Author: "Graham, Brett" / Database: Supplemental Index - Searchworks@Jio Institute Digital Library Search Results

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1. Synaptic wiring motifs in posterior parietal cortex support decision-making

Author: Kuan, Aaron T., Bondanelli, Giulio, Driscoll, Laura N., Han, Julie, Kim, Minsu, Hildebrand, David G. C., Graham, Brett J., Wilson, Daniel E., Thomas, Logan A., Panzeri, Stefano, Harvey, Christopher D., and Lee, Wei-Chung Allen
Abstract: The posterior parietal cortex exhibits choice-selective activity during perceptual decision-making tasks1–10. However, it is not known how this selective activity arises from the underlying synaptic connectivity. Here we combined virtual-reality behaviour, two-photon calcium imaging, high-throughput electron microscopy and circuit modelling to analyse how synaptic connectivity between neurons in the posterior parietal cortex relates to their selective activity. We found that excitatory pyramidal neurons preferentially target inhibitory interneurons with the same selectivity. In turn, inhibitory interneurons preferentially target pyramidal neurons with opposite selectivity, forming an opponent inhibition motif. This motif was present even between neurons with activity peaks in different task epochs. We developed neural-circuit models of the computations performed by these motifs, and found that opponent inhibition between neural populations with opposite selectivity amplifies selective inputs, thereby improving the encoding of trial-type information. The models also predict that opponent inhibition between neurons with activity peaks in different task epochs contributes to creating choice-specific sequential activity. These results provide evidence for how synaptic connectivity in cortical circuits supports a learned decision-making task.
Published: 2024
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2. Study of Rivaroxaban for Cerebral Venous Thrombosis: A Randomized Controlled Feasibility Trial Comparing Anticoagulation With Rivaroxaban to Standard-of-Care in Symptomatic Cerebral Venous Thrombosis.

Author: Field, Thalia S., Dizonno, Vanessa, Almekhlafi, Mohammed A., Bala, Fouzi, Alhabli, Ibrahim, Wong, Hubert, Norena, Monica, Villaluna, Maria Karina, King-Azote, Princess, Ratnaweera, Namali, Mancini, Steven, Van Gaal, Stephen C., Wilson, Laura K., Graham, Brett R., Sposato, Luciano A., Blacquiere, Dylan, Dewar, Brian M., Boulos, Mark I., Buck, Brian H., and Odier, Celine
Published: 2023
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3. Post Stroke Visual Impairment: Interdisciplinary Collaborative Program – Canadian Perspective

Author: Hyndman, Joel, Whelan, Ruth K., and Graham, Brett
Abstract: ABSTRACTPost-stroke visual impairment (PSVI) affects more than 60% of the people who have a stroke but visual function is not routinely assessed in most stroke units. Recent high-quality research in this field has produced evidence-based assessment and management practices for PSVI. Orthoptists have integrated into the stroke care team in the United Kingdom (UK) to provide this valuable service. This paper outlines the development and implementation of the first known orthoptic PSVI service in North America. A pilot program was developed between the Ophthalmology, Neurology, and Physical Medicine and Rehabilitation Departments in Saskatoon, Saskatchewan, Canada. A new referral pathway was established to refer stroke patients with PSVI directly to an orthoptist with specialization in PSVI. Clinical findings from the first year of operation are reported. One hundred and seven visual deficits were suspected by the referring service. Visual field deficits were the most commonly reported PSVI. Diplopia was the most commonly reported oculomotor deficit in this cohort, and visual neglect/inattention was the most common visual perceptual deficit reported. Reading issues were the most commonly reported functional issues. Following assessment by an orthoptist, 45 additional visual deficits were identified and addressed. Stroke patients require assessment and treatment for PSVI. Orthoptists are perfectly suited to PSVI assessment and management. There is an opportunity to increase orthoptists’ scope of practice in North America to ensure stroke patients receive specialized vision assessment and treatment.
Published: 2024
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4. Pancytopenia, Hepatomegaly, and Neurologic Abnormalities in Two Pediatric Patients

Author: Martin, Olufunke Y., Hamby, Deborah K., Graham, Brett H., and Jacob, Seethal A.
Published: 2023
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5. A Novel, Paresthesia-Free Spinal Cord Stimulation Waveform for Chronic Neuropathic Low Back Pain: Six-Month Results of a Prospective, Single-Arm, Dose-Response Study

Author: Russo, Marc A., Volschenk, Willem, Bailey, Dominic, Santarelli, Danielle M., Holliday, Elizabeth, Barker, Daniel, Dizon, Jason, and Graham, Brett
Abstract: The aim of this prospective, single-blinded, dose-response study was to evaluate the safety and efficacy of a novel, paresthesia-free (subperception) spinal cord stimulation (SCS) waveform designed to target dorsal horn dendrites for the treatment of chronic neuropathic low back pain (LBP).
Published: 2023
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6. The FAST VAN for Field Identification of Large Vessel Occlusion in Acute Stroke

Author: Wasyliw, Sanchea, Whelan, Ruth, Davy, Kim, Kelly, Michael E., Graham, Brett, Gould, Layla, and Hunter, Gary
Abstract: ABSTRACT:Background:There is definitive evidence for effectiveness of thrombectomy for acute stroke with large vessel occlusion (LVO). A clinical tool to identify patients with LVO is therefore required for effective triage and prehospital decision making. We developed the FAST VAN tool, which follows from the Heart and Stroke Foundation FAST stroke screen, with the addition of cortical features of vision, aphasia, and neglect, to differentiate from lacunar syndromes.Methods:Consecutive acute stroke alerts initiated by emergency medical services (EMS) were prospectively analyzed from April 2017 to Jan 2021. FAST VAN signs were recorded by first responders who had received online education about the tool. These findings were compared to the presence or absence of LVO on CT angiography. Analysis was also performed by appropriateness for comprehensive stroke centers (CSC) transfer if no LVO was present. EMS providers were surveyed regarding ease of use in terms of learning the tool and using in real-world practice.Results:Data from 1080 consecutive acute strokes included 440 patients considered to have VAN signs by EMS. Fifty-four percent of VAN-positive patients showed LVO on CTA. Sensitivity, specificity, and accuracy were 86%, 75%, and 77%, respectively. In 204 false-positive cases, 143 (70%) were considered appropriate for evaluation at the CSC. EMS providers reported high satisfaction with learning and using the tool.Discussion:The FAST VAN tool for identification of LVO meets desired characteristics of an effective screening tool in ease of use, efficiency, and accuracy. Aphasia remains the most challenging cortical feature to identify accurately.
Published: 2023
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7. Evaluating Communication Training at AVMA COE–Accredited Institutions and the Need to Consider Diversity within Simulated Client Pools

Author: Soltero, Elizabeth, Villalobos, César D., Englar, Ryane E., and Graham Brett, Teresa
Abstract: AbstractThe push for competency-based veterinary medical education by accrediting bodies has led to the inclusion of non-technical skills within curricula. Communication, self-awareness, and cultural humility are considered essential for post-graduate success. To facilitate skills development, veterinary educators have incorporated a variety of modalities including lecture, group discussions, virtual and peer-assisted learning, role play, video review of consultations, and simulated clients (SCs). The overarching goal is developing students into self-reflective practitioners through exposure to clinical scenarios that enhance and embody diversity. Decision making about case management is subject to stereotypes, bias, and assumptions. Racial and ethnic disparities reported in health care can adversely impact patient outcomes. This study was conducted to evaluate communication training and diversity among SC pools within veterinary colleges. A questionnaire was electronically disseminated to assistant/associate deans and/or directors of curriculum/education at 54 American Veterinary Medical Association Council on Education–accredited or provisionally accredited colleges of veterinary medicine. Twenty-one institutions are represented within the data set. Participating institutions summarized their communication curricula: 18 (85.71%) used SCs. Over 55% of these did not track SC demographic data or social identities; among institutions that did track, SCs were primarily monolingual English-speaking (77%), non-disabled (94.2%), white (90.4%), non-Hispanic/Latinx (98.6%) women (57%) over age 56 (64%). Sixteen institutions agreed with the statement “I do not feel that our SC pool is adequately diverse.” Respondents shared that lack of time and capacity for recruitment were barriers to diversifying SC pools and proposed strategies to improve outreach.
Published: 2023
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8. ID: 329657 Rationale for Dorsal Horn Dendrite Stimulation

Author: Russo, Marc, Santarelli, Danielle, Nash, Richard, and Graham, Brett
Published: 2024
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9. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial

Author: Menon, Bijoy K, Buck, Brian H, Singh, Nishita, Deschaintre, Yan, Almekhlafi, Mohammed A, Coutts, Shelagh B, Thirunavukkarasu, Sibi, Khosravani, Houman, Appireddy, Ramana, Moreau, Francois, Gubitz, Gord, Tkach, Aleksander, Catanese, Luciana, Dowlatshahi, Dar, Medvedev, George, Mandzia, Jennifer, Pikula, Aleksandra, Shankar, Jai, Williams, Heather, Field, Thalia S, Manosalva, Alejandro, Siddiqui, Muzaffar, Zafar, Atif, Imoukhuede, Oje, Hunter, Gary, Demchuk, Andrew M, Mishra, Sachin, Gioia, Laura C, Jalini, Shirin, Cayer, Caroline, Phillips, Stephen, Elamin, Elsadig, Shoamanesh, Ashkan, Subramaniam, Suresh, Kate, Mahesh, Jacquin, Gregory, Camden, Marie-Christine, Benali, Faysal, Alhabli, Ibrahim, Bala, Fouzi, Horn, MacKenzie, Stotts, Grant, Hill, Michael D, Gladstone, David J, Poppe, Alexandre, Sehgal, Arshia, Zhang, Qiao, Lethebe, Brendan Cord, Doram, Craig, Ademola, Ayoola, Shamy, Michel, Kenney, Carol, Sajobi, Tolulope T, Swartz, Richard H, Srivastava, Abhilekh, Aljammaz, Ahmed M, Akindotun, Akintomide Femi, Jin, Albert Y, Fraser, Alexander, Khaw, Alexander V, Lemnaru, Alexandru, Southwell, Alisia, Ramji, Alnar, Alvarado-Bolaños, Alonso, Mouminah, Amr, Lahlouh, Amro B, Yu, Amy Y, Alrohimi, Anas, Lavoie, Andre, Rogge, Andrea, Micieli, Andrew, Nguyen, Andrew Linh, Callaghan-Brown, Angelique, Florendo-Cumbermack, Anita, Wadhwa, Ankur, Beaudoin, Ann-Marie, Cayley, Anne, Liddy, Anne Marie, Trivedi, Anurag, Katsanos, Aristeidis H, Shuaib, Ashfaq, Butt, Asif Javed, Bereznyakova, Olena, Beauchamp, Beth, Mahlitz, Breane, Graham, Brett R, Dewar, Brian, Buck, Brian H, Durafourt, Bryce A, Holtby, Caitlin, Jackson-Tarlton, Caitlin S, Bockus, Caitlyn, Stephenson, Caroline, Galloway, Camille, Odier, Céline, Deacon, Charles, Zerna, Charlotte, Vekhande, Chetan C, Bocti, Christian, Stapf, Christian, Hawkes, Christine, Stables, Christine Anne, Bogiatzi, Chrysi, Rodriguez, Claudia, Candale-Radu, Claudia, Murphy, Colleen, Casserly, Courtney Sarah, Fok, Daniel, Boasquevisque, Danielle de Sa, Wile, Daryl, Volders, David, Sahlas, Demetrios J, Shand, Elaine, Cora, Elena Adela, Battista, Eliane Di, Stewart, Eileen, Junk, Emily, Harrison, Emma L, Frenette, Eric, Teleg, Ericka, Abdellah, Eslam, Ghrooda, Esseddeeg, Akthar, Farhana, Evoy, François, Klein, Gary M, Maclean, Genoveva, Jickling, Glen C, Hawthorne, Glenda, Boyd, Gordon, Walker, Gregory, Saposnik, Gustavo, Lau, H Lee, Badr, Hanan E, Toma, Hassanain, Kalashyan, Hayrapet, Marion-Moffet, Hugo, Grant, Ian, Fatakdawala, Idris, Beaulieu-Boire, Isabelle, Williams, Janice, Brar, Jaskiran, Rivest, Jean, Wang, Jeffrey Z, Dawe, Jessica, Stang, Jillian, Day, Joanne, Miller, Jodi, Gorman, Johnathon, Hopyan, Julia Jasmine, Lee, Julian, Kromm, Julie, Foster, Kaitlyn, Ratnayake, Kanchana, Perera, Kanjana S, Murray, Karina Villaluna, Ryckborst, Karla, Lin, Katie, Sage, Kayla, Sivakuma, Keithan, MacDonald, Kelly A, Ng, Kelvin Kuan, Merchant, Ketki, Khan, Khurshid, Ghavami, Kimia, Johnston, Kyra, Mai, Lauren M, White, Leah, Barratt, Lee, Longpre, Linda, Crellin, Lisa, Peeling, Lissa, Piquette, Lori, Lomax, Lysa Boissé, Sadeghi, Mahsa, Kamra, Maneesha, Lavoie-April, Manuel, Moores, Margaret, Bullrich, Maria Bres, McClelland, Marie, Salluzzi, Marina, Wilcox, Mark, Boulos, Mark I, Marko, Martha, Boyko, Matthew, Lantagne-Hurtubise, Maude, AlHamid, May Adel, Shawawrah, Mays, Kelly, Michael E, Thorne, Michael W D, Shamy, Michel, Bussiere, Miguel, Dominc Tse, Ming Yin, Benguzzi, Mowad, Sharma, Mukul, Horton, Myles, Newcommon, Nancy, Simon, Nandy-Shelwine, Parks, Natalie E, Sultan, Nazeem, Markovic, Nevena, Daneault, Nicole, Ishaque, Noman, Fairall, Paige, Kostyrko, Pawel B, Stys, Peter K, Teal, Philip, Couillard, Philippe, King-Azote, Princess, Collier, Quentin, Epp, Rachel, Nair, Radhika, Joundi, Raed A, Jassal, Rajive, Schneider, Raphael, Hosseini, Reza, Bouchard, Rosalie, Whelan, Ruth, Cooley, S Regan, Sujanthan, Sajeevan, Mansoor, Salman, Yip, Samuel, Wasyliw, Sanchea, Taylor, Sean W., Friedman, Sebastian, Mann, Sharan, Maley, Sharleen Weese, Chiasson, Sherry, Hu, Sherry Xueying, Althubait, Shorog, Himed, Shuhira, Chen, Shuo, Bal, Simerpreet S, Page, Stacey A, Beck, Stacey D, Woodroffe, Stephanie, Reiter, Stephanie D, Gaal, Stephen van, Peters, Steven Ray, Darvesh, Sultan, Save, Supriya, Alcock, Susan, Piercey, Susannah, Adam, Suzie, Gosselin, Sylvie, Fitzpatrick, Tess, Perron, Thomas-Louis, Stewart, Tim, Benstead, Timothy J, Naidoo, Vishaya, Wahab, Wasan Abd, Oczkowski, Wiesław, Kingston, William, Leduc, William, To, William T H, Yu, Yeyao Joe, Liu, Zhongyu A, and Aljundi, Ziad Ezzat
Abstract: Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care.
Published: 2022
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10. Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke Update 2020

