Sélection d'anticorps recombinants dirigés contre des matériaux inorganiques pour des applications en nanosciences

Les matériaux inorganiques ont des propriétés uniques à l'échelle nanométrique. Ces propriétés ont généré beaucoup d'intérêt pour fabriquer des nouveaux matériaux utilisant des nano-objets comme unité de construction. Nous avons suivi une approche biomimétique pour la fabrication de dispositifs à base de nanoparticules afin d'améliorer les méthodes actuelles de fabrication top-down et bottom-up. Certaines protéines naturelles se lient en effet spécifiquement à des matériaux inorganiques, et déclenchent notamment la croissance de cristaux inorganiques. Une première étape dans cette approche biomimétique est de comprendre comment des protéines se lient spécifiquement à des nanomatériaux inorganiques. Nous avons exploré ce mécanisme de reconnaissance en sélectionnant des anticorps (les protéines de notre système immunitaire spécialisées dans les interactions avec de nombreuses cibles) contre des matériaux inorganiques par la méthode combinatoire biotechnologique appelée "phage display". Cette technique permet d'obtenir la séquence génétique codante des anticorps sélectionnés se liant à leur cible à partir d'une banque aléatoire d'anticorps. L'analyse statistique des séquences des anticorps sélectionnés fournit de nouvelles informations sur les interactions protéines/matériaux inorganiques. Notre principale conclusion est l'identification de l'acide aminé arginine en tant que contributeur majeur dans les interactions protéine/or. L'ingénierie génétique des anticorps permet de fonctionnaliser ces nouvelles sondes de matériaux inorganiques en vue de leur utilisation pour des applications dans le domaine des nanomatériaux. Les anticorps recombinants sélectionnés et leurs dérivés fonctionnalisés peuvent être exprimés par sécrétion à l'aide d'un hôte eucaryote (Dictyostelium discoideum) mis au point au cours de cette thèse.Inorganic materials have unique properties at the nanometer scale. These properties have generated a lot of interest among researchers to fabricate novel materials using nano objects as building units. In this PhD thesis, we have attempted to mimick nature in the fabrication of nanoparticle based devices in order to improve upon current top-down and bottom-up nanomaterial fabrication methods. Proteins can specifically bind inorganic materials and trigger crystal growth and thus are considered as the main building units for a biomimetic approach of fabrication. The first step towards mimicking nature is to explore how proteins bind specifically to nanomaterials. We have explored this recognition mechanism by selecting antibodies (the protein binders of our immune system) against inorganic nanomaterials using the combinatorial biotechnology method of phage display. This technique provides us with the genetic sequence of selected antibodies from a random antibody library exposed against a target. Statistical analysis of selected antibody sequences provides new information on proteins/inorganics interactions. Our main finding in this regard is the identification of the amino acid arginine as a major contributor to protein/gold interactions. Additional functionality to these new binders of inorganic materials is obtained by antibody engineering, allowing for their value added use in nanomaterial science applications. Selected recombinant antibodies and their engineered derivatives along with other recombinant protein can be expressed and secreted using a eukaryotic expression platform (Dictyostelium discoideum) developed during this thesis.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Clinical, hematological and cytogenetic profile in fibroblast growth factor receptor 1 rearranged hematoloymphoid malignancies

The background of this study is FGFR1 belongs to a family of four, high-affinity receptor tyrosine kinase and is a legitimate oncogene associated with uterine, cervical, prostate, bladder, colorectal and lung cancers. It is rarely concomitant in myeloid and lymphoid neoplasms but has an aggressive clinical course with a high mortality rate when present. Cytogenetic abnormalities involving the FGFR1 gene is most frequently observed in AML, MPN with eosinophilia, T-ALL and T-LBL with ZMYM2 gene being the most common fusion partner. Methods of this study was to authors report a series of 4 cases with FGFR1 rearrangements. Results is three patients presented as T-cell Lymphoblastic lymphoma (T-LBL) and one as mixed phenotype acute leukemia (MPAL). The T-LBL cases harboured the FGFR1/ ZMYM2 fusion and the MPAL case harbored the CNTRL/FGFR1 fusion as identified by conventional cytogenetics and confirmed by molecular studies. Conclusion is authors herewith describe the clinical, biochemical, molecular and cytogenetic features observed in these cases

