37 results on '"Mighiu, A."'
Search Results
2. P783: CLINICAL, HUMANISTIC, AND ECONOMIC BURDEN IN PATIENTS WITH PNH RECEIVING C5 INHIBITION TREATMENT ACROSS UK, GERMANY, AND FRANCE. INSIGHTS FROM THE COMMODORE BURDEN OF ILLNESS STUDY
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Louis Terriou, Maria Piggin, Pascale Burmester, Fengkui Zhang, Alan Finnegan, Persefoni Kritikou, Claudia Mighiu, Christian Buehrer, Pablo Katz, Selma Mode, Xenia Studera, Huong Trinh, and Talha Munir
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. Downregulation of hsa-miR-4328 and target gene prediction in Acute Promyelocytic Leukemia
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Lupu Onda T., Popescu Bogdan, Avram Elena, Dragomir Mihaela, Cimponeriu Gheorghe Dănuț, Mighiu Ioana, Aposteanu Silvia, and Coriu Daniel
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mirna ,apl ,leukemia ,bioinformatics ,Medicine - Abstract
Introduction: Acute promyelocytic leukemia (APL) is defined by the PML-RARA fusion gene. APL treatment can have significant side effects, therefore the development of optimal therapeutic options is crucial. Although the study of miRNAs is still in its infancy, it has been shown that these molecules are involved in the pathogenesis of neoplasms by modulating the expression of target genes. miRNAs can be considered possible biomarkers in APL and can be used as therapeutic targets or as markers for the therapeutic response.
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- 2022
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4. Modulation of atrial fibrillation susceptibility by gp91phox-containing NADPH oxidases
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Mighiu, Alexandra, Casadei, Barbara, Simon, Jillian, and N.Reilly, Svetlana
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616.1 - Abstract
Atrial fibrillation (AF) is the most frequently encountered cardiac rhythm disorder in humans, with affected individuals facing an increased risk of stroke and mortality. Published findings implicate oxidative stress in triggering the new onset of AF and in promoting the atrial electrical and structural changes that drive disease progression. NOX2-containing NADPH oxidases are a significant source of superoxide production in atrial tissues. Previous work showed that a NOX2-mediated increase in superoxide accompanies AF in patients and animal models of tachypacing-induced AF, and further reported a strong independent association between atrial NOX2 activity and post-operative AF in patients undergoing cardiac surgery. However, a direct causal role for NOX2 in AF has not been investigated. This thesis aimed to test the hypothesis that superoxide released specifically from NOX2 directly contributes to the development of AF. To investigate the role of NOX2 in AF, mice with cardiac-specific overexpression of the human NOX2 gene (NOX2-Tg) were characterized. Atrial homogenates from these mice were found to show approximately 3-fold higher expression of NOX2 protein compared with wild-type controls, which was associated with a significant increase in NADPH-stimulated superoxide production. AF susceptibility assessed in vivo by transesophageal atrial burst stimulation was significantly higher in NOX2-Tg mice compared with wild-type, in the absence of significant alterations in cardiac function. However, dietary administration of atorvastatin (30 mg/kg daily for two weeks) did not eliminate AF susceptibility in NOX2-Tg mice, despite preventing the increase in NADPH-stimulated superoxide production in the left and right atria of these animals. Instead, atorvastatin significantly reduced the duration of pacing-induced AF, an effect which was found to be independent of genotype, and thus independent of NOX2 inhibition. Mechanistic studies do not support a role for NOX2 in promoting electrical or structural remodelling, as high-resolution optical mapping of di-4-ANEPPS-stained atrial tissue preparations revealed no significant differences in action potential duration or conduction velocity between wild-type and NOX2-Tg mice. Instead, NOX2 overexpression was associated with impaired atrial Ca
2+ handling. In left atrial myocytes of NOX2-Tg mice, the RyR2 Ca2+ leak-SR load ratio was lower when compared with wild-type, despite an increase in SR Ca2+ load. In the right atria, the leak-load ratio was similar between NOX2-Tg and wild-type myocytes, but the proportion of myocytes with 'leaky' RyR2 channels was greater among NOX2-Tg mice. RyR2 phosphorylation at Ser-2814 and Ser-2808 was not significantly different between WT and NOX2-Tg atrial homogenates, indicating that the changes in diastolic leak are not caused by differences in CaMKII or PKA activity.- Published
- 2018
5. Impact of progressive familial intrahepatic cholestasis on caregivers: caregiver-reported outcomes from the multinational PICTURE study
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Claudia Mighiu, Sonia O’Hara, Enrico Ferri Grazzi, Karen F. Murray, Jörn M. Schattenberg, Emily Ventura, Melanie Karakaidos, Alison Taylor, Harpreet Brrang, Anil Dhawan, Jose Willemse, and Alan Finnegan
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Progressive familial intrahepatic cholestasis ,Caregiver burden ,Work productivity ,Employment ,Patient-reported outcomes ,Medicine - Abstract
Abstract Background Progressive familial intrahepatic cholestasis (PFIC) is a spectrum of rare genetic diseases characterized by inadequate bile secretion that requires substantial ongoing care, though little research is published in this area. We report health-related quality of life (HRQoL) and work productivity outcomes from the retrospective, cross-sectional PICTURE study investigating the burden of PFIC on caregivers. Information from caregivers of patients with PFIC 1 or 2 in Germany, the United Kingdom and the United States from September 2020 to March 2021 was included. Results The PICTURE study sample comprised HRQoL responses from 22 PFIC caregivers. Patients were on average 8.2 years old; most caregivers were 30–49 years old (68%) and mothers (77%). Median CarerQoL-7D score was 67.7/100; mean CarerQoL-VAS score for general happiness was 5.7/10 (SD 2.1). Most caregivers reported fulfilment in their caregiving responsibilities, but problems with mental and physical health, finances, and relationships. When stratified by patient’s PFIC type, mean CarerQoL-7D and CarerQoL-VAS scores suggested worse HRQoL outcomes with PFIC2 versus PFIC1 (59.4 vs. 71.2, and 5.3 vs. 6.5, respectively). Additionally, more caregivers reported impact on sleep in the PFIC2 versus PFIC1 subgroup (93% vs. 75%). When stratified by history of PFIC-related surgeries, mean CarerQoL-7D and VAS scores were higher among those whose children had no specified surgeries (67.7 vs. 59.0/100 and 6.2 vs. 5.2/10, respectively). Nearly all caregivers reported an impact of caregiving responsibilities on sleeping (86%) and on personal relationships (82%). No caregivers reported having formal care support. Most caregivers were employed (73%); a third reported mean productivity loss of 12.9 days (SD 19.3) over the last 3 months, and a mean of 2.8 (SD 9.5) missed years of employment during their career. A higher number of workdays were missed by PFIC 2 caregivers compared to PFIC1 over last 3 months (16 days vs. 3 days). Conclusions The PICTURE study has demonstrated the prevalent, comprehensive, and meaningful burden that caring for an individual with PFIC has on caregivers. Despite fulfilment from caregiving, the breadth and depth of these responsibilities reduced caregiver reported HRQoL including mental and physical health, productivity, career prospects, sleep, relationships and finances.
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- 2022
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6. Impact of progressive familial intrahepatic cholestasis on caregivers: caregiver-reported outcomes from the multinational PICTURE study
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Mighiu, Claudia, O’Hara, Sonia, Ferri Grazzi, Enrico, Murray, Karen F., Schattenberg, Jörn M., Ventura, Emily, Karakaidos, Melanie, Taylor, Alison, Brrang, Harpreet, Dhawan, Anil, Willemse, Jose, and Finnegan, Alan
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- 2022
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7. COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay: A national systematic evaluation of sensitivity and specificity for mass-testing
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Affron, Dominic, Afrough, Babak, Agasu, Anita, Ainsworth, Mark, Allanson, Alison, Allen, Katherine, Allen, Collette, Archer, Lorraine, Ashbridge, Natasha, Aurfan, Iman, Avery, Miriam, Badenoch, Ellena, Bagga, Priya, Balaji, Rishab, Baldwin, Ella, Barraclough, Sophie, Beane, Carol, Bell, John, Benford, Tracy, Bird, Susan, Bishop, Marina, Bloss, Angela, Body, Richard, Boulton, Rosie, Bown, Abbie, Bratten, Carla, Bridgeman, Chris, Britton, Dominic, Brooks, Tim, Broughton-Smith, Margaret, Brown, Pauline, Buck, Beverley, Butcher, Elaine, Byrne, Wendy, Calderon, Gloria, Campbell, Siobhan, Carr, Olivia, Carter, Penny, Carter, Daniel, Cathrall, Megan, Catton, Matthew, Chadwick, Jim, Chapman, David, Chau, Kevin K., Chaudary, Tanzina, Chidavaenzi, Shaolin, Chilcott, Samatha, Choi, Bea, Claasen, Hannah, Clark, Simon, Clarke, Richard, Clarke, Dawn, Clayton, Richard, Collins, Kayleigh, Colston, Rima, Connolly, James, Cook, Eloïse, Corcoran, Marie, Corley, Ben, Costello, Laura, Coulson, Caroline, Crook, Ant, Crook, Derrick W., D'Arcangelo, Silvia, Darby, Mary-Anne, Davis, John, de Koning, Rosaline, Derbyshire, Pauline, Devall, Pam, Dolman, Mark, Draper, Natalie, Driver, Mark, Dyas, Sarah, Eaton, Emily, Edwards, Joy, Elderfield, Ruth, Ellis, Kate, Ellis, Graham, Elwell, Sue, Evans, Rachel, Evans, Becky, Evans, Marion, Evans, Ranoromanana, Eyre, David, Fahey, Codie, Fenech, Vanessa, Field, Janet, Field, Alice, Foord, Tom, Fowler, Tom, French, Mollie, Fuchs, Hannah, Gan, Jasmine, Gernon, Joseph, Ghadiali, Geeta, Ghuman, Narindar, Gibbons, Kerry, Gill, Gurvinder, Gilmour, Kate, Goel, Anika, Gordon, Sally, Graham, Tillie, Grassam-Rowe, Alexander, Green, David, Gronert, Anna, Gumsley-Read, Tegan, Hall, Claire, Hallis, Bassam, Hammond, Sally, Hammond, Peter, Hanney, Beth, Hardy, Victoria, Harker, Gabriella, Harris, Andrew, Havinden-Williams, May, Hazell, Elena, Henry, Joanne, Hicklin, Kim, Hollier, Kelly, Holloway, Ben, Hoosdally, Sarah