Author: Gladstone, David J., Lindsay, M. Patrice, Douketis, James, Smith, Eric E., Dowlatshahi, Dar, Wein, Theodore, Bourgoin, Aline, Cox, Jafna, Falconer, John B., Graham, Brett R., Labrie, Marilyn, McDonald, Lena, Mandzia, Jennifer, Ngui, Daniel, Pageau, Paul, Rodgerson, Amanda, Semchuk, William, Tebbutt, Tammy, Tuchak, Carmen, van Gaal, Stephen, Villaluna, Karina, Foley, Norine, Coutts, Shelagh, Mountain, Anita, Gubitz, Gord, Udell, Jacob A, McGuff, Rebecca, and Poppe, Alexandre Y.
Abstract: AbstractThe 2020 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for the Secondary Prevention of Strokeincludes current evidence-based recommendations and expert opinions intended for use by clinicians across a broad range of settings. They provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations address triage, diagnostic testing, lifestyle behaviors, vaping, hypertension, hyperlipidemia, diabetes, atrial fibrillation, other cardiac conditions, antiplatelet and anticoagulant therapies, and carotid and vertebral artery disease. This update of the previous 2017 guideline contains several new or revised recommendations. Recommendations regarding triage and initial assessment of acute transient ischemic attack (TIA) and minor stroke have been simplified, and selected aspects of the etiological stroke workup are revised. Updated treatment recommendations based on new evidence have been made for dual antiplatelet therapy for TIA and minor stroke; anticoagulant therapy for atrial fibrillation; embolic strokes of undetermined source; low-density lipoprotein lowering; hypertriglyceridemia; diabetes treatment; and patent foramen ovale management. A new section has been added to provide practical guidance regarding temporary interruption of antithrombotic therapy for surgical procedures. Cancer-associated ischemic stroke is addressed. A section on virtual care delivery of secondary stroke prevention services in included to highlight a shifting paradigm of care delivery made more urgent by the global pandemic. In addition, where appropriate, sex differences as they pertain to treatments have been addressed. The CSBPR include supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.
Published: 2022
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11. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial

Author: Hill, Michael D, Goyal, Mayank, Menon, Bijoy K, Nogueira, Raul G, McTaggart, Ryan A, Demchuk, Andrew M, Poppe, Alexandre Y, Buck, Brian H, Field, Thalia S, Dowlatshahi, Dar, van Adel, Brian A, Swartz, Richard H, Shah, Ruchir A, Sauvageau, Eric, Zerna, Charlotte, Ospel, Johanna M, Joshi, Manish, Almekhlafi, Mohammed A, Ryckborst, Karla J, Lowerison, Mark W, Heard, Kathy, Garman, David, Haussen, Diogo, Cutting, Shawna M, Coutts, Shelagh B, Roy, Daniel, Rempel, Jeremy L, Rohr, Axel CR, Iancu, Daniela, Sahlas, Demetrios J, Yu, Amy Y X, Devlin, Thomas G, Hanel, Ricardo A, Puetz, Volker, Silver, Frank L, Campbell, Bruce C V, Chapot, René, Teitelbaum, Jeanne, Mandzia, Jennifer L, Kleinig, Timothy J, Turkel-Parrella, David, Heck, Donald, Kelly, Michael E, Bharatha, Aditya, Bang, Oh Young, Jadhav, Ashutosh, Gupta, Rishi, Frei, Donald F, Tarpley, Jason W, McDougall, Cameron G, Holmin, Staffan, Rha, Joung-Ho, Puri, Ajit S, Camden, Marie-Christine, Thomalla, Götz, Choe, Hana, Phillips, Stephen J, Schindler, Joseph L, Thornton, John, Nagel, Simon, Heo, Ji Hoe, Sohn, Sung-Il, Psychogios, Marios-Nikos, Budzik, Ronald F, Starkman, Sidney, Martin, Coleman O, Burns, Paul A, Murphy, Seán, Lopez, George A, English, Joey, Tymianski, Michael, Demchuk, Andrew, Barber, Philip, Smith, Eric, Bal, Simerpreet, Subramaniam, Suresh, Peters, Steven, Couillard, Phillippe, Klein, Gary, Stys, Peter, Menon, Bijoy, Coutts, Shelagh, Almekhlafi, Mohammed, Hill, Michael, Goyal, Mayank, Wong, John, Mitha, Alim, Eesa, Muneer, Morrish, William, Alqatani, Saad, Kashani, Nima, Joshi, Manish, Zerna, Charlotte, Ospel, Johanna, Venkatesan, Prasanna, Teleg, Erika, Sitaram, Amith, Graham, Brett, Van Gaal, Stephen, Moussaddy, Aimen, Chakraborty, Debabrata, Maraj, Nicholas, Loockey, Andrew, Chen, Shuo, Singh, Ravinder, Alsultan, Abdulaziz, Asuncion, Ria, Tse, Dominic, Doshi, Darshan, Volny, Ondrej, Ojha, Piyush, Wadhwa, Ankur, Marko, Martha, Singh, Nishita, Wasyliw, Sanchea, Ryckborst, Karla, Kenney, Carol, Save, Supriya, Jambula, Anitha, Newcommon, Nancy, Hull, Gavin, Blackstock, Darcy, Kiszczak, Sharon, Zimmel, Leslie, Wright, Michelle, Jahraus, Cari, Andersen, Linda, Bohn, Shelly, Paul, Joseph, Zhang, Oiao, Doram, Craig, Lowerison, Mark, Hanley, Andrea, Campbell, Lori, Ure, Ashley, Taylor, Francis, Hul, Dominic, Wiebe, Samuel, Saluzzi, Marina, Blenkin, Nicole, Frayne, Richard, Buck, Brian, Butcher, Kenneth, Shuaib, Ashfaq, Jeerakathil, Tom, Jickling, Glen, Emery, Derek, Rempel, Jeremy, Owen, Richard, Ashforth, Robert, Yeo, Tom, Kotylak, Trevor, O'Kelly, Cian, Chow, Michael, Siddiqui, Muzaffer, Saqqur, Maher, D'Souza, Atlantic, Lloret, Mar, Butt, Asif, Nomani, Ali, Kalashyan, Hayrapet, Thirunavukkarasu, Sibi, Jabs, Juline, Fairall, Paige, Piquette, Lori, Phillips, Stephen, Green, A. Laine, Gubitz, Gordon, Heidenreich, Jens, Huynh, Thien, Shankar, Jai, Maloney, William, Vandorpe, Robert, Schmidt, Matthias, Pickett, Gwynedd, Weeks, Adrienne, Jarrett, Judith, MacDonald, Debbie, Arsenault, Joanna, Kinnear, Ruth, Mandzia, Jennifer, Mayich, Michael, Boulton, Melfort, Bullrich, Maria, Fridman, Sebastian, Kiwan, Ruba, Lee, Donald, Lownie, Stephen, Khaw, Alexander, Pandey, Sachin, Sharma, Manas, Sposato, Luciano, Wade, Kevin, Beauchamp, Beth, Lambourn, Lindsay, Amato-Marziali, Belinda, Poppe, Alexandre, Roy, Daniel, Daneault, Nicole, Deschaintre, Yan, Gioia, Laura, Jacquin, Grégory, Odier, Céline, Stapf, Christian, Iancu, Daniela, Raymond, Jean, Weill, Alain, Lapierre, Marlène, Jadil, Nadia, Jolteus, Judlène, Teitelbaum, Jeanne, Angle, Mark, Hannouche, Mathew, Badawy, Mohamed, Letourneau, Justin, Cortes, Maria, Linnell, Grant, Tampieri, Donateela, Vieira, Lucy, Moussaddy, Aimen, Legault, Catherine, Durcan, Liam, Moore, Angela, Cole, Erin, Magnussen, Claire, Salmon, Kristiana, Khalil, Salma, Desloges, Isabelle, Waxman, Lindsay, Abdon, Wynne, Lai, Sonia, Dowlatshahi, Dar, Iancu, Daniela, Shamy, Michel, Stotts, Grant, Blacquiere, Dylan, Lesiuk, Howard, Quateen, Aiman, Drake, Brian, Dewar, Brian, Daham, Zeinab, Kelly, Michael, Hunter, Gary, Peeling, Lissa, Graham, Brett, Whelan, Ruth, Garner, Aaron, Urroz, Lilian, Maley, Sharleen, Silver, Frank, Casaubon, Leanne, Pikula, Aleksandra, Del Campo, Martin, Schaafsma, Joanna, Jaigobin, Cheryl, Krings, Timo, Pereira, Vitor, Agid, Ronit, Farb, Richard, Kalman, Libby, Cayley, Anne, Williams, Janice, Stewart, Tim, Misquitta, Karen, Bharatha, Aditya, Selchen, Daniel, Marotta, Thomas, Sarma, Dipanka, Montanera, Walter, Spears, Juluan, Saposnik, Gustavo, Kostyrko, Pawel, Li, Yangmei, Parra-Farina, Carmen, Bengzon Diestro, Jose Danilo, Camden, Marie-Christine, Verreault, Steve, Mackey, Ariane, Audet, Marie-Eve, Milot, Geneviève, Lavoie, Pascale, Gariépy, Jean-Luc, Collard, Karine, Haché, Annette, Van Adel, Brian, Sahlas, Demetrios, Alshanbari, Ahmed, Baldwin, Josephine, Catanese, Luciana, Chen, Bing, De Sa Boasquevisque, Danielle, Deshmukh, Aviraj, Knapman, Jordan, Lamers, Shana, Larrazabal, Ramiro, MacMillan, Susan, Mai, Lauren, Mattia, Alicia, Nayar, Sumiti, Ng, Kuan, Oczkowski, Wieslaw, Perera, Kanjana, Shawawrah, Mays, Shoamanesh, Ashkan, Sobhi, Gita, Syed, Nabeel, Taher, Noran, Vandervelde, Cheyanne, Wang Pharm, Di, Field, Thalia, Van Gaal, Stephen, Teal, Philip, Benavente, Oscar, Wilson, Laura, Mann, Sharanpal, Yip, Samuel, Murphy, Colleen, Heran, Manraj, Rohr, Axel, Settecase, Fabio, Redekop, Gary, Haw, Charles, Maclean, Genoveva, Murray, Karina, Chiu, Rosalin, Flexman, Alana, Strecha, Eilidh, Gayton, Yolanda, Yip, Judy, Swartz, Richard, Boulos, Mark, Gladstone, David, Yu, Amy, Hopyan, Julia, Khosravani, Houman, Manosalva Alzate, Herbert, Southwell, Alisia, Kamra, Maneesha, Lopes, Kaitlyn, Kapoor, Arunima, da Costa, Leodante, Yang, Victor, Dyer, Erin, Shah, Ruchir, Knowles, Brenda, Nichols, Jennifer, Patterson, Jennifer, Cope, Krista, Dickerson, Lee, Barton, Katrina, Gray, Kimberly, Massengale, Ticey, Miller, Melanie, Simpson, Cindy, Walker, Sabrina, Tennyson-Yemm, Chlin, Devlin, Thomas, Frei, Donald, Bellon, Richard, Atchie, Benjamin, Kaminsky, Ian, Wilson, Duandelyn, Schraeder, Nicolle, Arias, Eric, Kodis, Lisa, Talley, Mark, Edinger, Alex, Talley, Tiffany, Dempsey, Ita, Williams, Laurie, Williams, Scott, Kupniewski, Sonny, Fasbinder, Brad, Snead, Joanna, Choe, Hana, Mackenzie, Larami, Weisman, Davi, Kozak, Osman, Shah, Qaisar, Gzesh, Dan, Kulandaivel, Kandan, Khoury, John, Klein, Brad, Bussinger, Patricia, Griffin, Lisa, dePalmo, Ashley, Oliva, Cynthia, Jadhav, Ashutosh, Jovin, Tudor, Kenmuir, Cynthia, Jankowitz, Brian, Gross, Bradley, Rocha, Marcelo, Starr, Matthew, Brown, Merritt, Hawkes, Christine, Shah, Kavit, Tememe, Danoushka, Walker, Gregory, Patel, Pratit, Klein, Bradley, Ziayee, Habibullah, Limaye, Kaustubh, Baxendell, Lisa, Gilchrist, Vicki, Feineigle, Patricia, Toseki Haibach, Kelsea, Van Every, Cathy, Desai, Shashyat, Zulfiqar, Maryam, Gibson, Linda, Barrett, Sean, Turkel-Parrella, David, Arcot, Karthikeyan, DiCrescento, Steven, Farkas, Jeffrey, Filipowski, Gregory, Frontera, Jennifer, Joset, Danielle, Liff, Jeremy, Scher, Erica, McDougall, Cameron, Kelly, Cheryl, Patel, Akshal, Monteith, Stephen, Starkman, Sidney, Atchaneeyasakul, Kunakorn, Burgos, Adrian, Chua, Janice Anne, Gaines, Nathan, Grunberg, Ileana, Guzy, Judy, Liu, Zuolu, Maluste, Neil, Ramirez, Lucas, Sharma, Latisha, Heck, Donald, Brown, Morry, McDonald, Colin, Calderon, Mateo, Hargis, Mitch, Roels, Christina, Emmady, Prabhu, Alvi, Talat, McTaggart, Ryan, Jayaraman, Mahesh, Cutting, Shawna, Smith, Wendy, Foley, Susan, Paolucci, Gino, Has, Richard, Quinn, Katie, Fuller, Lindsey, Brierley, Rebecca, Watkins, Christina, Demir, Nicole, Lopez, George, Vargas, Alejandro, Osteraas, Nicholas, Holtz, Becky, Sauvageau, Eric, Hanel, Ricardo, Aghaebrahim, Amin, Chmayssani, Mohamad, Naval, Neeraj, Day, Jason, Dellorso, Scott, Ludwig, Benjamin, Schemmel, Derek, Ebreo, Nancy, Bell, Karen, Lewis, Lanai, Delucia, Marjorie, Nogueira, Raul, Haussen, Diogo, Frankel, Michael, Bhatt, Nirav, Bianchi, Nicolas, Anderson, Aaron, Belagaje, Samir, Liberato, Bernardo, Rangaraju, Srikant, Al-Bayati, Alhamza, Grossberg, Jonathan, Craft, Leah, Schindler, Kiva, Schaad, Erin, Schultz, Meagan, Southerly, Lorretta, Doppelheuer, Shannon, Charlton, Jacquelyn, Faggard, Jason, Barbret, Zuzana, DukSoo Han, Ethan, Walters, Robin, Dolia, Jaydevsinh, El-Jamal, Sleiman, Eby, Brendan, Saleem, Yasir, Pearl, Harrison, Patel, Kishan, Rahman, Haseeb, Butt, Reema, English, Stephen, Puri, Ajit, Howk, Mary, Singh, Jasmeet, Massari, Francesco, DeMacedo Rodrigues, Katyucia, Kuhn, Anna, English, Joey, Barazangi, Nobl, Telischak, Nick, Kim, Warren, Ross, Josh, DeVole, Nata, Redford, Jessica, Ferreira, Milena, Ponting, Katie, Shen, Helen, Bedenk, Ann, Patel, Susila, Fernandess, Julia, Ke, Michael, Spokoyny, Ilanit, Gao, Billy, Tong, David, Chen, Charlene, Wong, Christine, Choe, Jessica, Martin, Coleman, Summers, Debbie, Boutwell, Christine, Olds, Karin, Crandall, Suzanne, Eatman, John, Akhtar, Naveed, Holloway, William, Halpin, Jared, Donegan, Brett, Schindler, Joseph, Hwang, David, Gilmore, Emily, Petersen, Nils, Sheth, Kevin, Brown, Stacy, Beekman, Rachel, George, Benjamin, Kaddouh, Firas, Falcone, Guido, Wira, Charles, Matouk, Charles, Loomis, Caitlin, Amin, Hardik, Stretz, Hans Christoph, Narula, Reshma, Jasne, Adam, Sansing, Lauren, Agarwal, Tijil, Jasak, Sara, Fontaine, Briana, King, Zachary, Kuohn, Lindsey, Orgass, Hailey, Leary, Megan, Nye, Joan, Halbert, Kelsey, Nystrom, Karin, Neuschatz, Kaile, Petrucci, Dawn, Coppola, Anna, Tarpley, Jason, Joyce, Treasure, Hou, Sam, Umekubo, Mark, Nakamura, Catrice, Ovando, Renee, Zuniga, Diana, Nien, Yih Lin, Basto, Fernando Mayor, Arch, Allison, Jong, Laura, Conrad, William, Abbott, Tara, Yao, Jay, Caganap, Scott, Jordan, John, Teitelbaum, George, Darflinger, Robert, Gupta, Rishi, Bain, Marianne, Budzik, Ronald, Czerniak, Jennifer, Groezinger, Katherine, Hicks II, William, Kaskar, Omran, Katz, Brian, Loochtan, Aaron, Pema, Peter, Rai, Vivek, Vora, Nirav, Brown, Amanda, Goodman, Diane, Danenbergs, Barb, Gossett, Monica, Bang, Oh Young, Chung, Jong-Won, Jeon, Pyoung, Kim, Keon Ha, Lim, Yun Jeong, Heo, Ji Hoe, Nam, Hyo Suk, Kim, Young Dae, Park, HyungJong, Hwang, In Gun, Ha, Wooseok, Choi, Jin Kyo, Jeong, Kyungsun, Rha, Joung-Ho, Park, Hee-Kwon, Yoon, Cindy, Kim, Bo-Kyung, Sohn, Sung-Il, Kim, Chang-hyun, Yoo, Joonsang, Hong, Jeong-Ho, Park, Hyungjong, Kim, Sohyeon, Choi, Moonkyung, Bae, Hyoeun, Lee, Jun Seok, Lee, Jae-Joon, Jun, Go-Eun, Jeon, Sujeong, Campbell, Bruce, Mitchell, Peter, Yassi, Nawaf, Davis, Stephen, Donnan, Geoffrey, Parsons, Mark, Yan, Bernard, Dowling, Richard, Bush, Steven, Wu, Teddy, Shah, Darshan, Zhao, Henry, Salvaris, Patrick, Alemseged, Fana, Ng, Felix, Williams, Cameron, Balabanski, Anna, Dos Santos, Angela, Ng, Jo-Lyn, McDonald, Amy, Jackson, David, Tsoleridis, Jessica, Pesavento, Lauren, Kleinig, Timothy John, Nurs, Roy Drew, Cranefield, Jennifer, Scroop, Rebecca, Cagi, Lavenia, Harvey, Jackson, Waters, Michael, Thornton, John, Brennan, Robert, O'Hare, Alan, Power, Sarah, Williams, David, Boyle, Karl, Moynihan, Barry, Liddy, Ann-Marie, Large, Margaret, Cullen, Ailbhe, Walsh, Roisin, Martin, Emma, Lynch, Julie, McElroy, Sinéad, Murphy, Seán, Coveney, Sarah, Deegan, Caroline, Horgan, Gillian, Kelly, Peter, Laffan, Aoife, Llamas-Osorio, Yudy, Lynch, Catherine, Mac Mahon, Peter, Marnane, Michael, McCabe, John, Burns, Paul, Tauro, Suzanne, Cuddy, Sarah, Rennie, Ian, Smyth, Graham, Flynn, Peter, Wiggam, Ivan, Kerr, Enda, Gordon, Patricia, Fearon, Patricia, Roberts, Geralt, Patterson, Cathy, Adams, Karen, Wells, Brian, McFarland, Margaret, Holmin, Staffan, Moreira, Tiago, Sjöstrand, Christina, Mazya, Michael, Almqvist, Håkan, Wahlgren, Nils, Steinberg, Anna, Cooray, Charith, Eriksson, Einar, Thorén, Magnus, Keselman, Boris, Ahmed, NIaz, Holmberg, Åke, Axelsson, Maria, Berglund, Annika, Thomalla, Götz, Golsari, Amir, Hoppe, Julia, Deb-Chatterji, Milani, Cheng, Bastian, Barrow, Ewgenia, Schlemm, Eckhard, Lettow, Iris, Jensen, Märit, Otto, Dagmar, Jaramillo, Kirsten, Appelbohm, Hannes, Fiehler, Jens, Bester, Maxim, Schönfeld, Michael, Brekenfeld, Caspar, Holst, Brigitte, Wortmann, Ginette, Koch, Friederike, Puetz, Volker, Gerber, Johannes, Abramyuk, Andrij, Kaiser, Daniel, Winzer, Simon, Prakapenia, Alexandra, Pallesen, Lars-Peder, Siepmann, Timo, Barlinn, Kristian, Haase, Kathrin, Sauer, Angela, Psychogios, Marios-Nikos, Liman, Jan, Brehm, Alex, Maus, Volker, Hollstein, Nicole, Reinke, Annika, Neitz, Gustav, Schnieder, Marlena, Schwarz, Margret, Ibrahim, Allam, Müller, Julia, Meister, Stefanie, Bäumle, Berit, Chapot, René, Pilgram-Pastor, Sara, Wallocha, Marta, Stauder, Michael, Celik, Ekin, Stracke, Paul, Müller, Nicole, Weber, Ralph, Velktamp, Roland, Nagel, Simon, Ringleb, Peter Arthur, Heyse, Miriam, Amiri, Hemasse, Mundiyanapurath, Sibu, Chen, Min, Bevrle, Elisabeth, Beck, Perdita, Möhlenbruch, Markus alfred, Tymianski, Michael, Potvin, Alphonse, Harris, Cameron, Wang, Chong, Adams, Corey, Mayor, Diana, Garman, Dave, Chau, Davis, Wu, Jane, Lunn, Janet, Heard, Kathy, Bermanis, Liat, Teyes, Lucy, Constant, Marc, Galsim, Maria, Helbin, Michael, Leroux, Michelle, Felix, Nicole, Bendre, Nilima, Cuthbert, Sandra, Brokx, Steve, Zhang, Yichuan, Lingham, Trudy, Kohli, Yatika, Salter, Michael, Liebeschuetz, Joseph, Hofmann, Frieder, Constant, John, Soeder, Tom, Snoke, Kara, Bologa, Monica, Stahl, Kimberly, and Graziewicz, Maria
Abstract: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke.
Published: 2020
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12. Influence of geography, stroke timing, and weather conditions on transport and workflow times: Results from a longitudinal 5-year Canadian provincial registry

