174 results on '"Wood, Matthew"'
Search Results
2. Enhanced efficiency urea fertilizers and timing effects on N2O emissions from spring wheat production in Manitoba.
- Author
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Wood, Matthew D., Gao, Xiaopeng, Tiessen, Kevin H. D., Tenuta, Mario, and Flaten, Donald N.
- Abstract
Opportunities exist to reduce nitrous oxide (N2O) emissions from nitrogen (N) fertilizers using enhanced efficiency fertilizers (EEFs) and managing application timing. This study examined (1) application timing (fall/spring) and (2) fertilizer N source on N2O emissions, yield, and N uptake of Canadian hard red spring wheat (Triticum aestivum L.) in Southern Manitoba. Fertilizer N sources included granular urea and four EEF products: (1) polymer‐coated urea (environmentally smart nitrogen [ESN]); (2) urea plus nitrification inhibitor (eNtrench); (3) urea plus urease inhibitor (Limus); and (4) urea plus nitrification and urease inhibitor (SuperU). Nitrification‐inhibited products most consistently reduced N2O emissions while maintaining productivity. Compared to urea alone, urea + eNtrench was most effective in reducing cumulative N2O emissions by 47%–64% at four of six site‐years. SuperU reduced N2O emissions by 37%–57% at three of six site‐years. ESN and urea + Limus did not affect emissions in most years. Wheat yield, protein, and N uptake were unaffected by N source in five of six site‐years. Compared to spring, fall application gave greater N2O emissions by 33%–67% at three of six site‐years due to spring‐thaw emissions. Fall was inferior to spring application in wetter site years with lower yield, protein, and N uptake. Overall, nitrification‐inhibited products—either alone or with a urease inhibitor—are a promising tool to reduce N2O emissions while maintaining wheat productivity in Manitoba. However, given that there were few consistent increases in yield or protein, the additional cost of the inhibitors will be a barrier to adoption. Core Ideas: EEF products with nitrification and nitrification/urease inhibitors consistently reduced N2O emissions.Controlled release urea and urease‐inhibited urea did not reduce N2O emissions.Fall application of urea increased N2O emissions in three site‐years compared to spring application.The nitrification inhibitors applied with urea in fall or spring were effective to reduce N2O emissions.Overall, fall application decreased yield, grain protein, and N uptake in relatively wet years. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Effect of Veau Class on Levator Veli Palatini Muscle Composition
- Author
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Chiang, Sarah N, Meyer, Gretchen A, Skolnick, Gary B, Hunter, Daniel A, Wood, Matthew D, Li, Xiaowei, Snyder-Warwick, Alison K, and Patel, Kamlesh B
- Abstract
Objective To examine levator veli palatini muscle composition in patients with nonsyndromic cleft palate and investigate the impact of Veau class.Design Prospective cohort study.Setting Tertiary care academic hospital.Patients/Participants Thirteen patients with nonsyndromic cleft palate were recruited.Interventions During primary palatoplasty, a sample of levator veli palatini muscle was excised and prepared for histological analysis.Main Outcome Measures Fat and collagen content were determined utilizing Oil Red and Sirius red stains, respectively, while muscle fiber cross-sectional areas were calculated from H&E-stained samples, with analysis using histomorphometric methods. Immunofluorescent staining of myosin heavy chain isoforms was performed.Results Patients underwent repair at 10.8 months of age (interquartile range [IQR] 10.2-12.9). Fat content of the levator veli palatini muscle was low in both groups, ranging from 0% to 5.2%. Collagen content ranged from 8.5% to 39.8%; neither fat nor collagen content showed an association with Veau classes. Mean muscle fiber cross-sectional area decreased with increasing Veau class, from 808 µm2(range 692-995 µm2) in Veau II to 651 µm2(range 232-750 µm2) in Veau III (P= .02). There was also a nonsignificant decrease in proportion of type I muscle fibers with increasing Veau class (44.3% [range 31.4%-84.4%] in Veau II vs 35.3% [range 17.4%-61.3%] in Veau III).Conclusions Muscle fiber area in levator veli palatini muscles decreases in Veau III clefts in comparison to Veau II. The impact of these differences in velopharyngeal dysfunction requires further analysis of a larger cohort.
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- 2024
- Full Text
- View/download PDF
4. Enhanced efficiency urea fertilizers and timing effects on N2O emissions from spring wheat production in Manitoba
- Author
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Wood, Matthew D., Gao, Xiaopeng, Tiessen, Kevin H. D., Tenuta, Mario, and Flaten, Donald N.
- Abstract
Opportunities exist to reduce nitrous oxide (N2O) emissions from nitrogen (N) fertilizers using enhanced efficiency fertilizers (EEFs) and managing application timing. This study examined (1) application timing (fall/spring) and (2) fertilizer N source on N2O emissions, yield, and N uptake of Canadian hard red spring wheat (Triticum aestivumL.) in Southern Manitoba. Fertilizer N sources included granular urea and four EEF products: (1) polymer‐coated urea (environmentally smart nitrogen [ESN]); (2) urea plus nitrification inhibitor (eNtrench); (3) urea plus urease inhibitor (Limus); and (4) urea plus nitrification and urease inhibitor (SuperU). Nitrification‐inhibited products most consistently reduced N2O emissions while maintaining productivity. Compared to urea alone, urea + eNtrench was most effective in reducing cumulative N2O emissions by 47%–64% at four of six site‐years. SuperU reduced N2O emissions by 37%–57% at three of six site‐years. ESN and urea + Limus did not affect emissions in most years. Wheat yield, protein, and N uptake were unaffected by N source in five of six site‐years. Compared to spring, fall application gave greater N2O emissions by 33%–67% at three of six site‐years due to spring‐thaw emissions. Fall was inferior to spring application in wetter site years with lower yield, protein, and N uptake. Overall, nitrification‐inhibited products—either alone or with a urease inhibitor—are a promising tool to reduce N2O emissions while maintaining wheat productivity in Manitoba. However, given that there were few consistent increases in yield or protein, the additional cost of the inhibitors will be a barrier to adoption. EEF products with nitrification and nitrification/urease inhibitors consistently reduced N2O emissions.Controlled release urea and urease‐inhibited urea did not reduce N2O emissions.Fall application of urea increased N2O emissions in three site‐years compared to spring application.The nitrification inhibitors applied with urea in fall or spring were effective to reduce N2O emissions.Overall, fall application decreased yield, grain protein, and N uptake in relatively wet years.
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- 2024
- Full Text
- View/download PDF
5. HOIL1 regulates group 2 innate lymphoid cell numbers and type 2 inflammation in the small intestine
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Wood, Matthew J., Marshall, Jeffrey N., Hartley, Victoria L., Liu, Ta-Chiang, Iwai, Kazuhiro, Stappenbeck, Thaddeus S., and MacDuff, Donna A.