J., Hopkins, Susan, Hughes, Lucy, Hurdowar, Steve, Hurford, Sally-Anne, Jackman, Joanne, Jackson, Harriet, Johns, Ruth, Johnston, Susan, Jones, Juliet, Kanyowa, Tinashe, Keating-Fedders, Katie, Kempson, Sharon, Khan, Iftikhar, Khulusi, Beinn, Knight, Thomas, Krishna, Anuradha, Lahert, Patrick, Lampshire, Zoe, Lasserson, Daniel, Lee, Kirsten, Lee, Lennard Y.W., Legard, Arabella, Leggio, Cristina, Liu, Justin, Lockett, Teresa, Logue, Christopher, Lucas, Vanessa, Lumley, Sheila F., Maripuri, Vindhya, Markham, Des, Marshall, Emma, Matthews, Philippa C., Mckee, Sarah, McKee, Deborah F., McLeod, Neil, McNulty, Antoinette, Mellor, Freddie, Michel, Rachel, Mighiu, Alex, Miller, Julie, Mirza, Zarina, Mistry, Heena, Mitchell, Jane, Moeser, Mika Erik, Moore, Sophie, Muthuswamy, Akhila, Myers, Daniel, Nanson, Gemma, Newbury, Mike, Nicol, Scott, Nuttall, Harry, Nwanaforo, Jewel Jones, Oliver, Louise, Osbourne, Wendy, Osbourne, Jake, Otter, Ashley, Owen, Jodie, Panchalingam, Sulaksan, Papoulidis, Dimitris, Pavon, Juan Dobaldo, Peace, Arro, Pearson, Karen, Peck, Liam, Pegg, Ashley, Pegler, Suzannah, Permain, Helen, Perumal, Prem, Peto, Leon, Peto, Tim E.A., Pham, Thanh, Pickford, Hayleah L., Pinkerton, Mark, Platton, Michelle, Price, Ashley, Protheroe, Emily, Purnell, Hellen, Rawden, Lottie, Read, Sara, Reynard, Charles, Ridge, Susan, Ritter, Tom G., Robinson, James, Robinson, Patrick, Rodger, Gillian, Rowe, Cathy, Rowell, Bertie, Rowlands, Alexandra, Sampson, Sarah, Saunders, Kathryn, Sayers, Rachel, Sears, Jackie, Sedgewick, Richard, Seeney, Laura, Selassie, Amanda, Shail, Lloyd, Shallcross, Jane, Sheppard, Lucy, Sherkat, Anna, Siddiqui, Shelha, Sienkiewicz, Alex, Sinha, Lavanya, Smith, Jennifer, Smith, Ella, Stanton, Emma, Starkey, Thomas, Stawiarski, Aleksander, Sterry, Amelia, Stevens, Joe, Stockbridge, Mark, Stoesser, Nicole, Sukumaran, Anila, Sweed, Angela, Tatar, Sami, Thomas, Hema, Tibbins, Carly, Tiley, Sian, Timmins, Julie, Tomas-Smith, Cara, Topping, Oliver, Turek, Elena, Neibler, Toi, Trigg-Hogarth, Kate, Truelove, Elizabeth, Turnbull, Chris, Tyrrell, David, Vaughan, Alison, Vertannes, John, Vipond, Richard, Wagstaff, Linda, Waldron, Joanne, Walker, Philip, Walker, Ann Sarah, Walters, Mary, Wang, Jenny Y, Watson, Ellie, Webberley, Kate, Webster, Kimerbley, Westland, Grace, Wickens, Ian, Willcocks, Jane, Willis, Herika, Wilson, Stephen, Wilson, Barbara, Woodhead, Louise, Wright, Deborah, Xavier, Bindhu, Yelnoorkar, Fiona, Zeidan, Lisa, Zinyama, Rangeni, and Peto, Tim
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- 2021
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8. Maternal trauma due to motor vehicle crashes and pregnancy outcomes: a systematic review and meta-analysis
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Ewelina Rogozinska, Shakila Thangaratinam, Virginia Martínez-Ruiz, Karim Brohi, Carmen Amezcua-Prieto, Jennifer Ross, Patritia Mighiu, Aurora Bueno-Cavanillas, and Khalid Saeed Khan
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Medicine - Abstract
Objectives To systematically review and quantify the effect of motor vehicle crashes (MVCs) in pregnancy on maternal and offspring outcomes.Design Systematic review and meta-analysis of observational data searched from inception until 1 July 2018. Searching was from June to August 2018 in Medline, Embase, Web of Science, Scopus, Latin-American and Caribbean System on Health Sciences Information, Scientific Electronic Library Online, TRANSPORT, International Road Research Documentation, European Conference of Ministers of Transportation Databases, Cochrane Database of Systematic Reviews and Cochrane Central Register.Participants Studies were selected if they focused on the effects of exposure MVC during pregnancy versus non-exposure, with follow-up to verify outcomes in various settings, including secondary care, collision and emergency, and inpatient care.Data synthesis For incidence data, we calculated a pooled estimate per 1000 women. For comparison of outcomes between women involved and those not involved in MVC, we calculated ORs with 95% CIs. Where possible, we statistically pooled the data using the random-effects model. The quality of studies used in the comparative analysis was assessed with Newcastle–Ottawa Scale.Results We included 19 studies (3 222 066 women) of which the majority was carried out in high-income countries (18/19). In population-level studies of women involved in MVC, maternal death occurred in 3.6 per 1000 (95% CI 0.25–10.42; 3 studies, 12 000 women; Tau=1.77), and fetal death or stillbirth in 6.6 per 1000 (95% CI 3.81–10.12; 8 studies, 47 992 women; I2=92.6%). Pooled incidence of complications per 1000 women involved in MVC was labour induction (276.43), preterm delivery (191.90) and caesarean section (166.65). Compared with women not involved in MVC, those involved had increased odds of placental abruption (OR 1.43, 95% CI 1.27–1.63; 3 studies, 1 500 825 women) and maternal death (OR 202.27; 95% CI 110.60–369.95; 1 study, 1 094 559 women).Conclusion Pregnant women involved in MVC were at higher risk of maternal death and complications than those not involved.PROSPERO registration number CRD42018100788.
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- 2020
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9. The autonomic nervous system and cardiac GLP-1 receptors control heart rate in mice
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Baggio, Laurie L., Ussher, John R., McLean, Brent A., Cao, Xiemin, Kabir, M. Golam, Mulvihill, Erin E., Mighiu, Alexandra S., Zhang, Hangjun, Ludwig, Andreas, Seeley, Randy J., Heximer, Scott P., and Drucker, Daniel J.
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- 2017
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10. Laboratory Assessment for Determining Microplastics in Freshwater Systems—Characterization and Identification along the Somesul Mic River.
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Gheorghe, Stefania, Stoica, Catalina, Harabagiu, Anca Maria, Neidoni, Dorian-Gabriel, Mighiu, Emanuel Daniel, Bumbac, Costel, Ionescu, Ioana Alexandra, Pantazi, Aida, Enache, Laura-Bianca, and Enachescu, Marius
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MICROPLASTICS ,FRESH water ,ENVIRONMENTAL protection ,SCANNING electron microscopy ,POLYPROPYLENE ,MONOCHROMATIC light ,IDENTIFICATION - Abstract
Microplastics (MPs) pollution has become a persisting problem over the last decades and is a critical issue for environmental protection and human health. In this context, scientific data able to reveal MPs presence and improve the characterization and identification of this pollution via different systems are valuable. The aim of this paper is to assess available techniques for determining MPs in real freshwater samples and subsequently to highlight the occurrence and type of MPs in the study case area (Somesul Mic River). The MPs sampling was performed from fresh water and sediment using planktonic nets and sieves with different mesh sizes (from 20 to 500 µm). Using both classical microscopic techniques as well as scanning electron microscopy (SEM), large (1–5 mm) and small (1 µm to 1 mm) MPs were observed in the shape of fibers, fragments, foam, foils and spheres in various colors (red, green, blue, purple, pink, white, black, transparent, and opaque). Raman and FT-IR spectroscopic methods were used for MPs identification. The presence of polyethylene (PE), polypropylene (PP), and polystyrene (PS) was registered for all sampling points. The MPs laboratory investigations have raised some issues regarding the identification of MPs particles smaller than 500 µm, these being characterized especially under microscope. Some small MPs particles were identified using micro-Raman spectroscopy that highlighted the same type of polymers. No differences were registered between the sampling points due to the widespread presence of MPs. The sediment samples presented a greater abundance as compared to the water samples. Overall, it is necessary to continue the optimization of MPs separation protocol and identification according to the complexity of samples, mainly due to the limitation and lack of spectral databases. [ABSTRACT FROM AUTHOR]
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- 2024
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11. RGS4-Deficiency Alters Intracellular Calcium and PKA-Mediated Control of Insulin Secretion in Glucose-Stimulated Beta Islets
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Guillaume Bastin, Lemieux Luu, Battsetseg Batchuluun, Alexandra Mighiu, Stephanie Beadman, Hangjung Zhang, Changhao He, Dana Al Rijjal, Michael B. Wheeler, and Scott P. Heximer
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RGS proteins ,glucose-stimulated insulin secretion ,intracellular Ca2+ ,cAMP ,Biology (General) ,QH301-705.5 - Abstract
A number of diverse G-protein signaling pathways have been shown to regulate insulin secretion from pancreatic β-cells. Accordingly, regulator of G-protein signaling (RGS) proteins have also been implicated in coordinating this process. One such protein, RGS4, is reported to show both positive and negative effects on insulin secretion from β-cells depending on the physiologic context under which it was studied. We here use an RGS4-deficient mouse model to characterize previously unknown G-protein signaling pathways that are regulated by RGS4 during glucose-stimulated insulin secretion from the pancreatic islets. Our data show that loss of RGS4 results in a marked deficiency in glucose-stimulated insulin secretion during both phase I and phase II of insulin release in intact mice and isolated islets. These deficiencies are associated with lower cAMP/PKA activity and a loss of normal calcium surge (phase I) and oscillatory (phase II) kinetics behavior in the RGS4-deficient β-cells, suggesting RGS4 may be important for regulation of both Gαi and Gαq signaling control during glucose-stimulated insulin secretion. Together, these studies add to the known list of G-protein coupled signaling events that are controlled by RGS4 during glucose-stimulated insulin secretion and highlight the importance of maintaining normal levels of RGS4 function in healthy pancreatic tissues.