Author: Kashani, Nima, Ospel, Johanna Maria, Singh, Nishita, Zhou, Amy, Ganesh, Aravind, Holodinsky, Jessalyn Kathryn, Almekhlafi, Mohammed, Fouladirad, Saman, Frost, Adam, Yang, Lotus, Otani, Robert, Newton, Braedon, Persad, Amit, Wasyliw, Sanchea, Graham, Brett R, Hunter, Gary, Gardner, Aaron, Cooley, Regan, Ahmed, Syed Uzair, Peeling, Lissa, and Kelly, Michael E
Abstract: Background In areas with high population spread such as Saskatchewan, it can be challenging to provide timely endovascular stroke treatment (EVT) to patients living far away from comprehensive stroke centres (CSC). We assessed the association of geography, stroke timing and weather conditions on EVT workflow times and clinical outcomes in Saskatchewan.Methods We included patients who underwent EVT between January 2017 and December 2022 in the province of Saskatchewan, Canada. Univariable and multivariable associations of time from last known well-to-CSC arrival, CSC arrival-to-reperfusion, and 90-day modified Rankin Score (mRS) with driving distance from patient home to CSC, transport mode, outdoor temperature and stroke timing (day & time) were assessed using descriptive statistics and multivariable regression.Results Three-hundred-three patients in the province of Saskatchewan underwent EVT between January 2017 and December 2022. Distance from patient home to CSC (beta-coefficient per 10 km increase = 0.02, 95% CI: 0.01–0.03) and direct to CSC transport (beta-coefficient = −0.76, 95% CI = −1.01–[−0.51]) were associated with last known well to CSC arrival time. In-hospital stroke (beta-coefficient = 0.37, 95% CI: 0.16–0.58), direct-to-CSC transfer (beta-coefficient = 0.27, 95% CI: 0.13–0.41) and daytime stroke onset (beta-coefficient = −0.15, 95% CI: −0.28–[−0.04]) were associated with time from CSC arrival to reperfusion. No association with 90-day mRS was seen.Conclusion Geographic factors and stroke timing were associated with EVT workflow times. However, no association with clinical outcomes was seen, suggesting that EVT patients living remote areas of Saskatchewan have similar benefit from EVT compared to urban areas. Every effort should be made to offer timely EVT to patients from remote areas.
Published: 2024
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13. Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals

Author: Bosch, Elisabeth, Popp, Bernt, Güse, Esther, Skinner, Cindy, van der Sluijs, Pleuntje J., Maystadt, Isabelle, Pinto, Anna Maria, Renieri, Alessandra, Bruno, Lucia Pia, Granata, Stefania, Marcelis, Carlo, Baysal, Özlem, Hartwich, Dewi, Holthöfer, Laura, Isidor, Bertrand, Cogne, Benjamin, Wieczorek, Dagmar, Capra, Valeria, Scala, Marcello, De Marco, Patrizia, Ognibene, Marzia, Jamra, Rami Abou, Platzer, Konrad, Carter, Lauren B., Kuismin, Outi, van Haeringen, Arie, Maroofian, Reza, Valenzuela, Irene, Cuscó, Ivon, Martinez-Agosto, Julian A., Rabani, Ahna M., Mefford, Heather C., Pereira, Elaine M., Close, Charlotte, Anyane-Yeboa, Kwame, Wagner, Mallory, Hannibal, Mark C., Zacher, Pia, Thiffault, Isabelle, Beunders, Gea, Umair, Muhammad, Bhola, Priya T., McGinnis, Erin, Millichap, John, van de Kamp, Jiddeke M., Prijoles, Eloise J., Dobson, Amy, Shillington, Amelle, Graham, Brett H., Garcia, Evan-Jacob, Galindo, Maureen Kelly, Ropers, Fabienne G., Nibbeling, Esther A.R., Hubbard, Gail, Karimov, Catherine, Goj, Guido, Bend, Renee, Rath, Julie, Morrow, Michelle M., Millan, Francisca, Salpietro, Vincenzo, Torella, Annalaura, Nigro, Vincenzo, Kurki, Mitja, Stevenson, Roger E., Santen, Gijs W.E., Zweier, Markus, Campeau, Philippe M., Severino, Mariasavina, Reis, André, Accogli, Andrea, and Vasileiou, Georgia
Abstract: Coffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort.
Published: 2023
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14. Rewards, perils and pitfalls of untangling spinal pain circuits

Author: Graham, Brett A and Hughes, David I
Abstract: Pain is a complex perception that is fundamental to our daily survival. Under normal circumstances, it serves an important protective function to guard against tissue damage or alert the body to dangerous environments. Under pathological states, however, the perception of pain can become chronic, maladaptive, resistant to treatment, and presents a serious clinical and societal problem. A wealth of literature suggests that disruption of sensory processing within the spinal cord contributes to chronic pain, but our limited understanding of spinal circuitry in health and disease remains a barrier to the development of new therapeutic strategies. The aim of this brief review is to outline current thinking about how individual components of functionally distinct spinal microcircuits can be identified and manipulated to determine their role in influencing our perception of pain in acute and chronic states.
Published: 2019
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15. Untargeted metabolomic profiling reveals multiple pathway perturbations and new clinical biomarkers in urea cycle disorders

