9 results on '"Leung, Jacqueline M."'
Search Results
2. Prion-induced photoreceptor degeneration begins with misfolded prion protein accumulation in cones at two distinct sites: cilia and ribbon synapses
- Author
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Striebel, James F., Race, Brent, Leung, Jacqueline M., Schwartz, Cindi, and Chesebro, Bruce
- Published
- 2021
- Full Text
- View/download PDF
3. A doublecortin-domain protein of Toxoplasma and its orthologues bind to and modify the structure and organization of tubulin polymers
- Author
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Leung, Jacqueline M., Nagayasu, Eiji, Hwang, Yu-Chen, Liu, Jun, Pierce, Phillip G., Phan, Isabelle Q., Prentice, Robin A., Murray, John M., and Hu, Ke
- Published
- 2020
- Full Text
- View/download PDF
4. Surface attachment, promoted by the actomyosin system of Toxoplasma gondii is important for efficient gliding motility and invasion
- Author
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Whitelaw, Jamie A., Latorre-Barragan, Fernanda, Gras, Simon, Pall, Gurman S., Leung, Jacqueline M., Heaslip, Aoife, Egarter, Saskia, Andenmatten, Nicole, Nelson, Shane R., Warshaw, David M., Ward, Gary E., and Meissner, Markus
- Subjects
Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,macromolecular substances - Abstract
Background: Apicomplexan parasites employ a unique form of movement, termed gliding motility, in order to\ud invade the host cell. This movement depends on the parasite’s actomyosin system, which is thought to generate\ud the force during gliding. However, recent evidence questions the exact molecular role of this system, since mutants\ud for core components of the gliding machinery, such as parasite actin or subunits of the MyoA-motor complex (the\ud glideosome), remain motile and invasive, albeit at significantly reduced efficiencies. While compensatory\ud mechanisms and unusual polymerisation kinetics of parasite actin have been evoked to explain these findings, the\ud actomyosin system could also play a role distinct from force production during parasite movement.\ud Results: In this study, we compared the phenotypes of different mutants for core components of the actomyosin\ud system in Toxoplasma gondii to decipher their exact role during gliding motility and invasion. We found that, while\ud some phenotypes (apicoplast segregation, host cell egress, dense granule motility) appeared early after induction of\ud the act1 knockout and went to completion, a small percentage of the parasites remained capable of motility and\ud invasion well past the point at which actin levels were undetectable. Those act1 conditional knockout (cKO) and\ud mlc1 cKO that continue to move in 3D do so at speeds similar to wildtype parasites. However, these mutants are\ud virtually unable to attach to a collagen-coated substrate under flow conditions, indicating an important role for the\ud actomyosin system of T. gondii in the formation of attachment sites.\ud Conclusion: We demonstrate that parasite actin is essential during the lytic cycle and cannot be compensated by\ud other molecules. Our data suggest a conventional polymerisation mechanism in vivo that depends on a critical\ud concentration of G-actin. Importantly, we demonstrate that the actomyosin system of the parasite functions in\ud attachment to the surface substrate, and not necessarily as force generator.
- Published
- 2017
5. Adherence to recommended practices for perioperative anesthesia care for older adults among US anesthesiologists: results from the ASA Committee on Geriatric Anesthesia-Perioperative Brain Health Initiative ASA member survey.
