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Showing 621–640 of 2058 publications.
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Chen, Yunfeng; Ju, Lining Arnold; Zhou, Fangyuan; Liao, Jiexi; Xue, Lingzhou; Su, Qian Peter; Jin, Dayong; Yuan, Yuping; Lu, Hang; Jackson, Shaun P.; Zhu, ChengIntegrins are membrane receptors that mediate cell adhesion and mechanosensing. The structurefunction relationship of integrins remains incompletely understood, despite the extensive studies carried out because of its importance to basic cell biology and translational medicine. Using a fluorescence dual biomembrane force probe, microfluidics and cone-and-plate rheometry, we applied precisely controlled mechanical stimulations to platelets and identified an intermediate state of integrin ?<inf>IIb</inf>?<inf>3</inf> that is characterized by an ectodomain conformation, ligand affinity and bond lifetimes that are all intermediate between the well-known inactive and active states. This intermediate state is induced by ligand engagement of glycoprotein (GP) Ib? via a mechanosignalling pathway and potentiates the outside-in mechanosignalling of ?<inf>IIb</inf>?<inf>3</inf> for further transition to the active state during integrin mechanical affinity maturation. Our work reveals distinct ?<inf>IIb</inf>?<inf>3</inf> state transitions in response to biomechanical and biochemical stimuli, and identifies a role for the ?<inf>IIb</inf>?<inf>3</inf> intermediate state in promoting biomechanical platelet aggregation. 2019, The Author(s), under exclusive licence to Springer Nature Limited.
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Indja, Ben Elias; Woldendorp, Kei; Vallely, Michael P.; Grieve, Stuart M.Background: Silent brain infarcts (SBI) are increasingly being recognized as an important complication of cardiac procedures as well as a potential surrogate marker for studies on brain injury. The extent of subclinical brain injury is poorly defined. Methods and Results: We conducted a systematic review and meta-analysis utilizing studies of SBIs and focal neurologic deficits following cardiac procedures. Our final analysis included 42 studies with 49 separate intervention groups for a total of 2632 patients. The prevalence of SBIs following transcatheter aortic valve implantation was 0.71 (95% CI 0.64-0.77); following aortic valve replacement 0.44 (95% CI 0.31-0.57); in a mixed cardiothoracic surgery group 0.39 (95% CI 0.28-0.49); coronary artery bypass graft 0.25 (95% CI 0.15-0.35); percutaneous coronary intervention 0.14 (95% CI 0.10-0.19); and off-pump coronary artery bypass 0.14 (0.00-0.58). The risk ratio of focal neurologic deficits to SBI in aortic valve replacement was 0.22 (95% CI 0.15-0.32); in off-pump coronary artery bypass 0.21 (95% CI 0.02-2.04); with mixed cardiothoracic surgery 0.15 (95% CI 0.07-0.33); coronary artery bypass graft 0.10 (95% CI 0.05-0.18); transcatheter aortic valve implantation 0.10 (95% CI 0.07-0.14); and percutaneous coronary intervention 0.06 (95% CI 0.03-0.14). The mean number of SBIs per patient was significantly higher in the transcatheter aortic valve implantation group (4.58 2.09) compared with both the aortic valve replacement group (2.16 1.62, P=0.03) and the percutaneous coronary intervention group (1.88 1.02, P=0.03). Conclusions: SBIs are a very common complication following cardiac procedures, particularly those involving the aortic valve. The high frequency of SBIs compared with strokes highlights the importance of recording this surrogate measure in cardiac interventional studies. We suggest that further work is required to standardize reporting in order to facilitate the use of SBIs as a routine outcome measure. 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
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Pinget, Gabriela Veronica; Tan, Jian; Janac, Bartlomiej; Kaakoush, Nadeem O.; Angelatos, Alexandra Sophie; OSullivan, John F.; Koay, Yen Chin; Sierro, Fric; Davis, Joel; Divakarla, Shiva Kamini; Khanal, Dipesh; Moore, Robert J.; Stanley, Dragana M.; Chrzanowski, Wojciech; Macia, Laurence M.The interaction between gut microbiota and host plays a central role in health. Dysbiosis, detrimental changes in gut microbiota and inflammation have been reported in non-communicable diseases. While diet has a profound impact on gut microbiota composition and function, the role of food additives such as titanium dioxide (TiO<inf>2</inf>), prevalent