Author: Burrage, Lindsay C., Thistlethwaite, Lillian, Stroup, Bridget M., Sun, Qin, Miller, Marcus J., Nagamani, Sandesh C.S., Craigen, William, Scaglia, Fernando, Sutton, V. Reid, Graham, Brett, Kennedy, Adam D., Milosavljevic, Aleksandar, Lee, Brendan H., and Elsea, Sarah H.
Abstract: Untargeted metabolomic analysis is increasingly being used in the screening and management of individuals with inborn errors of metabolism (IEM). We aimed to test whether untargeted metabolomic analysis in plasma might be useful for monitoring the disease course and management of urea cycle disorders (UCDs).
Published: 2019
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16. ID: 210002 A Novel Spinal Cord Stimulation Waveform Targeting the Dorsal Horn: 12-Month Clinical Trial Results

Author: Russo, Marc, Volschenk, Willem, Bailey, Dominic, Santarelli, Danielle, and Graham, Brett
Published: 2023
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17. Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke Update 2020 – ADDENDUM

Author: Gladstone, David J., Patrice Lindsay, M., Douketis, James, Smith, Eric E., Dowlatshahi, Dar, Wein, Theodore, Bourgoin, Aline, Cox, Jafna, Falconer, John B., Graham, Brett R., Labrie, Marilyn, McDonald, Lena, Mandzia, Jennifer, Ngui, Daniel, Pageau, Paul, Rodgerson, Amanda, Semchuk, William, Tebbutt, Tammy, Tuchak, Carmen, van Gaal, Stephen, Villaluna, Karina, Foley, Norine, Coutts, Shelagh, Mountain, Anita, Gubitz, Gord, Udell, Jacob A, McGuff, Rebecca, Heran, Manraj K.S., Lavoie, Pascale, and Poppe, Alexandre Y.
Published: 2023
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18. Whole-brain serial-section electron microscopy in larval zebrafish

Author: Hildebrand, David Grant Colburn, Cicconet, Marcelo, Torres, Russel Miguel, Choi, Woohyuk, Quan, Tran Minh, Moon, Jungmin, Wetzel, Arthur Willis, Scott Champion, Andrew, Graham, Brett Jesse, Randlett, Owen, Plummer, George Scott, Portugues, Ruben, Bianco, Isaac Henry, Saalfeld, Stephan, Baden, Alexander David, Lillaney, Kunal, Burns, Randal, Vogelstein, Joshua Tzvi, Schier, Alexander Franz, Lee, Wei-Chung Allen, Jeong, Won-Ki, Lichtman, Jeff William, and Engert, Florian
Abstract: High-resolution serial-section electron microscopy (ssEM) makes it possible to investigate the dense meshwork of axons, dendrites, and synapses that form neuronal circuits. However, the imaging scale required to comprehensively reconstruct these structures is more than ten orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons, some of which span nearly the entire brain. Difficulties in generating and handling data for large volumes at nanoscale resolution have thus restricted vertebrate studies to fragments of circuits. These efforts were recently transformed by advances in computing, sample handling, and imaging techniques, but high-resolution examination of entire brains remains a challenge. Here, we present ssEM data for the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post-fertilization. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management requirements. The resulting dataset can be analysed to reconstruct neuronal processes, permitting us to survey all myelinated axons (the projectome). These reconstructions enable precise investigations of neuronal morphology, which reveal remarkable bilateral symmetry in myelinated reticulospinal and lateral line afferent axons. We further set the stage for whole-brain structure–function comparisons by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. All obtained images and reconstructions are provided as an open-access resource.
Published: 2017
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19. The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families

Author: Fountain, Michael D., Aten, Emmelien, Cho, Megan T., Juusola, Jane, Walkiewicz, Magdalena A., Ray, Joseph W., Xia, Fan, Yang, Yaping, Graham, Brett H., Bacino, Carlos A., Potocki, Lorraine, van Haeringen, Arie, Ruivenkamp, Claudia A.L., Mancias, Pedro, Northrup, Hope, Kukolich, Mary K., Weiss, Marjan M., van Ravenswaaij-Arts, Conny M.A., Mathijssen, Inge B., Levesque, Sebastien, Meeks, Naomi, Rosenfeld, Jill A., Lemke, Danielle, Hamosh, Ada, Lewis, Suzanne K., Race, Simone, Stewart, Laura L., Hay, Beverly, Lewis, Andrea M., Guerreiro, Rita L., Bras, Jose T., Martins, Marcia P., Derksen-Lubsen, Gerarda, Peeters, Els, Stumpel, Connie, Stegmann, Sander, Bok, Levinus A., Santen, Gijs W.E., and Schaaf, Christian P.
Abstract: Purpose:Truncating mutations in the maternally imprinted, paternally expressed gene MAGEL2, which is located in the Prader-Willi critical region 15q11–13, have recently been reported to cause Schaaf-Yang syndrome, a Prader-Willi-like disease that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties, and autism spectrum disorder. The causality of the reported variants in the context of the patients’ phenotypes was questioned, as MAGEL2 whole-gene deletions seem to cause little or no clinical phenotype.Methods:Here we report a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families, including 1 family with 3 individuals found to be affected with a truncating variant of MAGEL2, 11 individuals who are clinically affected but were not tested molecularly, and a presymptomatic fetal sibling carrying the pathogenic MAGEL2 variant.Results:All cases harbor truncating mutations of MAGEL2, and nucleotides c.1990–1996 arise as a mutational hotspot, with 10 individuals and 1 fetus harboring a c.1996dupC (p.Q666fs) mutation and 2 fetuses harboring a c.1996delC (p.Q666fs) mutation. The phenotypic spectrum of Schaaf-Yang syndrome ranges from fetal akinesia to neurobehavioral disease and contractures of the small finger joints.Conclusion:This study provides strong evidence for the pathogenicity of truncating mutations of the paternal allele of MAGEL2, refines the associated clinical phenotypes, and highlights implications for genetic counseling for affected families.Genet Med 19 1, 45–52.
Published: 2017
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20. The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Author: Redin, Claire, Brand, Harrison, Collins, Ryan L, Kammin, Tammy, Mitchell, Elyse, Hodge, Jennelle C, Hanscom, Carrie, Pillalamarri, Vamsee, Seabra, Catarina M, Abbott, Mary-Alice, Abdul-Rahman, Omar A, Aberg, Erika, Adley, Rhett, Alcaraz-Estrada, Sofia L, Alkuraya, Fowzan S, An, Yu, Anderson, Mary-Anne, Antolik, Caroline, Anyane-Yeboa, Kwame, Atkin, Joan F, Bartell, Tina, Bernstein, Jonathan A, Beyer, Elizabeth, Blumenthal, Ian, Bongers, Ernie M H F, Brilstra, Eva H, Brown, Chester W, Brüggenwirth, Hennie T, Callewaert, Bert, Chiang, Colby, Corning, Ken, Cox, Helen, Cuppen, Edwin, Currall, Benjamin B, Cushing, Tom, David, Dezso, Deardorff, Matthew A, Dheedene, Annelies, D'Hooghe, Marc, de Vries, Bert B A, Earl, Dawn L, Ferguson, Heather L, Fisher, Heather, FitzPatrick, David R, Gerrol, Pamela, Giachino, Daniela, Glessner, Joseph T, Gliem, Troy, Grady, Margo, Graham, Brett H, Griffis, Cristin, Gripp, Karen W, Gropman, Andrea L, Hanson-Kahn, Andrea, Harris, David J, Hayden, Mark A, Hill, Rosamund, Hochstenbach, Ron, Hoffman, Jodi D, Hopkin, Robert J, Hubshman, Monika W, Innes, A Micheil, Irons, Mira, Irving, Melita, Jacobsen, Jessie C, Janssens, Sandra, Jewett, Tamison, Johnson, John P, Jongmans, Marjolijn C, Kahler, Stephen G, Koolen, David A, Korzelius, Jerome, Kroisel, Peter M, Lacassie, Yves, Lawless, William, Lemyre, Emmanuelle, Leppig, Kathleen, Levin, Alex V, Li, Haibo, Li, Hong, Liao, Eric C, Lim, Cynthia, Lose, Edward J, Lucente, Diane, Macera, Michael J, Manavalan, Poornima, Mandrile, Giorgia, Marcelis, Carlo L, Margolin, Lauren, Mason, Tamara, Masser-Frye, Diane, McClellan, Michael W, Mendoza, Cinthya J Zepeda, Menten, Björn, Middelkamp, Sjors, Mikami, Liya R, Moe, Emily, Mohammed, Shehla, Mononen, Tarja, Mortenson, Megan E, Moya, Graciela, Nieuwint, Aggie W, Ordulu, Zehra, Parkash, Sandhya, Pauker, Susan P, Pereira, Shahrin, Perrin, Danielle, Phelan, Katy, Aguilar, Raul E Piña, Poddighe, Pino J, Pregno, Giulia, Raskin, Salmo, Reis, Linda, Rhead, William, Rita, Debra, Renkens, Ivo, Roelens, Filip, Ruliera, Jayla, Rump, Patrick, Schilit, Samantha L P, Shaheen, Ranad, Sparkes, Rebecca, Spiegel, Erica, Stevens, Blair, Stone, Matthew R, Tagoe, Julia, Thakuria, Joseph V, van Bon, Bregje W, van de Kamp, Jiddeke, van Der Burgt, Ineke, van Essen, Ton, van Ravenswaaij-Arts, Conny M, van Roosmalen, Markus J, Vergult, Sarah, Volker-Touw, Catharina M L, Warburton, Dorothy P, Waterman, Matthew J, Wiley, Susan, Wilson, Anna, Yerena-de Vega, Maria de la Concepcion A, Zori, Roberto T, Levy, Brynn, Brunner, Han G, de Leeuw, Nicole, Kloosterman, Wigard P, Thorland, Erik C, Morton, Cynthia C, Gusella, James F, and Talkowski, Michael E
Abstract: Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology.
Published: 2017
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21. The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families

Author: Fountain, Michael D., Aten, Emmelien, Cho, Megan T., Juusola, Jane, Walkiewicz, Magdalena A., Ray, Joseph W., Xia, Fan, Yang, Yaping, Graham, Brett H., Bacino, Carlos A., Potocki, Lorraine, van Haeringen, Arie, Ruivenkamp, Claudia A.L., Mancias, Pedro, Northrup, Hope, Kukolich, Mary K., Weiss, Marjan M., van Ravenswaaij-Arts, Conny M.A., Mathijssen, Inge B., Levesque, Sebastien, Meeks, Naomi, Rosenfeld, Jill A., Lemke, Danielle, Hamosh, Ada, Lewis, Suzanne K., Race, Simone, Stewart, Laura L., Hay, Beverly, Lewis, Andrea M., Guerreiro, Rita L., Bras, Jose T., Martins, Marcia P., Derksen-Lubsen, Gerarda, Peeters, Els, Stumpel, Connie, Stegmann, Sander, Bok, Levinus A., Santen, Gijs W.E., and Schaaf, Christian P.
Abstract: Truncating mutations in the maternally imprinted, paternally expressed gene MAGEL2, which is located in the Prader-Willi critical region 15q11–13, have recently been reported to cause Schaaf-Yang syndrome, a Prader-Willi-like disease that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties, and autism spectrum disorder. The causality of the reported variants in the context of the patients’ phenotypes was questioned, as MAGEL2whole-gene deletions seem to cause little or no clinical phenotype.
Published: 2017
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22. Solid organ transplantation in methylmalonic acidemia and propionic acidemia: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG)

Author: Sen, Kuntal, Burrage, Lindsay C., Chapman, Kimberly A., Ginevic, Ilona, Mazariegos, George V., and Graham, Brett H.
Published: 2023
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23. The GABA Transaminase, ABAT, Is Essential for Mitochondrial Nucleoside Metabolism.

Author: Besse, Arnaud, Wu, Ping, Bruni, Francesco, Donti, Taraka, Graham, Brett H., Craigen, William J., McFarland, Robert, Moretti, Paolo, Lalani, Seema, Scott, Kenneth L., Taylor, Robert W., and Bonnen, Penelope E.
Abstract: Summary ABAT is a key enzyme responsible for catabolism of principal inhibitory neurotransmitter γ-aminobutyric acid (GABA). We report an essential role for ABAT in a seemingly unrelated pathway, mitochondrial nucleoside salvage, and demonstrate that mutations in this enzyme cause an autosomal recessive neurometabolic disorder and mtDNA depletion syndrome (MDS). We describe a family with encephalomyopathic MDS caused by a homozygous missense mutation in ABAT that results in elevated GABA in subjects’ brains as well as decreased mtDNA levels in subjects’ fibroblasts. Nucleoside rescue and co-IP experiments pinpoint that ABAT functions in the mitochondrial nucleoside salvage pathway to facilitate conversion of dNDPs to dNTPs. Pharmacological inhibition of ABAT through the irreversible inhibitor Vigabatrin caused depletion of mtDNA in photoreceptor cells that was prevented through addition of dNTPs in cell culture media. This work reveals ABAT as a connection between GABA metabolism and nucleoside metabolism and defines a neurometabolic disorder that includes MDS. [ABSTRACT FROM AUTHOR]
Published: 2015
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24. OP006: Is it time to move beyond acylcarnitine profiles? Lessons from the clinical application of a high-definition LC-MS/MS acylcarnitine method.