- Abstract
Patients with mutations in HOIL1experience a complex immune disorder including intestinal inflammation. To investigate the role of HOIL1in regulating intestinal inflammation, we employed a mouse model of partial HOIL1 deficiency. The ileum of HOIL1-deficient mice displayed features of type 2 inflammation including tuft cell and goblet cell hyperplasia, and elevated expression of Il13, Il5and Il25mRNA. Inflammation persisted in the absence of T and B cells, and bone marrow chimeric mice revealed a requirement for HOIL1 expression in radiation-resistant cells to regulate inflammation. Although disruption of IL-4 receptor alpha (IL4Rα) signaling on intestinal epithelial cells ameliorated tuft and goblet cell hyperplasia, expression of Il5and Il13mRNA remained elevated. KLRG1hiCD90logroup 2 innate lymphoid cells were increased independent of IL4Rα signaling, tuft cell hyperplasia and IL-25 induction. Antibiotic treatment dampened intestinal inflammation indicating commensal microbes as a contributing factor. We have identified a key role for HOIL1, a component of the Linear Ubiquitin Chain Assembly Complex, in regulating type 2 inflammation in the small intestine. Understanding the mechanism by which HOIL1 regulates type 2 inflammation will advance our understanding of intestinal homeostasis and inflammatory disorders and may lead to the identification of new targets for treatment.
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- 2024
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6. Intraoperative Challenges in Hand Surgery
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Wallace, Doyle R., Shiver, Austin Luke, Whitehead, Jonathon, Wood, Matthew, and Snoddy, Mark C.
- Abstract
A wide array of intraoperative issues can arise during surgery involving the hand and upper extremity. An understanding of the common pitfalls within hand surgery may help practicing hand surgeons circumvent such issues. Within this manuscript, we first identify problems with the increasingly popular technique of wide-awake local anesthesia no tourniquet (WALANT). Achieving appropriate hemostasis and anesthetic can be bothersome, especially for procedures proximal to the distal palmar crease. We discuss our local anesthetic timing and concentrations to help mitigate such issues, as well as other problems that may arise in WALANT procedures. There also lies a barrier in connecting the traumatized patient to care in the outpatient/ambulatory setting. Additionally, the polytraumatized patient increases the complexity of care coordination for not just the hand surgeon, but all surgical providers involved. The order in which multidisciplinary surgical procedures are performed is influenced by both the complexity of the patient’s case as well as the institution’s current protocol. All academic institutions are faced with challenges in providing optimal intraoperative education to trainees. We acknowledge that there should be a balance between the attending surgeon executing key portions of the procedure and the trainee gaining the appropriate hands-on experience. This manuscript elaborates on the issues of intraoperative education provided to residents and anecdotal methods that may help overcome such challenges. Resources within hand surgery can often be limited and become particularly problematic in the operative setting. Specific examples include but are not limited to the lack of dedicated teams, inability to obtain appropriate intraoperative imaging, access to appropriate hardware, and intraoperative complications in an ambulatory surgery center setting.
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- 2024
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7. Therapeutic approaches for Duchenne muscular dystrophy
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Roberts, Thomas C., Wood, Matthew J. A., and Davies, Kay E.
- Abstract
Duchenne muscular dystrophy (DMD) is a monogenic muscle-wasting disorder and a priority candidate for molecular and cellular therapeutics. Although rare, it is the most common inherited myopathy affecting children and so has been the focus of intense research activity. It is caused by mutations that disrupt production of the dystrophin protein, and a plethora of drug development approaches are under way that aim to restore dystrophin function, including exon skipping, stop codon readthrough, gene replacement, cell therapy and gene editing. These efforts have led to the clinical approval of four exon skipping antisense oligonucleotides, one stop codon readthrough drug and one gene therapy product, with other approvals likely soon. Here, we discuss the latest therapeutic strategies that are under development and being deployed to treat DMD. Lessons from these drug development programmes are likely to have a major impact on the DMD field, but also on molecular and cellular medicine more generally. Thus, DMD is a pioneer disease at the forefront of future drug discovery efforts, with these experimental treatments paving the way for therapies using similar mechanisms of action being developed for other genetic diseases.
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- 2023
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8. Response to Preoperative Dexamethasone Predicts Postoperative Neurological Improvement of Focal Neurological Deficits in Patients With Brain Metastases.
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Bowden, Stephen G., Lopez Ramos, Christian G., Cheaney II, Barry, Richie, Emma, Yaghi, Nasser K., Munger, Daniel N., Mazur-Hart, David J., Tan, Hao, Wood, Matthew D., Cetas, Justin S., Dogan, Aclan, Raslan, Ahmed M., and Han, Seunggu J.
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- 2023
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9. Engineered bacteria combined with doxorubicin nanoparticles suppress angiogenesis and metastasis in murine melanoma models.
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Yang, Meiyang, Conceição, Mariana, Chen, Weijun, Yang, Fuwei, Zhao, Bingke, Wood, Matthew J.A., Qiu, Lipeng, and Chen, Jinghua
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HEPARIN ,DOXORUBICIN ,BACTERIAL enzymes ,NEOVASCULARIZATION ,SULFATASES ,BIOMACROMOLECULES ,SYNTHETIC biology - Abstract
Methods capable of distributing antitumour therapeutics uniformly throughout an entire tumour and that can suppress metastasis at the same time, would be of great significance in improving cancer treatment. Bacteria-mediated synergistic therapies have been explored for better specificity, temporal and spatial controllability, as well for providing regulation of the immune microenvironment, in order to provide improved cancer treatment. To achieve this goal, here we developed an engineered bacteria delivery system (GDOX@HSEc) using synthetic biology and interfacial chemistry technologies. The engineered bacteria were concurrently modified to express heparin sulfatase 1 (HSulf-1) inside (HSEc), to attach doxorubicin-loaded glycogen nanoparticles (GDOX NPs) on their surface. Here we demonstrate that HSEc can actively target and colonise tumour sites resulting in HSulf-1 overexpression, thereby suppressing angiogenesis and metastasis. Simultaneously, the GDOX NPs were able to penetrate into tumour cells, leading to intracellular DNA damage. Our results confirmed that a combination of biotherapy and chemotherapy using GDOX@HSEc resulted in significant melanoma suppression in murine models, with reduced side effects. This study provides a powerful platform for the simultaneous delivery of biomacromolecules and chemotherapeutic drugs to tumours, representing an innovative strategy potentially more effective in treating solid tumours. An original engineered bacteria-based system (GDOX@HSEc) was developed using synthetic biology and interfacial chemistry technologies to concurrently produce naturally occurring heparin sulfatase 1 (HSulf-1) inside and anchor doxorubicin-loaded glycogen nanoparticles on the surface. GDOX@HSEc allowed for combined local delivery of chemotherapeutic agents along with the enzymes and immunostimulatory bacterial adjuvants, which resulted in a synergistic action in the inhibition of tumour growth and metastasis. The study provides a potential therapeutic approach that allows therapeutic agents to be distributed in a spatiotemporally controllable manner in tumours for combinatorial enhanced therapy. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2023
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10. Response to Preoperative Dexamethasone Predicts Postoperative Neurological Improvement of Focal Neurological Deficits in Patients With Brain Metastases
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Bowden, Stephen G., Lopez Ramos, Christian G., Cheaney, Barry, Richie, Emma, Yaghi, Nasser K., Munger, Daniel N., Mazur-Hart, David J., Tan, Hao, Wood, Matthew D., Cetas, Justin S., Dogan, Aclan, Raslan, Ahmed M., and Han, Seunggu J.
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- 2023
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11. Adipose Tissue in Lymphedema: A Central Feature of Pathology and Target for Pharmacologic Therapy.
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Burton, Jackson S., Sletten, Arthur C., Marsh, Evan, Wood, Matthew D., and Sacks, Justin M.