Absence of toll-like receptor 9 Pro99Leu polymorphism in cervical cancer [version 2; referees: 2 approved, 1 not approved]

Background: Toll-like receptor 9 (TLR9) plays a key role in the elimination of viral pathogens by recognising their CpG DNA. Polymorphisms in the TLR9 gene may influence their recognition and subsequent elimination. Therefore, the present study was designed to elucidate the role of a rare unexplored TLR9 gene polymorphism C296T/ Pro99Leu (rs5743844) in cervical cancer susceptibility among Indian women. Methods: The genotyping of TLR9 Pro99Leu polymorphism in 110 cervical cancer patients and 141 healthy controls was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: The genotype frequency detected in both cervical cancer and control populations was 1.0 (CC), 0.0 (CT) and 0.0 (TT); while the allele frequency was found to be 1.0 (C) and 0.0 (T). Conclusions: The present study demonstrates no involvement of TLR9 C296T/ Pro99Leu polymorphism in cervical cancer susceptibility and supports minor allele frequency (MAF) (0.0002) status of the same as no nucleotide variation was detected in any of the study subjects

EGFR Dynamics Change during Activation in Native Membranes as Revealed by NMR

The epidermal growth factor receptor (EGFR) represents one of the most common target proteins in anti-cancer therapy. To directly examine the structural and dynamical properties of EGFR activation by the epidermal growth factor (EGF) in native membranes, we have developed a solid-state nuclear magnetic resonance (ssNMR)-based approach supported by dynamic nuclear polarization (DNP). In contrast to previous crystallographic results, our experiments show that the ligand-free state of the extracellular domain (ECD) is highly dynamic, while the intracellular kinase domain (KD) is rigid. Ligand binding restricts the overall and local motion of EGFR domains, including the ECD and the C-terminal region. We propose that the reduction in conformational entropy of the ECD by ligand binding favors the cooperative binding required for receptor dimerization, causing allosteric activation of the intracellular tyrosine kinase

EGFR Dynamics Change during Activation in Native Membranes as Revealed by NMR

The epidermal growth factor receptor (EGFR) represents one of the most common target proteins in anti-cancer therapy. To directly examine the structural and dynamical properties of EGFR activation by the epidermal growth factor (EGF) in native membranes, we have developed a solid-state nuclear magnetic resonance (ssNMR)-based approach supported by dynamic nuclear polarization (DNP). In contrast to previous crystallographic results, our experiments show that the ligand-free state of the extracellular domain (ECD) is highly dynamic, while the intracellular kinase domain (KD) is rigid. Ligand binding restricts the overall and local motion of EGFR domains, including the ECD and the C-terminal region. We propose that the reduction in conformational entropy of the ECD by ligand binding favors the cooperative binding required for receptor dimerization, causing allosteric activation of the intracellular tyrosine kinase

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Selection of recombinant antibodies against inorganic materials for applications in nanosciences