Author: Luna, Carolina, Griffin, Chandler, Lah, Melissa, Conboy, Erin, McPheron, Molly, Graham, Brett, Hainline, Bryan, and Miller, Marcus
Published: 2022
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25. Loss of succinyl-CoA synthetase in mouse forebrain results in hypersuccinylation with perturbed neuronal transcription and metabolism

Author: Lancaster, Makayla S., Kim, Byungwook, Doud, Emma H., Tate, Mason D., Sharify, Ahmad D., Gao, Hongyu, Chen, Duojiao, Simpson, Ed, Gillespie, Patrick, Chu, Xiaona, Miller, Marcus J., Wang, Yue, Liu, Yunlong, Mosley, Amber L., Kim, Jungsu, and Graham, Brett H.
Abstract: Lysine succinylation is a subtype of protein acylation associated with metabolic regulation of succinyl-CoA in the tricarboxylic acid cycle. Deficiency of succinyl-CoA synthetase (SCS), the tricarboxylic acid cycle enzyme catalyzing the interconversion of succinyl-CoA to succinate, results in mitochondrial encephalomyopathy in humans. This report presents a conditional forebrain-specific knockout (KO) mouse model of Sucla2, the gene encoding the ATP-specific beta isoform of SCS, resulting in postnatal deficiency of the entire SCS complex. Results demonstrate that accumulation of succinyl-CoA in the absence of SCS leads to hypersuccinylation within the murine cerebral cortex. Specifically, increased succinylation is associated with functionally significant reduced activity of respiratory chain complex I and widescale alterations in chromatin landscape and gene expression. Integrative analysis of the transcriptomic data also reveals perturbations in regulatory networks of neuronal transcription in the KO forebrain. Together, these findings provide evidence that protein succinylation plays a significant role in the pathogenesis of SCS deficiency.
Published: 2023
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26. Online, low-volume meditation does not alter immune-related biomarkers

Author: Graham, Brett, Jin, Yuxuan, Bazeley, Peter, Husni, Elaine, and Calabrese, Leonard H.
Abstract: Prior studies of mindfulness meditation have demonstrated anti-inflammatory and immunoregulatory effects but whether meditation courses delivered online can exert similar effects is poorly understood. Barriers to large scale implementation of traditional mindfulness meditation programs has created an increased interest in the effect of less time- and resource-intensive online meditation courses. The purpose of this study was to determine whether a 6-week online mindfulness program with low time demands on nurses would lead to changes in gene expression, cytokine profiles, telomerase activity, and cortisol profiles.
Published: 2022
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27. Anatomy and function of an excitatory network in the visual cortex

Author: Lee, Wei-Chung Allen, Bonin, Vincent, Reed, Michael, Graham, Brett J., Hood, Greg, Glattfelder, Katie, and Reid, R. Clay
Abstract: Two-photon calcium imaging and electron microscopy were used to explore the relationship between structure and function in mouse primary visual cortex, showing that layer 2/3 neurons are connected in subnetworks, that pyramidal neurons with similar orientation selectivity preferentially form synapses with each other, and that neurons with similar orientation tuning form larger synapses; this study exemplifies functional connectomics as a powerful method for studying the organizational logic of cortical networks.
Published: 2016
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28. Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer

Author: Park, Jun Hyoung, Vithayathil, Sajna, Kumar, Santosh, Sung, Pi-Lin, Dobrolecki, Lacey Elizabeth, Putluri, Vasanta, Bhat, Vadiraja B., Bhowmik, Salil Kumar, Gupta, Vineet, Arora, Kavisha, Wu, Danli, Tsouko, Efrosini, Zhang, Yiqun, Maity, Suman, Donti, Taraka R., Graham, Brett H., Frigo, Daniel E., Coarfa, Cristian, Yotnda, Patricia, Putluri, Nagireddy, Sreekumar, Arun, Lewis, Michael T., Creighton, Chad J., Wong, Lee-Jun C., and Kaipparettu, Benny Abraham
Abstract: Transmitochondrial cybrids and multiple OMICs approaches were used to understand mitochondrial reprogramming and mitochondria-regulated cancer pathways in triple-negative breast cancer (TNBC). Analysis of cybrids and established breast cancer (BC) cell lines showed that metastatic TNBC maintains high levels of ATP through fatty acid β oxidation (FAO) and activates Src oncoprotein through autophosphorylation at Y419. Manipulation of FAO including the knocking down of carnitine palmitoyltransferase-1A (CPT1) and 2 (CPT2), the rate-limiting proteins of FAO, and analysis of patient-derived xenograft models confirmed the role of mitochondrial FAO in Src activation and metastasis. Analysis of TCGA and other independent BC clinical data further reaffirmed the role of mitochondrial FAO and CPT genes in Src regulation and their significance in BC metastasis.
Published: 2016
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29. Ménage-à-Trois 1 Is Critical for the Transcriptional Function of PPARγ Coactivator 1.

Author: Sano, Motoaki, Izumi, Yasukatsu, Helenius, Katja, Asakura, Masanori, Rossi, Derrick J., Xie, Min, Taffet, George, Hu, Lingyun, Pautler, Robia G., Wilson, Christopher R., Boudina, Sihem, Abel, E. Dale, Taegtmeyer, Heinrich, Scaglia, Fernando, Graham, Brett H., Kralli, Anastasia, Shimizu, Noriaki, Tanaka, Hirotoshi, Mäkelä, Tomi P., and Schneider, Michael D.
Subjects: TRANSCRIPTION factors, MYOCARDIUM, CELL metabolism, ENERGY metabolism
Abstract: Summary: The Cdk7/cyclin H/ménage-à-trois 1 (MAT1) heterotrimer has proposed functions in transcription as the kinase component of basal transcription factor TFIIH and is activated in adult hearts by Gq-, calcineurin-, and biomechanical stress-dependent pathways for hypertrophic growth. Using cardiac-specific Cre, we have ablated MAT1 in myocardium. Despite reduced Cdk7 activity, MAT1-deficient hearts grew normally, but fatal heart failure ensued at 6–8 weeks. By microarray profiling, quantitative RT-PCR, and western blotting at 4 weeks, genes for energy metabolism were found to be suppressed selectively, including targets of peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1). Cardiac metabolic defects were substantiated in isolated perfused hearts and isolated mitochondria. In culture, deleting MAT1 with Cre disrupted PGC-1 function: PGC-1α failed to activate PGC-1-responsive promoters and nuclear receptors, GAL4-PGC-1α was functionally defective, and PGC-1β was likewise deficient. PGC-1 bound to both MAT1 and Cdk7 in coprecipitation assays. Thus, we demonstrate a requirement for MAT1 in the operation of PGC-1 coactivators that control cell metabolism. [Copyright &y& Elsevier]
Published: 2007
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30. Clopidogrel Load Reduces Emboli in Carotid Artery Stenosis With Free-Floating Thrombus

Author: Graham, Brett R. and Menon, Bijoy K.
Published: 2017
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31. Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum–associated degradation pathway

Author: Enns, Gregory M., Shashi, Vandana, Bainbridge, Matthew, Gambello, Michael J., Zahir, Farah R., Bast, Thomas, Crimian, Rebecca, Schoch, Kelly, Platt, Julia, Cox, Rachel, Bernstein, Jonathan A., Scavina, Mena, Walter, Rhonda S., Bibb, Audrey, Jones, Melanie, Hegde, Madhuri, Graham, Brett H., Need, Anna C., Oviedo, Angelica, Schaaf, Christian P., Boyle, Sean, Butte, Atul J., Chen, Rong, Clark, Michael J., Haraksingh, Rajini, Cowan, Tina M., He, Ping, Langlois, Sylvie, Zoghbi, Huda Y., Snyder, Michael, Gibbs, Richard A., Freeze, Hudson H., and Goldstein, David B.
Abstract: Purpose:The endoplasmic reticulum–associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum–associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1.Methods:Whole-genome, whole-exome, or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data.Results:All patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypolacrima or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele.Conclusion:NGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum–associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a broader range of mutations are detected.Genet Med 16 10, 751–758.
Published: 2014
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32. Mutations in NGLY1cause an inherited disorder of the endoplasmic reticulum–associated degradation pathway

Author: Enns, Gregory M., Shashi, Vandana, Bainbridge, Matthew, Gambello, Michael J., Zahir, Farah R., Bast, Thomas, Crimian, Rebecca, Schoch, Kelly, Platt, Julia, Cox, Rachel, Bernstein, Jonathan A., Scavina, Mena, Walter, Rhonda S., Bibb, Audrey, Jones, Melanie, Hegde, Madhuri, Graham, Brett H., Need, Anna C., Oviedo, Angelica, Schaaf, Christian P., Boyle, Sean, Butte, Atul J., Chen, Rong, Clark, Michael J., Haraksingh, Rajini, Cowan, Tina M., He, Ping, Langlois, Sylvie, Zoghbi, Huda Y., Snyder, Michael, Gibbs, Richard A., Freeze, Hudson H., and Goldstein, David B.
Abstract: The endoplasmic reticulum–associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum–associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1.
Published: 2014
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33. Screen for abnormal mitochondrial phenotypes in mouse embryonic stem cells identifies a model for succinyl-CoA ligase deficiency and mtDNA depletion

Author: Donti, Taraka R., Stromberger, Carmen, Ge, Ming, Eldin, Karen W., Craigen, William J., and Graham, Brett H.
Abstract: Mutations in subunits of succinyl-CoA synthetase/ligase (SCS), a component of the citric acid cycle, are associated with mitochondrial encephalomyopathy, elevation of methylmalonic acid (MMA), and mitochondrial DNA (mtDNA) depletion. A FACS-based retroviral-mediated gene trap mutagenesis screen in mouse embryonic stem (ES) cells for abnormal mitochondrial phenotypes identified a gene trap allele of Sucla2 (Sucla2SAβgeo), which was used to generate transgenic mice. Sucla2 encodes the ADP-specific β-subunit isoform of SCS. Sucla2SAβgeo homozygotes exhibited recessive lethality, with most mutants dying late in gestation (e18.5). Mutant placenta and embryonic (e17.5) brain, heart and muscle showed varying degrees of mtDNA depletion (20–60%). However, there was no mtDNA depletion in mutant liver, where the gene is not normally expressed. Elevated levels of MMA were observed in embryonic brain. SCS-deficient mouse embryonic fibroblasts (MEFs) demonstrated a 50% reduction in mtDNA content compared with wild-type MEFs. The mtDNA depletion resulted in reduced steady state levels of mtDNA encoded proteins and multiple respiratory chain deficiencies. mtDNA content could be restored by reintroduction of Sucla2. This mouse model of SCS deficiency and mtDNA depletion promises to provide insights into the pathogenesis of mitochondrial diseases with mtDNA depletion and into the biology of mtDNA maintenance. In addition, this report demonstrates the power of a genetic screen that combines gene trap mutagenesis and FACS analysis in mouse ES cells to identify mitochondrial phenotypes and to develop animal models of mitochondrial dysfunction.
Published: 2014
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34. Comprehensive next-generation sequence analyses of the entire mitochondrial genome reveal new insights into the molecular diagnosis of mitochondrial DNA disorders

Author: Cui, Hong, Li, Fangyuan, Chen, David, Wang, Guoli, Truong, Cavatina K., Enns, Gregory M., Graham, Brett, Milone, Margherita, Landsverk, Megan L., Wang, Jing, Zhang, Wei, and Wong, Lee-Jun C.
Abstract: Purpose:The application of massively parallel sequencing technology to the analysis of the mitochondrial genome has demonstrated great improvement in the molecular diagnosis of mitochondrial DNA–related disorders. The objective of this study was to investigate the performance characteristics and to gain new insights into the analysis of the mitochondrial genome.Methods:The entire mitochondrial genome was analyzed as a single amplicon using a long-range PCR–based enrichment approach coupled with massively parallel sequencing. The interference of the nuclear mitochondrial DNA homologs was distinguished from the actual mitochondrial DNA sequences by comparison with the results obtained from conventional PCR–based Sanger sequencing using multiple pairs of primers.Results:Our results demonstrated the uniform coverage of the entire mitochondrial genome. Massively parallel sequencing of the single amplicon revealed the presence of single-nucleotide polymorphisms and nuclear homologs of mtDNA sequences that cause the erroneous and inaccurate variant calls when PCR/Sanger sequencing approach was used. This single amplicon massively parallel sequencing strategy provides an accurate quantification of mutation heteroplasmy as well as the detection and mapping of mitochondrial DNA deletions.Conclusion:The ability to quantitatively and qualitatively evaluate every single base of the entire mitochondrial genome is indispensible to the accurate molecular diagnosis and genetic counseling of mitochondrial DNA–related disorders. This new approach may be considered as first-line testing for comprehensive analysis of the mitochondrial genome.Genet Med 2013:15(5):388–394
Published: 2013
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35. An integrated approach for classifying mitochondrial DNA variants: one clinical diagnostic laboratory’s experience

Author: Wang, Jing, Schmitt, Eric S., Landsverk, Megan L., Zhang, Victor Wei, Li, Fang-Yuan, Graham, Brett H., Craigen, William J., and Wong, Lee-Jun C.
Abstract: Purpose:The mitochondrial genome is highly polymorphic. A unique feature of deleterious mitochondrial DNA (mtDNA) mutations is heteroplasmy. Genetic background and variable penetrance also play roles in the pathogenicity for a mtDNA variant. Clinicians are increasingly interested in requesting mtDNA testing. However, interpretation of uncharacterized mtDNA variants is a great challenge. We suggest a stepwise interpretation procedure for clinical service.Methods:We describe the algorithms used to interpret novel and rare mtDNA variants. mtDNA databases and in silico predictive algorithms are used to evaluate the pathogenic potential of novel and/or rare mtDNA variants.Results:mtDNA variants can be classified into three categories: benign variants, unclassified variants, and deleterious mutations based on database search and in silico prediction. Targeted DNA sequence analysis of matrilineal relatives, heteroplasmy quantification, and functional studies are useful to classify mtDNA variants.Conclusion:Clinical significance of a novel or rare variant is critical in the diagnosis of the disease and counseling of the family. Based on the results from clinical, biochemical, and molecular genetic studies of multiple family members, proper interpretation of mtDNA variants is important for clinical laboratories and for patient care.Genet Med 2012:14(6):620–626
Published: 2012
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36. An integrated approach for classifying mitochondrial DNA variants: one clinical diagnostic laboratory’s experience