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- 2021
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12. The autonomic nervous system and cardiac GLP-1 receptors control heart rate in mice
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Laurie L. Baggio, John R. Ussher, Brent A. McLean, Xiemin Cao, M. Golam Kabir, Erin E. Mulvihill, Alexandra S. Mighiu, Hangjun Zhang, Andreas Ludwig, Randy J. Seeley, Scott P. Heximer, and Daniel J. Drucker
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GLP-1 ,Diabetes ,Cardiac ,Cardiovascular disease ,Heart rate ,Autonomic nervous system ,Internal medicine ,RC31-1245 - Abstract
Objectives: Glucagon-like peptide-1 (GLP-1) is secreted from enteroendocrine cells and exerts a broad number of metabolic actions through activation of a single GLP-1 receptor (GLP-1R). The cardiovascular actions of GLP-1 have garnered increasing attention as GLP-1R agonists are used to treat human subjects with diabetes and obesity that may be at increased risk for development of heart disease. Here we studied mechanisms linking GLP-1R activation to control of heart rate (HR) in mice. Methods: The actions of GLP-1R agonists were examined on the control of HR in wild type mice (WT) and in mice with cardiomyocyte-selective disruption of the GLP-1R (Glp1rCM−/−). Complimentary studies examined the effects of GLP-1R agonists in mice co-administered propranolol or atropine. The direct effects of GLP-1R agonism on HR and ventricular developed pressure were examined in isolated perfused mouse hearts ex vivo, and atrial depolarization was quantified in mouse hearts following direct application of liraglutide to perfused atrial preparations ex vivo. Results: Doses of liraglutide and lixisenatide that were equipotent for acute glucose control rapidly increased HR in WT and Glp1rCM−/− mice in vivo. The actions of liraglutide to increase HR were more sustained relative to lixisenatide, and diminished in Glp1rCM−/− mice. The acute chronotropic actions of GLP-1R agonists were attenuated by propranolol but not atropine. Neither native GLP-1 nor lixisenatide increased HR or developed pressure in perfused hearts ex vivo. Moreover, liraglutide had no direct effect on sinoatrial node firing rate in mouse atrial preparations ex vivo. Despite co-localization of HCN4 and GLP-1R in primate hearts, HCN4-directed Cre expression did not attenuate levels of Glp1r mRNA transcripts, but did reduce atrial Gcgr expression in the mouse heart. Conclusions: GLP-1R agonists increase HR through multiple mechanisms, including regulation of autonomic nervous system function, and activation of the atrial GLP-1R. Surprisingly, the isolated atrial GLP-1R does not transduce a direct chronotropic effect following exposure to GLP-1R agonists in the intact heart, or isolated atrium, ex vivo. Hence, cardiac GLP-1R circuits controlling HR require neural inputs and do not function in a heart-autonomous manner.
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- 2017
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13. Intraperitoneal drain placement and outcomes after elective colorectal surgery: International matched, prospective, cohort study
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Sgro A., Blanco-Colino R., Ahmed W. U. R., Brindl N., Gujjuri R. R., Lapolla P., Mills E. C., Perez-Ajates S., Soares A. S., Varghese C., Xu W., McLean K. A., Chapman S. J., Espin-Basany E., Glasbey J. C., Mihaljevic A., Nepogodiev D., Pata F., Pellino G., Pockney P., Dudi-Venkata N. N., Egoroff N., Ludbrook I., Raubenheimer K., Richards T., Delibegovic S., Salibasic M., Amjad T., Dorr-Harim C., Gedeon N., Gsenger J., Tachezy M., Bini S., Gallo G., Gori A., Picciariello A., Podda M., Riboni C., Machatschek M. J., Nguyen A., Jakubauskas M., Kryzauskas M., Poskus T., Kuiper S. Z., Wang J., Wells C. I., Bissett I. P., Augestad K. M., Steinholt I., Vieira B. N., Juloski J., Anabitarte Bautista O., El Kasmy El Kasmy Y., Martin-Borregon P., Ossola Revilla M., Van Straten S., Aktas M. K., Baki B. E., Akhbari M., Baker D., Bhatia S., Brown S., Cambridge W., Kamarajah S. K., Khaw R. A., Kouli O., Murray V., Trout I., Yasin I., Wong J. Y., Reyhani H., Wong K. H. F., Pancharatnam R., Chia W. L., Walmsley A., Hassane A., Saeed D., Wang B., Walters B., Nowinka Z., Alsaif A., Mirza M., Foster K., Luu J., Kakodkar P., Hughes J. T., Yogarajah T., Antypas A., Rahman A., Bradbury M., McLarnon M., Nagi S., Riad A. M., Erotocritou M., Kyriacou H., Kaminskaite V., Alfadhel S., Fatimah Hussain Q., Handa A., Massy-Westropp C., Custovic S., Dimov R., Mughal H., Slavchev M., Ivanov T., Gouvas N., Hegazi A., Kocian P., Kjaer M. D., Mark-Christensen A., Papakonstantinou D., Machairas N., Triantafyllou T., Garoufalia Z., Korkolis D., Castaldi A., Giaccari S., Spolverato G., Pagano G., Milone M., Turri G., Colombo F., Cucinotta E., Poillucci G., Perra T., Tutino R., Belia F., Coletta D., Belli A., Rega D., Cianci P., Pirozzolo G., Di Lena M., Perrone F., Giani A., Lovisetto F., Grassia M., Pipitone Federico N. S., Ferrara F., Biancafarina A., Tamini N., Sinibaldi G., Tuminello F., Galleano R., Sasia D., Bragaglia L., de Manzoni Garberini A., Pesce A., Cassaro F., Venturelli P., Canu G. L., Esposito G., Campanelli M., Cardia R., Ricciardiello M., Sagnotta A., Canonico G., De Marco G., Cappiello A., Pinotti E., Carlei F., Lisi G., Bagaglini G., Farrugia M., Meima-Van Praag E. M., Monteiro C., Pereira M., Botelho P., Quigley A., O'Neill A., Gaule L., Crone L., Arnold A., Grama F., Beuca A., Tulina I., Litvin A., Panyko A., Ossola M. E., Trujillo Diaz J., Marin Santos J. M., Alonso Batanero E., Gortazar de las Casas S., Soldevila Verdeguer C., Colas-Ruiz E., Talal El-Abur I., Garcia Dominguez M., Delorme M., Sauvain M., Ozmen B. B., Ozkan B. B., Calikoglu F., Kural S., Zafer F., Kaya Y., Yalcinkaya A., Kargici K., Tepe M. D., Tatar O. C., Kabadayi E., Yildirim A., Hurmuzlu D., Korkmaz K., Sharma P., Troller R., Hagan N., Mooney J., Light A., Tansey M., Bhojwani D., McGing R. M., Mallon A., Fadel M., Spilsbury C., James R., O'Brien S., Isaac A., Balasubramanya S., Sadik H., Gala T., Chen J. Y., Turner B., Goh E., Hassan K., Karam M., Mason P., Tzoumas N., Noton T., Seehra J. K., Ahmed N., Motiwale R., Tanna V., Argyriou A., Bylapudi S. K., Grace N., Latif S., Hounat A., Kiam J. S., Zaidi M., Elsamani K., Hughes C., Suresh A., Sinan L. O. H., El-Dalil D., Khoo E. J. M., Salim E. E., Stark D., Minhas N., Fowler G., Rees E., Giudiceandrea I., Bardon A., Jayawardena P., Dieseru N., Murphy A., Yates C., Ziolkowska K., Rafie A., Khoda F., Okocha M., Ashdown T., Vitish-Sharma P., Gilliland J., Toh S., Jones K., Devine A., Berry A., McDonnell S., Olivier J., Richardson G., Lim H. J., Slim N., Elsayeh K., Sammour T., Sarpanov A., Belev N., Dimitrov D., Dusek T., Ntomi V., Sotiropoulos G. C., Theodorou D., Nikiteas N., Balalis D., Antropoli C., Altomare D. F., Luglio G., De Palma G. D., Pedrazzani C., Simonelli L., Brozzetti S., Porcu A., Massani M., Grazi G. L., Izzo F., Delrio P., Restini E., Chetta G., Lantone G., Ferrari G., Lucchi A., De Prizio M., Caristo G., Borghi F., Petrucciani N., Huscher C., Cocorullo G., Tonini V., Medas F., Sica G., Cillara N., Anastasi A., Bianco F., Giuliani A., Carlini M., Selvaggi F., Sammarco G., Ozolins A., Malasonoks A., Andrejevic P., Tanis P., van de Ven A., Gerhards M., Ribeiro da Silva B., Silva A., Lima M. J., Kavanagh D., McCawley N., Bintintan V., Karamarkovic A., Sanz Ortega G., De Andres-Asenjo B., Nevado Garcia C., Garcia Florez L. J., Segura-Sampedro J. J., Blas Laina J. L., Ponchietti L., Buchwald P., Gialamas E., Ozben V., Rencuzogullari A., Gecim I. E., Altinel Y., Isik O., Yoldas T., Isik A., Leventoglu S., Erturk M. S., Guner A., Guler S. A., Attaallah W., Ugur M., Ozbalci G. S., Marzook H., Eardley N., Smolarek S., Morgan R., Roxburgh C., Lala A. K., Salama Y., Singh B., Khanna A., Evans M., Shaikh I., Maradi Thippeswamy K., Appleton B., Moug S., Smith I., Smart N., Shah P., Williams G., Khera G., Goede A., Varcada M., Parmar C., Duff S., Hargest R., Marriott P., Speake D., Ben Sassi A., Furfaro B., Daudu D., Golijanin N., Yek W. Y., Capasso G., Mansour L. 