- Abstract
Lymphedema is a chronic condition of impaired lymphatic flow that results in limb swelling and debilitation. The pathophysiology of lymphedema is characterized by lymphatic stasis that triggers inflammation, fibrosis, and adipose tissue deposition in the extremities. Most often, this condition occurs in cancer survivors in the years after treatment with combinations of surgery, radiation, or chemotherapy, with the major risk factor being lymph node dissection. Interestingly, obesity and body mass index are independent risk factors for development of lymphedema, suggesting interactions between adipose and lymphatic tissue biology. Currently, treatment of lymphedema involves palliative approaches, including compression garments and physical therapy, and surgical approaches, including liposuction, lymphovenous bypass, and vascularized lymph node transfer. Emerging lymphedema therapies that focus on weight loss or reducing inflammation have been tested in recent clinical trials, yielding mixed results with no effect on limb volumes or changes in bioimpedance measurements. These studies highlight the need for novel therapeutic strategies that target the driving forces of lymphedema. In this light, animal models of lymphedema demonstrate a role of adipose tissue in the progression of lymphedema and suggest these processes may be targeted in the treatment of lymphedema. Herein, we review both conventional and experimental therapies for lymphedema as well as the defining characteristics of its pathophysiology. We place emphasis on the aberrant fibroadipose tissue accumulation in lymphedema and propose a new approach to experimental treatment at the level of adipocyte metabolism. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Family and community interventions: A meta-analysis on family and community resilience, cohesion, and functioning.
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Galaitsi, S.E., Wells, Emily, Zemba, Valerie, Blue, Shala, Cato, Colando, Wood, Matthew, Trump, Benjamin, and Linkov, Igor
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Community resilience determines a communities' ability to prepare for disruptions, absorb their effects, recover, and adapt if the situation requires it. This meta-analysis of pre-pandemic (1980–2017) academic literature in military and non-military contexts to examine community resilience interventions and performance outcomes or community functioning. The study also incorporates the role of cohesion because this emerged as a strong theme in the literature. The analysis aims specifically to identify benefits of resilience interventions for military communities that are frequently subjects of disruptions. The analysis connects interventions to the phases of resilience to identify which are well-covered by existing interventions, as well as gaps in that could indicate the need to update existing interventions or establishing new interventions. The recovery phase of resilience is strongly represented in interventions, while interventions to improve planning and adaptation capacities were sparsely represented in pre-pandemic literature. [ABSTRACT FROM AUTHOR]
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- 2024
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13. I Can't See That! Considering the Readability of Small Objects in Virtual Environments
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Young, Jacob, Pantidi, Nadia, and Wood, Matthew
- Abstract
Though virtual reality has repeatedly seen usability improvements through higher fidelity headsets, interacting with small objects has remained an issue due to a reduction in visual acuity. Given the current uptake of virtual reality platforms and the range of real world applications that they may be used for, it is worth considering how such interactions can be accounted for. We propose three techniques for improving the usability of small objects in virtual environments: i) expanding them in place, ii) showing a zoomed-in twin above the original object, and iii) showing a large readout of the object's current state. We conducted a study comparing each technique's usability, induced presence, and effect on short-term knowledge retention in a VR training scenario that simulated the common geoscience exercise of measuring strike and dip. Participant feedback highlighted the need for this research, however simply scaling the area of interest may not be enough to improve the usability of information-bearing objects, while displaying this information in large text format can make tasks faster to complete at the cost of reducing the user's ability to transfer knowledge they've learned to the real world. We discuss these results and their implications for the design of future virtual reality experiences.
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- 2023
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14. Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19
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Kotanidis, Christos P, Xie, Cheng, Alexander, Donna, Rodrigues, Jonathan C L, Burnham, Katie, Mentzer, Alexander, O’Connor, Daniel, Knight, Julian, Siddique, Muhammad, Lockstone, Helen, Thomas, Sheena, Kotronias, Rafail, Oikonomou, Evangelos K, Badi, Ileana, Lyasheva, Maria, Shirodaria, Cheerag, Lumley, Sheila F, Constantinides, Bede, Sanderson, Nicholas, Rodger, Gillian, Chau, Kevin K, Lodge, Archie, Tsakok, Maria, Gleeson, Fergus, Adlam, David, Rao, Praveen, Indrajeet, Das, Deshpande, Aparna, Bajaj, Amrita, Hudson, Benjamin J, Srivastava, Vivek, Farid, Shakil, Krasopoulos, George, Sayeed, Rana, Ho, Ling-Pei, Neubauer, Stefan, Newby, David E, Channon, Keith M, Deanfield, John, Antoniades, Charalambos, Ahern, David J, Ai, Zhichao, Ainsworth, Mark, Allan, Chris, Allcock, Alice, Angus, Brian, Ansari, M Azim, Arancibia-Cárcamo, Carolina, Aschenbrenner, Dominik, Attar, Moustafa, Baillie, J Kenneth, Barnes, Eleanor, Bashford-Rogers, Rachael, Bashyal, Archana, Beer, Sally, Berridge, Georgina, Beveridge, Amy, Bibi, Sagida, Bicanic, Tihana, Blackwell, Luke, Bowness, Paul, Brent, Andrew, Brown, Andrew, Broxholme, John, Buck, David, Burnham, Katie, Byrne, Helen, Camara, Susana, Ferreira, Ivan Candido, Charles, Philip, Chen, Wentao, Chen, Yi-Ling, Chong, Amanda, Clutterbuck, Elizabeth, Coles, Mark, Conlon, Christopher, Cornall, Richard, Cribbs, Adam, Curion, Fabiola, Davenport, Emma, Davidson, Neil, Davis, Simon, Dendrou, Calliope, Dequaire, Julie, Dib, Lea, Docker, James, Dold, Christina, Dong, Tao, Downes, Damien, Drakesmith, Hal, Dunachie, Susanna, Duncan, David, Eijsbouts, Chris, Esnouf, Robert, Espinosa, Alexis, Etherington, Rachel, Fairfax, Benjamin, Fairhead, Rory, Fang, Hai, Fassih, Shayan, Felle, Sally, Fernandez Mendoza, Maria, Ferreira, Ricardo, Fischer, Roman, Foord, Thomas, Forrow, Aden, Frater, John, Fries, Anastasia, Gallardo Sanchez, Veronica, Garner, Lucy, Geeves, Clementine, Georgiou, Dominique, Godfrey, Leila, Golubchik, Tanya, Gomez