in processed food, is less established. In this project, we investigated the impact of food grade TiO<inf>2</inf> on gut microbiota of mice when orally administered via drinking water. While TiO<inf>2</inf> had minimal impact on the composition of the microbiota in the small intestine and colon, we found that TiO<inf>2</inf> treatment could alter the release of bacterial metabolites in vivo and affect the spatial distribution of commensal bacteria in vitro by promoting biofilm formation. We also found reduced expression of the colonic mucin 2 gene, a key component of the intestinal mucus layer, and increased expression of the beta defensin gene, indicating that TiO<inf>2</inf> significantly impacts gut homeostasis. These changes were associated with colonic inflammation, as shown by decreased crypt length, infiltration of CD8+ T cells, increased macrophages as well as increased expression of inflammatory cytokines. These findings collectively show that TiO<inf>2</inf> is not inert, but rather impairs gut homeostasis which may in turn prime the host for disease development. 2019 Pinget, Tan, Janac, Kaakoush, Angelatos, O'Sullivan, Koay, Sierro, Davis, Divakarla, Khanal, Moore, Stanley, Chrzanowski and Macia.
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Vanichkitrungruang, Siriluck; Chuang, Christine Y.; Hawkins, Clare L.; Hammer, Astrid; Hoefler, Gerald; Malle, Ernst; Davies, Michael J.Dysfunction of endothelial cells of the artery wall is an early event in cardiovascular disease and atherosclerosis. The cause(s) of this dysfunction are unresolved, but accumulating evidence suggests that oxidants arising from chronic low-grade inflammation are contributory agents, with increasing data implicating myeloperoxidase (MPO, released by activated leukocytes), and the oxidants it generates (e.g. HOCl and HOSCN). As these are formed extracellularly and react rapidly with proteins, we hypothesized that MPO-mediated damage to the matrix glycoprotein fibronectin (FN) would modulate FN structure and function, and its interactions with human coronary artery endothelial cells (HCAEC). Exposure of human plasma FN to HOCl resulted in modifications to FN and its functional epitopes. A dose-dependent loss of methionine and tryptophan residues, together with increasing concentrations of methionine sulfoxide, and modification of the cell-binding fragment (CBF) and heparin-binding fragment (HBF) domains was detected with HOCl, but not HOSCN. FN modification resulted in a loss of HCAEC adhesion, impaired cell spreading and reduced cell proliferation. Exposure to HCAEC to HOCl-treated FN altered the expression of HCAEC genes associated with extracellular matrix (ECM) synthesis and adhesion. Modifications were detected on HCAEC-derived ECM pre-treated with HOCl, but not HOSCN, with a loss of antibody recognition of the CBF, HBF and extra-domain A. Co-localization of epitopes arising from MPO-generated HOCl and cell-derived FN was detected in human atherosclerotic lesions. Damage was also detected on FN extracted from lesions. These data support the hypothesis that HOCl, but not HOSCN, targets and modifies FN resulting in arterial wall endothelial cell dysfunction. 2019
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James, Natalie L.; Milijasevic, Zoran; Ujhazy, Anthony; Edwards, Glenn Anthony; Jermyn, Kieri; Mynard, Jonathan P.; Celermajer, David S.Background: It has been established that the central elastic arteries of the mammalian circulation dampen the high pulse pressure emanating from the left ventricle, so that the pulsations in distal arterioles, such as in the cerebral circulation, are of lower amplitude than more centrally. However, the contribution of the common carotid artery (CCA) to protection of the cerebral microvasculature from high pulse pressure is not known, specifically to what extent viscoelastic energy dissipation in the arterial wall might contribute to the shock absorbing function of the large conduit arteries. Methods: Young adult sheep (n = 6) were anaesthetised and their CCAs (n = 7) exposed. Pressure catheters were inserted 1015 cm apart, proximally and distally in the CCA; a flow probe was placed proximally on the vessel. Results: The median dp/dt<inf>max</inf> on the pressure rise of the arterial wave upstroke for the proximal CCA was 619 mm Hg/s and for the distal CCA it was significantly lower, at 197 mm Hg/s (p = 0.0156; n = 7). The median pulse pressure of the proximal CCA was 24 mm Hg/s; distal pulse pressure was significantly lower, at 18 mm Hg/s (p = 0.0156; n = 7). The median flow rate was 0.97 L/min with an interquartile range from 0.51 to 1.15 L/min. Conclusions: The native CCA in the young adult sheep is an effective pressure dampener in the arterial circulation, reducing both pressure slope and pulse pressure, most likely via viscous dampening in the arterial wall. 2019 The Authors