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Randisi B., Dominici D.M., Sartarelli L., Zanni M., Pisanu A., Soddu C., Delogu D., Erdas E., Campus F., Cappellacci F., Casti F., Marcialis J., Atzeni J., Podda M.G., Sensi B., Franceschilli M., Bellato V., Cannavera A., Putzu G., di Mola F.F., Picardi B., Solinas L., Loponte M., Rossi del Monte S., Di Martino C., Linari C., Spagni G., Capezzuoli L., Tirloni L., Nelli T., Caridi A., Elter C., Camassa M., D'Amico S., Bargellini T., Incollingo P., Montuori M., Maffione F., Romano L., Valiyeva S., Spoletini D., Menegon Tasselli F., Sciaudone G., Selvaggi L., Menna M.P., De Paola G., Fulginiti S., Truskovs A., Weiss C., Saknitis G., Rauscher J.T.R., Larnovskis J., Jeyarajan-Davidsson M., Nitisa D., Gille N., Reiser S.C., Roshan M.H.K., Leseman C., Chen J., van Dalen A.S., Top C., Detering R., Matos C., Silva C., Pinto D., Mendes J., Couto J., Leite M., Velez C., Damasio Cotovio M., Cinza A.M., Pedroso de Lima R., Boyle E., Yang H.W., Banerjee I., Rahmat S., Afzal Z., Reid C., Dumitrascu F., Croyle J.A., Gressmann K., Cullen N., Graham A., Nasehi A., Montano King C., Martin B., Stokell C., Sanderson N., Farnan R., Jassim S., Chan B., Chua Vi Long K., Kaka N., Pandey S., Neo W.X., Chitul A., Bezede C., Cincilei D., David A., Blaga M., Blaga S.N., Fagarasan V., Khetagurova M., Rodimov S., Kapustina A., Mekhralyzade A., Zabiyaka M., Jankovic U., Cuk V., Hajska M., Dubovsky M., Hrosova M., Ferancikova N., Camarero Rodriguez E., Laguna Alcantara F., Adarraga J., Jezieniecki C., Ruiz Soriano M., Gomez Sanz T., Suarez A., Sanchez Garcia C., Cifrian Canales I., Llosa Perez J., Merayo M., Urbieta A., Gegundez Simon A., Tone J.F., Gazo Martinez J., Vicario Bravo M., Chavarrias N., Gil Catalan A., Oseira A., Villalonga B., Jeri S., Perez Calvo J., Nogues A., Cros B., Yanez C., Utrilla Fornals A., Roldon Golet M., Colsa P., Gimenez Maurel T., Axmarker T., Chevallay M., Pham T.V., Sel E.K., Atar C., Aba M., Sarkin M., Akkaya Y.M., Durmaz A.G., Gullu H.F., Boga A., Aktas A., Bakar 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B., Zaffaroni, G., Benuzzi, L., Ferrario, L., Cigognini, M., Mazzeo, C., Badessi, G., Pintabona, G., Fassari, A., Mingoli, A., Cirillo, B., D'Alterio, C., Brachini, G., Tancredi, M., Zambon, M., Aulicino, M., Sapienza, P., Liberatore, P., Scanu, A. M., Feo, C. F., Iacomino, A., Pelizzo, P., Rossi, S., Vigna, S. A., Grossi, U., Grillo, V., Agnes, A., Schena, C. A., Marincola, G., Oddi, A., Perotti, B., Mario, V., Perri, P., Zazza, S., Aversano, A., Scala, D., Di Lauro, K., Leongito, M., Piccirillo, M., Patrone, R., Capuzzolo, S., Vignotto, C., Bao, Q. R., Giuseppe, C., Angarano, E., Marino, F., Pezzolla, F., Gigante, G., Magistro, C., Crippa, J., Maspero, M., Carnevali, P., Trapani, R., Zonta, S., Agostinelli, L., Vittori, L., Romeo, L., Doria, E., Farnesi, F., Danna, R., Andolfi, E., Pellicano', G. A., Angelini, M., Scricciolo, M., Zanframundo, C., Ciulli, C., Ripamonti, L., Cigagna, L., Oldani, M., Larcinese, A., Rossi, D., Picone, E., Crescentini, G., Marano, A., Migliore, M., Giuffrida, M. C., Palagi, S., Testa, V., Borrello, A., Lucarini, A., Garofalo, E., Canali, G., Orlandi, P., Nervegna, F., Marchegiani, F., Damoli, I., Licata, A., Trovato, C., Alicata, F., Sardo, F., Milazzo, M., Randisi, B., Dominici, D. M., Sartarelli, L., Zanni, M., Pisanu, A., Soddu, C., Delogu, D., Erdas, E., Campus, F., Cappellacci, F., Casti, F., Marcialis, J., Atzeni, J., Podda, M. G., Sensi, B., Franceschilli, M., Bellato, V., Cannavera, A., Putzu, G., di Mola, F. F., Picardi, B., Solinas, L., Loponte, M., Rossi del Monte, S., Di Martino, C., Linari, C., Spagni, G., Capezzuoli, L., Tirloni, L., Nelli, T., Caridi, A., Elter, C., Camassa, M., D'Amico, S., Bargellini, T., Incollingo, P., Montuori, M., Maffione, F., Romano, L., Valiyeva, S., Spoletini, D., Menegon Tasselli, F., Sciaudone, G., Selvaggi, L., Menna, M. P., De Paola, G., Fulginiti, S., Truskovs, A., Weiss, C., Saknitis, G., Rauscher, J. T. R., Larnovskis, J., Jeyarajan-Davidsson, M., Nitisa, D., Gille, N., Reiser, S. C., Roshan, M. H. K., Leseman, C., Chen, J., van Dalen, A. S., Top, C., Detering, R., Matos, C., Silva, C., Pinto, D., Mendes, J., Couto, J., Leite, M., Velez, C., Damasio Cotovio, M., Cinza, A. M., Pedroso de Lima, R., Boyle, E., Yang, H. W., Banerjee, I., Rahmat, S., Afzal, Z., Reid, C., Dumitrascu, F., Croyle, J. A., Gressmann, K., Cullen, N., Graham, A., Nasehi, A., Montano King, C., Martin, B., Stokell, C., Sanderson, N., Farnan, R., Jassim, S., Chan, B., Chua Vi Long, K., Kaka, N., Pandey, S., Neo, W. X., Chitul, A., Bezede, C., Cincilei, D., David, A., Blaga, M., Blaga, S. N., Fagarasan, V., Khetagurova, M., Rodimov, S., Kapustina, A., Mekhralyzade, A., Zabiyaka, M., Jankovic, U., Cuk, V., Hajska, M., Dubovsky, M., Hrosova, M., Ferancikova, N., Camarero Rodriguez, E., Laguna Alcantara, F., Adarraga, J., Jezieniecki, C., Ruiz Soriano, M., Gomez Sanz, T., Suarez, A., Sanchez Garcia, C., Cifrian Canales, I., Llosa Perez, J., Merayo, M., Urbieta, A., Gegundez Simon, A., Tone, J. F., Gazo Martinez, J., Vicario Bravo, M., Chavarrias, N., Gil Catalan, A., Oseira, A., Villalonga, B., Jeri, S., Perez Calvo, J., Nogues, A., Cros, B., Yanez, C., Utrilla Fornals, A., Roldon Golet, M., Colsa, P., Gimenez Maurel, T., Axmarker, T., Chevallay, M., Pham, T. V., Sel, E. K., Atar, C., Aba, M., Sarkin, M., Akkaya, Y. M., Durmaz, A. G., Gullu, H. F., Boga, A., Aktas, A., Bakar, B., Demirel, M. T., Hysejni, X., Taser, M., Guzel, O. R., Bozbiyik, O., Ozen, D., Olmez, M., Uyar, B., Gulcek, E., Kayacan, G. S., Atici, N., Gul, O. F., Altiner, S., Ibis, B., Altunsu, S., Banaz, T., Diler, C., Demirbas, I., Usta, M. A., Erkul, O., Orman, R., Salih, S., Utkan, N. Z., Acil, C., Ozgur, E., Maddahali, M., Turhan, A. B., Eskici, A. B., Ular, B., Dogru, M., Ozturk, O. U., Arslan, E. R., Panahi Sharif, A., Dikmen, E., Ates, J., Bircan, R., Cavus, T., Sever, A. E., Balak, B., Duman, E., Altay, L., Emanet, O., Cullen, F., Tan, J. Y., Nathan, A., Rottenberg, A., Williams, C. Y., Mitrofan, C. G., Xu, D., Bawa, J. H., Morris, P., Gordon, D., Richmond, G., Hui, J. C., Ighomereho, O., Rocks, R., Mccabe, S., Fitzpatrick, A., Nicoletti, J., Auterson, L., Darrah, N., Soh, V. W. Y., Ong, C. S., Utukuri, M., Gallagher, C., Stuart, L. M., Hipolito, M., Douglas, N., Ghazal, R., Parris, G., Catchpole, J., Bryden, M., Jamal, S., Karim, Z., Lyon-Dean, C., Rowley, G., Lee, K. S., Whitehurst, O., Mirza, A., Sheikh, F., Yousaf, H., Bilbao, J., Sinclair, R., Takar, S., Kressel, H., Chan, V., Schack, K., Osborne, R., Baldemor, S., Smyth, S., Gilmour, S., Ting, A., Bozonelou, I., Saunders, P., Qhaireel