Les matériaux inorganiques ont des propriétés uniques à l'échelle nanométrique. Ces propriétés ont généré beaucoup d'intérêt pour fabriquer des nouveaux matériaux utilisant des nano-objets comme unité de construction. Nous avons suivi une approche biomimétique pour la fabrication de dispositifs à base de nanoparticules afin d'améliorer les méthodes actuelles de fabrication top-down et bottom-up. Certaines protéines naturelles se lient en effet spécifiquement à des matériaux inorganiques, et déclenchent notamment la croissance de cristaux inorganiques. Une première étape dans cette approche biomimétique est de comprendre comment des protéines se lient spécifiquement à des nanomatériaux inorganiques. Nous avons exploré ce mécanisme de reconnaissance en sélectionnant des anticorps (les protéines de notre système immunitaire spécialisées dans les interactions avec de nombreuses cibles) contre des matériaux inorganiques par la méthode combinatoire biotechnologique appelée "phage display". Cette technique permet d'obtenir la séquence génétique codante des anticorps sélectionnés se liant à leur cible à partir d'une banque aléatoire d'anticorps. L'analyse statistique des séquences des anticorps sélectionnés fournit de nouvelles informations sur les interactions protéines/matériaux inorganiques. Notre principale conclusion est l'identification de l'acide aminé arginine en tant que contributeur majeur dans les interactions protéine/or. L'ingénierie génétique des anticorps permet de fonctionnaliser ces nouvelles sondes de matériaux inorganiques en vue de leur utilisation pour des applications dans le domaine des nanomatériaux. Les anticorps recombinants sélectionnés et leurs dérivés fonctionnalisés peuvent être exprimés par sécrétion à l'aide d'un hôte eucaryote (Dictyostelium discoideum) mis au point au cours de cette thèse.Inorganic materials have unique properties at the nanometer scale. These properties have generated a lot of interest among researchers to fabricate novel materials using nano objects as building units. In this PhD thesis, we have attempted to mimick nature in the fabrication of nanoparticle based devices in order to improve upon current top-down and bottom-up nanomaterial fabrication methods. Proteins can specifically bind inorganic materials and trigger crystal growth and thus are considered as the main building units for a biomimetic approach of fabrication. The first step towards mimicking nature is to explore how proteins bind specifically to nanomaterials. We have explored this recognition mechanism by selecting antibodies (the protein binders of our immune system) against inorganic nanomaterials using the combinatorial biotechnology method of phage display. This technique provides us with the genetic sequence of selected antibodies from a random antibody library exposed against a target. Statistical analysis of selected antibody sequences provides new information on proteins/inorganics interactions. Our main finding in this regard is the identification of the amino acid arginine as a major contributor to protein/gold interactions. Additional functionality to these new binders of inorganic materials is obtained by antibody engineering, allowing for their value added use in nanomaterial science applications. Selected recombinant antibodies and their engineered derivatives along with other recombinant protein can be expressed and secreted using a eukaryotic expression platform (Dictyostelium discoideum) developed during this thesis

Sélection d'anticorps recombinants dirigés contre des matériaux inorganiques pour des applications en nanosciences

Inorganic materials have unique properties at the nanometer scale. These properties have generated a lot of interest among researchers to fabricate novel materials using nano objects as building units. In this PhD thesis, we have attempted to mimick nature in the fabrication of nanoparticle based devices in order to improve upon current top-down and bottom-up nanomaterial fabrication methods. Proteins can specifically bind inorganic materials and trigger crystal growth and thus are considered as the main building units for a biomimetic approach of fabrication. The first step towards mimicking nature is to explore how proteins bind specifically to nanomaterials. We have explored this recognition mechanism by selecting antibodies (the protein binders of our immune system) against inorganic nanomaterials using the combinatorial biotechnology method of phage display. This technique provides us with the genetic sequence of selected antibodies from a random antibody library exposed against a target. Statistical analysis of selected antibody sequences provides new information on proteins/inorganics interactions. Our main finding in this regard is the identification of the amino acid arginine as a major contributor to protein/gold interactions. Additional functionality to these new binders of inorganic materials is obtained by antibody engineering, allowing for their value added use in nanomaterial science applications. Selected recombinant antibodies and their engineered derivatives along with other recombinant protein can be expressed and secreted using a eukaryotic expression platform (Dictyostelium discoideum) developed during this thesis.Les matériaux inorganiques ont des propriétés uniques à l'échelle nanométrique. Ces propriétés ont généré beaucoup d'intérêt pour fabriquer des nouveaux matériaux utilisant des nano-objets comme unité de construction. Nous avons suivi une approche biomimétique pour la fabrication de dispositifs à base de nanoparticules afin d'améliorer les méthodes actuelles de fabrication top-down et bottom-up. Certaines protéines naturelles se lient en effet spécifiquement à des matériaux inorganiques, et déclenchent notamment la croissance de cristaux inorganiques. Une première étape dans cette approche biomimétique est de comprendre comment des protéines se lient spécifiquement à des nanomatériaux inorganiques. Nous avons exploré ce mécanisme de reconnaissance en sélectionnant des anticorps (les protéines de notre système immunitaire spécialisées dans les interactions avec de nombreuses cibles) contre des matériaux inorganiques par la méthode combinatoire biotechnologique appelée "phage display". Cette technique permet d'obtenir la séquence génétique codante des anticorps sélectionnés se liant à leur cible à partir d'une banque aléatoire d'anticorps. L'analyse statistique des séquences des anticorps sélectionnés fournit de nouvelles informations sur les interactions protéines/matériaux inorganiques. Notre principale conclusion est l'identification de l'acide aminé arginine en tant que contributeur majeur dans les interactions protéine/or. L'ingénierie génétique des anticorps permet de fonctionnaliser ces nouvelles sondes de matériaux inorganiques en vue de leur utilisation pour des applications dans le domaine des nanomatériaux. Les anticorps recombinants sélectionnés et leurs dérivés fonctionnalisés peuvent être exprimés par sécrétion à l'aide d'un hôte eucaryote (Dictyostelium discoideum) mis au point au cours de cette thèse