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Lima-Silveira, Ludmila; Accorsi-Mendon, Daniela; Bonagamba, Leni Gomes Heck; Almado, Carlos Eduardo L.; da Silva, Melina Pires; Nedoboy, Polina E.; Pilowsky, Paul M.; MacHado, Benedito HonioKey points: Rats subjected to sustained hypoxia (SH) present increases in arterial pressure (AP) and in glutamatergic transmission in the nucleus tractus solitarius (NTS) neurons sending projections to ventrolateral medulla (VLM). Treatment with minocycline, a microglial inhibitor, attenuated the increase in AP in response to SH. The increase in the amplitude of glutamatergic postsynaptic currents in the NTS-VLM neurons, induced by postsynaptic mechanisms, was blunted by minocycline treatment. The number of microglial cells was increased in the NTS of vehicle-treated SH rats but not in the NTS of minocycline-treated rats. The data show that microglial recruitment/proliferation induced by SH is associated with the enhancement of excitatory neurotransmission in NTS-VLM neurons, which may contribute to the observed increase in AP. Abstract: Short-term sustained hypoxia (SH) produces significant autonomic and respiratory adjustments and triggers activation of microglia, the resident immune cells in the brain. SH also enhances glutamatergic neurotransmission in the NTS. Here we evaluated the role of microglial activation induced by SH on the cardiovascular changes and mainly on glutamatergic neurotransmission in NTS neurons sending projections to the ventrolateral medulla (NTS-VLM), using a microglia inhibitor (minocycline). Direct measurement of arterial pressure (AP) in freely moving rats showed that SH (24h, fraction of inspired oxygen (F<inf>1</inf>, o<inf>2</inf>) 0.1) in vehicle and minocycline (30mg/kg i.p. for 3days)-treated groups produced a significant increase in AP in relation to control groups under normoxic conditions, but this increase was significantly lower in minocycline-treated rats. Whole-cell patch-clamp recordings revealed that the active properties of the membrane were comparable among the groups. Nevertheless, the amplitudes of glutamatergic postsynaptic currents, evoked by tractus solitarius stimulation, were increased in NTS-VLM neurons of SH rats. Changes in asynchronous glutamatergic currents indicated that the observed increase in amplitude was due to postsynaptic mechanisms. These changes were blunted in the SH group previously treated with minocycline. Using immunofluorescence, we found that the number of microglial cells was increased in the NTS of vehicle-treated SH rats but not in the NTS neurons of minocycline-treated rats. Our data support the concept that microglial activation induced by SH is associated with the enhancement of excitatory neurotransmission in NTS-VLM neurons, which may contribute to the increase in AP observed in this experimental model. 2019 The Authors. The Journal of Physiology 2019 The Physiological Society
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Chen, Yunfeng; Li, Zhiyong; Ju, Lining ArnoldReceptor-mediated cell mechanosensing plays critical roles in cell spreading, migration, growth, and survival. Dynamic force spectroscopy (DFS) techniques have recently been advanced to visualize such processes, which allow the concurrent examination of molecular binding dynamics and cellular response to mechanical stimuli on single living cells. Notably, the live-cell DFS is able to manipulate the force waveforms such as tensile versus compressive, ramped versus clamped, static versus dynamic, and short versus long lasting forces, thereby deriving correlations of cellular responses with ligand binding kinetics and mechanical stimulation profiles. Here, by differentiating extracellular mechanical stimulations into two major categories, tensile force and compressive force, we review the latest findings on receptor-mediated mechanosensing mechanisms that are discovered by the state-of-the-art live-cell DFS technologies. 2019, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature.