Anwar, Q. A., Tirimanna, R., Jauhari, S., Gardener, A., Walker, B., Wenban, C., Reddy, H., Conway-Jones, R., Loganathan, S., Clynch, A., James, C., Matey, E., Cameron, F., Roberts, W., Gicquel, A., Milliken, C., Forbes, J., Rubinchik, P., Azmi, A., Hawkes, C., Cornett, L., Adarkwah, P., Mcconville, R., O'Hara, S., Tijare, C., Parkes, J., Yao, L., Ahmad, R., Shafiq, U., Mhaisalkar, A., Gurung, A., de Stadler, K., Elias, S., Thomas, T., Madras, A., Jani, A., Daler, H. K., Tong, K. S., Sundaralingam, S. S., Szal, A., Khan, A., O'Sullivan, C., Baker, E., Joseph-Gubral, J., Hadley, E., Trivedi, R., Igwelaezoh, E., Barton, H., Allison, W., Hurst, W., Alam, F., Parkes, I., Jamshaid, M., Azizan, N., Burgher, T., Afzal, A., Eltilib, I., Zahid, M., Sadiq, O., Lloyd, A., Ho, R., Brazukas, A., Li, C. H., Kamdar, M., Mohamed Nazeer, M. N., Mighiu, A., Kim, D., Wilkins, L., Kuo, L., Rafe, T., Maduka, D., Cheema, H., Farag, K., Abdellatif, M., Nzewi, R., Kruczynska, A., Grasselli, H., Yousuff, M., Bassi, R., Mann, A. K., Chopra, J., Shaikh, M., Sa, D. S., Tsimplis, V., Ghanchi, A., Skene, E., Asim, K., Zaheer, M., Chan, S., Dalton, H., Gibbons, K., Adderley, O., Chukwujindu, I., Jayasuriya, I., Sivanu, K., Borumand, M., Chick, G., Bridges, I., Tomlin, J., Mckenna, J., Nandra, N., Grieco, C., Quek, F. F., Mercer, R., Brankin-Frisby, T., Sattar, A., Aslam, A., Edelsten, E., Shafi, S., Kouli, T., Ford, V., Gurung, F., Fernandes, M., Deader, N., Ponniah, R., Jamieson, S., Davies, A., Taubwurcel, J., Aung, M. T., Desai, R., Begum, S., Jamadar, T., Kangatharan, A., Rzeszowski, B., Ho, C., Yap, S. H. K., Prendergast, M., Sethi, R., Duku, A., Lowe, C., Bray, J., Ghobrial, M., Nichita, V., Wagstaff, A., Rengasamy, E., Abu Hassan, F., Mahmood, H., Savill, N., Shah, S., Almeida, T., Edwards, A., Catchpole, B., Halford, Z., Carmichael, A., Alsusa, H., Boyd, M., Williams, J., Feyi-Waboso, J., Patel, M., Zeidan, Z., Bailey, E., Bapty, J., Brazkiewicz, M., Tremlett, A., Pringle, H., Mankal, S., Chung, W., Parry-Jones, E., Anderson, K., Mcforrester, A., Stanley, A., Hoather, A., Wise, H., Laid, I., Scriven, J., Braniste, A., Wilson, A., Le Blevec, L., Pakunwanich, N., Evans, N., Chong, H. L., White, C., Hunter, J., Haque, M., Vanalia, P., Murdoch, S., Choudhary, T., Mccann, A., Harun, A., Shah, H., Hunt, S., Shafiq, Y., Bickley-Morris, E., Emms, L., Dare, M., Akula, Y., Deliyannis, E., Mayes, F., Ellacott, M., Zagorac, Z., Farren, A., Manning, C., Hughed, C., Stewart, E. G., Lim, K. H., Chohan, N., Thaker, A., Thompson, B., Ahari, D., Burdekin, E., Okwu, U., Akintunde, A., Lhaf, F., Douthwaite, J., Govindan, R., Leelamanthep, S., Gull, E., Wright, F., Dundas, L., Mackdermott, N., Burchi-Khairy, T., Campbell, I., Walsh, J., Yeo, J. Y., Meehan, S., Banerjee, D., Fu, M., Kawka, M., Ali, T., Hussain, Z., Thomas, C., Ahmad, H., Moroney, J., Yick, C., Risquet, R., Ntuiabane, D., Shimato, M., Khan, M., Ilangovan, S., Vaselli, N. M., Smithers, R., Uhanowita Marage, R., Valnarov-Boulter, A., Kayran, J., Banerjee, M., Parekh-Hill, N., Hooper, A., Bowen, J., Jagdish, R., Mcquoid, C., Khan, N., O'Hare, R., Jeffery, S., Zahid, A., Elsworth, C., Walter, L., Dhillon, S., Rao, S., Anthony, A., Ashaye, A., Phillips, N., Faderani, R., Pengelly, S., Choi, S., Kwak, S. Y., Lau, Y. H. L., Bagheri, K., Ong, D. Y. C., Kerr, E., Falconer, K., Clancy, N., Douglas, S., Zhang, Y., Greenfield, F., Mutanga, I., Mcalinden, J., Willis, L., Adefolaju, A., Agarwal, H., Barter, R., Harris, G., Spencer, G., Lee, M. W., Vadiveloo, V. T., Herbert, G., Patel, R., Shah, M., El Falaha, S., Wong, C., Soare, C., Akram, J., Bozhkova, L., Ma, Y., Vo, U. G., Tan, H. W. N., Leto, L., Kamal, M. A., Hadzhieva, E., Krastev, P., Tonchev, P., Kokkinos, G., Pozotou, I., Sabbagh, D., Votava, J., St, F., Koliakos, N., Tsaparas, P., Zografos, G., Mantas, D., Tsourouflis, G., Fradelos, E., Trigiante, G., Labellarte, G., Resta, G., Capelli, G., D'Amore, A., Verlingieri, V., Campagnaro, T., Maffioli, A., Viscosi, F., De Lucia, C., Meneghini, S., Fancellu, A., Colella, M., Biondi, A., De Peppo, V., Pace, U., Albino, V., Gattulli, D., Piangerelli, A., Kalivaci, D., Sisto, G., Mazzola, M., Caneparo, A., Lunghi, E. G., Nespoli, L. C., Angrisani, M., Langone, A., Gelarda, E., Virgilio, E., Angelini, E., Fornasier, C., Asero, S., Filippone, E., Frongia, F., Calo, P. G., Panaccio, P., Ipponi, P., Gili, S., Braccio, B., Tiesi, V., Stolcers, K., Kokaine, L., Novikovs, V., Capel, L., Bastiaenen, V., Heijmans, H., Henriques, S., Gan, S. Z., Ramanayake, H., Nolan, M., Temperley, H., Ciofic, E., Pop, B. A., Kurtenkov, M., Jovanovic, M., Vician, M., Egea Arias, P., Beltran de Heredia, J., Labalde Martinez, M., De Santiago Alvarez, I., Alvarez-Gallego, M., Rodriguez Artigas, J. M., Dwidar, O., Korkmaz, H. K., Eray, I. C., Meric, S., Aydin, R., Cetin, B., Karaca, B. E., Kuyumcu, O. F., Yuksel, E., Uprak, T. K., Karabulut, K., Kavukcu, E., Mansor, A., Hackett, R., Zammit-Maempel, M., Sabaratnam, R., Maan, A., Ferarrio, I., Dixon, L., Halai, H., Sethi, S., Nelson, L., Grassam-Rowe, A., Krishnan, E., Deeny, D., Mckeever, M., George Pandeth, A., Dhavala, P., Sreenivasan, S., Sundaram Venkatesan, G., Zhu, L., Atiyah, Z., Gregory, J., Morey, T., Seymour, Z., Holdsworth, L., Abdelmahmoud, S., Bourhill, J., Bisheet, G., Shaw, J., Kulkarni, K., Kumarakulasingam, P., Pillay, S., Al-Habsi, R., Kungwengwe, G., Richards, J., Davoudi, K., Ibrahim, B., Tailor, B., Zayed, M., Chen, F., Bailey, S., Sheefat, S., Nawaz, G., Pawar, R., Marsh, S., Sam, Z. H., Roy Bentley, S., Simpson, C., Hughes, J., Lim, Y., Ooi, R., Toh, W. H., Mannion, P., Lovett, A., Kincius, A., Hussein, S., Kirby, E., Beckett, R. G., Salmon, J., Glynn, T., Choo, S. Y., Lyons, S., Browne, D., Ravindran, W., Ahmad, S., Zhu, X., Mcnulty, J., Mccarthy, L., Ng, J., Karmally, Z., Mcteir, K., Hanna, M., Tan, E., Namdeo, S., Schembri, R., and Pusey, E.
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Adult ,Elective Surgical Procedure ,Aged ,Cohort Studies ,Drainage ,Elective Surgical Procedures ,Female ,Humans ,Postoperative Complications ,Prospective Studies ,Surgical Wound Infection ,Colorectal Surgery ,drain ,intrabdominal ,Adult, Aged, Cohort Studies, Colorectal Surgery, Drainage, Elective Surgical Procedures, Female, Humans, Postoperative Complications, Prospective Studies, Surgical Wound Infection ,Settore MED/18 ,Settore MED/18 - Chirurgia Generale ,Prospective Studie ,Surgery ,Postoperative Complication ,Cohort Studie ,drain, intrabdominal ,Human - Abstract
Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien–Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk.
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- 2022
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14. Amino-terminal Cysteine Residues Differentially Influence RGS4 Protein Plasma Membrane Targeting, Intracellular Trafficking, and Function
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Bastin, Guillaume, Singh, Kevin, Dissanayake, Kaveesh, Mighiu, Alexandra S., Nurmohamed, Aliya, and Heximer, Scott P.