Author: Wang, Jing, Schmitt, Eric S., Landsverk, Megan L., Zhang, Victor Wei, Li, Fang-Yuan, Graham, Brett H., Craigen, William J., and Wong, Lee-Jun C.
Abstract: The mitochondrial genome is highly polymorphic. A unique feature of deleterious mitochondrial DNA (mtDNA) mutations is heteroplasmy. Genetic background and variable penetrance also play roles in the pathogenicity for a mtDNA variant. Clinicians are increasingly interested in requesting mtDNA testing. However, interpretation of uncharacterized mtDNA variants is a great challenge. We suggest a stepwise interpretation procedure for clinical service.
Published: 2012
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37. Maternal systemic primary carnitine deficiency uncovered by newborn screening: Clinical, biochemical, and molecular aspects

Author: El-Hattab, Ayman W, Li, Fang-Yuan, Shen, Joseph, Powell, Berkley R, Bawle, Erawati V, Adams, Darius J, Wahl, Erica, Kobori, Joyce A, Graham, Brett, Scaglia, Fernando, and Wong, Lee-Jun
Abstract: Background: Systemic primary carnitine deficiency is an autosomal recessive disorder of the carnitine cycle caused by mutations in the SLC22A5 gene that encodes the carnitine transporter, organic cation transporter. Systemic primary carnitine deficiency typically presents in childhood with either metabolic decompensation or cardiomyopathy. We report five families in which low free carnitine levels in the infants' newborn screening have led to the diagnosis of maternal systemic primary carnitine deficiency.Methods: Blood samples from the infants and /or their family members were used to extract the DNA. The entire coding regions of the SLC22A5 gene were sequenced. The clinical data were obtained from the referring metabolic specialists.Result: Sequencing the SLC22A5 gene allowed molecular confirmation with identification of three novel mutations: c.1195C>T (p.R399W), c.1324_1325GC>AT (p.A442I), and c.43G>T (p.G15W). All infants were asymptomatic at the time of diagnosis, and one was found to have systemic primary carnitine deficiency. Three mothers are asymptomatic, one had decreased stamina during pregnancy, and one has mild fatigability and developed preeclampsia.Discussion: These findings provide further evidence that systemic primary carnitine deficiency presents with a broad clinical spectrum from a metabolic decompensation in infancy to an asymptomatic adult. The maternal systemic primary carnitine deficiency was uncovered by the newborn screening results supporting the previous notion that newborn screening can identify some of the maternal inborn errors of metabolism. It also emphasizes the importance of maternal evaluation after identification of a low free carnitine level in the newborn screening.
Published: 2010
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38. Maternal systemic primary carnitine deficiency uncovered by newborn screening: Clinical, biochemical, and molecular aspects

Author: El-Hattab, Ayman W., Li, Fang-Yuan, Shen, Joseph, Powell, Berkley R., Bawle, Erawati V., Adams, Darius J., Wahl, Erica, Kobori, Joyce A., Graham, Brett, Scaglia, Fernando, and Wong, Lee-Jun
Abstract: Systemic primary carnitine deficiency is an autosomal recessive disorder of the carnitine cycle caused by mutations in the SLC22A5gene that encodes the carnitine transporter, organic cation transporter. Systemic primary carnitine deficiency typically presents in childhood with either metabolic decompensation or cardiomyopathy. We report five families in which low free carnitine levels in the infants' newborn screening have led to the diagnosis of maternal systemic primary carnitine deficiency.
Published: 2010
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39. Integrating Communication Skills, Awareness of Self and Others, and Reflective Feedback into One Inclusive Anatomical Representation of Relationship-Centered Health Care

Author: Englar, Ryane E. and Graham Brett, Teresa
Abstract: AbstractThe American Veterinary Medical Association Council on Education mandates in standard 11 that all accredited colleges of veterinary medicine must develop and deliver formal processes by which students are observed and assessed in nine competencies. The eighth competency combines clinical communication and sensitivity toward soliciting and understanding individual narratives across a diverse clientele to facilitate health care delivery. Several frameworks have been designed to structure health care consultations for teaching and coaching purposes. The Calgary–Cambridge guide (CCG) provides an evidence-based approach to outlining the flow of consultations, incorporating foundational communication skills and elements of relationship-centered care into a series of sequential tasks. Although the CCG was intended for use as a flexible tool kit, it lacks visible connections between concrete experiences (e.g., the consultation) and reflective observation (e.g., the feedback). This teaching tip describes the development of a novel anatomical representation of the consultation that integrates process elements of the CCG with other core curricular concepts. By combining knowledge, technical skills, critical thinking, reflection, cultural humility, and self-awareness into a skeletal consultation model, linkages are established between communication and intergroup dialogue skills, diversity and inclusion (D&I). This model has been further adapted as feline, caprine, porcine, equine, avian, and reptilian versions for in-class use as strategic visual aids that highlight key areas of focus for Professional Skills class sessions. Future developments by the authors will explore how to link species-specific consultation models to assessment rubrics to reinforce the connection between content (what) and process (how).
Published: 2022
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40. Fine–Lubinsky syndrome: Sibling pair suggests possible autosomal recessive inheritanceHow to cite this article: Holder AM, Graham BH, Lee B, Scott DA. 2007. Fine–Lubinsky syndrome: Sibling pair suggests possible autosomal recessive inheritance. Am J Med Genet Part A 143A:2576–2580.

Author: Holder, Ashley M., Graham, Brett H., Lee, Brendan, and Scott, Daryl A.
Abstract: In 1983, Fine and Lubinsky reported a single patient with craniofacial anomalies, hearing loss, cataracts, microstomia, CNS anomalies, and developmental delay. Since that time, three additional patients with similar findings have been described. In each case the patients was the only affected child in his or her family. Here we describe the first brother and sister sibling pair with features suggestive of Fine–Lubinsky syndrome. Features present in one or both of our patients, and the majority of previously described individuals with Fine–Lubinsky syndrome, include: craniosynostosis/abnormal calvaria, prominent frontal bones, flat facial profiles, small noses, microstomia, hearing loss, developmental delay/mental retardation, and abnormal digits. Unusual anomalies present in our patients include marked brachydactyly of fingers and toes, camptodactyly most severely affecting the second fingers, and permanence of decidual teeth. The identification of a sibling pair with Fine–Lubinsky suggests a possible autosomal recessive inheritance pattern. It is important that parents of children with Fine–Lubinsky be informed of the increased recurrence risk associated with that type of inheritance. © 2007 Wiley‐Liss, Inc.
Published: 2007
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41. The Physiological Properties of a Novel Family of VDAC-Like Proteins from Drosophila melanogaster

Author: Komarov, Alexander G., Graham, Brett H., Craigen, William J., and Colombini, Marco
Abstract: VDAC, a major protein of the mitochondrial outer membrane, forms voltage-dependent, anion-selective channels permeable to most metabolites. Although multiple isoforms of VDAC have been found in different organisms, only one isoform (porin/DVDAC) has been previously reported for Drosophila melanogaster. We have examined the physiological properties of three other Drosophila proteins (CG17137, CG17139, and CG17140) whose primary sequences have significant homology to DVDAC. A comparison of their hydropathy profiles (β-pattern) with known VDAC sequences indicates the same fundamental folding pattern but with major insertions and deletions. The ability of these proteins to form channels was tested on planar membranes and liposomes. Channel activity was observed with varying degrees of similarity to VDAC. Two of these proteins (CG17137 and CG17140) produced channels with anionic selectivity in the open state. Sometimes channels exhibited closure and voltage gating, but for CG17140 this occurred at much higher voltages than is typical for VDAC. CG17139 was not able to form channels. DVDAC and CG17137 were able to rescue the temperature-sensitive conditional-lethal phenotype of VDAC-deficient yeast, whereas CG17139 and CG17140 demonstrated no complementation. Similar structure and channel formation indicate that VDAC-like proteins are part of the larger VDAC family but the modifications are indicative of specialized functions.
Published: 2004
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42. Marked Changes in Mitochondrial DNA Deletion Levels in Alzheimer Brains

Author: Corral-Debrinski, Marisol, Horton, Terzah, Lott, Marie T., Shoffner, John M., McKee, Ann C., Beal, M. Flint, Graham, Brett H., and Wallace, Douglas C.
Abstract: Levels of the common 4977 nucleotide pair (np) mitochondrial DNA (mtDNA) deletion (mtDNA⁴⁹⁷⁷) were quantitated in the cortex, putamen, and cerebellum of patients with Alzheimer disease (AD) and compared to age-matched controls. Although cerebellum deletion levels were comparably low in AD patients and controls of all ages, cortical deletion levels were clearly different. The levels of mtDNA deletions in control brains started low, but rose markedly after age 75, while those of AD patients started high and declined to low levels by age 80. Choosing age 75 to arbitrarily delineate between younger and older subjects, younger patients had 15 times more mtDNA deletions than younger controls, while older patients had one-fifth the deletion level of older controls. Younger AD patients also had fourfold more deletions than older AD patients. These results support the hypothesis that OXPHOS defects resulting from somatic mtDNA mutations may play a role in AD pathophysiology. Copyright 1994, 1999 Academic Press
Published: 1994
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43. A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator

Author: Graham, Brett H., Waymire, Katrina G., Cottrell, Barbara, Trounce, Ian A., MacGregor, Grant R., and Wallace, Douglas C.
Abstract: In an attempt to create an animal model of tissue-specif ic mitochondrial disease, we generated ‘knockout’ mice deficient in the heart/muscle isoform of the adenine nucleotide translocator (Ant1). Histological and ultrastructural examination of skeletal muscle from Ant1 null mutants revealed ragged-red muscle fibers and a dramatic proliferation of mitochondria, while examination of the heart revealed cardiac hypertrophy with mitochondrial proliferation. Mitochondria isolated from mutant skeletal muscle exhibited a severe defect in coupled respiration. Ant1mutant adults also had a resting serum lactate level fourfold higher than that of controls, indicative of metabolic acidosis. Significantly, mutant adults manifested severe exercise intolerance. Therefore, Ant1 mutant mice have the biochemical, histological, metabolic and physiological characteristics of mitochondrial myopathy and cardiomyopathy.
Published: 1997
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44. Anticoagulant selection in relation to the SAMe-TT2R2score in patients with atrial fibrillation: The GLORIA-AF registry

