MS and the future possibility of the application of derived metrics as surrogate outcomes in trials of therapies for cognitive impairment. Copyright 2020, Mary Ann Liebert, Inc., publishers 2020.
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Hatchwell, Luke M.; Harney, Dylan James; Cielesh, Michelle E.; Young, Kieren; Koay, Yen Chin; OSullivan, John F.; Larance, MarkEvery-other-day fasting (EODF) is an effective intervention for the treatment of metabolic disease, including improvements in liver health. But how the liver proteome is reprogrammed by EODF is currently unknown. Here, we use EODF in mice and multi-omics analysis to identify regulated pathways. Many changes in the liver proteome are distinct after EODF and absent after a single fasting bout. Key among these is the simultaneous induction by EODF of de novo lipogenesis and fatty acid oxidation enzymes. Together with activation of oxidative stress defenses, this contributes to the improvements in glucose tolerance and lifespan after EODF. Enrichment analysis shows unexpected downregulation of HNF4? targets by EODF, and we confirm HNF4? inhibition. Suppressed HNF4? targets include bile synthetic enzymes and secreted proteins, such as ?1-antitrypsin or inflammatory factors, which reflect EODF phenotypes. Interactive online access is provided to a data resource (https://www.larancelab.com/eodf), which provides a global view of fasting-induced mechanisms in mice.; Intermittent fasting is an effective intervention for the treatment of metabolic disease. In this study, we dissect the liver's metabolic response to this intervention with a multi-omics approach and find concomitant induction of fatty acid oxidation, de novo lipogenesis, and antioxidant response pathways. HNF4? is also inhibited during intermittent fasting. 2020 The Author(s); 2020 The Author(s)
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Orchard, Jessica Joan; Orchard, John William; La Gerche, AndrCrossed D.Sign; Raju, Hariharan; Semsarian, Christopher[No abstract available]
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Shen, Kaikai; Welton, Thomas; Lyon, Matthew; McCorkindale, Andrew N.; Sutherland, G. T.; Burnham, Samantha C.; Fripp, Jgen; Martins, Ralph Nigel; Grieve, Stuart M.Executive function (EF) is a set of cognitive capabilities considered essential for successful daily living, and is negatively affected by ageing and neurodegenerative conditions. Underpinning EF performance are functional nodes in the executive control network (ECN), while the structural connectivity underlying this network is not well understood. In this paper, we evaluated the structural white matter tracts that interconnect the ECN and investigated their relationship to the EF performance. Using high-angular resolution diffusion MRI data, we performed tractography analysis of structural connectivity in a cognitively normal cohort (n = 140), specifically targeting the connectivity between ECN nodes. Our data revealed the presence of a strongly-connected structural core of the ECN comprising three components: interhemispheric frontal connections, a fronto-parietal subnetwork and fronto-striatal connections between right dorsolateral prefrontal cortex and right caudate. These pathways were strongly correlated with EF performance (p =.003). Post-hoc analysis of subregions within the significant ECN connections showed that these effects were driven by a highly specific subset of interconnected cortical regions. The structural core subnetwork of the functional ECN may be an important feature crucial to a better future understanding of human cognition and behaviour. 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.
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Welton, Thomas; Indja, Ben Elias; Maller, Jerome Joseph; Fanning, Jonathon Paul; Vallely, Michael P.; Grieve, Stuart M.Diffusion MRI (dMRI) is sensitive to anisotropic diffusion within bundles of nerve axons and can be used to make objective measurements of brain networks. Many brain disorders are now recognised as being caused by network dysfunction or are secondarily associated with changes in networks. There is therefore great potential in using dMRI measures that reflect network integrity as a future clinical tool to help manage these conditions. Here, we used dMRI to identify replicable, robust and objective markers that meaningfully reflect cognitive and emotional performance. Using diffusion kurtosis analysis and a battery of cognitive and emotional tests, we demonstrated strong relationships between white matter structure across networks of anatomically and functionally specific brain regions with both emotional bias and emotional memory performance in a large healthy cohort. When the connectivity of these regions was examined using diffusion tractography, the terminations of the identified tracts overlapped precisely with cortical loci relating to these domains, drawn from an independent spatial meta-analysis of available functional neuroimaging literature. The association with emotional bias was then replicated using an independently acquired healthy cohort drawn from the Human Connectome Project. These results demonstrate that, even in healthy individuals, white matter dMRI structural features underpin important cognitive and emotional functions. Our robust cross-correlation and replication supports the potential of structural brain biomarkers from diffusion kurtosis MRI to characterise early neurological changes and risk in individuals with a reduced threshold for cognitive dysfunction, with further testing required to demonstrate clinical utility. 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.