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- 2012
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15. Health state utilities for beta-thalassemia: a time trade-off study
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Grazzi, EF, Chevali, M, Mighiu, C, and Martin, Antony
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- 2022
16. RGS4-Deficiency Alters Intracellular Calcium and PKA-Mediated Control of Insulin Secretion in Glucose-Stimulated Beta Islets
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Stephanie Beadman, Scott P. Heximer, Hangjung Zhang, Lemieux Luu, Alexandra Mighiu, Dana Al Rijjal, Guillaume Bastin, Michael B. Wheeler, Changhao He, and Battsetseg Batchuluun
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medicine.medical_specialty ,QH301-705.5 ,medicine.medical_treatment ,Gi alpha subunit ,Medicine (miscellaneous) ,Context (language use) ,General Biochemistry, Genetics and Molecular Biology ,Calcium in biology ,Article ,RGS4 ,03 medical and health sciences ,0302 clinical medicine ,intracellular Ca2+ ,Internal medicine ,cAMP ,medicine ,Biology (General) ,glucose-stimulated insulin secretion ,030304 developmental biology ,0303 health sciences ,biology ,Chemistry ,Insulin ,Pancreatic islets ,RGS proteins ,Endocrinology ,medicine.anatomical_structure ,Gq alpha subunit ,biology.protein ,Signal transduction ,030217 neurology & neurosurgery - Abstract
A number of diverse G-protein signaling pathways have been shown to regulate insulin secretion from pancreatic β-cells. Accordingly, regulator of G-protein signaling (RGS) proteins have also been implicated in coordinating this process. One such protein, RGS4, is reported to show both positive and negative effects on insulin secretion from β-cells depending on the physiologic context under which it was studied. We here use an RGS4-deficient mouse model to characterize previously unknown G-protein signaling pathways that are regulated by RGS4 during glucose-stimulated insulin secretion from the pancreatic islets. Our data show that loss of RGS4 results in a marked deficiency in glucose-stimulated insulin secretion during both phase I and phase II of insulin release in intact mice and isolated islets. These deficiencies are associated with lower cAMP/PKA activity and a loss of normal calcium surge (phase I) and oscillatory (phase II) kinetics behavior in the RGS4-deficient β-cells, suggesting RGS4 may be important for regulation of both Gαi and Gαq signaling control during glucose-stimulated insulin secretion. Together, these studies add to the known list of G-protein coupled signaling events that are controlled by RGS4 during glucose-stimulated insulin secretion and highlight the importance of maintaining normal levels of RGS4 function in healthy pancreatic tissues.
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- 2021
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17. Hypothalamic glucagon signaling inhibits hepatic glucose production
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Mighiu, Patricia I., Yu, Jessica T.Y., Filippi, Beatrice M., Abraham, Mona A., Chari, Madhu, Lam, Carol K.L., Yang, Clair S., Christian, Nikita R., Charron, Maureen J., and Lam, Tony K.T.
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Cellular signal transduction -- Physiological aspects -- Genetic aspects -- Research ,Glucose metabolism -- Physiological aspects -- Genetic aspects -- Research ,Glucagon -- Physiological aspects -- Genetic aspects -- Research ,Biological sciences ,Health - Abstract
Glucagon activates hepatic protein kinase A (PKA) to increase glucose production (1), (2), but the glucostimulatory effect is transient even in the presence of continuous intravenous glucagon infusion (3-5). Continuous [...]
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- 2013
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18. Melatonin in children with autistic spectrum disorders: recent and practical data
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Doyen, C., Mighiu, D., Kaye, K., Colineaux, C., Beaumanoir, C., Mouraeff, Y., Rieu, C., Paubel, P., and Contejean, Y.
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- 2011
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19. Differential occupational risks to healthcare workers from SARS-CoV-2 observed during a prospective observational study
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Eyre, DW, Lumley, SF, O'Donnell, D, Campbell, M, Sims, E, Lawson, E, Warren, F, James, T, Cox, S, Howarth, A, Doherty, G, Hatch, SB, Kavanagh, J, Chau, KK, Fowler, PW, Swann, J, Volk, D, Yang-Turner, F, Stoesser, N, Matthews, PC, Dudareva, M, Davies, T, Shaw, RH, Peto, L, Downs, LO, Vogt, A, Amini, A, Young, BC, Drennan, PG, Mentzer, AJ, Skelly, DT, Karpe, F, Neville, MJ, Andersson, M, Brent, AJ, Jones, N, Martins Ferreira, L, Christott, T, Marsden, BD, Hoosdally, S, Cornall, R, Crook, DW, Stuart, DI, Screaton, G, Group, Oxford University Hospitals Staff Testing, Watson, AJ, Taylor, A, Chetwynd, A, Grassam-Rowe, A, Mighiu, AS, Peck, LJ, Ebner, D, and Conlon, CP
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Male ,0301 basic medicine ,serology ,law.invention ,0302 clinical medicine ,law ,Surveys and Questionnaires ,Health care ,Epidemiology ,Medicine ,risk factors ,030212 general & internal medicine ,Young adult ,Biology (General) ,Asymptomatic Infections ,Incidence ,General Neuroscience ,Incidence (epidemiology) ,Age Factors ,General Medicine ,Middle Aged ,Intensive care unit ,Virus ,3. Good health ,Intensive Care Units ,Female ,medicine.symptom ,Coronavirus Infections ,Covid-19 ,Research Article ,Adult ,Risk ,medicine.medical_specialty ,Infectious Disease Transmission, Patient-to-Professional ,Adolescent ,QH301-705.5 ,Health Personnel ,Science ,Pneumonia, Viral ,030106 microbiology ,Asymptomatic ,General Biochemistry, Genetics and Molecular Biology ,Betacoronavirus ,Young Adult ,03 medical and health sciences ,Humans ,Hospitals, Teaching ,Pandemics ,Aged ,General Immunology and Microbiology ,business.industry ,SARS-CoV-2 ,healthcare workers ,Odds ratio ,United Kingdom ,Epidemiology and Global Health ,Family medicine ,symptoms ,Observational study ,business - Abstract
We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034 (11.2%) staff had evidence of Covid-19 at some time. Using questionnaire data provided on potential risk-factors, staff with a confirmed household contact were at greatest risk (adjusted odds ratio [aOR] 4.82 [95%CI 3.45–6.72]). Higher rates of Covid-19 were seen in staff working in Covid-19-facing areas (22.6% vs. 8.6% elsewhere) (aOR 2.47 [1.99–3.08]). Controlling for Covid-19-facing status, risks were heterogenous across the hospital, with higher rates in acute medicine (1.52 [1.07–2.16]) and sporadic outbreaks in areas with few or no Covid-19 patients. Covid-19 intensive care unit staff were relatively protected (0.44 [0.28–0.69]), likely by a bundle of PPE-related measures. Positive results were more likely in Black (1.66 [1.25–2.21]) and Asian (1.51 [1.28–1.77]) staff, independent of role or working location, and in porters and cleaners (2.06 [1.34–3.15]).
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- 2020
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20. PCR67 Health State Utilities for Achondroplasia: A Time Trade-Off Study
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Mighiu, C., Morgan, G., Bharali, R., Butt, T., and Due, C.
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- 2023
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21. Linking Inflammation to the Brain-Liver Axis
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Mighiu, Patricia I., Filippi, Beatrice M., and Lam, Tony K.T.
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- 2012
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22. Is Insulin Action in the Brain Clinically Relevant?
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Filippi, Beatrice M., Mighiu, Patricia I., and Lam, Tony K.T.
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- 2012
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23. Glucose Transporter-1 in the Hypothalamic Glial Cells Mediates Glucose Sensing to Regulate Glucose Production In Vivo
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Chari, Madhu, Yang, Clair S., Lam, Carol K.L., Lee, Katie, Mighiu, Patricia, Kokorovic, Andrea, Cheung, Grace W.C., Lai, Teresa Y.Y., Wang, Penny Y.T., and Lam, Tony K.T.
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- 2011
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24. Inducibility, but not stability, of atrial fibrillation is increased by NOX2 overexpression in mice.
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Mighiu, Alexandra S, Recalde, Alice, Ziberna, Klemen, Carnicer, Ricardo, Tomek, Jakub, Bub, Gil, Brewer, Alison C, Verheule, Sander, Shah, Ajay M, Simon, Jillian N, and Casadei, Barbara
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ATRIAL fibrillation , *SUPEROXIDES , *MYOCARDIAL depressants , *LEFT heart atrium , *MICE , *HIGH performance liquid chromatography , *OXIDASES - Abstract
Aims Gp91-containing NADPH oxidases (NOX2) are a significant source of myocardial superoxide production. An increase in NOX2 activity accompanies atrial fibrillation (AF) induction and electrical remodelling in animal models and predicts incident AF in humans; however, a direct causal role for NOX2 in AF has not been demonstrated. Accordingly, we investigated whether myocardial NOX2 overexpression in mice (NOX2-Tg) is sufficient to generate a favourable substrate for AF and further assessed the effects of atorvastatin, an inhibitor of NOX2, on atrial superoxide production and AF susceptibility. Methods and results NOX2-Tg mice showed a 2- to 2.5-fold higher atrial protein content of NOX2 compared with wild-type (WT) controls, which was associated with a significant (twofold) increase in NADPH-stimulated superoxide production (2-hydroxyethidium by HPLC) in left and right atrial tissue homogenates (P = 0.004 and P = 0.019, respectively). AF susceptibility assessed in vivo by transoesophageal atrial burst stimulation was modestly increased in NOX2-Tg compared with WT (probability of AF induction: 88% vs. 69%, respectively; P = 0.037), in the absence of significant alterations in AF duration, surface ECG parameters, and LV mass or function. Mechanistic studies did not support a role for NOX2 in promoting electrical or structural remodelling, as high-resolution optical mapping of atrial tissues showed no differences in action potential duration and conduction velocity between genotypes. In addition, we did not observe any genotype difference in markers of fibrosis and inflammation, including atrial collagen content and Col1a1, Il-1β, Il-6, and Mcp-1 mRNA. Similarly, NOX2 overexpression did not have consistent effects on RyR2 Ca2+ leak nor did it affect PKA or CaMKII-mediated RyR2 phosphorylation. Finally, treatment with atorvastatin significantly inhibited atrial superoxide production in NOX2-Tg but had no effect on AF induction in either genotype. Conclusion Together, these data indicate that while atrial NOX2 overexpression may contribute to atrial arrhythmogenesis, NOX2-derived superoxide production does not affect the electrical and structural properties of the atrial myocardium. [ABSTRACT FROM AUTHOR]
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- 2021
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- View/download PDF
25. Burden of illness of progressive familial intrahepatic cholestasis in the US, UK, France, and Germany: study rationale and protocol of the PICTURE study.