Vazquez, Maria, Green, Angie, Harper, Hong, Harrington, Heather, Heilig, Raphael, Hester, Svenja, Hill, Jennifer, Hinds, Charles, Hird, Clare, Ho, Ling-Pei, Hoekzema, Renee, Hollis, Benjamin, Hughes, Jim, Hutton, Paula, Jackson-Wood, Matthew, Jainarayanan, Ashwin, James-Bott, Anna, Jansen, Kathrin, Jeffery, Katie, Jones, Elizabeth, Jostins, Luke, Kerr, Georgina, Kim, David, Klenerman, Paul, Knight, Julian, Kumar, Vinod, Kumar Sharma, Piyush, Kurupati, Prathiba, Kwok, Andrew, Lee, Angela, Linder, Aline, Lockett, Teresa, Lonie, Lorne, Lopopolo, Maria, Lukoseviciute, Martyna, Luo, Jian, Marinou, Spyridoula, Marsden, Brian, Martinez, Jose, Matthews, Philippa, Mazurczyk, Michalina, McGowan, Simon, McKechnie, Stuart, Mead, Adam, Mentzer, Alexander, Mi, Yuxin, Monaco, Claudia, Montadon, Ruddy, Napolitani, Giorgio, Nassiri, Isar, Novak, Alex, O'Brien, Darragh, O'Connor, Daniel, O'Donnell, Denise, Ogg, Graham, Overend, Lauren, Park, Inhye, Pavord, Ian, Peng, Yanchun, Penkava, Frank, Pereira Pinho, Mariana, Perez, Elena, Pollard, Andrew, Powrie, Fiona, Psaila, Bethan, Quan, T Phuong, Repapi, Emmanouela, Revale, Santiago, Silva-Reyes, Laura, Richard, Jean-Baptiste, Rich-Griffin, Charlotte, Ritter, Thomas, Rollier, Christine, Rowland, Matthew, Ruehle, Fabian, Salio, Mariolina, Sansom, Stephen Nicholas, Sanches Peres, Raphael, Santos Delgado, Alberto, Sauka-Spengler, Tatjana, Schwessinger, Ron, Scozzafava, Giuseppe, Screaton, Gavin, Seigal, Anna, Semple, Malcolm, Sergeant, Martin, Simoglou Karali, Christina, Sims, David, Skelly, Donal, Slawinski, Hubert, Sobrinodiaz, Alberto, Sousos, Nikolaos, Stafford, Lizzie, Stockdale, Lisa, Strickland, Marie, Sumray, Otto, Sun, Bo, Taylor, Chelsea, Taylor, Stephen, Taylor, Adan, Thongjuea, Supat, Thraves, Hannah, Todd, John, Tomic, Adriana, Tong, Orion, Trebes, Amy, Trzupek, Dominik, Tucci, Felicia Anna, Turtle, Lance, Udalova, Irina, Uhlig, Holm, van Grinsven, Erinke, Vendrell, Iolanda, Verheul, Marije, Voda, Alexandru, Wang, Guanlin, Wang, Lihui, Wang, Dapeng, Watkinson, Peter, Watson, Robert, Weinberger, Michael, Whalley, Justin, Witty, Lorna, Wray, Katherine, Xue, Luzheng, Yuen Yeung, Hing, Yin, Zixi, Young, Rebecca, Youngs, Jonathan, Zhang, Ping, Zurke, Yasemin-Xiomara, Banning, Adrian, Antonopoulos, Alexios, Bajaj, Amrita, Kelion, Andrew, Deshpande, Aparna, Kardos, Attila, Hudson, Benjamin, Koo, Bon-Kwon, Shirodaria, Cheerag, Xie, Cheng, Kotanidis, Christos, Mahon, Ciara, Berry, Colin, Adlam, David, Newby, David, Connolly, Derek, Scaletta, Diane, Alexander, Donna, Nicol, Ed, McAlindon, Elisa, Oikonomou, Evangelos, Pugliese, Francesca, Pontone, Gianluca, Benedetti, Giulia, He, Guo-Wei, West, Henry, Kondo, Hidekazu, Benedek, Imre, Das, Intrajeet, Deanfield, John, Graby, John, Greenwood, John, Rodrigues, Jonathan, Ge, Junbo, Channon, Keith, Fabritz, Larissa, Fan, Li-Juan, Kingham, Lucy, Guglielmo, Marco, Lyasheva, Maria, Schmitt, Matthias, Beer, Meinrad, Anderson, Michelle, Desai, Milind, Marwan, Mohamed, Takahashi, Naohiko, Mehta, Nehal, Dai, Neng, Screaton, Nicholas, Sabharwal, Nikant, Maurovich-Horvat, Pál, Rao, Praveen, Kotronias, Rafail, Kharbanda, Rajesh, Preston, Rebecca, Wood, Richard, Blankstein, Ron, Rajani, Ronak, Mirsadraee, Saeed, Munir, Shahzad, Thomas, Sheena, Neubauer, Stefan, Klömpken, Steffen, Petersen, Steffen, Achenbach, Stephan, Anthony, Susan, Mak, Sze, Mittal, Tarun, Benedek, Theodora, Sharma, Vinoda, and Lin, Wen-Hua
- Abstract
Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19.
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- 2022
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15. The Genesis of Pain in Osteoarthritis: Inflammation as a Mediator of Osteoarthritis Pain
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Wood, Matthew J., Miller, Rachel E., and Malfait, Anne-Marie
- Abstract
Chronic pain is a substantial personal and societal burden worldwide. Osteoarthritis (OA) is one of the leading causes of chronic pain and is increasing in prevalence in accordance with a global aging population. In addition to affecting patients’ physical lives, chronic pain also adversely affects patients’ mental wellbeing. However, there remain no pharmacologic interventions to slow down the progression of OA and pain-alleviating therapies are largely unsuccessful. The presence of low-level inflammation in OA has been recognized for many years as a major pathogenic driver of joint damage. Inflammatory mechanisms can occur locally in joint tissues, such as the synovium, within the sensory nervous system, as well as systemically, caused by modifiable and unmodifiable factors. Understanding how inflammation may contribute to, and modify pain in OA will be instrumental in identifying new druggable targets for analgesic therapies. In this narrative review, we discuss recent insights into inflammatory mechanisms in OA pain. We discuss how local inflammation in the joint can contribute to mechanical sensitization and to the structural neuroplasticity of joint nociceptors, through pro-inflammatory factors such as nerve growth factor, cytokines, and chemokines. We consider the role of synovitis, and the amplifying mechanisms of neuroimmune interactions. We then explore emerging evidence around the role of neuroinflammation in the dorsal root ganglia and dorsal horn. Finally, we discuss how systemic inflammation associated with obesity may modify OA pain and suggest future research directions.
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- 2022
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16. HOIL1 regulates group 2 innate lymphoid cell numbers and type 2 inflammation in the small intestine
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Wood, Matthew J., Marshall, Jeffrey N., Hartley, Victoria L., Liu, Ta-Chiang, Iwai, Kazuhiro, Stappenbeck, Thaddeus S., and MacDuff, Donna A.
- Abstract
Patients with mutations in HOIL1experience a complex immune disorder including intestinal inflammation. To investigate the role of HOIL1in regulating intestinal inflammation, we employed a mouse model of partial HOIL1 deficiency. The ileum of HOIL1-deficient mice displayed features of type 2 inflammation including tuft cell and goblet cell hyperplasia, and elevated expression of Il13, Il5and Il25mRNA. Inflammation persisted in the absence of T and B cells, and bone marrow chimeric mice revealed a requirement for HOIL1 expression in radiation-resistant cells to regulate inflammation. Although disruption of IL-4 receptor alpha (IL4Rα) signaling on intestinal epithelial cells ameliorated tuft and goblet cell hyperplasia, expression of Il5and Il13mRNA remained elevated. KLRG1hiCD90logroup 2 innate lymphoid cells were increased independent of IL4Rα signaling, tuft cell hyperplasia and IL-25 induction. Antibiotic treatment dampened intestinal inflammation indicating commensal microbes as a contributing factor. We have identified a key role for HOIL1, a component of the Linear Ubiquitin Chain Assembly Complex, in regulating type 2 inflammation in the small intestine. Understanding the mechanism by which HOIL1 regulates type 2 inflammation will advance our understanding of intestinal homeostasis and inflammatory disorders and may lead to the identification of new targets for treatment.