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Shanmugalingam, Renuka; Wang, Xiaosuo; Motum, Penelope I.; Fulcher, Ian; Lee, Gaksoo; Kumar, Roshika; Hennessy, Annemarie; Makris, AngelaAspirin nonadherence and its associated increase in cardiovascular and cerebrovascular events is well described; however, the prevalence of aspirin nonadherence among high-risk pregnant women at risk of preeclampsia and its influence on clinical outcomes remains unclear. Our study examined the prevalence of aspirin nonadherence and resistance among high-risk pregnant women quantitatively (platelet function analyzer 100 and plasma salicylic acid) and clinical outcomes relative to adherence. High-risk pregnant women were recruited across 3 centers in the South West Sydney Local Health District. Simultaneous clinic data, blood sample, and self-reported adherence assessment were prospectively collected at 4-week intervals from 12 to 36 weeks of gestation. Nonadherence was defined as normal platelet function analyzer 100 and nondetectable plasma salicylic acid in <90% of time points. Value of <90% is based on current data. Two hundred twenty women were recruited over 25 months. No woman was aspirin resistant, and 63 (44%) women demonstrated inadequate adherence. Women with inadequate adherence had higher incidence of early-onset preeclampsia (17% versus 2%; odds ratio [OR], 1.9 [95% CI, 1.1-8.7]; P=0.04), late-onset preeclampsia (41% versus 5%; OR, 4.2 [95% CI, 1.4-19.8]; P=0.04), intrauterine growth restriction (29% versus 5%; OR, 5.8; [95% CI, 1.2-8.3]; P=0.001), preterm delivery (27% versus 10%; OR, 5.2 [95% CI, 1.5-8.7]; P=0.008), and higher likelihood of increase in antihypertensives antenatally (60% versus 10%; OR, 4.6 [95% CI, 1.2-10.5]; P=0.003). Kaplan-Meier analysis demonstrated lower incidence of premature delivery in the ?90% adherent group (HR, 0.3 [95% CI, 0.2-0.5]; P<0.001).Kappa coefficient agreement between qualitative and quantitative assessment of adherence was moderate (?=0.48; SE=0.029; P<0.0001). Our data demonstrates that aspirin is an effective prophylactic agent with an absolute risk reduction of 51% (number needed to treat, 2) when adherence is ?90%, compared with women with inadequate adherence. Women who were <90% adherent had higher rates of preeclampsia, intrauterine growth restriction, preterm delivery, and increase in antenatal antihypertensive requirements. Self-reported adherence does not accurately reflect actual adherence. 2020 Lippincott Williams and Wilkins. All rights reserved.
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Breukelaar, Isabella A.; Erlinger, May; Harris, Anthony W.F.; Boyce, Philip M.; Hazell, Philip L.; Grieve, Stuart M.; Antees, Cassandra; Foster, Sheryl L.; Gomes, Lavier J.; Williams, Leanne M.; Malhi, Gin S.; Korgaonkar, Mayuresh S.Objectives: Dysfunction of cognitive control is a feature of both bipolar disorder (BP) and major depression (MDD) and persists through to remission. However, it is unknown whether these disorders are characterized by common or distinct disruptions of cognitive control function and its neural basis. We investigated this gap in knowledge in asymptomatic BP and MDD participants, interpreted within a framework of normative function. Methods: Participants underwent fMRI scans engaging cognitive control through a working memory task and completed a cognitive battery evaluating performance across multiple subdomains of cognitive control, including attention, impulsivity, processing speed, executive function, and memory. Analysis was performed in two stages: (i) cognitive control-related brain activation and deactivation were correlated with cognitive control performance in 115 healthy controls (HCs), then, (ii) significantly correlated regions from (i) were compared between 25 asymptomatic BP, 25 remitted MDD, and with 25 different HCs, matched for age and gender. Results: Impulsivity and executive function performance were significantly worse in BP compared to both MDD and HCs. Both BP and MDD had significantly poorer memory performance compared to HCs. Greater deactivation of the medial prefrontal cortex (MPFC) during the fMRI task was associated with better executive function in healthy controls. Significantly less deactivation in this region was present in both BP and MDD compared to HCs. Conclusions: Failure to deactivate the MPFC, a key region of the default mode network, during working memory processing is a shared neural feature present in both bipolar and major depression and could be a source of common cognitive dysfunction. 