- Author
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Deiner, Stacie, Fleisher, Lee A., Leung, Jacqueline M., Peden, Carol, Miller, Thomas, Neuman, Mark D., on behalf of the ASA Committee on Geriatric Anesthesia and the ASA Perioperative Brain Health Initiative, Akhtar, Shamsuddin, Arora, Sona, Bentov, Itay, Bhandary, Sujatha, Brzezinski, Marek, Burstrom, Ruth E., Evans, Kevin, Leung, Jacqueline, Lewis, Michael C., Mahboobi, Sohail, McSwain, Julie, Rooke, Alec, and Whittington, Robert
- Subjects
OLDER people ,PERIOPERATIVE care ,NURSE anesthetists ,ANESTHESIOLOGISTS ,PREOPERATIVE education ,PHYSICIAN adherence ,GERIATRIC surgery ,GERIATRIC assessment ,KNOWLEDGE gap theory - Abstract
Background: While specific practices for perioperative care of older adults have been recommended, little is known regarding adherence by US physician anesthesiologists to such practices. To address this gap in knowledge, the ASA Committee on Geriatric Anesthesia and the ASA Perioperative Brain Health Initiative undertook a survey of ASA members to characterize current practices related to perioperative care of older adults. Methods: We administered a web-based questionnaire with items assessing the proportion of practice focused on delivery of care to older adults, adherence to recommended practices for older surgical patients, resource needs to improve care, and practice characteristics. Results: Responses were collected between May 24, 2018, and June 29, 2018. A total of 25,587 ASA members were invited to participate, and 1737 answered at least one item (6.8%). 96.4% of respondents reported that they had cared for a patient aged 65 or older within the last year. 47.1% of respondents (95% confidence interval, 44.6%, 49.7%) reported using multimodal analgesia among patients aged 65 and older at least 90% of the time, and 25.5% (95% CI, 23.3%, 27.7%) provided preoperative information regarding postoperative cognitive changes at least 90% of the time. Over 80% of respondents reported that preoperative screening for frailty or dementia, postoperative screening for delirium, and preoperative geriatric consultation occurred in fewer than 10% of cases. Development of practice guidelines for geriatric anesthesia care and expansion of web-based resources were most frequently prioritized by respondents as initiatives to improve care in this domain. Discussion: Most survey respondents reported providing anesthesia care to older adults, but adherence to recommended practices varied across the six items assessed. Reported rates of screening for common geriatric syndromes, such as frailty, delirium, and dementia, were low among survey respondents. Respondents identified multiple opportunities for ASA initiatives to support efforts to improve care for older surgical patients. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
6. Perioperative cerebrospinal fluid and plasma inflammatory markers after orthopedic surgery.
- Author
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Hirsch, Jan, Vacas, Susana, Terrando, Niccolo, Miao Yuan, Sands, Laura P., Kramer, Joel, Bozic, Kevin, Maze, Mervyn M., Leun, Jacqueline M., Yuan, Miao, and Leung, Jacqueline M
- Subjects
NEUROLOGICAL disorders ,DELIRIUM ,COGNITION disorders ,ORTHOPEDIC surgery complications ,CEREBROSPINAL fluid ,CYTOKINES ,ENZYME-linked immunosorbent assay ,DIAGNOSIS of delirium ,INFLAMMATORY mediators ,NEUROPSYCHOLOGICAL tests ,ORTHOPEDIC surgery ,RESEARCH funding ,SURGICAL complications ,TOTAL knee replacement ,PERIOPERATIVE care ,DIAGNOSIS - Abstract
Background: Postoperative delirium is prevalent in older patients and associated with worse outcomes. Recent data in animal studies demonstrate increases in inflammatory markers in plasma and cerebrospinal fluid (CSF) even after aseptic surgery, suggesting that inflammation of the central nervous system may be part of the pathogenesis of postoperative cognitive changes. We investigated the hypothesis that neuroinflammation was an important cause for postoperative delirium and cognitive dysfunction after major non-cardiac surgery.Methods: After Institutional Review Board approval and informed consent, we recruited patients undergoing major knee surgery who received spinal anesthesia and femoral nerve block with intravenous sedation. All patients had an indwelling spinal catheter placed at the time of spinal anesthesia that was left in place for up to 24 h. Plasma and CSF samples were collected preoperatively and at 3, 6, and 18 h postoperatively. Cytokine levels were measured using ELISA and Luminex. Postoperative delirium was determined using the confusion assessment method, and cognitive dysfunction was measured using validated cognitive tests (word list, verbal fluency test, digit symbol test).Results: Ten patients with complete datasets were included. One patient developed postoperative delirium, and six patients developed postoperative cognitive dysfunction. Postoperatively, at different time points, statistically significant changes compared to baseline were present in IL-5, IL-6, I-8, IL-10, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, IL-6/IL-10, and receptor for advanced glycation end products in plasma and in IFN-γ, IL-6, IL-8, IL-10, MCP-1, MIP-1α, MIP-1β, IL-8/IL-10, and TNF-α in CSF.Conclusions: Substantial pro- and anti-inflammatory activity in the central neural system after surgery was found. If confirmed by larger studies, persistent changes in cytokine levels may serve as biomarkers for novel clinical trials. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
7. The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial.
- Author
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Leung, Jacqueline M., Chau Tran Thi Hong, Nghia Ho Dang Trung, Hoa Nhu Thi, Chau Nguyen Ngoc Minh, Thuy Vu Thi, Dinh Thanh Hong, Dinh Nguyen Huy Man, Knowles, Sarah C. L., Wolbers, Marcel, Nhat Le Thanh Hoang, Thwaites, Guy, Graham, Andrea L., and Baker, Stephen
- Subjects
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ANTHELMINTICS , *ALBENDAZOLE , *MIXED infections , *SCHOOL children , *HELMINTHIC therapy , *CHILDREN , *THERAPEUTICS , *JUVENILE diseases ,INFECTION treatment - Abstract
Background: Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam. Methods/design: This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events. Discussion: In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens. Trial registration: ClinicalTrials.gov: NCT02597556. Registered on 3 November 2015. [ABSTRACT FROM AUTHOR]
- Published
- 2016
8. Surface attachment, promoted by the actomyosin system of Toxoplasma gondii is important for efficient gliding motility and invasion.