Vocal Adduction Exercises for Swallowing Rehabilitation in Adults with Typical and Disordered Swallowing: A Scoping Review

Authors Purvi Jain1 Beatrice Tenchini1 Ciarán Kenny1 1. Trinity College Dublin, Ireland Abstract Objective: The objective of this scoping review is to understand the extent and type of evidence on different rehabilitative vocal adduction exercises and their effect on swallow physiology, in adults with typical or disordered swallowing. An account of the proposed principles of rehabilitation and outcome measures will be reported. Introduction: In healthy individuals, airway protection during swallowing involves closure of the larynx at multiple levels, including adduction of the true vocal folds and approximation of the false vocal folds (Vose &amp; Humbert, 2019). Different exercises to improve glottic closure during swallowing have been reported in dysphagia research. This review aims to map the evidence on vocal adduction exercises and their physiological effects in swallowing rehabilitation. Inclusion criteria: All published studies in adults (age&gt;=18years) with healthy swallowing and/or dysphagia investigating vocal adduction exercises and their effects on swallow physiology will be included in this review, with no restrictions on time, language or setting. Selected studies must instrumentally measure impact on swallow function, as this provides more valid and quantitative evidence of the physiological effects of the exercises. Methods: The Joanna Briggs Institute methods and PRISMA-ScR guidelines will be used to inform this review. Electronic databases (MEDLINE (PubMed), EMBASE (Ovid), CINAHL (EBSCO) and Web of Science) and grey literature will be searched from inception to March 2022 inclusive, to find studies on vocal adduction exercises and swallowing rehabilitation. Articles will be assessed by two independent reviewers, utilizing a three-step search strategy, to meet the following criteria: (1) exercises targeting vocal cord adduction (2) physiological outcomes measured instrumentally during swallowing, and (3) in typical healthy adults or persons with dysphagia. The resulting evidence map will be reported in tabular form along with a narrative summary. Introduction Vocal fold adduction is a crucial line of defense for airway protection during swallowing. The true and false vocal folds prevent aspiration by restricting entry of material into the lower airway and contribute to the forceful ejection of any material that has already penetrated the laryngeal vestibule (Voce &amp; Humbert, 2019). While compensatory strategies for laryngeal adduction during swallowing are well documented (Logemann, 1983), no comprehensive review has been conducted describing the use or efficacy of vocal adduction exercises in swallowing rehabilitation. Rehabilitative exercises, are intended to change and improve the swallowing physiology in force, speed or timing, with the goal of being able to produce a long-term effect, as compared to compensatory interventions used for a short-term effect (Langmore &amp; Pisenga, 2015). Based on the shared anatomical, physiological, and neurophysiological underpinnings of the voice and swallow mechanism, different rehabilitative exercises targeting glottic closure have been studied to find impact on swallowing function. The complex and heterogenous nature of these studies makes it imperative for a scoping review to map the existing evidence in dysphagia literature. No past or currently underway literature reviews on this topic were identified from our preliminary search. This exploratory project aims to assess the extent of the body of published literature and identify key concepts and knowledge gaps related to vocal adduction exercises for swallowing rehabilitation in healthy adults and, or persons with dysphagia, to apprise clinical practice and future research. Review question Primary questions: What exercises target vocal adduction for swallowing rehabilitation and what are their effects on swallowing physiology in adults with typical swallowing and, or dysphagia? Secondary questions: (1) What are the proposed principles of rehabilitation, and (2) what outcome measures