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Passam, Freda H.; Chiu, JoyceDisulphide bonds are covalent linkages of two cysteine residues (R-S-S-R?) in proteins. Unlike peptide bonds, disulphide bonds are reversible in nature allowing cleaved bonds to reform. Disulphide bonds are important structural elements that stabilise protein conformation. They can be of catalytic function found in enzymes that facilitate redox reactions in the cleavage/formation of disulphide bonds in their substrates. Emerging evidence also indicates that disulphide bonds can be of regulatory function which alter protein activity when they are cleaved or formed. This class of regulatory disulphide bonds is known as allosteric disulphide bonds. Allosteric disulphide bonds are mechano-sensitive, and stretching or twisting the sulphur-sulphur bond by mechanical force can make it easier or harder to be cleaved. This makes allosteric disulphide bonds an ideal type of mechano-sensitive switches for regulating protein functions in the vasculature where cells are continuously subjected to fluid shear force. This review will discuss the chemistry and biophysical properties of allosteric disulphide bonds and how they emerge to be mechano-sensitive switches in regulating platelet function and clot formation. 2019, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature.
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MacEr-Wright, Jessica L.; Stanley, Naomi R.; Portman, Neil; Tan, Joanne Tsui Ming; Bursill, C. A.; Rayner, Benjamin Saul; Hawkins, Clare L.During inflammation, myeloperoxidase released from activated phagocytes generates the highly reactive oxidant hypochlorous acid (HOCl). This oxidant plays an important role in the immune response but can also promote tissue damage and has been strongly linked with the development of numerous inflammatory diseases. HOCl reacts with cellular DNA forming chlorinated nucleobases, which induce strand breaks, mutations, and cross-links. Although it has been shown that chlorinated nucleosides are present within inflammatory pathologies and diseased tissue, whether or not these species are biomarkers formed as a byproduct of chronic inflammation or play a role in the disease progression has not been ascertained. In this study, we show that exposure of J774A.1 macrophage-like cells to chlorinated ribose and deoxyribose nucleosides results in the incorporation of 5-chloro-cytidine (5ClC), 8-chloro-adenosine (8ClA), and 8-chloro-guanosine (8ClG) into the cellular RNA and 5-chloro-deoxycytidine (5CldC) but not 8-chloro-deoxyguanosine (8CldG) or 8-chloro-deoxyadenosine (8CldA) into cellular DNA. Evidence was obtained for the clearance of 5ClC from the RNA, with a loss of 8ClA and 8ClG observed to a lesser extent, whereas an increase in the level of 5CldC in DNA was seen on further incubation of treated cells in the absence of chlorinated nucleosides. Importantly, exposure of the macrophages to chlorinated nucleosides, particularly 8ClG and 5ClC, resulted in the increased expression of interleukin-1?, and other pro-inflammatory cytokines and chemokines. With 5ClC, this inflammatory response was associated with the increased nuclear translocation of the NF-?B subunit, p65, rather than inflammasome activation. This alteration in gene expression appeared to be unrelated to the extent of incorporation of the chlorinated nucleosides into RNA or DNA and was not associated with any significant changes in cell viability or proliferation. Taken together, these results highlight a potential biological role for chlorinated nucleosides to promote inflammatory disease, in addition to their utility as biomarkers. 2019 American Chemical Society.