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- 2022
- Full Text
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17. Short-Duration, Pulsatile, Electrical Stimulation Therapy Accelerates Axon Regeneration and Recovery following Tibial Nerve Injury and Repair in Rats
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Roh, Joseph, Schellhardt, Lauren, Keane, Grace C., Hunter, Daniel A., Moore, Amy M., Snyder-Warwick, Alison K., Mackinnon, Susan E., and Wood, Matthew D.
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- 2022
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18. Emerging Oligonucleotide Therapeutics for Rare Neuromuscular Diseases
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Aoki, Yoshitsugu and Wood, Matthew J.A.
- Abstract
Research and drug development concerning rare diseases are at the cutting edge of scientific technology. To date, over 7,000 rare diseases have been identified. Despite their individual rarity, 1 in 10 individuals worldwide is affected by a rare condition. For the majority of these diseases, there is no treatment, much less cure; therefore, there is an urgent need for new therapies to extend and improve quality of life for persons who suffer from them. Here we focus specifically on rare neuromuscular diseases. Currently, genetic medicines using short antisense oligonucleotides (ASO) or small interfering ribonucleic acids that target RNA transcripts are achieving spectacular success in treating these diseases. For Duchenne muscular dystrophy (DMD), the state-of-the-art is an exon skipping therapy using an antisense oligonucleotide, which is prototypical of advanced precision medicines. Very recently, golodirsen and viltolarsen, for treatment of DMD patients amenable to skipping exon 53, have been approved by regulatory agencies in the USA and Japan, respectively. Here, we review scientific and clinical progress in developing new oligonucleotide therapeutics for selected rare neuromuscular diseases, discussing their efficacy and limitations.
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- 2021
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19. Video-based Learning in Surgery: Establishing Surgeon Engagement and Utilization of Variable-duration Videos.
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Yee, Andrew, Padovano, William M., Fox, Ida K., Hill, Elspeth J. R., Rowe, Amanda G., Brunt, L. Michael, Moore, Amy M., Snyder-Warwick, Alison K., Kahn, Lorna C., Wood, Matthew D., Coert, Jan Henk, and Mackinnon, Susan E.
- Abstract
Objective: To measure surgeon engagement and preferred video duration in a video-based learning program for nerve surgery. Background: Educational videos can improve, standardize, and democratize best practices in surgery. To improve care internationally, educators must optimize their videos for learning. However, surgeon engagement and optimal video duration remain undefined. Methods: A YouTube channel and a video-based learning website, PASSIO Education (passioeducation.com), were examined from 2011 to 2017. We assessed views, geographic location, audience engagement (average percent of video watched), audience retention (percent of viewers at each timepoint), and usage of short (median 7.4, range 4.1-20.3 min) and long (median 17.2, range 6.1-47.7 min) video formats for the same procedures. A survey of PASSIO Education membership examined preferred video duration. Results: Our 117 nerve surgery videos attained over 3 million views with 69% originating outside of the United States. While YouTube achieved more international exposure, PASSIO Education attained a greater mean engagement of 48.4% (14.3% absolute increase, P < 0.0001). Surveyed surgeons (n = 304) preferred longer videos when preparing for infrequent or difficult cases compared with routine cases (P < 0.0001). Engagement declined with video duration, but audience retention between short and long video formats was correlated (τB = 0.52, P < 0.0001). Conclusions: For effective spread of best practices, we propose the joint use of YouTube for audience outreach and a surgeon-focused platform to maximize educational value. Optimal video duration is surgeon- and case-dependent and can be addressed through offering multiple video durations and interactive viewing options. [ABSTRACT FROM AUTHOR]
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- 2020
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20. Molecular correction of Duchenne muscular dystrophy by splice modulation and gene editing
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Hanson, Britt, Wood, Matthew J.A., and Roberts, Thomas C.
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ABSTRACTDuchenne muscular dystrophy (DMD) is a currently incurable X-linked neuromuscular disorder, characterized by progressive muscle wasting and premature death, typically as a consequence of cardiac failure. DMD-causing mutations in the dystrophin gene are highly diverse, meaning that the development of a universally-applicable therapy to treat all patients is very challenging. The leading therapeutic strategy for DMD is antisense oligonucleotide-mediated splice modulation, whereby one or more specific exons are excluded from the mature dystrophin mRNA in order to correct the translation reading frame. Indeed, three exon skipping oligonucleotides have received FDA approval for use in DMD patients. Second-generation exon skipping drugs (i.e. peptide-antisense oligonucleotide conjugates) exhibit enhanced potency, and also induce dystrophin restoration in the heart. Similarly, multiple additional antisense oligonucleotide drugs targeting various exons are in clinical development in order to treat a greater proportion of DMD patient mutations. Relatively recent advances in the field of genome engineering (specifically, the development of the CRISPR/Cas system) have provided multiple promising therapeutic approaches for the RNA-directed genetic correction of DMD, including exon excision, exon reframing via the introduction of insertion/deletion mutations, disruption of splice signals to promote exon skipping, and the templated correction of point mutations by seamless homology directed repair or base editing technology. Potential limitations to the clinical translation of the splice modulation and gene editing approaches are discussed, including drug delivery, the importance of uniform dystrophin expression in corrected myofibres, safety issues (e.g. renal toxicity, viral vector immunogenicity, and off-target gene editing), and the high cost of therapy.
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- 2021
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21. Extracellular vesicles as a next-generation drug delivery platform
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Herrmann, Inge Katrin, Wood, Matthew John Andrew, and Fuhrmann, Gregor
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Extracellular-vesicle-based cell-to-cell communication is conserved across all kingdoms of life. There is compelling evidence that extracellular vesicles are involved in major (patho)physiological processes, including cellular homoeostasis, infection propagation, cancer development and cardiovascular diseases. Various studies suggest that extracellular vesicles have several advantages over conventional synthetic carriers, opening new frontiers for modern drug delivery. Despite extensive research, clinical translation of extracellular-vesicle-based therapies remains challenging. Here, we discuss the uniqueness of extracellular vesicles along with critical design and development steps required to utilize their full potential as drug carriers, including loading methods, in-depth characterization and large-scale manufacturing. We compare the prospects of extracellular vesicles with those of the well established liposomes and provide guidelines to direct the process of developing vesicle-based drug delivery systems.
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- 2021
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22. Long Acellular Nerve Allografts Cap Transected Nerve to Arrest Axon Regeneration and Alter Upstream Gene Expression in a Rat Neuroma Model
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Pan, Deng, Bichanich, Miles, Wood, Ian S., Hunter, Daniel A., Tintle, Scott M., Davis, Thomas A., Wood, Matthew D., and Moore, Amy M.
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- 2021
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23. Editorial Commentary of “Nerve Reconstruction Using Processed Nerve Allograft in the US Military”
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Jacobson, Lauren A, Wood, Matthew D, and Mackinnon, Susan E
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- 2021
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24. Interpretation of Data from Translational Rodent Nerve Injury and Repair Models
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Marsh, Evan B., Snyder-Warwick, Alison K., Mackinnon, Susan E., and Wood, Matthew D.
