Anatomy and Neuroscience - Research Publications

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    Control of Neuronal Survival and Development Using Conductive Diamond
    Falahatdoost, S ; Prawer, YDJ ; Peng, D ; Chambers, A ; Zhan, H ; Pope, L ; Stacey, A ; Ahnood, A ; Al Hashem, HN ; De Leon, SE ; Garrett, DJ ; Fox, K ; Clark, MB ; Ibbotson, MR ; Prawer, S ; Tong, W (AMER CHEMICAL SOC, 2024-01-17)
    This study demonstrates the control of neuronal survival and development using nitrogen-doped ultrananocrystalline diamond (N-UNCD). We highlight the role of N-UNCD in regulating neuronal activity via near-infrared illumination, demonstrating the generation of stable photocurrents that enhance neuronal survival and neurite outgrowth and foster a more active, synchronized neuronal network. Whole transcriptome RNA sequencing reveals that diamond substrates improve cellular-substrate interaction by upregulating extracellular matrix and gap junction-related genes. Our findings underscore the potential of conductive diamond as a robust and biocompatible platform for noninvasive and effective neural tissue engineering.
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    A novel model for hands-on laparoscopic pelvic surgery training on Genelyn-embalmed body: an initial feasibility study
    Kong, CY ; Fogg, QA ; Allam, M (SPRINGER, 2023-01)
    The human donor body provides a well-accepted ex vivo model for laparoscopic surgical training. Unembalmed, or fresh-frozen, bodies comprise high-fidelity models. However, their short life span and high cost relatively limit the hands-on training benefits. In contrast, soft embalmed body of donors has a relatively longer usability without compromising tissue flexibility. This study reports the initial experience of the utility and feasibility of human donor Genelyn-embalmed body as a novel soft-embalmed cadaveric model for laparoscopic surgical training. An expert laparoscopic surgeon, who organised many fresh-frozen body donor courses, performed deep laparoscopic pelvic dissection and laparoscopic surgical tasks including suturing and electrosurgery on a single Genelyn-embalmed body. The three sessions were performed over a course of 3 weeks. The body was fully embalmed using the Genelyn technique. The technique consisted of a single-point closed arterial perfusion of embalming solution via the carotid artery with no further exposure to or immersion in embalming fluids thereafter. The donor's Genelyn-embalmed body provided a feasible model for laparoscopic surgical training. Initial experience shows evidence of this model being feasible and realistic. There was reproducibility of these qualities across a minimum of 3 weeks in this single-donor study. Initial experience shows that donor's Genelyn-embalmed body provides a novel model for laparoscopic surgical training, which possesses fidelity and is feasible for laparoscopic training. While further studies are needed to validate these findings, this technical note provides perspectives from an expert trainer regarding this model and provides a photographic and videographic atlas of this model's use in laparoscopy.
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    The role of the gastrointestinal barrier in obesity-associated systemic inflammation
    Acciarino, A ; Diwakarla, S ; Handreck, J ; Bergola, C ; Sahakian, L ; Mcquade, RM (WILEY, 2023-12-18)
    Systemic inflammation is a key contributor to the onset and progression of several obesity-associated diseases and is thought to predominantly arise from the hyperplasia and hypertrophy of white adipose tissue. However, a growing body of works suggests that early changes in the gastrointestinal (GI) barrier may contribute to both local, within the GI lining, and systemic inflammation in obesity. Intestinal barrier dysfunction is well-characterized in inflammatory GI disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and is known to contribute to systemic inflammation. Thus, drawing parallels between GI disorders, where intestinal permeability and systemic inflammation are prominent features, and obesity-induced GI manifestations may provide insights into the potential role of the intestinal barrier in systemic inflammation in obesity. This review summarizes the current literature surrounding intestinal barrier dysfunction in obesity and explores the potential role of intestinal hyperpermeability and intestinal barrier dysfunction in the development of systemic inflammation and GI dysfunction in obesity.