- Author
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Ruiz-Casas, Leonardo, O'Hara, Sonia, Mighiu, Claudia, Finnegan, Alan, Taylor, Alison, Ventura, Emily, Dhawan, Anil, Murray, Karen F, Schattenberg, Jorn, Willemse, Jose, Karakaidos, Melanie, and Brrang, Harpreet
- Abstract
Background: Progressive familial intrahepatic cholestasis (PFIC) is an ultra-rare disease with a considerable burden on pediatric patients and their caregivers, impacting quality of life (QoL). The mortality rates highlight a significant need for efficacious treatments. Real-world data on associated costs and QoL are needed to gauge the potential impact of new pharmacological treatments.Methods: Clinical and socio-economic burden of PFIC on patients/caregivers, health systems, and society will be assessed. Patient/caregiver- and physician-level retrospective cross-sectional data will be collected from the US, UK, France, and Germany, for PFIC types 1, 2, 3.A representative sample of physicians will provide clinical and resource utilization information using an electronic Case Report Form (eCRF). Patient/caregiver surveys will collect socio-economic and QoL data, enabling assessment of PFIC impact on QoL. Mean costs (direct medical/non-medical, indirect) will be calculated.The study materials were reviewed by medical professionals and patient representatives and received ethical approval from the University of Chester.Discussion: The study aims to reveal the unmet medical need, disease burden, resource utilization, and costs of PFIC, to raise awareness with policymakers and healthcare professionals, and provide support for the patient/caregiver community. As novel PFIC therapies recently emerged, this study will yield quantifiable data for health technology assessments. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
26. PMU95 A Systematic Literature Review of Preference Studies in Haemophilia
- Author
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Morgan, G., Martin, A., Mighiu, C., Sagar, A., O'hara, J., Sawyer, E.K., and Li, N.
- Published
- 2020
- Full Text
- View/download PDF
27. Atrial fibrillation promotion by endurance exercise : demonstration and mechanistic exploration in an animal model
- Author
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Guasch, Eduard, Benito, Begoña, Qi, Xiaoyan, Cifelli, Carlo, Naud, Patrice, Shi, Yanfen, Mighiu, Alexandra, Tardif, Jean-Claude, Tadevosyan, Artavazd, Chen, Yu, Gillis, Marc-Antoine, Iwasaki, Yu-Ki, Dobrev, Dobromir, Mont, Lluis, Heximer, Scott, and Nattel, Stanley
- Subjects
Medizin ,ion currents ,arrhythmia mechanisms ,exercise training ,potassium channel - Abstract
ObjectivesThe goal of this study was to assess mechanisms underlying atrial fibrillation (AF) promotion by exercise training in an animal model.BackgroundHigh-level exercise training promotes AF, but the underlying mechanisms are unclear.MethodsAF susceptibility was assessed by programmed stimulation in rats after 8 (Ex8) and 16 (Ex16) weeks of daily 1-h treadmill training, along with 4 and 8 weeks after exercise cessation and time-matched sedentary (Sed) controls. Structural remodeling was evaluated by using serial echocardiography and histopathology, autonomic nervous system with pharmacological tools, acetylcholine-regulated potassium current (IKACh) with patch clamp recording, messenger ribonucleic acid expression with quantitative polymerase chain reaction, and regulators of G protein–signaling (RGS) 4 function in knockout mice.ResultsAF inducibility increased after 16 weeks of training (e.g., AF >30 s in 64% of Ex16 rats vs 15% of Sed rats; p < 0.01) and rapidly returned to baseline levels with detraining. Atropine restored sinus rhythm in 5 of 5 Ex rats with AF sustained >15 min. Atrial dilation and fibrosis developed after 16 weeks of training and failed to fully recover with exercise cessation. Parasympathetic tone was increased in Ex16 rats and normalized within 4 weeks of detraining. Baroreflex heart rate responses to phenylephrine-induced blood pressure elevation and IKACh sensitivity to carbachol were enhanced in Ex16 rats, implicating both central and end-organ mechanisms in vagal enhancement. Ex rats showed unchanged cardiac adrenergic and cholinergic receptor and IKACh-subunit gene expression, but significant messenger ribonucleic acid downregulation of IKACh-inhibiting RGS proteins was present at 16 weeks. RGS4 knockout mice showed significantly enhanced sensitivity to AF induction in the presence of carbachol.ConclusionsChronic endurance exercise increased AF susceptibility in rats, with autonomic changes, atrial dilation, and fibrosis identified as potential mechanistic contributors. Vagal promotion is particularly important and occurs via augmented baroreflex responsiveness and increased cardiomyocyte sensitivity to cholinergic stimulation, possibly due to RGS protein downregulation.
- Published
- 2013
28. P783: CLINICAL, HUMANISTIC, AND ECONOMIC BURDEN IN PATIENTS WITH PNH RECEIVING C5 INHIBITION TREATMENT ACROSS UK, GERMANY, AND FRANCE. INSIGHTS FROM THE COMMODORE BURDEN OF ILLNESS STUDY.
- Author
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Terriou, Louis, Piggin, Maria, Burmester, Pascale, Zhang, Fengkui, Finnegan, Alan, Kritikou, Persefoni, Mighiu, Claudia, Buehrer, Christian, Katz, Pablo, Mode, Selma, Studera, Xenia, Trinh, Huong, and Munir, Talha
- Published
- 2023
- Full Text
- View/download PDF
29. Controlling Parasympathetic Regulation of Heart Rate: A Gatekeeper Role for RGS Proteins in the Sinoatrial Node
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Alexandra Mighiu and Scott P. Heximer
- Subjects
Chronotropic ,medicine.medical_specialty ,sinoatrial node ,Physiology ,Review Article ,lcsh:Physiology ,RGS4 ,Physiology (medical) ,Internal medicine ,Muscarinic acetylcholine receptor ,Heart rate ,medicine ,G protein-coupled inwardly-rectifying potassium channel ,bradyarrhythmia ,lcsh:QP1-981 ,biology ,business.industry ,Sinoatrial node ,Potassium channel ,medicine.anatomical_structure ,Endocrinology ,biology.protein ,RGS protein ,parasympathetic signaling ,GIRK channels ,business ,RGS Proteins ,Neuroscience - Abstract
Neurotransmitters released from sympathetic and parasympathetic nerve terminals in the SAN exert their effects via G-protein-coupled receptors. Integration of these different G-protein signals within pacemaker cells of the sinoatrial node (SAN) is critical for proper regulation of heart rate and function. For example, excessive parasympathetic signaling can be associated with sinus node dysfunction and supraventricular arrhythmias. Our previous work has shown that one member of the regulator of G-protein signaling (RGS) protein family, RGS4, is highly and selectively expressed in pacemaker cells of the SAN. Consistent with its role as an inhibitor of parasympathetic signaling, RGS4-knockout mice have reduced basal heart rates and enhanced negative chronotropic responses to parasympathetic agonists. Moreover, RGS4 appears to be an important part of SA nodal myocyte signaling pathways that mediate G protein-coupled inwardly-rectifying potassium channel (GIRK) channel activation/deactivation and desensitization. Since RGS4 acts immediately downstream of M2 muscarinic receptors, it is tempting to speculate that RGS4 functions as a master regulator of parasympathetic signaling upstream of GIRKs, HCNs and L-type Ca2+ channels in the SAN. Thus, loss of RGS4 function may lead to increased susceptibility to conditions associated with increased parasympathetic signaling, including bradyarrhythmia, sinus node dysfunction, and atrial fibrillation.
- Published
- 2012
- Full Text
- View/download PDF
30. Melatonin in children with autistic spectrum disorders: recent and practical data
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Y. Mouraeff, C. Colineaux, D. Mighiu, Y. Contejean, C. Beaumanoir, K. Kaye, P. Paubel, C. Doyen, C. Rieu, Department of Child and Adolescent Psychopathology, Sainte Anne Hospital, and Department of Pharmacy and Sterilization
- Subjects
Sleep Wake Disorders ,medicine.medical_specialty ,Pediatrics ,endocrine system ,Autism ,Neurological disorder ,behavioral disciplines and activities ,Melatonin ,03 medical and health sciences ,0302 clinical medicine ,mental disorders ,Developmental and Educational Psychology ,medicine ,Child and adolescent psychiatry ,Pervasive developmental disorder ,Humans ,0501 psychology and cognitive sciences ,Child ,Psychiatry ,Sleep disorder ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Disorders ,05 social sciences ,General Medicine ,medicine.disease ,Childhood ,3. Good health ,Developmental disorder ,Psychiatry and Mental health ,Child Development Disorders, Pervasive ,Autism spectrum disorder ,Pediatrics, Perinatology and Child Health ,Psychology ,Sleep ,030217 neurology & neurosurgery ,hormones, hormone substitutes, and hormone antagonists ,050104 developmental & child psychology ,medicine.drug - Abstract
International audience; Over the last 20 years, melatonin, a pineal hormone synthesized from serotonin, has been implicated in various studies on the autism spectrum disorder (ASD) and altered melatonin levels were detected in subgroups of subjects with ASD. Its effect on sleep disturbances got the attention of clinicians and several investigations were carried out to determine the usefulness and safety of melatonin administration in this disorder. Hypotheses were also raised regarding the possibility that the dysfunctional synthesis and secretion of melatonin detected in subgroups of subjects with ASD may increase the risk as well the severity of ASD. The purpose of this paper is to review our pharmacokinetic knowledge on melatonin and present results from recent studies on sleep disorders in autism, their treatment with melatonin and the impact of melatonin prescription in children with ASD evaluated in a Diagnostic Center for Autism Spectrum Disorder in Paris, France.
- Published
- 2011
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31. Controlling parasympathetic regulation of heart rate: a gatekeeper role for RGS proteins in the sinoatrial node.
- Author
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Mighiu, Alexandra S. and Heximer, Scott P.