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This article highlights the use of rodents as preclinical models to evaluate the management of nerve injuries, describing the pitfalls and value from rodent nerve injury and regeneration outcomes, as well as treatments derived from these rodent models. The anatomic structure, size, and cellular and molecular differences and similarities between rodent and human nerves are summarized. Specific examples of success and failure when assessing outcome metrics are presented for context. Evidence for translation to clinical practice includes the topics of electrical stimulation, Tacrolimus (FK506), and acellular nerve allografts.
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- 2024
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25. Isolated Osseous Excision in the Adult Carpus: A Narrative Review
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Dolan, Joshua D., Shiver, Luke, Wallace, Doyle, Whitehead, Jonathon, Wood, Matthew, and Fulcher, S. Mark
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- 2024
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26. T cells modulate IL-4 expression by eosinophil recruitment within decellularized scaffolds to repair nerve defects.
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Pan, Deng, Hunter, Daniel A., Schellhardt, Lauren, Fuchs, Anja, Halevi, Alexandra E., Snyder-Warwick, Alison K., Mackinnon, Susan E., and Wood, Matthew D.
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T cells ,NERVOUS system regeneration ,NERVES ,EOSINOPHILS ,TISSUE engineering ,BIOMATERIALS - Abstract
Decellularized nerve, or acellular nerve allografts (ANAs), are an increasingly used alternative to nerve autografts to repair nerve gaps to facilitate regeneration. The adaptive immune system, specifically T cells, plays a role in promoting regeneration upon these ANA scaffolds. However, how T cells promote regeneration across ANAs is not clear. Here, we show that T cells accumulate within ANAs repairing nerve gaps resulting in regulation of cytokine expression within the ANA environment. This in turn ultimately leads to robust nerve regeneration and functional recovery. Nerve regeneration across ANAs and functional recovery in Rag1KO mice was limited compared to wild-type (WT) mice. Prior to appreciable nerve regeneration, ANAs from Rag1KO mice contained fewer eosinophils and reduced IL-4 expression compared to ANAs from WT mice. During this period, both T cells and eosinophils regulated IL-4 expression within ANAs. Eosinophils represented the majority of IL-4 expressing cells within ANAs, while T cells regulated IL-4 expression. Finally, an essential role for IL-4 during nerve regeneration across ANAs was confirmed as nerves repaired using ANAs had reduced regeneration in IL-4 KO mice compared to WT mice. Our data demonstrate T cells regulate the expression of IL-4 within the ANA environment via their effects on eosinophils. The immune system has been emerging as a critical component for tissue regeneration, especially when regeneration is supported upon biomaterials. The role of T cells, and their roles in the regeneration of nerve repaired with biomaterials, is still unclear. We demonstrated that when nerves are repaired with decellularized nerve scaffolds, T cells contribute to regeneration by regulating cytokines. We focused on their regulation of cytokine IL-4. Unexpectedly, T cells do not produce IL-4, but instead regulate IL-4 by recruiting eosinophils, which are major cellular sources of IL-4 within these scaffolds. Thus, our work demonstrated how IL-4 is regulated in a model biomaterial, and has implications for improving the design of biomaterials and understanding immune responses to biomaterials. Image, graphical abstract [ABSTRACT FROM AUTHOR]
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- 2020
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27. Application of CRISPR-Cas9-Mediated Genome Editing for the Treatment of Myotonic Dystrophy Type 1
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Marsh, Seren, Hanson, Britt, Wood, Matthew J.A., Varela, Miguel A., and Roberts, Thomas C.
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Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder, caused by expansion of a CTG microsatellite repeat in the 3ʹ untranslated region of the DMPK(dystrophia myotonicaprotein kinase) gene. To date, novel therapeutic approaches have focused on transient suppression of the mutant, repeat-expanded RNA. However, recent developments in the field of genome editing have raised the exciting possibility of inducing permanent correction of the DM1 genetic defect. Specifically, repurposing of the prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system has enabled programmable, site-specific, and multiplex genome editing. CRISPR-based strategies for the treatment of DM1 can be applied either directly to patients, or indirectly through the ex vivomodification of patient-derived cells, and they include excision of the repeat expansion, insertion of synthetic polyadenylation signals upstream of the repeat, steric interference with RNA polymerase II procession through the repeat leading to transcriptional downregulation of DMPK, and direct RNA targeting of the mutant RNA species. Potential obstacles to such therapies are discussed, including the major challenge of Cas9 and guide RNA transgene/ribonuclear protein delivery, off-target gene editing, vector genome insertion at cut sites, on-target unintended mutagenesis (e.g., repeat inversion), pre-existing immunity to Cas9 or AAV antigens, immunogenicity, and Cas9 persistence.
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- 2020
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28. Video-based Learning in Surgery
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Yee, Andrew, Padovano, William M., Fox, Ida K., Hill, Elspeth J. R., Rowe, Amanda G., Brunt, L. Michael, Moore, Amy M., Snyder-Warwick, Alison K., Kahn, Lorna C., Wood, Matthew D., Coert, Jan Henk, and Mackinnon, Susan E.
- Abstract
Supplemental Digital Content is available in the text
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- 2020
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29. Mutation-independent Proteomic Signatures of Pathological Progression in Murine Models of Duchenne Muscular Dystrophy
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van Westering, Tirsa L.E., Johansson, Henrik J., Hanson, Britt, Coenen-Stass, Anna M.L., Lomonosova, Yulia, Tanihata, Jun, Motohashi, Norio, Yokota, Toshifumi, Takeda, Shin'ichi, Lehtiö, Janne, Wood, Matthew J.A., EL Andaloussi, Samir, Aoki, Yoshitsugu, and Roberts, Thomas C.
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In this study we report the highest resolution proteomics analysis performed in dystrophic muscle to date. The use of two mouse models of Duchenne muscular dystrophy, at three different ages, has enabled the identification of mutation-independent protein signatures associated with dystrophic muscle, and the progression of disease pathology.
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- 2020
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30. Updates in Pediatric Glioma Pathology
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Hakar, Melanie H. and Wood, Matthew D.
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Gliomas are a diverse group of primary central nervous system tumors with astrocytic, oligodendroglial, and/or ependymal features and are an important cause of morbidity/mortality in pediatric patients. Glioma classification relies on integrating tumor histology with key molecular alterations. This approach can help establish a diagnosis, guide treatment, and determine prognosis. New categories of pediatric glioma have been recognized in recent years, due to increasing application of molecular profiling in brain tumors. The aim of this review is to alert pediatric pathologists to emerging diagnostic concepts in pediatric glioma neuropathology, emphasizing the incorporation of molecular features into diagnostic practice.
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- 2020
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31. Advances in oligonucleotide drug delivery
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Roberts, Thomas C., Langer, Robert, and Wood, Matthew J. A.
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Oligonucleotides can be used to modulate gene expression via a range of processes including RNAi, target degradation by RNase H-mediated cleavage, splicing modulation, non-coding RNA inhibition, gene activation and programmed gene editing. As such, these molecules have potential therapeutic applications for myriad indications, with several oligonucleotide drugs recently gaining approval. However, despite recent technological advances, achieving efficient oligonucleotide delivery, particularly to extrahepatic tissues, remains a major translational limitation. Here, we provide an overview of oligonucleotide-based drug platforms, focusing on key approaches — including chemical modification, bioconjugation and the use of nanocarriers — which aim to address the delivery challenge.