- Author
-
Whitelaw JA, Latorre-Barragan F, Gras S, Pall GS, Leung JM, Heaslip A, Egarter S, Andenmatten N, Nelson SR, Warshaw DM, Ward GE, and Meissner M
- Subjects
- Actins metabolism, Animals, Apicoplasts drug effects, Apicoplasts metabolism, Cell Adhesion drug effects, Cell Membrane drug effects, Cell Membrane metabolism, Cells, Cultured, Cytoplasmic Granules metabolism, Gene Knockout Techniques, Kinetics, Mutation genetics, Parasites drug effects, Parasites metabolism, Phenotype, Protozoan Proteins metabolism, Rheology, Sirolimus pharmacology, Stress, Mechanical, Toxoplasma metabolism, Actomyosin metabolism, Cell Movement drug effects, Toxoplasma cytology, Toxoplasma pathogenicity
- Abstract
Background: Apicomplexan parasites employ a unique form of movement, termed gliding motility, in order to invade the host cell. This movement depends on the parasite's actomyosin system, which is thought to generate the force during gliding. However, recent evidence questions the exact molecular role of this system, since mutants for core components of the gliding machinery, such as parasite actin or subunits of the MyoA-motor complex (the glideosome), remain motile and invasive, albeit at significantly reduced efficiencies. While compensatory mechanisms and unusual polymerisation kinetics of parasite actin have been evoked to explain these findings, the actomyosin system could also play a role distinct from force production during parasite movement., Results: In this study, we compared the phenotypes of different mutants for core components of the actomyosin system in Toxoplasma gondii to decipher their exact role during gliding motility and invasion. We found that, while some phenotypes (apicoplast segregation, host cell egress, dense granule motility) appeared early after induction of the act1 knockout and went to completion, a small percentage of the parasites remained capable of motility and invasion well past the point at which actin levels were undetectable. Those act1 conditional knockout (cKO) and mlc1 cKO that continue to move in 3D do so at speeds similar to wildtype parasites. However, these mutants are virtually unable to attach to a collagen-coated substrate under flow conditions, indicating an important role for the actomyosin system of T. gondii in the formation of attachment sites., Conclusion: We demonstrate that parasite actin is essential during the lytic cycle and cannot be compensated by other molecules. Our data suggest a conventional polymerisation mechanism in vivo that depends on a critical concentration of G-actin. Importantly, we demonstrate that the actomyosin system of the parasite functions in attachment to the surface substrate, and not necessarily as force generator.
- Published
- 2017
- Full Text
- View/download PDF
9. Does using a femoral nerve block for total knee replacement decrease postoperative delirium?
- Author
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Kinjo S, Lim E, Sands LP, Bozic KJ, and Leung JM
- Abstract
Background: The effect of peripheral nerve blocks on postoperative delirium in older patients has not been studied. Peripheral nerve blocks may reduce the incidence of postoperative opioid use and its side effects such as delirium via opioid-sparing effect., Methods: A prospective cohort study was conducted in patients who underwent total knee replacement. Baseline cognitive function was assessed using the Telephone Interview for Cognitive Status. Postoperative delirium was measured using the Confusion Assessment Method postoperatively. Incidence of postoperative delirium was compared in two postoperative management groups: femoral nerve block ± patient-controlled analgesia and patient-controlled analgesia only. In addition, pain levels (using numeric rating scales) and opioid use were compared in two groups., Results: 85 patients were studied. The overall incidence of postoperative delirium either on postoperative day one or day two was 48.1%. Incidence of postoperative delirium in the femoral nerve block group was lower than patient controlled analgesia only group (25% vs. 61%, P = 0.002). However, there was no significant difference between the groups with respect to postoperative pain level or the amount of intravenous opioid use., Conclusions: Femoral nerve block reduces the incidence of postoperative delirium. These results suggest that a larger randomized control trial is necessary to confirm these preliminary findings.
- Published
- 2012
- Full Text
- View/download PDF
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