have been reported, in the selected studies? Keywords Dysphagia; Exercise; Rehabilitation; Vocal Adduction; Larynx Eligibility criteria Participants Persons (age&gt;=18years) with healthy swallowing and/or dysphagia are included. Those with typical swallowing are included to examine proof of principle. Those with dysphagia help to generalise results across sampled populations. Paediatric populations will be excluded from the review due to structural and functional differences in body systems and rehabilitative practice. Concept Studies investigating rehabilitative exercises for vocal adduction, that instrumentally examine their effects on swallow function are included in this review. The earlier definition of rehabilitative exercise (Langmore &amp; Pisenga, 2015) is used to guide the review. Instrumental assessment is considered a more valid and reliable way of visualising and assessing movement patterns of swallowing-related structures to formulate inferences regarding the long-term effect of the rehabilitative exercise on physiologic function and integrity of deglutition, as compared to non-instrumental evaluations (e.g. clinical bedside swallow exam, patient reported outcome measures, quality of life, etc). Context Articles published from inception to March 2022, inclusive, will be selected. Randomised control trials (RCT), non-RCTs, cohort studies, case control studies and case series type of studies will be included. Literature reviews will be excluded from the study, but screened for original articles in their reference lists. No restrictions on culture, gender, ethnicity, language, time or setting will be applied to increase the reviews’ comprehensiveness. Gray literature will be manually searched to cover a wide and inclusive range of evidence and reduce publication bias. Types of Sources No restrictions are imposed on study design or quality (PRISMA-ScR; Tricco et al., 2018). This scoping review will consider both experimental and observational study designs, including individual case reports. In addition, systematic reviews that meet the inclusion criteria will also be screened for original articles in their reference lists. Gray literature consisting of text and opinion papers like letters to the editor will also be considered for inclusion in this scoping review to cover a wide and inclusive range of evidence and reduce publication bias. Methods The proposed scoping review will be conducted in accordance with the JBI methodology for scoping reviews (Peters et al., 2020). Search strategy An initial limited search of PubMed and Embase will be undertaken to identify articles on the topic. The text words contained in the titles and abstracts of relevant articles, and the index terms used to describe the articles will be used to develop a full search strategy for PubMed database, in an iterative process, and adapted for each included database and/or information source. The reference list of all included sources of evidence will be screened for additional studies. No limitations on publication date or language are applied. The databases to be searched include MEDLINE (PubMed); EMBASE (Ovid); CINAHL (EBSCO); Web of Science. All included sources of grey literature evidence like conference papers, letters to the editor, dissertations and theses will be included in the appendix. Study/Source of Evidence selection Following the search, all identified citations will be collated and uploaded into Covidence systematic review online software, Veritas Health Innovation, Melbourne, Australia, for deduplication. Following a pilot test on a sample of 25 titles and abstracts, search results will be screened by PJ and BT independently for assessment against the eligibility criteria for the review, once 75% agreement is achieved. Reasons for exclusion of sources of evidence will be recorded and reported in the scoping review. Any disagreements that arise between the reviewers will be resolved through discussion with the third reviewer. The Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR) flow diagram will guide the reporting of results of the search and the study inclusion process. Data Extraction A data extraction