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Kakall, Zohra Mohtat; Cohen, E. Myfanwy; Farnham, M. M. J.; Kim, Seung Jae; Nedoboy, Polina E.; Pilowsky, Paul M.Autonomic reflex responses are critical in restoring changes to circulatory factors reduced beyond the domain of homeostasis. Intermittent hypoxia triggers repeated activation of chemoreflexes, resulting in baroreflex dysfunction and widespread changes in cellular and neuronal activity regulated by sensory/motor pathways. Hypoglycaemia initiates a rapid neurally-mediated counter-regulatory response. This counter-regulatory response to hypoglycaemia increases plasma adrenaline levels, liver glycogenolysis, and thus blood glucose levels. Context-dependent activation of rostral ventral medullary neurons initiates baroreceptor unloading, peripheral chemoreflex firing and the counter-regulatory response to hypoglycaemia. In this review, we briefly focus on the functional integration between peripheral and medullary pathways comprising the sympathetic baroreflex, chemoreflexes, and the counter-regulatory response to hypoglycaemia. 2018
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Ha, Jeffrey T.; Neuen, Brendon L.; Cheng, Lap P.; Jun, Min; Toyama, Tadashi; Gallagher, Martin P.; Jardine, Meg J.; Sood, Manish M.; Garg, Amit X.; Palmer, Suetonia C.; Mark, Patrick Barry; Wheeler, David Collins; Jha, Vivekanand K.; Freedman, Ben Ben; Johnson, David W.; Perkovic, Vlado; Badve, Sunil V.Background: Effects of oral anticoagulation in chronic kidney disease (CKD) are uncertain. Purpose: To evaluate the benefits and harms of Vitamin K antagonists (VKAs) and non-Vitamin K oral anticoagulants (NOACs) in adults with CKD stages 3 to 5, including those with dialysisdependent end-stage kidney disease (ESKD). Data Sources: English-language searches of MEDLINE, EMBASE, and Cochrane databases (inception to February 2019); review bibliographies; and ClinicalTrials.gov (25 February 2019). Study Selection: Randomized controlled trials evaluating VKAs or NOACs for any indication in patients with CKD that reported efficacy or bleeding outcomes. Data Extraction: Two authors independently extracted data, assessed risk of bias, and rated certainty of evidence. Data Synthesis: Forty-five trials involving 34 082 participants who received anticoagulation for atrial fibrillation (AF) (11 trials), venous thromboembolism (VTE) (11 trials), thromboprophylaxis (6 trials), prevention of dialysis access thrombosis (8 trials), and cardiovascular disease other than AF (9 trials) were included. All but the 8 trials involving patients with ESKD excluded participants with creatinine clearance less than 20 mL/min or estimated glomerular filtration rate less than 15 mL/min/1.73 m2. In AF, compared with VKAs, NOACs reduced risks for stroke or systemic embolism (risk ratio [RR], 0.79 [95% CI, 0.66 to 0.93]; highcertainty evidence) and hemorrhagic stroke (RR, 0.48 [CI, 0.30 to 0.76]; moderate-certainty evidence). Compared with VKAs, the effects of NOACs on recurrent VTE or VTE-related death were uncertain (RR, 0.72 [CI, 0.44 to 1.17]; low-certainty evidence). In all trials combined, NOACs seemingly reduced major bleeding risk compared with VKAs (RR, 0.75 [CI, 0.56 to 1.01]; lowcertainty evidence). Limitation: Scant evidence for advanced CKD or ESKD; data mostly from subgroups of large trials. Conclusion: In early-stage CKD, NOACs had a benefit-risk profile superior to that of VKAs. For advanced CKD or ESKD, there was insufficient evidence to establish benefits or harms of VKAs or NOACs. 2019 American College of Physicians.
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Left arm structure and function late after subclavian flap repair of aortic coarctation in childhoodDennis, Mark R.; Cusick, Anne; Borilovic, Jacinta; Nicholson, Calum; Derwin, Tanya; Puranik, Rajesh; Celermajer, David S.Objectives: Concerns exist over the long-term consequences of subclavian artery ligation in subclavian flap repair for coarctation of the aorta. We sought to analyse upper limb structural and functional performance in adults who have had surgery in childhood for coarctation of the aorta, using either subclavian flap repair or end to end aortic anastomosis.Methods: Two-group observational design using anatomical and upper limb functional performance measures. Purposive sampling from our specialist adult congenital heart disease database of patients who received subclavian flap repair or end to end anastomosis for coarctation of the aorta as children. Upper limb measurements were completed using MRI and blood flow velocity with ultrasound imaging. Bilateral standardised upper limb functional testing of assessment of strength, dexterity and a standardised self-report of upper limb disability was completed.Results: Eighteen right-handed patients, 9 with subclavian repair, (38 12 years, 78% males) were studied. Age at repair was 4.7 5.9 years; mean time from initial repair 32 9 years. The subclavian group had a larger difference between right and left when compared the end to end anastomosis group in: lower arm muscle mass (94.5 42.3 mls versus 37.8 94.5 mls, p = 0.008), lower arm maximal cross-sectional area, (5.9 2.8 cm2 versus 2.9 2.6 cm2, p = 0.038) and grip strength (14.7 8.3 lbs versus 5.9 5.3 lbs, p = 0.016) There were no significant functional differences between groups.Conclusions: In adults with repaired coarctation of the aorta, those with subclavian flap repair had a greater right to left arm muscle mass and grip strength differential when compared to those with end to end anastomosis repair. Cambridge University Press 2019.