Author: Ntaios, George, Huisman, Menno V., Diener, Hans-Christoph, Halperin, Jonathan L., Teutsch, Christine, Marler, Sabrina, Gurusamy, Venkatesh K., Thompson, Milla, Lip, Gregory Y.H., Olshansky, Brian, Abban, Dzifa Wosornu, Abdul, Nasser, Abud, Atilio Marcelo, Adams, Fran, Addala, Srinivas, Adragão, Pedro, Ageno, Walter, Aggarwal, Rajesh, Agosti, Sergio, Agostoni, Piergiuseppe, Aguilar, Francisco, Linares, Julio Aguilar, Aguinaga, Luis, Ahmed, Jameel, Aiello, Allessandro, Ainsworth, Paul, Aiub, Jorge Roberto, Al-Dallow, Raed, Alderson, Lisa, Aldrete Velasco, Jorge Antonio, Alexopoulos, Dimitrios, Manterola, Fernando Alfonso, Aliyar, Pareed, Alonso, David, Alves da Costa, Fernando Augusto, Amado, José, Amara, Walid, Amelot, Mathieu, Amjadi, Nima, Ammirati, Fabrizio, Andrade, Marianna, Andrawis, Nabil, Annoni, Giorgio, Ansalone, Gerardo, Ariani, M.Kevin, Arias, Juan Carlos, Armero, Sébastien, Arora, Chander, Aslam, Muhammad Shakil, Asselman, M., Audouin, Philippe, Augenbraun, Charles, Aydin, S., Ayryanova, Ivaneta, Aziz, Emad, Backes, Luciano Marcelo, Badings, E., Bagni, Ermentina, Baker, Seth H., Bala, Richard, Baldi, Antonio, Bando, Shigenobu, Banerjee, Subhash, Bank, Alan, Esquivias, Gonzalo Barón, Barr, Craig, Bartlett, Maria, Kes, Vanja Basic, Baula, Giovanni, Behrens, Steffen, Bell, Alan, Benedetti, Raffaella, Mazuecos, Juan Benezet, Benhalima, Bouziane, Bergler-Klein, Jutta, Berneau, Jean-Baptiste, Bernstein, Richard A., Berrospi, Percy, Berti, Sergio, Berz, Andrea, Best, Elizabeth, Bettencourt, Paulo, Betzu, Robert, Bhagwat, Ravi, Bhatta, Luna, Biscione, Francesco, BISIGNANI, Giovanni, Black, Toby, Bloch, Michael J., Bloom, Stephen, Blumberg, Edwin, Bo, Mario, Bøhmer, Ellen, Bollmann, Andreas, Bongiorni, Maria Grazia, Boriani, Giuseppe, Boswijk, D.J., Bott, Jochen, Bottacchi, Edo, Kalan, Marica Bracic, Bradman, Drew, Brautigam, Donald, Breton, Nicolas, Brouwers, P.J.A.M., Browne, Kevin, Cortada, Jordi Bruguera, Bruni, A., Brunschwig, Claude, Buathier, Hervé, Buhl, Aurélie, Bullinga, John, Cabrera, Jose Walter, Caccavo, Alberto, Cai, Shanglang, Caine, Sarah, Calò, Leonardo, Calvi, Valeria, Sánchez, Mauricio Camarillo, Candeias, Rui, Capuano, Vincenzo, Capucci, Alessandro, Caputo, Ronald, Rizo, Tatiana Cárdenas, Cardona, Francisco, Carlos da Costa Darrieux, Francisco, Duarte Vera, Yan Carlos, Carolei, Antonio, Carreño, Susana, Carvalho, Paula, Cary, Susanna, Casu, Gavino, Cavallini, Claudio, Cayla, Guillaume, Celentano, Aldo, Cha, Tae-Joon, Cha, Kwang Soo, Chae, Jei Keon, Chalamidas, Kathrine, Challappa, Krishnan, Chand, Sunil Prakash, Chandrashekar, Harinath, Chartier, Ludovic, Chatterjee, Kausik, Chavez Ayala, Carlos Antero, Cheema, Aamir, Cheema, Amjad, Chen, Lin, Chen, Shih-Ann, Chen, Jyh Hong, Chiang, Fu-Tien, Chiarella, Francesco, Chih-Chan, Lin, Cho, Yong Keun, Choi, Jong-Il, Choi, Dong Ju, Chouinard, Guy, Hoi-Fan Chow, Danny, Chrysos, Dimitrios, Chumakova, Galina, José Roberto Chuquiure Valenzuela, Eduardo Julián, Nica, Nicoleta Cindea, Cislowski, David J., Clay, Anthony, Clifford, Piers, Cohen, Andrew, Cohen, Michael, Cohen, Serge, Colivicchi, Furio, Collins, Ronan, Colonna, Paolo, Compton, Steve, Connolly, Derek, Conti, Alberto, Buenostro, Gabriel Contreras, Coodley, Gregg, Cooper, Martin, Coronel, Julian, Corso, Giovanni, Sales, Juan Cosín, Cottin, Yves, Covalesky, John, Cracan, Aurel, Crea, Filippo, Crean, Peter, Crenshaw, James, Cullen, Tina, Darius, Harald, Dary, Patrick, Dascotte, Olivier, Dauber, Ira, Davalos, Vicente, Davies, Ruth, Davis, Gershan, Davy, Jean-Marc, Dayer, Mark, De Biasio, Marzia, De Bonis, Silvana, De Caterina, Raffaele, De Franceschi, Teresiano, de Groot, J.R., De Horta, José, De La Briolle, Axel, Topete, Gilberto de la Pena, Vicenzo de Paola, Angelo Amato, de Souza, Weimar, de Veer, A., De Wolf, Luc, Decoulx, Eric, Deepak, Sasalu, Defaye, Pascal, Del-Carpio Munoz, Freddy, Brkljacic, Diana Delic, Deumite, N. Joseph, Di Legge, Silvia, Diemberger, Igor, Dietz, Denise, Dionísio, Pedro, Dong, Qiang, Rossi dos Santos, Fabio, Dotcheva, Elena, Doukky, Rami, D'Souza, Anthony, Dubrey, Simon, Ducrocq, Xavier, Dupljakov, Dmitry, Duque, Mauricio, Dutta, Dipankar, Duvilla, Nathalie, Duygun, A., Dziewas, Rainer, Eaton, Charles B., Eaves, William, Ebels-Tuinbeek, L.A., Ehrlich, Clifford, Eichinger-Hasenauer, Sabine, Eisenberg, Steven J., El Jabali, Adnan, El Shahawy, Mahfouz, Hernandes, Mauro Esteves, Izal, Ana Etxeberria, Evonich, Rudolph, Evseeva, Oksana, Ezhov, Andrey, Fahmy, Raed, Fang, Quan, Farsad, Ramin, Fauchier, Laurent, Favale, Stefano, Fayard, Maxime, Fedele, Jose Luis, Fedele, Francesco, Fedorishina, Olga, Fera, Steven R., Gomes Ferreira, Luis Gustavo, Ferreira, Jorge, Ferri, Claudio, Ferrier, Anna, Ferro, Hugo, Finsen, Alexandra, First, Brian, Fischer, Stuart, Fonseca, Catarina, Almeida, Luísa Fonseca, Forman, Steven, Frandsen, Brad, French, William, Friedman, Keith, Friese, Athena, Fruntelata, Ana Gabriela, Fujii, Shigeru, Fumagalli, Stefano, Fundamenski, Marta, Furukawa, Yutaka, Gabelmann, Matthias, Gabra, Nashwa, Gadsbøll, Niels, Galinier, Michel, Gammelgaard, Anders, Ganeshkumar, Priya, Gans, Christopher, Quintana, Antonio Garcia, Gartenlaub, Olivier, Gaspardone, Achille, Genz, Conrad, Georger, Frédéric, Georges, Jean-Louis, Georgeson, Steven, Giedrimas, Evaldas, Gierba, Mariusz, Ortega, Ignacio Gil, Gillespie, Eve, Giniger, Alberto, Giudici, Michael C., Gkotsis, Alexandros, Glotzer, Taya V., Gmehling, Joachim, Gniot, Jacek, Goethals, Peter, Goldbarg, Seth, Goldberg, Ronald, Goldmann, Britta, Golitsyn, Sergey, Gómez, Silvia, Mesa, Juan Gomez, Gonzalez, Vicente Bertomeu, Gonzalez Hermosillo, Jesus Antonio, González López, Víctor Manuel, Gorka, Hervé, Gornick, Charles, Gorog, Diana, Gottipaty, Venkat, Goube, Pascal, Goudevenos, Ioannis, Graham, Brett, Greer, G. Stephen, Gremmler, Uwe, Grena, Paul G., Grond, Martin, Gronda, Edoardo, Grönefeld, Gerian, Gu, Xiang, Torres Torres, Ivett Guadalupe, Guardigli, Gabriele, Guevara, Carolina, Guignier, Alexandre, Gulizia, Michele, Gumbley, Michael, Günther, Albrecht, Ha, Andrew, Hahalis, Georgios, Hakas, Joseph, Hall, Christian, Han, Bing, Han, Seongwook, Hargrove, Joe, Hargroves, David, Harris, Kenneth B., Haruna, Tetsuya, Hayek, Emil, Healey, Jeff, Hearne, Steven, Heffernan, Michael, Heggelund, Geir, Heijmeriks, J.A., Hemels, Maarten, Hendriks, I., Henein, Sam, Her, Sung-Ho, Hermany, Paul, Hernández Del Río, Jorge Eduardo, Higashino, Yorihiko, Hill, Michael, Hisadome, Tetsuo, Hishida, Eiji, Hoffer, Etienne, Hoghton, Matthew, Hong, Kui, Hong, Suk keun, Horbach, Stevie, Horiuchi, Masataka, Hou, Yinglong, Hsing, Jeff, Huang, Chi-Hung, Huckins, David, Hughes, kathy, Huizinga, A., Hulsman, E.L., Hung, Kuo-Chun, Hwang, Gyo-Seung, Ikpoh, Margaret, Imberti, Davide, Ince, Hüseyin, Indolfi, Ciro, Inoue, Shujiro, Irles, Didier, Iseki, Harukazu, Israel, C. Noah, Iteld, Bruce, Iyer, Venkat, Jackson-Voyzey, Ewart, Jaffrani, Naseem, Jäger, Frank, James, Martin, Jang, Sung-Won, Jaramillo, Nicolas, Jarmukli, Nabil, Jeanfreau, Robert J., Jenkins, Ronald D., Sánchez, Carlos Jerjes, Jimenez, Javier, Jobe, Robert, Joen-Jakobsen, Tomas, Jones, Nicholas, Moura Jorge, Jose Carlos, Jouve, Bernard, Jung, Byung Chun, Jung, Kyung Tae, Jung, Werner, Kachkovskiy, Mikhail, Kafkala, Krystallenia, Kalinina, Larisa, Kallmünzer, Bernd, Kamali, Farzan, Kamo, Takehiro, Kampus, Priit, Kashou, Hisham, Kastrup, Andreas, Katsivas, Apostolos, Kaufman, Elizabeth, Kawai, Kazuya, Kawajiri, Kenji, Kazmierski, John F., Keeling, P., Kerr Saraiva, José Francisco, Ketova, Galina, Khaira, AJIT Singh, Khripun, Aleksey, Kim, Doo-Il, Kim, Young Hoon, Kim, Nam Ho, Kim, Dae Kyeong, Kim, Jeong Su, Kim, June Soo, Kim, Ki Seok, Kim, Jin bae, Kinova, Elena, Klein, Alexander, Kmetzo, James J., Kneller, G. Larsen, Knezevic, Aleksandar, Angela Koh, Su Mei, Koide, Shunichi, Kollias, Athanasios, Kooistra, J.A., Koons, Jay, Koschutnik, Martin, Kostis, William J., Kovacic, Dragan, Kowalczyk, Jacek, Koziolova, Natalya, Kraft, Peter, Kragten, Johannes A., Krantz, Mori, Krause, Lars, Krenning, B.J., Krikke, F., Kromhout, Z., Krysiak, Waldemar, Kumar, Priya, Kümler, Thomas, Kuniss, Malte, Kuo, Jen-Yuan, Küppers, Achim, Kurrelmeyer, Karla, Kwak, Choong Hwan, Laboulle, Bénédicte, Labovitz, Arthur, Lai, Wen Ter, Lam, Andy, Lam, Yat Yin, Zanetti, Fernando Lanas, Landau, Charles, Landini, Giancarlo, Figueiredo, Estêvão Lanna, Larsen, Torben, Lavandier, Karine, LeBlanc, Jessica, Lee, Moon Hyoung, Lee, Chang-Hoon, Lehman, John, Leitão, Ana, Lellouche, Nicolas, Lelonek, Malgorzata, Lenarczyk, Radoslaw, Lenderink, T., González, Salvador León, Leong-Sit, Peter, Leschke, Matthias, Ley, Nicolas, Li, Zhanquan, Li, Xiaodong, Li, Weihua, Li, Xiaoming, Lichy, Christhoh, Lieber, Ira, Limon Rodriguez, Ramon Horacio, Lin, Hailong, Lip, Gregory Y.H., Liu, Feng, Liu, Hengliang, Esperon, Guillermo Llamas, Navarro, Nassip Llerena, Lo, Eric, Lokshyn, Sergiy, López, Amador, López-Sendón, José Luís, Lorga Filho, Adalberto Menezes, Lorraine, Richard S., Luengas, Carlos Alberto, Luke, Robert, Luo, Ming, Lupovitch, Steven, Lyrer, Philippe, Ma, Changsheng, Ma, Genshan, Madariaga, Irene, Maeno, Koji, Magnin, Dominique, Maid, Gustavo, Mainigi, Sumeet K., Makaritsis, Konstantinos, Malhotra, Rohit, Manning, Rickey, Manolis, Athanasios, Manrique Hurtado, Helard Andres, Mantas, Ioannis, Jattin, Fernando Manzur, Maqueda, Vicky, Marchionni, Niccolo, Ortuno, Francisco Marin, Santana, Antonio Martín, Martinez, Jorge, Maskova, Petra, Hernandez, Norberto Matadamas, Matsuda, Katsuhiro, Maurer, Tillmann, Mauro, Ciro, May, Erik, Mayer, Nolan, McClure, John, McCormack, Terry, McGarity, William, McIntyre, Hugh, McLaurin, Brent, Medina Palomino, Feliz Alvaro, Melandri, Francesco, Meno, Hiroshi, Menzies, Dhananjai, Mercader, Marco, Meyer, Christian, Meyer, Beat j., Miarka, Jacek, Mibach, Frank, Michalski, Dominik, Michel, Patrik, Chreih, Rami Mihail, Mikdadi, Ghiath, Mikus, Milan, Milicic, Davor, Militaru, Constantin, Minaie, Sedi, Minescu, Bogdan, Mintale, Iveta, Mirault, Tristan, Mirro, Michael J., Mistry, Dinesh, Miu, Nicoleta Violeta, Miyamoto, Naomasa, Moccetti, Tiziano, Mohammed, Akber, Nor, Azlisham Mohd, Mollerus, Michael, Molon, Giulio, Mondillo, Sergio, Moniz, Patrícia, Mont, Lluis, Montagud, Vicente, Montaña, Oscar, Monti, Cristina, Moretti, Luciano, Mori, Kiyoo, Moriarty, Andrew, Morka, Jacek, Moschini, Luigi, Moschos, Nikitas, Mügge, Andreas, Mulhearn, Thomas J., Muresan, Carmen, Muriago, Michela, Musial, Wlodzimierz, Musser, Carl W., Musumeci, Francesco, Nageh, Thuraia, Nakagawa, Hidemitsu, Nakamura, Yuichiro, Nakayama, Toru, Nam, Gi-Byoung, Nanna, Michele, Natarajan, Indira, Nayak, Hemal M., Naydenov, Stefan, Nazli, Jurica, Nechita, Alexandru Cristian, Nechvatal, Libor, Negron, Sandra Adela, Neiman, James, Neuenschwander, Fernando Carvalho, Neves, David, Neykova, Anna, Miguel, Ricardo Nicolás, Nijmeh, George, Nizov, Alexey, Campos, Rodrigo Noronha, Nossan, Janko, Novikova, Tatiana, Nowalany-Kozielska, Ewa, Nsah, Emmanuel, Nunez Fragoso, Juan Carlos, Nurgalieva, Svetlana, Nuyens, Dieter, Nyvad, Ole, Odin de Los Rios Ibarra, Manuel, O'Donnell, Philip, O'Donnell, Martin, Oh, Seil, Oh, Yong Seog, Oh, Dongjin, O'Hara, Gilles, Oikonomou, Kostas, Olivares, Claudia, Oliver, Richard, Ruiz, Rafael Olvera, Olympios, Christoforos, omaszuk-Kazberuk, Anna, Asensi, Joaquín Osca, jose, eena Padayattil, Padilla Padilla, Francisco Gerardo, Rios, Victoria Padilla, Pajes, Giuseppe, Pandey, A. Shekhar, Paparella, Gaetano, Paris, F., Park, Hyung Wook, Park, Jong Sung, Parthenakis, Fragkiskos, Passamonti, Enrico, Patel, Rajesh J., Patel, Jaydutt, Patel, Mehool, Patrick, Janice, Jimenez, Ricardo Pavón, Paz, Analía, Pengo, Vittorio, Pentz, William, Pérez, Beatriz, Pérez Ríos, Alma Minerva, Pérez-Cabezas, Alejandro, Perlman, Richard, Persic, Viktor, Perticone, Francesco, Peters, Terri K., Petkar, Sanjiv, Pezo, Luis Felipe, Pflücke, Christian, Pham, David N., Phillips, Roland T., Phlaum, Stephen, Pieters, Denis, Pineau, Julien, Pinter, Arnold, Pinto, Fausto, Pisters, R., Pivac, Nediljko, Pocanic, Darko, Podoleanu, Cristian, Politano, Alessandro, Poljakovic, Zdravka, Pollock, Stewart, Garcéa, Jose Polo, Poppert, Holger, Porcu, Maurizio, Reino, Antonio Pose, Prasad, Neeraj, Précoma, Dalton Bertolim, Prelle, Alessandro, Prodafikas, John, Protasov, Konstantin, Pye, Maurice, Qiu, Zhaohui, Quedillac, Jean-Michel, Raev, Dimitar, Raffo Grado, Carlos Antonio, Rahimi, Sidiqullah, Raisaro, Arturo, Rama, Bhola, Ramos, Ricardo, Ranieri, Maria, Raposo, Nuno, Rashba, Eric, Rauch-Kroehnert, Ursula, Reddy, Ramakota, Renda, Giulia, Reza, Shabbir, Ria, Luigi, Richter, Dimitrios, Rickli, Hans, Rieker, Werner, Vera, Tomas Ripolil, Ritt, Luiz Eduardo, Roberts, Douglas, Briones, Ignacio Rodriguez, Rodriguez Escudero, Aldo Edwin, Pascual, Carlos Rodríguez, Roman, Mark, Romeo, Francesco, Ronner, E., Roux, Jean-Francois, Rozkova, Nadezda, Rubacek, Miroslav, Rubalcava, Frank, Russo, Andrea M., Rutgers, Matthieu Pierre, Rybak, Karin, Said, Samir, Sakamoto, Tamotsu, Salacata, Abraham, Salem, Adrien, Bodes, Rafael Salguero, Saltzman, Marco A., Salvioni, Alessandro, Vallejo, Gregorio Sanchez, Fernández, Marcelo Sanmartín, Saporito, Wladmir Faustino, Sarikonda, Kesari, Sasaoka, Taishi, Sati, Hamdi, Savelieva, Irina, Scala, Pierre-Jean, Schellinger, Peter, Scherr, Carlos, Schmitz, Lisa, Schmitz, Karl-Heinz, Schmitz, Bettina, Schnabel, Teresa, Schnupp, Steffen, Schoeniger, Peter, Schön, Norbert, Schwimmbeck, Peter, Seamark, Clare, Searles, Greg, Seidl, Karl-Heinz, Seidman, Barry, Sek, Jaroslaw, Sekaran, Lakshmanan, SERRATI, Carlo, Shah, Neerav, Shah, Vinay, Shah, Anil, Shah, Shujahat, Sharma, Vijay Kumar, Shaw, Louise, Sheikh, Khalid H., Shimizu, Naruhito, Shimomura, Hideki, Shin, Dong-Gu, Shin, Eun-Seok, Shite, Junya, Sibilio, Gerolamo, Silver, Frank, Sime, Iveta, Simmers, Tim A., Singh, Narendra, Siostrzonek, Peter, Smadja, Didier, Smith, David W., Snitman, Marcelo, Filho, Dario Sobral, Soda, Hassan, Sofley, Carl, Sokal, Adam, Oi Yan, Yannie Soo, Sotolongo, Rodolfo, Ferreira de Souza, Olga, Sparby, Jon Arne, Spinar, Jindrich, Sprigings, David, Spyropoulos, Alex C., Stakos, Dimitrios, Steinwender, Clemens, Stergiou, Georgios, Stiell, Ian, Stoddard, Marcus, Stoikov, Anastas, Streb, Witold, Styliadis, Ioannis, Su, Guohai, Su, Xi, Sudnik, Wanda, Sukles, Kai, Sun, Xiaofei, Swart, H., Szavits-Nossan, Janko, Taggeselle, Jens, Takagi, Yuichiro, Singh Takhar, Amrit Pal, Tamm, Angelika, Tanaka, Katsumi, Tanawuttiwat, Tanyanan, Tang, Sherman, Tang, Aylmer, Tarsi, Giovanni, Tassinari, Tiziana, Tayal, Ashis, Tayebjee, Muzahir, Berg, J.M. ten, Tesloianu, Dan, The, Salem H.K., Thomas, Dierk, Timsit, Serge, Tobaru, Tetsuya, Tomasik, Andrzej R., Torosoff, Mikhail, Touze, Emmanuel, Trendafilova, Elina, Tsai, W. Kevin, Tse, Hung Fat, Tsutsui, Hiroshi, Tu, Tian Ming, Tuininga, Ype, Turakhia, Minang, Turk, Samir, Tcurner, Wayne, Tveit, Arnljot, Tytus, Richard, Valadão, C., van Bergen, P.F.M.M., van de Borne, Philippe, van den Berg, B.J., van der Zwaan, C., Van Eck, M., Vanacker, Peter, Vasilev, Dimo, Vasilikos, Vasileios, Vasilyev, Maxim, Veerareddy, Srikar, Miño, Mario Vega, Venkataraman, Asok, Verdecchia, Paolo, Versaci, Francesco, Vester, Ernst Günter, Vial, Hubert, Victory, Jason, Villamil, Alejandro, Vincent, Marc, Vlastaris, Anthony, Dahl, Jürgen vom, Vora, Kishor, Vranian, Robert B., Wakefield, Paul, Wang, Ningfu, Wang, Mingsheng, Wang, Xinhua, Wang, Feng, Wang, Tian, Warner, Alberta L., Watanabe, Kouki, Wei, Jeanne, Weimar, Christian, Weiner, Stanislav, Weinrich, Renate, Wen, Ming-Shien, Wiemer, Marcus, Wiggers, Preben, Wilke, Andreas, Williams, David, Williams, Marcus L., Witzenbichler, Bernhard, Wong, Brian, Lawrence Wong, Ka Sing, Wozakowska-Kaplon, Beata, Wu, Shulin, Wu, Richard C., Wunderlich, Silke, Wyatt, Nell, Wylie, John (Jack), Xu, Yong, Xu, Xiangdong, Yamanoue, Hiroki, Yamashita, Takeshi, Bryan Yan, Ping Yen, Yang, Tianlun, Yao, Jing, Yeh, Kuo-Ho, Yin, Wei Hsian, Yotov, Yoto, Zahn, Ralf, Zarich, Stuart, Zenin, Sergei, Zeuthen, Elisabeth Louise, Zhang, Huanyi, Zhang, Donghui, Zhang, Xingwei, Zhang, Ping, Zhang, Jun, Zhao, Shui Ping, Zhao, Yujie, Zhao, Zhichen, Zheng, Yang, Zhou, Jing, Zimmermann, Sergio, Zini, Andrea, Zizzo, Steven, Zong, Wenxia, and Zukerman, L Steven
Abstract: The SAMe-TT2R2score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2scores >2 than to patients with lower scores.
Published: 2021
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45. Megaloblastic Anemia Progressing to Severe Thrombotic Microangiopathy in Patients with Disordered Vitamin B12 Metabolism: Case Reports and Literature Review.