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- 2020
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32. Muscle overexpression of Klf15 via an AAV8-Spc5-12 construct does not provide benefits in spinal muscular atrophy mice
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Ahlskog, Nina, Hayler, Daniel, Krueger, Anja, Kubinski, Sabrina, Claus, Peter, Hammond, Suzan M., Wood, Matthew J. A., ez-Mun, Bowerman, Melissa, and oz
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Spinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the survival motor neuron(SMN) gene. While there are currently two approved gene-based therapies for SMA, availability, high cost, and differences in patient response indicate that alternative treatment options are needed. Optimal therapeutic strategies will likely be a combination of SMN-dependent and -independent treatments aimed at alleviating symptoms in the central nervous system and peripheral muscles. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates key metabolic and ergogenic pathways in muscle. We have recently reported significant downregulation of Klf15in muscle of presymptomatic SMA mice. Importantly, perinatal upregulation of Klf15via transgenic and pharmacological methods resulted in improved disease phenotypes in SMA mice, including weight and survival. In the current study, we designed an adeno-associated virus serotype 8 (AAV8) vector to overexpress a codon-optimized Klf15cDNA under the muscle-specific Spc5-12 promoter (AAV8-Klf15). Administration of AAV8-Klf15to severe Taiwanese Smn-/-;SMN2or intermediate Smn2B/-SMA mice significantly increased Klf15expression in muscle. We also observed significant activity of the AAV8-Klf15vector in liver and heart. AAV8-mediated Klf15overexpression moderately improved survival in the Smn2B/-model but not in the Taiwanese mice. An inability to specifically induce Klf15 expression at physiological levels in a time- and tissue-dependent manner may have contributed to this limited efficacy. Thus, our work demonstrates that an AAV8-Spc5-12 vector induces high gene expression as early as P2 in several tissues including muscle, heart, and liver, but highlights the challenges of achieving meaningful vector-mediated transgene expression of Klf15.
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- 2019
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33. Full Steam Ahead or Abandon Ship? An Empirical Investigation of Complete Pivot Decisions
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Wood, Matthew S., Palich, Leslie E., and Browder, Russell E.
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New products or services often misalign with customer preferences, and sometimes these initial offerings must be abandoned and replaced. Factors influencing these “complete pivot” decisions are poorly understood. We use behavioral decision theory to develop a theoretical model of pivot decisions that tests our predictions via a conjoint analysis experiment. We find that magnitude of the miss (revenues compared to plan), length of the runway (cash available/burn rate), and attribution for the miss (reason for customer misreads) significantly influence complete pivot decisions, and we simultaneously consider interactions. Individual grit and impulsiveness also shape the effects of some attributes.
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- 2019
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34. Cerebral amyloidoma: A mimicker of granulomatous disease on brain MRI
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Radmanesh, Alireza, Wood, Matthew D., and Bollen, Andrew W.
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- 2019
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35. A Postoperative Care Bundle Reduces Surgical Site Infections in Pediatric Patients Undergoing Cardiac Surgeries.
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Caruso, Thomas J., Wang, Ellen Y., Schwenk, Hayden, Marquez, Juan Luis S., Cahn, Julie, Ling Loh, Shaffer, Jenny, Chen, Kevin, Wood, Matthew, and Sharek, Paul J.
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- 2019
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36. Improving Satisfaction with Pediatric Pain Management by Inviting the Conversation.
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Caruso, Thomas J., Kung, Tiffany H., Good, Julie, Taylor, Kristine, Ashland, Michele, Cunningham, Christine, Gonzalez, Elena, Wood, Matthew, and Sharek, Paul
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- 2018
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37. Adaptation of self-tuning spectral clustering and CNN texture model for detection of threats in volumetric CT images
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Ashok, Amit, Greenberg, Joel A., Gehm, Michael E., Song, Samuel M., Kim, Namho, Lee, Jongkyu, Wood, Matthew, Bedford, Simon, and Boyd, Douglas P.
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- 2019
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38. RETRACTED: Resilience, Parenting Style, and Children’s Eating Behavior
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Wood, Matthew and Shukla, Paurav
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- 2019
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39. Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics
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Coenen-Stass, Anna M. L., Pauwels, Marie J., Hanson, Britt, Martin Perez, Carla, Conceição, Mariana, Wood, Matthew J. A., Mäger, Imre, and Roberts, Thomas C.
- Abstract
ABSTRACTMultiple studies have described extracellular microRNAs (ex-miRNAs) as being remarkably stable despite the hostile extracellular environment, when stored at 4ºC or lower. Here we show that many ex-miRNAs are rapidly degraded when incubated at 37ºC in the presence of serum (thereby simulating physiologically relevant conditions). Stability varied widely between miRNAs, with half-lives ranging from ~1.5 hours to more than 13 hours. Notably, ex-miRNA half-lives calculated in two different biofluids (murine serum and C2C12 mouse myotube conditioned medium) were highly similar, suggesting that intrinsic sequence properties are a determining factor in miRNA stability. By contrast, ex-miRNAs associated with extracellular vesicles (isolated by size exclusion chromatography) were highly stable. The release of ex-miRNAs from C2C12 myotubes was measured over time, and mathematical modelling revealed miRNA-specific release kinetics. While some ex-miRNAs reached the steady state in cell culture medium within 24 hours, the extracellular level of miR-16 did not reach equilibrium, even after 3 days in culture. These findings are indicative of miRNA-specific release and degradation kinetics with implications for the utility of ex-miRNAs as biomarkers, and for the potential of ex-miRNAs to transfer gene regulatory information between cells.
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- 2019
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40. Exosome-Mediated miR-29 Transfer Reduces Muscle Atrophy and Kidney Fibrosis in Mice
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Wang, Haidong, Wang, Bin, Zhang, Aiqing, Hassounah, Faten, Seow, Yiqi, Wood, Matthew, Ma, Fuying, Klein, Janet D., Price, S. Russ, and Wang, Xiaonan H.
- Abstract
Our previous study showed that miR-29 attenuates muscle wasting in chronic kidney disease. Other studies found that miR-29 has anti-fibrosis activity. We hypothesized that intramuscular injection of exosome-encapsulated miR-29 would counteract unilateral ureteral obstruction (UUO)-induced muscle wasting and renal fibrosis. We used an engineered exosome vector, which contains an exosomal membrane protein gene Lamp2b that was fused with the targeting peptide RVG (rabies viral glycoprotein peptide). RVG directs exosomes to organs that express the acetylcholine receptor, such as kidney. The intervention of Exo/miR29 increased muscle cross-sectional area and decreased UUO-induced upregulation of TRIM63/MuRF1 and FBXO32/atrogin-1. Interestingly, renal fibrosis was partially depressed in the UUO mice with intramuscular injection of Exo/miR29. This was confirmed by decreased TGF-β, alpha-smooth muscle actin, fibronectin, and collagen 1A1 in the kidney of UUO mice. When we used fluorescently labeled Exo/miR29 to trace the Exo/miR route in vivoand found that fluorescence was visible in un-injected muscle and in kidneys. We found that miR-29 directly inhibits YY1 and TGF-β3, which provided a possible mechanism for inhibition of muscle atrophy and renal fibrosis by Exo/miR29. We conclude that Exo/miR29 ameliorates skeletal muscle atrophy and attenuates kidney fibrosis by downregulating YY1 and TGF-β pathway proteins.