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Koay, Yen Chin; Wali, Jibran A.; Luk, Alison W.S.; Macia, Laurence M.; Cogger, Victoria Carroll; Pulpitel, Tamara Jayne; Wahl, Devin; Solon-Biet, Samantha M.; Holmes, Andrew J.; Simpson, Stephen James; OSullivan, John F.Recent research has shown significant health benefits deriving from high-dietary fiber or microbiome-accessible carbohydrate consumption. Compared with native starch (NS), dietary resistant starch (RS) is a high microbiome-accessible carbohydrate that significantly alters the gut microbiome. The aim of this study was to determine the systemic metabolic effects of high microbiome-accessible carbohydrate. Male C57BL/6 mice were divided into 2 groups and fed either NS or RS for 18 wk (n = 20/group). Metabolomic analyses revealed that plasma levels of numerous metabolites were significantly different between the RS-fed and NS-fed mice, many of which are microbiome-derived. Most strikingly, we observed a 22-fold increase in gut microbiome-derived tryptophan metabolite indole-3-propionate (IPA), which was positively correlated with several gut microbiota, including Allobaculum, Bifidobacterium, and Lachnospiraceae, with Allobaculum having the most consistently increased abundance of all the IPA-associated taxa across all RS-fed mice. In addition, major changes were observed for metabolites solely or primarily metabolized in the gut (e.g., trimethylamine-N-oxide), metabolites that have a significant entero-hepatic circulation (i.e., bile acids), lipid metabolites (e.g., cholesterol sulfate), metabolites indicating increased energy turnover (e.g., tricarboxylic acid cycle intermediates and ketone bodies), and increased antioxidants such as reduced glutathione. Our findings reveal potentially novel mediators of high microbiome-accessible carbohydratederived health benefits. FASEB.
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Pinget, Gabriela Veronica; Tan, Jian; Janac, Bartlomiej; Kaakoush, Nadeem O.; Angelatos, Alexandra Sophie; OSullivan, John F.; Koay, Yen Chin; Sierro, Fric; Davis, Joel; Divakarla, Shiva Kamini; Khanal, Dipesh; Moore, Robert J.; Stanley, Dragana M.; Chrzanowski, Wojciech; Macia, Laurence M.In the original article, there was an error. In the Materials and Methods section, there was an error concerning the supplier of E171. A correction has been made to the Materials and Methods section, subsection E171 Characterization, Size and Morphology: Food grade TiO<inf>2</inf> was purchased from All Color Supplies PTY. Average hydrodynamic diameter, polydispersity index and zeta potential of the TiO<inf>2</inf> nanoparticles dispersed in drinking water were determined with a Malvern Zetasizer Nano ZS at 25? C. The dispersion was measured 3 times for both size and zeta potential. The size distribution and shape of the TiO<inf>2</inf> nanoparticles dispersed in mice drinking water were determined using a NanoSight NS300 (equipped with a sCMOS camera) at 25? C. The dispersion was measured 5 times (1 min per measurement). The size distribution and shape of the TiO<inf>2</inf> nanoparticles dispersed in drinking water were further investigated using a Zeiss Ultra Plus scanning electron microscope operated at an accelerating voltage of 10 kV. A drop of the nanoparticle dispersion was allowed to dry on a stub, after which ?20 of platinum metal was sputter coated onto the stub under vacuum to prevent charging. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. 2019 Pinget, Tan, Janac, Kaakoush, Angelatos, OSullivan, Koay, Sierro, Davis, Divakarla, Khanal, Moore, Stanley, Chrzanowski and Macia.