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    The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
    Alexander, SPH ; Christopoulos, A ; Davenport, AP ; Kelly, E ; Mathie, AA ; Peters, JA ; Veale, EL ; Armstrong, JF ; Faccenda, E ; Harding, SD ; Davies, JA ; Abbracchio, MP ; Abraham, G ; Agoulnik, A ; Alexander, W ; Al-hosaini, K ; Baeck, M ; Baker, JG ; Barnes, NM ; Bathgate, R ; Beaulieu, J-M ; Beck-Sickinger, AG ; Behrens, M ; Bernstein, KE ; Bettler, B ; Birdsall, NJM ; Blaho, V ; Boulay, F ; Bousquet, C ; Braeuner-Osborne, H ; Burnstock, G ; Calo, G ; Castano, JP ; Catt, KJ ; Ceruti, S ; Chazot, P ; Chiang, N ; Chini, B ; Chun, J ; Cianciulli, A ; Civelli, O ; Clapp, LH ; Couture, R ; Cox, HM ; Csaba, Z ; Dahlgren, C ; Dent, G ; Douglas, SD ; Dournaud, P ; Eguchi, S ; Escher, E ; Filardo, EJ ; Fong, T ; Fumagalli, M ; Gainetdinov, RR ; Garelja, ML ; de Gasparo, M ; Gerard, C ; Gershengorn, M ; Gobeil, F ; Goodfriend, TL ; Goudet, C ; Graetz, L ; Gregory, KJ ; Gundlach, AL ; Hamann, J ; Hanson, J ; Hauger, RL ; Hay, DL ; Heinemann, A ; Herr, D ; Hollenberg, MD ; Holliday, ND ; Horiuchi, M ; Hoyer, D ; Hunyady, L ; Husain, A ; Ijzerman, AP ; Inagami, T ; Jacobson, KA ; Jensen, RT ; Jockers, R ; Jonnalagadda, D ; Karnik, S ; Kaupmann, K ; Kemp, J ; Kennedy, C ; Kihara, Y ; Kitazawa, T ; Kozielewicz, P ; Kreienkamp, H-J ; Kukkonen, JP ; Langenhan, T ; Larhammar, D ; Leach, K ; Lecca, D ; Lee, JD ; Leeman, SE ; Leprince, J ; Li, XX ; Lolait, SJ ; Lupp, A ; Macrae, R ; Maguire, J ; Malfacini, D ; Mazella, J ; Mcardle, CA ; Melmed, S ; Michel, MC ; Miller, LJ ; Mitolo, V ; Mouillac, B ; Mueller, CE ; Murphy, PM ; Nahon, J-L ; Ngo, T ; Norel, X ; Nyimanu, D ; O'Carroll, A-M ; Offermanns, S ; Panaro, MA ; Parmentier, M ; Pertwee, RG ; Pin, J-P ; Prossnitz, ER ; Quinn, M ; Ramachandran, R ; Ray, M ; Reinscheid, RK ; Rondard, P ; Rovati, GE ; Ruzza, C ; Sanger, GJ ; Schoeneberg, T ; Schulte, G ; Schulz, S ; Segaloff, DL ; Serhan, CN ; Singh, KD ; Smith, CM ; Stoddart, LA ; Sugimoto, Y ; Summers, R ; Tan, VP ; Thal, D ; Thomas, WW ; Timmermans, PBMWM ; Tirupula, K ; Toll, L ; Tulipano, G ; Unal, H ; Unger, T ; Valant, C ; Vanderheyden, P ; Vaudry, D ; Vaudry, H ; Vilardaga, J-P ; Walker, CS ; Wang, JM ; Ward, DT ; Wester, H-J ; Willars, GB ; Williams, TL ; Woodruff, TM ; Yao, C ; Ye, RD (WILEY, 2023-10)
    The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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    An adeno-associated viral labeling approach to visualize the meso- and microanatomy of mechanosensory afferents and autonomic innervation of the rat urinary bladder
    Wiedmann, NM ; Fuller-Jackson, J-P ; Osborne, PB ; Keast, JR (WILEY, 2024-01)
    The urinary bladder is supplied by a rich network of sensory and autonomic axons, commonly visualized by immunolabeling for neural markers. This approach demonstrates overall network patterning but is less suited to understanding the structure of individual motor and sensory terminals within these complex plexuses. There is a further limitation visualizing the lightly myelinated (A-delta) class of sensory axons that provides the primary mechanosensory drive for initiation of voiding. Whereas most unmyelinated sensory axons can be revealed by immunolabeling for specific neuropeptides, to date no unique neural marker has been identified to immunohistochemically label myelinated visceral afferents. We aimed to establish a non-surgical method to visualize and map myelinated afferents in the bladder in rats. We found that in rats, the adeno-associated virus (AAV), AAV-PHP.S, which shows a high tropism for the peripheral nervous system, primarily transduced myelinated dorsal root ganglion neurons, enabling us to identify the structure and regional distribution of myelinated (mechanosensory) axon endings within the muscle and lamina propria of the bladder. We further identified the projection of myelinated afferents within the pelvic nerve and lumbosacral spinal cord. A minority of noradrenergic and cholinergic neurons in pelvic ganglia were transduced, enabling visualization and regional mapping of both autonomic and sensory axon endings within the bladder. Our study identified a sparse labeling approach for investigating myelinated sensory and autonomic axon endings within the bladder and provides new insights into the nerve-bladder interface.