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- 2019
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41. A Postoperative Care Bundle Reduces Surgical Site Infections in Pediatric Patients Undergoing Cardiac Surgeries
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Caruso, Thomas J., Wang, Ellen Y., Schwenk, Hayden, Marquez, Juan Luis S, Cahn, Julie, Loh, Ling, Shaffer, Jenny, Chen, Kevin, Wood, Matthew, and Sharek, Paul J.
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Pediatric patients undergoing cardiac surgeries are at an increased surgical site infection (SSI) risk, given prolonged cardiopulmonary bypasses and delayed sternal closures. At one institution, the majority of cardiac patients developed SSIs during prolonged recoveries in the cardiovascular intensive care unit (CVICU). Although guidelines have been published to reduce SSIs in the perioperative period, there have been few guidelines to reduce the risk during prolonged hospital recoveries. The aim of this project was to study a postoperative SSI reduction care bundle, with a goal of reducing cardiac SSIs by 50%, from 3.4 to 1.7 per 100 procedures.
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- 2019
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42. The Potential for Anthropomorphism in Communicating Science: Inspiration from Japan
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Wood, Matthew
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Anthropomorphism—the attribution of human characteristics to non-human animals or inanimate objects—is commonplace in many cultures around the world, but is particularly prominent and pervasive in Japan. Talking furniture on children's TV, vegetable mascots for city governments, an animated letter ‘e’ to promote online tax returns—there seems to be no limit to what can be anthropomorphized, and no corner of the culture where it is considered out of place. This of course includes efforts to communicate science, where we can find test tube narrators, angry viruses, friendly chemical elements, and a whole lot more. Scientists, on the other hand, are less enthusiastic about anthropomorphism in scientific discussions and tend to consider it to be inaccurate and unscientific. In science, thinking or communicating in anthropomorphic terms is generally derided. Where, then, does this leave the talking microbes and smiling proteins of Japanese science communication? While the literature has quite a lot to say about anthropomorphism, there is nothing specifically about its use for science communication. This paper draws on examples from Japan to consider the potential roles of anthropomorphism in the communication of science and related issues.
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- 2019
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43. Increasing Nerve Autograft Length Increases Senescence and Reduces Regeneration
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Hoben, Gwendolyn M., Ee, Xueping, Schellhardt, Lauren, Yan, Ying, Hunter, Daniel A., Moore, Amy M., Snyder-Warwick, Alison K., Stewart, Sheila, Mackinnon, Susan E., and Wood, Matthew D.
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- 2018
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44. Ponatinib coronary microangiopathy: novel bedside diagnostic approach and management with N-acetylcysteine
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Wu, Melinda D., Hodovan, James, Kumar, Kris, Moulton, Bart, Olson, Sven, Gilbert, Aubre, Wood, Matthew D., and Lindner, Jonathan R.
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- 2020
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45. Ponatinib coronary microangiopathy: novel bedside diagnostic approach and management with N-acetylcysteine
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Wu, Melinda D., Hodovan, James, Kumar, Kris, Moulton, Bart, Olson, Sven, Gilbert, Aubre, Wood, Matthew D., and Lindner, Jonathan R.
- Abstract
•Ponatinib produces a coronary microangiopathy that mimics myocardial infarction and can be detected rapidly by contrast echocardiography.•N-acetylcysteine therapy can potentially resolve ischemic complications caused by ponatinib-related microangiopathy.
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- 2020
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46. RNase-H-mediated silencing in the CNS proves predictably nontrivial
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Moazami, Michael P. and Wood, Matthew J.A.
- Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily affecting motor neurons. Recently,1Miller et al. presented phase 3 data for the RNase-H-recruiting antisense oligonucleotide (ASO) targeting superoxide dismutase 1 (SOD1) in ALS, which represents a step forward in the deployment of ASO therapeutics against CNS targets.
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- 2022
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47. Improving Communication with Primary Care Physicians at the Time of Hospital Discharge.
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Destino, Lauren A., Dixit, Amy, Pantaleoni, Julie L., Wood, Matthew S., Pageler, Natalie M., Kim, Joe, and Platchek, Terry S.
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- 2017
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48. Discussion: Functional Outcome after Reconstruction of a Long Nerve Gap in Rabbits Using Optimized Decellularized Nerve Allografts
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Mackinnon, Susan E., Pan, Deng, and Wood, Matthew D.
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- 2020
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49. Predictors of Antimicrobial Stewardship Program Recommendation Disagreement
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Bio, Laura L., Kruger, Jenna F., Lee, Betty P., Wood, Matthew S., and Schwenk, Hayden T.
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OBJECTIVETo identify predictors of disagreement with antimicrobial stewardship prospective audit and feedback recommendations (PAFR) at a free-standing children’s hospital.DESIGNRetrospective cohort study of audits performed during the antimicrobial stewardship program (ASP) from March 30, 2015, to April 17, 2017.METHODSThe ASP included audits of antimicrobial use and communicated PAFR to the care team, with follow-up on adherence to recommendations. The primary outcome was disagreement with PAFR. Potential predictors for disagreement, including patient-level, antimicrobial, programmatic, and provider-level factors, were assessed using bivariate and multivariate logistic regression models.RESULTSIn total, 4,727 antimicrobial audits were performed during the study period; 1,323 PAFR (28%) and 187 recommendations (15%) were not followed due to disagreement. Providers were more likely to disagree with PAFR when the patient had a gastrointestinal infection (odds ratio [OR], 5.50; 95% confidence interval [CI], 1.99–15.21), febrile neutropenia (OR, 6.14; 95% CI, 2.08–18.12), skin or soft-tissue infections (OR, 6.16; 95% CI, 1.92–19.77), or had been admitted for 31–90 days at the time of the audit (OR, 2.08; 95% CI, 1.36–3.18). The longer the duration since the attending provider had been trained (ie, the more years of experience), the more likely they were to disagree with PAFR recommendations (OR, 1.02; 95% CI, 1.01–1.04).CONCLUSIONSEvaluation of our program confirmed patient-level predictors of PAFR disagreement and identified additional programmatic and provider-level factors, including years of attending experience. Stewardship interventions focused on specific diagnoses and antimicrobials are unlikely to result in programmatic success unless these factors are also addressed.Infect Control Hosp Epidemiol2018;806–813
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- 2018
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50. Improving Satisfaction with Pediatric Pain Management by Inviting the Conversation
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Caruso, Thomas J., Kung, Tiffany H., Good, Julie, Taylor, Kristine, Ashland, Michele, Cunningham, Christine, Gonzalez, Elena, Wood, Matthew, and Sharek, Paul
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Patient satisfaction with pain management is associated with improved patient adherence to medical management and efficient service utilization. Pediatric pain control is challenging, given the inability to elicit reliable histories, particularly in younger patients. Several studies have suggested that communication surrounding pain management can improve satisfaction, although there are limited data describing structured interventions with measurable outcomes. A quality improvement project was conducted to determine if reliably asking families about pain management was associated with improved patient satisfaction with pain management.
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- 2018
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