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Baxter, Kathleen; Hellewell, Sarah ClaireTraumatic brain injury (TBI) resulting from episodes of domestic violence (DV) is a serious yet greatly underreported issue. Head injuries arising in these circumstances are often concussive or sub-concussive in nature, and are unlikely to be isolated incidents, with victims frequently suffering repetitive TBIs over time. Although men may also be victims of DV, women and children are most at risk of DV via intimate partners and parents, respectively. Due to the complexities of these interpersonal relationships, victims of DV are not always able to receive appropriate clinical diagnoses, care or follow-up after TBI. TBI arising from DV is also likely to occur in a complex milieu of fear, anxiety and depression, the physical and psychological consequences of which may worsen or perpetuate the pathology of TBI. This review examines the complexities of TBI arising from DV from several perspectives, with focus on three pertinent and interrelated topics: 1) pathobiology and complications of single and repetitive TBI, encompassing direct neural consequences, inflammation and hormonal changes; 2) behavioral, cognitive and psychosocial consequences of TBI; and 3) contributing factors to TBI and complications, including strategies to increase clinician recognition of TBI in DV patients, and programs and policies in place in Australia and abroad to decrease rates of offending. 2019, 2019 Taylor & Francis.
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Carotid artery wave intensity in mid-to late-life predicts cognitive decline: The Whitehall II studyChiesa, Scott T.; Masi, Stefano; Shipley, Martin John; Ellins, Elizabeth A.; Fraser, Alan Gordon; Hughes, Alun D.; Patel, Riyaz S.; Khir, Ashraf William; Halcox, Julian PJ J.; Singh-Manoux, Archana; Kivimaki, Mika Shipley; Celermajer, David S.; Deanfield, John EricAims: Excessive arterial pulsatility may contribute to cognitive decline and risk of dementia via damage to the fragile cerebral microcirculation. We hypothesized that the intensity of downstream-Travelling pulsatile waves measured by wave intensity analysis in the common carotid artery during mid-to late-life would be associated with subsequent cognitive decline. Methods and results: Duplex Doppler ultrasound was used to calculate peak forward-Travelling compression wave intensity (FCWI) within the common carotid artery in 3191 individuals [mean standard deviation (SD), age = 61 6 years; 75% male] assessed as part of the Whitehall II study in 2003-05. Serial measures of cognitive function were taken between 2002-04 and 2015-16. The relationship between FCWI and cognitive decline was adjusted for sociodemographic variables, genetic and health-related risk factors, and health behaviours. Mean (SD) 10-year change in standardized global cognitive score was-0.39 (0.18). Higher FCWI at baseline was associated with accelerated cognitive decline during follow-up [difference in 10-year change of global cognitive score per 1 SD higher FCWI =-0.02 (95% confidence interval-0.04 to-0.00); P = 0.03]. This association was largely driven by cognitive changes in individuals with the highest FCWI [Q4 vs. Q1-Q3 =-0.05 (-0.09 to-0.01), P = 0.01], equivalent to an age effect of 1.9 years. Compared to other participants, this group was ?50% more likely to exhibit cognitive decline (defined as the top 15% most rapid reductions in cognitive function during follow-up) even after adjustments for multiple potential confounding factors [odds ratio 1.49 (1.17-1.88)]. Conclusion: Elevated carotid artery wave intensity in mid-to late-life predicts faster cognitive decline in long-Term follow-up independent of other cardiovascular risk factors. 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.
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Cao, Jacob Y.; Koay, Yen Chin; Quek, Lake Ee; Parker, Benjamin L.; Lal, Sean P.; OSullivan, John F.[No abstract available]
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Bartlett, Benjamin; Ludewick, Herbert P.; Misra, Ashish K.; Lee, Silvia; Dwivedi, GirishAtherosclerosis is now considered a chronic maladaptive in-flammatory disease. The hallmark feature in both human and murine disease is atherosclerotic plaques. Macrophages and various T-cell lineages play a crucial role in atherosclerotic plaque establishment and disease progression. Humans and mice share many of the same processes that occur within atherogenesis. The various similarities enable considerable insight into disease mechanisms and those which contribute to cardiovascular complications. The apolipoprotein E-null and low-density lipoprotein receptor-null mice have served as the foundation for further immunological pathway manipulation to identify pro-and antiatherogenic pathways in attempt to reveal more novel therapeutic targets. In this review, we provide a translational perspective and discuss the roles of macrophages and various T-cell lineages in contrasting proatherosclerotic and atheroprotective settings. 2019 the American Physiological Society.