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    Exploring mobile mixed reality for critical thinking in nursing and healthcare education: A systematic review
    Stretton, T ; Cochrane, T ; Sevigny, C ; Rathner, J (CHURCHILL LIVINGSTONE, 2024-02)
    BACKGROUND: The shortage of nursing and healthcare clinical placements has prompted the investigation of ways to supplement authentic learning. Mobile mixed reality has become increasingly available, however, the affordances and design principles for the facilitation of critical thinking are yet to be explored. OBJECTIVE: To examine how mobile mixed reality facilitates critical thinking in nursing and healthcare higher education. DESIGN: Systematic review. REVIEW METHODS: A search in seven databases (MEDLINE, PsychINFO, AMED, ERIC, Scopus, Cochrane, and Web of Science) was conducted with 3488 titles and abstracts screened. The quality of the included studies was evaluated using the Mixed Methods Assessment Tool (MMAT). RESULTS: A total of 12 studies with 1108 participants were included. The breadth of healthcare disciplines was limited to five disciplines that utilised bespoke scenarios on head-mounted displays. Most scenarios were emergency or critical response, with limited time for pre-brief, debrief, or overall user time. Only two studies directly measured critical thinking, with others including indirect reference to diagnoses, interpretation, analysis, or evaluation of healthcare scenarios. Affordances and design principles for the future development of mobile mixed reality for critical thinking in nursing and healthcare higher education are identified. CONCLUSIONS: While some pedagogical affordances of mobile mixed reality can be identified in a narrow number of healthcare disciplines, there remain to be limited valid measures of critical thinking used to quantify effectiveness. Future studies would benefit from considering scenarios beyond emergency and critical responses, including longitudinal studies that reflect the development of critical thinking over time, and exploration of co-designed scenarios with and by nursing and healthcare students.
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    Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
    Liau, W-S ; Zhao, Q ; Bademosi, A ; Gormal, RS ; Gong, H ; Marshall, PR ; Periyakaruppiah, A ; Madugalle, SU ; Zajaczkowski, EL ; Leighton, LJ ; Ren, H ; Musgrove, M ; Davies, J ; Rauch, S ; He, C ; Dickinson, BC ; Li, X ; Wei, W ; Meunier, FA ; Fernandez-Moya, SM ; Kiebler, MA ; Srinivasan, B ; Banerjee, S ; Clark, M ; Spitale, RC ; Bredy, TW (NATURE PORTFOLIO, 2023-11-22)
    Long noncoding RNAs (lncRNAs) represent a multidimensional class of regulatory molecules that are involved in many aspects of brain function. Emerging evidence indicates that lncRNAs are localized to the synapse; however, a direct role for their activity in this subcellular compartment in memory formation has yet to be demonstrated. Using lncRNA capture-seq, we identified a specific set of lncRNAs that accumulate in the synaptic compartment within the infralimbic prefrontal cortex of adult male C57/Bl6 mice. Among these was a splice variant related to the stress-associated lncRNA, Gas5. RNA immunoprecipitation followed by mass spectrometry and single-molecule imaging revealed that this Gas5 isoform, in association with the RNA binding proteins G3BP2 and CAPRIN1, regulates the activity-dependent trafficking and clustering of RNA granules. In addition, we found that cell-type-specific, activity-dependent, and synapse-specific knockdown of the Gas5 variant led to impaired fear extinction memory. These findings identify a new mechanism of fear extinction that involves the dynamic interaction between local lncRNA activity and RNA condensates in the synaptic compartment.