Author: Mullikin, Dolores, Pillai, Nishitha, Sanchez, Rossana, O'Donnell- Luria, Anne H., Kritzer, Amy, Tal, Leyat, Almannai, Mohammed, Berry, Gerard T., Gambello, Michael J., Li, Hong, Graham, Brett, Srivaths, Lakshmi, Sutton, Vernon Reid, and Grimes, Amanda
Abstract: We describe 2 children with cobalamin G disease, a disorder of vitamin B12 metabolism with normal serum B12 levels. They presented with megaloblastic anemia progressing rapidly to severe thrombotic microangiopathy. In infants presenting with acute thrombotic microangiopathy, cobalamin disorders should be considered early as diagnosis and targeted treatment can be lifesaving. [ABSTRACT FROM AUTHOR]
Published: 2018
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46. Defining a Spinal Microcircuit that Gates Myelinated Afferent Input: Implications for Tactile Allodynia

Author: Boyle, Kieran A., Gradwell, Mark A., Yasaka, Toshiharu, Dickie, Allen C., Polgár, Erika, Ganley, Robert P., Orr, Desmond P.H., Watanabe, Masahiko, Abraira, Victoria E., Kuehn, Emily D., Zimmerman, Amanda L., Ginty, David D., Callister, Robert J., Graham, Brett A., and Hughes, David I.
Abstract: Chronic pain presents a major unmet clinical problem. The development of more effective treatments is hindered by our limited understanding of the neuronal circuits underlying sensory perception. Here, we show that parvalbumin (PV)-expressing dorsal horn interneurons modulate the passage of sensory information conveyed by low-threshold mechanoreceptors (LTMRs) directly via presynaptic inhibition and also gate the polysynaptic relay of LTMR input to pain circuits by inhibiting lamina II excitatory interneurons whose axons project into lamina I. We show changes in the functional properties of these PV interneurons following peripheral nerve injury and that silencing these cells unmasks a circuit that allows innocuous touch inputs to activate pain circuits by increasing network activity in laminae I–IV. Such changes are likely to result in the development of tactile allodynia and could be targeted for more effective treatment of mechanical pain.
Published: 2019
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47. Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management

Author: Meng, Linyan, Pammi, Mohan, Saronwala, Anirudh, Magoulas, Pilar, Ghazi, Andrew Ray, Vetrini, Francesco, Zhang, Jing, He, Weimin, Dharmadhikari, Avinash V., Qu, Chunjing, Ward, Patricia, Braxton, Alicia, Narayanan, Swetha, Ge, Xiaoyan, Tokita, Mari J., Santiago-Sim, Teresa, Dai, Hongzheng, Chiang, Theodore, Smith, Hadley, Azamian, Mahshid S., Robak, Laurie, Bostwick, Bret L., Schaaf, Christian P., Potocki, Lorraine, Scaglia, Fernando, Bacino, Carlos A., Hanchard, Neil A., Wangler, Michael F., Scott, Daryl, Brown, Chester, Hu, Jianhong, Belmont, John W., Burrage, Lindsay C., Graham, Brett H., Sutton, Vernon Reid, Craigen, William J., Plon, Sharon E., Lupski, James R., Beaudet, Arthur L., Gibbs, Richard A., Muzny, Donna M., Miller, Marcus J., Wang, Xia, Leduc, Magalie S., Xiao, Rui, Liu, Pengfei, Shaw, Chad, Walkiewicz, Magdalena, Bi, Weimin, Xia, Fan, Lee, Brendan, Eng, Christine M., Yang, Yaping, and Lalani, Seema R.
Abstract: IMPORTANCE: While congenital malformations and genetic diseases are a leading cause of early infant death, to our knowledge, the contribution of single-gene disorders in this group is undetermined. OBJECTIVE: To determine the diagnostic yield and use of clinical exome sequencing in critically ill infants. DESIGN, SETTING, AND PARTICIPANTS: Clinical exome sequencing was performed for 278 unrelated infants within the first 100 days of life who were admitted to Texas Children’s Hospital in Houston, Texas, during a 5-year period between December 2011 and January 2017. Exome sequencing types included proband exome, trio exome, and critical trio exome, a rapid genomic assay for seriously ill infants. MAIN OUTCOMES AND MEASURES: Indications for testing, diagnostic yield of clinical exome sequencing, turnaround time, molecular findings, patient age at diagnosis, and effect on medical management among a group of critically ill infants who were suspected to have genetic disorders. RESULTS: The mean (SEM) age for infants participating in the study was 28.5 (1.7) days; of these, the mean (SEM) age was 29.0 (2.2) days for infants undergoing proband exome sequencing, 31.5 (3.9) days for trio exome, and 22.7 (3.9) days for critical trio exome. Clinical indications for exome sequencing included a range of medical concerns. Overall, a molecular diagnosis was achieved in 102 infants (36.7%) by clinical exome sequencing, with relatively low yield for cardiovascular abnormalities. The diagnosis affected medical management for 53 infants (52.0%) and had a substantial effect on informed redirection of care, initiation of new subspecialist care, medication/dietary modifications, and furthering life-saving procedures in select patients. Critical trio exome sequencing revealed a molecular diagnosis in 32 of 63 infants (50.8%) at a mean (SEM) of 33.1 (5.6) days of life with a mean (SEM) turnaround time of 13.0 (0.4) days. Clinical care was altered by the diagnosis in 23 of 32 patients (71.9%). The diagnostic yield, patient age at diagnosis, and medical effect in the group that underwent critical trio exome sequencing were significantly different compared with the group who underwent regular exome testing. For deceased infants (n = 81), genetic disorders were molecularly diagnosed in 39 (48.1%) by exome sequencing, with implications for recurrence risk counseling. CONCLUSIONS AND RELEVANCE: Exome sequencing is a powerful tool for the diagnostic evaluation of critically ill infants with suspected monogenic disorders in the neonatal and pediatric intensive care units and its use has a notable effect on clinical decision making.
Published: 2017
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48. Elevations of C14:1 and C14:2 Plasma Acylcarnitines in Fasted Children: A Diagnostic Dilemma.

Author: Burrage, Lindsay C., Miller, Marcus J., Wong, Lee-Jun, Kennedy, Adam D., Sutton, V. Reid, Sun, Qin, Elsea, Sarah H., and Graham, Brett H.
Abstract: Objectives: To test whether follow-up testing for very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency uncovers a diagnosis in patients with elevations of C14:1 and C14:2 plasma acylcarnitines after a controlled fasting study performed for clinically suspected hypoglycemia and to compare the acylcarnitine profiles from fasted patients without VLCAD deficiency vs patients with known VLCAD deficiency to determine whether metabolite testing distinguishes these groups.Study Design: We performed a retrospective chart review and identified 17 patients with elevated C14:1 and C14:2 plasma acylcarnitine levels after a controlled fast and with testing for VLCAD deficiency (ACADVL sequencing or fibroblast fatty acid oxidation studies). The follow-up testing in all patients was inconsistent with a diagnosis of VLCAD deficiency. We compared the plasma acylcarnitine profiles from these fasted patients vs patients with VLCAD deficiency.Results: C14:1/C12:1 was significantly lower (P < .001) in fasted patients vs patients with VLCAD deficiency. Metabolomics analysis performed in 2 fasted patients and 1 patient with VLCAD deficiency demonstrated evidence for up-regulated lipolysis and β-oxidation in the fasted state.Conclusions: Elevations of plasma C14:1 and C14:2 acylcarnitines appear to be a physiologic result of lipolysis that occurs with fasting. Both metabolomics analysis and/or C14:1/C12:1 may distinguish C14:1 elevations from physiologic fasting-induced lipolysis vs VLCAD deficiency. [ABSTRACT FROM AUTHOR]
Published: 2016
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