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Kakall, Zohra Mohtat; Kavurma, Mary M.; Cohen, E. Myfanwy; Howe, Peter R.C.; Nedoboy, Polina E.; Pilowsky, Paul M.The impaired ability of the autonomic nervous system to respond to hypoglycemia is termed hypoglycemia-associ-ated autonomic failure (HAAF). This life-threatening phenomenon results from at least two recent episodes of hypoglycemia, but the pathology underpinning HAAF remains largely unknown. Although naloxone appears to improve hypoglycemia counterregulation under controlled conditions, hypoglycemia prevention remains the current mainstay therapy for HAAF. Epinephrine-synthesizing neurons in the rostroventrolateral (C1) and dorsomedial (C3) medulla project to the subset of sympathetic preganglionic neurons that regulate peripheral epinephrine release. Here we determined whether or not C1 and C3 neuronal activation is impaired in HAAF and whether or not 1 wk of hypoglycemia prevention or treatment with naloxone could restore C1 and C3 neuronal activation and improve HAAF. Twenty male Sprague-Dawley rats (250 300 g) were used. Plasma epinephrine levels were significantly increased after a single episode of hypoglycemia (n = 4; 5,438 783 pg/ml vs. control 193 27 pg/ml, P < 0.05). Repeated hypoglycemia significantly reduced the plasma epinephrine response to subsequent hypoglycemia (n = 4; 2,179 220 pg/ml vs. 5,438 783 pg/ml, P < 0.05). Activation of medullary C1 (n = 4; 50 5% vs. control 3 1%, P < 0.05) and C3 (n = 4; 45 5% vs. control 4 1%, P < 0.05) neurons was significantly increased after a single episode of hypoglycemia. Activation of C1 (n = 4; 12 3%, P < 0.05) and C3 (n = 4; 19 5%, P < 0.05) neurons was significantly reduced in the HAAF groups. Hypoglycemia prevention or treatment with naloxone did not restore the plasma epinephrine response or C1 and C3 neuronal activation. Thus repeated hypoglycemia reduced the activation of C1 and C3 neurons mediating adrenal medullary responses to subsequent bouts of hypoglycemia. the American Physiological Society.
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Ribeiro, Rosilene V.; Solon-Biet, Samantha M.; Pulpitel, Tamara Jayne; Senior, Alistair M.; Cogger, Victoria Carroll; Clark, Ximonie; OSullivan, John F.; Koay, Yen Chin; Hirani, Vasant; Blyth, Fiona M.; Seibel, Marcus J.; Waite, Louise M.; Naganathan, Vasi; Cumming, Robert G.; Handelsman, David J.; Simpson, Stephen James; Le Couteur, David G.Protein and branched-chain amino acid (BCAA) intake are associated with changes in circulating BCAAs and influence metabolic health in humans and rodents. However, the relationship between BCAAs and body composition in both species is unclear, with many studies questioning the translatability of preclinical findings to humans. Here, we assessed and directly compared the relationship between circulating BCAAs, body composition, and intake in older mice and men. Body weight and body fat were positively associated with circulating BCAA levels in both mouse and human, which remained significant after adjustments for age, physical activity, number of morbidities, smoking status, and source of income in the human cohort. Macronutrient intakes were similarly associated with circulating BCAA levels; however, the relationship between protein intake and BCAAs were more pronounced in the mice. These findings indicate that the relationship between circulating BCAAs, body composition, and intakes are comparable in both species, suggesting that the mouse is an effective model for examining the effects of BCAAs on body composition in older humans. 2019 by the authors. Licensee MDPI, Basel, Switzerland.