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    Assessments Used for Summative Purposes during Internal Medicine Specialist Training: A Rapid Review
    Patterson, S ; Shaw, L ; Rank, MM ; Vaughan, B (MDPI, 2023-10)
    Assessments used for summative purposes of patient-facing clinical competency in specialist internal medicine training are high-stakes, both to doctors in training, as it is a prerequisite for qualification, as well as their community of prospective patients. A rapid review of the literature evaluated methods of assessments used for summative purposes of patient-facing clinical competency during specialist internal medicine training in Australia. Four online databases identified literature published since the year 2000 that reported on summative assessment in specialist medical training. Two reviewers screened and selected eligible studies and extracted data, with a focus on evidence of support for the criteria for good assessment as set out in the 2010 Ottawa Consensus framework for good assessment. Ten eligible studies were included. Four studied the mini-clinical evaluation exercise (mini-CEX), two the Royal Australasian College of Physicians short case exam, three a variety of Entrustable Professional Activities (EPAs) or summative entrustment and progression review processes, and one a novel clinical observation tool. The mini-CEX assessment demonstrated the most evidence in support of the Ottawa criteria. There was a paucity of published evidence regarding the best form of summative assessment of patient-facing clinical competency in specialist internal medicine training.
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    Selective transduction and photoinhibition of pre-Bötzinger complex neurons that project to the facial nucleus in rats affects nasofacial activity
    Melo, MR ; Wykes, AD ; Connelly, AA ; Bassi, JK ; Cheung, SD ; Mcdougall, SJ ; Menuet, C ; Bathgate, RAD ; Allen, AM (eLIFE SCIENCES PUBL LTD, 2023-09-29)
    The pre-Bötzinger complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetized and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviors. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviors have been associated with the development and progression of diseases.
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    The Tolerogenic Influence of Dexamethasone on Dendritic Cells Is Accompanied by the Induction of Efferocytosis, Promoted by MERTK.
    Li, V ; Binder, MD ; Kilpatrick, TJ (MDPI AG, 2023-11-02)
    Many treatments for autoimmune diseases, caused by the loss of immune self-tolerance, are broadly immunosuppressive. Dendritic cells (DCs) can be induced to develop anti-inflammatory/tolerogenic properties to suppress aberrant self-directed immunity by promoting immune tolerance in an antigen-specific manner. Dexamethasone can generate tolerogenic DCs and upregulates MERTK expression. As MERTK can inhibit inflammation, we investigated whether dexamethasone's tolerogenic effects are mediated via MERTK, potentially providing a novel therapeutic approach. Monocyte-derived DCs were treated with dexamethasone, and with and without MERTK ligands or MERTK inhibitors. Flow cytometry was used to assess effects of MERTK modulation on co-stimulatory molecule expression, efferocytosis, cytokine secretion and T cell proliferation. The influence on expression of Rab17, which coordinates the diversion of efferocytosed material away from cell surface presentation, was assessed. Dexamethasone-treated DCs had upregulated MERTK expression, decreased expression of co-stimulatory molecules, maturation and proliferation of co-cultured T cells and increased uptake of myelin debris. MERTK ligands did not potentiate these properties, whilst specific MERTK inhibition only reversed dexamethasone's effect on myelin uptake. Cells undergoing efferocytosis had higher Rab17 expression. Dexamethasone-enhanced efferocytosis in DCs is MERTK-dependent and could exert its tolerogenic effects by increasing Rab17 expression to prevent the presentation of efferocytosed material on the cell surface to activate adaptive immune responses.