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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Alves da Costa, Filipa Augusto; MalLov Katerina; Lee, Vivian Wing Yan; Tous I Trepat, Salvador; Papastergiou, John; Griffiths, Dale; Chaumais, Marie Camille; Hersberger, Kurt Eduard; Viola, Ra; Paulino, Ema I.; Lobban, Trudie C.A.; Neubeck, Lis; Freedman, Ben Ben; Antoniou, SotirisAtrial fibrillation (AF) accounts for up to one third of strokes, one of the lead mortality causes worldwide. The European Society of Cardiology guidelines recommend opportunistic screening as a means to increase the odds of early detection and institution of appropriate treatment according to risk factors identified. However, in most countries there are various barriers to effective uptake of screening, including low awareness. The Atrial Fibrillation Association is a patient association engaged with raising awareness of AF. Establishing a partnership with the International Pharmacists for Anticoagulation Care Taskforce, we set as goals to test a model for raising awareness of AF involving pharmacists globally; and to identify barriers and enablers to its implementation. A cross-sectional study was conducted during the Arrhythmia Alliance World Heart Rhythm Week. Pharmacists from 10 countries invited individuals (? 40years; without anticoagulation therapy of AF) to participate in the awareness campaign. Participants agreeing were engaged in the early detection of AF (EDAF) using pulse palpation. Individuals with rhythm discrepancies were referred and prospectively assessed to have information on the proportion of confirmed diagnosis, leading to estimate the detection rate. Interviews with country coordinators explored barriers and enablers to implementation. The study involved 4193 participants in the awareness campaign and 2762 in the EDAF event (mean age 65.3 13.0), of whom 46.2% individuals were asymptomatic, recruited across 120 sites. Most common CHA<inf>2</inf>DS<inf>2</inf>-VASc risk factor was hypertension. Among 161 patients referred to physician, feedback was obtained for 32 cases, of whom 12 new arrhythmia diagnoses were confirmed (5 for AF, 2 for atrial flutter), all among elders (? 65years). Qualitative evaluation suggested a local champion to enable pharmacists success; technology enhanced engagement amongst patients and increased pharmacists confidence in referring to physicians; interprofessional relationship was crucial in success. This study suggests pharmacists can contribute to greater outreach of awareness campaigns. Effective communication pathways for inter-professional collaboration were suggested enablers to gain full benefits of EDAF. 2019, Springer Science+Business Media, LLC, part of Springer Nature.
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Xu, Bei; Shanmugalingam, Renuka; Chau, Katrina; Makris, Angela; Hennessy, AnnemarieDuring normal trophoblast invasion, integrins ?6?4 are downregulated, and ?1?1 are upregulated in invasive cytotrophoblast cells. In preeclampsia both interstitial and endovascular invasion are shallow and cytotrophoblasts fail to upregulate ?1?1 and downregulate ?6?4. This study aims to investigate the role of integrins ?1?1 and ?6?4 on cellular pathways influencing trophoblast integration into endothelial cellular networks in vitro. Red fluorescent-labeled human uterine myometrial microvascular endothelial cells (UtMVECs) were seeded on Matrigel to form endothelial networks. Green fluorescent-labeled trophoblastic HTR-8/SVneo cells pre-incubated with 20?g/ml of neutralizing antibodies (anti-?1, ?1, ?6, ?4, ?1+?1, or ?6+?4) for 1h were then co-cultured with endothelial networks with the neutralizing antibodies for 24h. Fluorescent images were captured, and quantified utilizing Image J. Cells were retrieved to analyze mRNA expression of galectin-1, TIMP-1, and PAI-1 by quantitative PCR. MMP-2, MMP-9, free sFlt-1, and PlGF from conditioned media were measured by ELISA. The integration of trophoblast cells into endothelial cellular networks was inhibited by anti-?1(? 28 3%, p< 0.0001), and increased by anti-?6(+ 19 5%, p< 0.01). Galectin-1 mRNA expression was decreased by anti-?1(? 35 7%, p< 0.001), anti-?1(?23 5%, p< 0.05), and anti-?1+?1(? 35 5%, p< 0.001). The mRNA expression of TIMP-1 was inhibited by anti-?1(? 59 9%, p< 0.01) and anti-?1(? 63 7%, p< 0.001) while PAI-1 mRNA expression was increased by anti-?1 + ?1(+ 285 70%, p< 0.0001). In the conditioned medium, anti-?1 reduced MMP-2(?28 1%, p< 0.001), MMP-9(?27 8%, p< 0.01), and sFlt-1(?27 5%, p< 0.001) production. Anti-?1 reduced MMP-2(? 15 2%, p< 0.05) production. There were no changes in PlGF. Appropriate integrins ?1?1 modulate trophoblast cell integration into endothelial cellular networks in vitro through invasive pathways including galectin-1, TIMP-1, PAI-1, MMP-2, and MMP-9 production. 2019, Society for Reproductive Investigation.