- Subjects
HEART beat ,PARASYMPATHETIC nervous system ,NERVE endings ,SINOATRIAL node ,G proteins ,PACEMAKER cells ,POTASSIUM channels ,PHYSIOLOGY - Abstract
Neurotransmitters released from sympathetic and parasympathetic nerve terminals in the sinoatrial node (SAN) exert their effects via G-protein-coupled receptors. Integration of these different G-protein signals within pacemaker cells of the SAN is critical for proper regulation of heart rate and function. For example, excessive parasympathetic signaling can be associated with sinus node dysfunction (SND) and supraventricular arrhythmias. Our previous work has shown that one member of the regulator of G-protein signaling (RGS) protein family, RGS4, is highly and selectively expressed in pacemaker cells of the SAN. Consistent with its role as an inhibitor of parasympathetic signaling, RGS4-knockout mice have reduced basal heart rates and enhanced negative chronotropic responses to parasympathetic agonists. Moreover, RGS4 appears to be an important part of SA nodal myocyte signaling pathways that mediate G-protein-coupled inwardly rectifying potassium channel (GIRK) channel activation/deactivation and desensitization. Since RGS4 acts immediately downstream of M2 muscarinic receptors, it is tempting to speculate that RGS4 functions as a master regulator of parasympathetic signaling upstream of GIRKs, HCNs, and L-type Ca
2+ channels in the SAN. Thus, loss of RGS4 function may lead to increased susceptibility to conditions associated with increased parasympathetic signaling, including bradyarrhythmia, SND, and atrial fibrillation. [ABSTRACT FROM AUTHOR]- Published
- 2012
- Full Text
- View/download PDF
32. Glycine Normalizes Hepatic Triglyceride-Rich VLDL Secretion by Triggering the CNS in High-Fat Fed Rats.
- Author
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Yue, Jessica T.Y., Mighiu, Patricia I., Naples, Mark, Adeli, Khosrow, and Lam, Tony K.T.
- Published
- 2012
- Full Text
- View/download PDF
33. RGS4-Deficiency Alters Intracellular Calcium and PKA-Mediated Control of Insulin Secretion in Glucose-Stimulated Beta Islets.
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Bastin, Guillaume, Luu, Lemieux, Batchuluun, Battsetseg, Mighiu, Alexandra, Beadman, Stephanie, Zhang, Hangjung, He, Changhao, Al Rijjal, Dana, Wheeler, Michael B., and Heximer, Scott P.
- Subjects
INTRACELLULAR calcium ,INSULIN ,SECRETION ,LABORATORY mice ,ISLANDS of Langerhans - Abstract
A number of diverse G-protein signaling pathways have been shown to regulate insulin secretion from pancreatic β-cells. Accordingly, regulator of G-protein signaling (RGS) proteins have also been implicated in coordinating this process. One such protein, RGS4, is reported to show both positive and negative effects on insulin secretion from β-cells depending on the physiologic context under which it was studied. We here use an RGS4-deficient mouse model to characterize previously unknown G-protein signaling pathways that are regulated by RGS4 during glucose-stimulated insulin secretion from the pancreatic islets. Our data show that loss of RGS4 results in a marked deficiency in glucose-stimulated insulin secretion during both phase I and phase II of insulin release in intact mice and isolated islets. These deficiencies are associated with lower cAMP/PKA activity and a loss of normal calcium surge (phase I) and oscillatory (phase II) kinetics behavior in the RGS4-deficient β-cells, suggesting RGS4 may be important for regulation of both Gαi and Gαq signaling control during glucose-stimulated insulin secretion. Together, these studies add to the known list of G-protein coupled signaling events that are controlled by RGS4 during glucose-stimulated insulin secretion and highlight the importance of maintaining normal levels of RGS4 function in healthy pancreatic tissues. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
34. A fatty acid-dependent hypothalamic-DVC neurocircuitry that regulates hepatic secretion of triglyceride-rich lipoproteins.
- Author
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Yue, Jessica T. Y., Abraham, Mona A., LaPierre, Mary P., Mighiu, Patricia I., Light, Peter E., Filippi, Beatrice M., and Lam, Tony K. T.
- Published
- 2015
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- View/download PDF
35. Atrial Fibrillation Promotion by Endurance Exercise.
- Author
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Guasch, Eduard, Benito, Begona, Xiaoyan Qi, Cifelli, Carlo, Naud, Patrice, Yanfen Shi, Mighiu, Alexandra, Tardif, Jean-Claude, Tadevosyan, Artavazd, Yu Chen, Gillis, Marc-Antoine, Iwasaki, Yu-Ki, Dobrev, Dobromir, Mont, Lluis, Heximer, Scott, and Nattel, Stanley
- Subjects
- *
ATRIAL fibrillation , *DISEASE susceptibility , *TREADMILL exercise , *ECHOCARDIOGRAPHY , *G proteins , *POTASSIUM channels , *LABORATORY rats - Abstract
Objectives: The goal of this study was to assess mechanisms underlying atrial fibrillation (AF) promotion by exercise training In an animal model. Background: High-level exercise training promotes AF, but the underlying mechanisms are unclear. Methods: AF susceptibility was assessed by programmed stimulation in rats after 8 (Ex8) and 16 (Exl6) weeks of daily 1-h treadmill training, along with 4 and 8 weeks after exercise cessation and time-matched sedentary (Sed) controls. Structural remodeling was evaluated by using serial echocardiography and hlstopathology, autonomic nervous system with pharmacological tools, acetylcholine-regulated potassium current (lKAch) with patch clamp recording, messenger ribonucleic acid expression with quantitative polymerase chain reaction, and regulators of G protein-signaling (RGS) 4 function in knockout mice. Results: AF inducibility Increased after 16 weeks of training (e.g., AF >30 s in 64% of Exl6 rats vs 15% of Sed rats; p < 0.01) and rapidly returned to baseline levels with detraining. Atropine restored sinus rhythm in 5 of 5 Ex rats with AF sustained >15 min. Atrial dilation and fibrosis developed after 16 weeks of training and failed to fully recover with exercise cessation. Parasympathetic tone was increased in Exl6 rats and normalized within 4 weeks of detraining. Baroreflex heart rate responses to phenylephrine-induced blood pressure elevation and 'KACh sensitivity to carbachol were enhanced In Exl6 rats, implicating both central and end-organ mechanisms in vagal enhancement. Ex rats showed unchanged cardiac adrenergic and cholinergic receptor and lKAch-subunit gene expression, but significant messenger ribonucleic acid downregulation of lch-inhlbltlng RGS proteins was present at 16 weeks. RGS4 knockout mice showed significantly enhanced sensitivity to AF Induction in the presence of carbachol. Conclusions: Chronic endurance exercise Increased AF susceptibility in rats, with autonomic changes, atrial dilation, and fibrosis Identified as potential mechanistic contributors. Vagal promotion Is particularly important and occurs via augmented baroreflex responsiveness and increased cardiomyocyte sensitivity to cholinergic stimulation, possibly due to RGS protein downregulation. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
36. Prognostic factors and predictive models in hot gallbladder surgery: A prospective observational study in a high-volume center.
- Author
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Tebala GD, Shabana A, Patel M, Samra B, Chetwynd A, Nixon M, Pradhan S, Elhag B, Mok G, Mighiu A, Antunes D, Slack Z, Cirocchi R, and Bond-Smith G
- Abstract
Backgrounds/aims: The standard treatment for acute cholecystitis, biliary pancreatitis and intractable biliary colics ("hot gallbladder") is emergency laparoscopic cholecystectomy (LC). This paper aims to identify the prognostic factors and create statistical models to predict the outcomes of emergency LC for "hot gallbladder.", Methods: A prospective observational cohort study was conducted on 466 patients having an emergency LC in 17 months. Primary endpoint was "suboptimal treatment," defined as the use of escape strategies due to the impossibility to complete the LC. Secondary endpoints were postoperative morbidity and length of postoperative stay., Results: About 10% of patients had a "suboptimal treatment" predicted by age and low albumin. Postop morbidity was 17.2%, predicted by age, admission day, and male sex. Postoperative length of stay was correlated to age, low albumin, and delayed surgery., Conclusions: Several predictive prognostic factors were found to be related to poor emergency LC outcomes. These can be useful in the decision-making process and to inform patients of risks and benefits of an emergency vs. delayed LC for hot gallbladder.
- Published
- 2024
- Full Text
- View/download PDF
37. Risks of infection, hospital and ICU admission, and death from COVID-19 in people with asthma: systematic review and meta-analyses.
- Author
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Otunla A, Rees K, Dennison P, Hobbs R, Suklan J, Schofield E, Gunnell J, Mighiu A, and Hartmann-Boyce J
- Subjects
- Adult, Child, Hospitalization, Humans, Intensive Care Units, SARS-CoV-2, Asthma complications, Asthma epidemiology, Asthma therapy, COVID-19, Cross Infection
- Abstract
Objectives: To determine if and to what degree asthma may predispose to worse COVID-19 outcomes in order to inform treatment and prevention decisions, including shielding and vaccine prioritisation., Design: Systematic review and meta-analysis., Setting: Electronic databases were searched (October 2020) for clinical studies reporting at least one of the following stratified by asthma status: risk of infection with SARS-CoV-2; hospitalisation, intensive care unit (ICU) admission or mortality with COVID-19., Participants: Adults and children who tested positive for or were suspected to have COVID-19., Main Outcome Measures: Main outcome measures were the following stratified by asthma status: risk of infection with SARS-CoV-2; hospitalisation, ICU admission or mortality with COVID-19. We pooled odds ratios (ORs) and presented these with 95% confidence intervals (CI). Certainty was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations)., Results: 30 (n=112 420) studies were included (12 judged high quality, 15 medium, 3 low). Few provided indication of asthma severity. Point estimates indicated reduced risks in people with asthma for all outcomes, but in all cases the evidence was judged to be of very low certainty and 95% CIs all included no difference and the possibility of increased risk (death: OR 0.90, 95% CI 0.72 to 1.13, I
2 =58%; hospitalisation: OR 0.95, 95% CI 0.71 to 1.26; ICU admission: OR 0.96, 95% CI 0.75 to 1.24). Findings on hospitalisation are also limited by substantial unexplained statistical heterogeneity. Within people with asthma, allergic asthma was associated with less COVID-19 risk and concurrent chronic obstructive pulmonary disease was associated with increased risk. In some studies, corticosteroids were associated with increased risk, but this may reflect increased risk in people with more severe asthma., Conclusions: Though absence of evidence of a clear association between asthma and worse outcomes from COVID-19 should not be interpreted as evidence of absence, the data reviewed indicate that risks from COVID-19 in people with asthma, as a whole, may be less than originally anticipated., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2022
- Full Text
- View/download PDF
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