charting form will be developed by the primary reviewer in collaboration with the supervisor on Microsoft Excel, based on the research objectives, and examination of ten percent of the full texts identified as eligible for charting. The two reviewers will independently pilot the charting form on ten percent of the selected articles, discuss the results and continuously update the data-charting form in an iterative process. Disagreements will be resolved in collaboration with the research team through discussion. This is in an attempt to ensure the recommendations of data charting are met; that all relevant data is captured, keeping in mind the research aims and allow for the creation of a descriptive summary of results (Arksey &amp; O’Malley, 2005). If necessary, authors of papers will be contacted to request missing or additional data, where required. Critical appraisal will not be carried, because this study focuses on literature synthesis. The data extracted will include details about the participants, concept, context, study methods and key findings relevant to the review questions. The final charting form with clear definitions of each item will be attached. Any study information reviewers feel may be of relevance for interpreting outcomes will be included in a comment box and discussed between reviewers following conclusion of the data charting phase. Data items that are not considered as possibly useful towards answering the research questions before beginning the charting may be added if they present as reoccurring themes. Amendments to the data charting form will be reported. Data Analysis and Presentation A descriptive numerical analysis and qualitative thematic analysis will be done by the first author, presenting findings in a narrative format with tabular and visual representation, in relation to the primary and secondary review questions (Levac et al., 2010). Broadly, the results will be classified under main conceptual categories of rehabilitative vocal adduction exercises, patient populations, physiological effects on swallow function, principles/rationale for rehabilitation and outcome measures. Acknowledgements This literature review is being carried out as a part of the Master’s degree in Clinical Speech and Language Studies, dissertation project, at Trinity College Dublin, for the academic year 2021-2022, under the supervision of Dr. Ciarán Kenny. Funding The project received no professional or institutional funding as it is undertaken as part of the Master’s degree project at Trinity College Dublin. Conflicts of interest The authors report no conflicts of interest. References Arksey, H., &amp; O’Malley, L. (2005). Scoping studies: Towards a methodological framework. International Journal of Social Research Methodology: Theory and Practice, 8(1), 19–32. https://doi.org/10.1080/1364557032000119616 Ekberg O Closure of the laryngeal vestibule during deglutition. Acta Oto Laryngol. 1982;93:123–9. https://www.ncbi.nlm.nih.gov/pubmed/7064688 El Sharkawi, A., Ramig, L., Logemann, J. A., Pauloski, B. R., Rademaker, A. W., Smith, C. H., Pawlas, A., Baum, S., &amp; Werner, C. (2002). Swallowing and voice effects of Lee Silverman Voice Treatment (LSVT): a pilot study. Journal of neurology, neurosurgery, and psychiatry, 72(1), 31–36. https://doi.org/10.1136/jnnp.72.1.31 Kawasaki A, Fukuda H, Shiotani A, Kanzaki J. Study of movements of individual structures of the larynx during swallowing. Auris Nasus Larynx. 2001;28:75–84. https://www.ncbi.nlm.nih.gov/pubmed/11137367 Khalil, H., Peters, M., Godfrey, C. M., McInerney, P., Soares, C. B., &amp; Parker, D. (2016). An Evidence-Based Approach to Scoping Reviews. Worldviews on evidence-based nursing, 13(2), 118–123. https://doi.org/10.1111/wvn.12144 Langmore, S. E., &amp; Pisegna, J. M. (2015). Efficacy of exercises to rehabilitate dysphagia: A critique of the literature. International journal of speech-language pathology, 17(3), 222–229. https://doi.org/10.3109/17549507.2015.1024171 Levac, D., Colquhoun, H., &amp; O’Brien, K. K. (2010). Scoping studies: advancing the methodology. Implementation Science, 5(1), 69. https://doi.org/10.1186/1748-5908-5-69 Logemann JA, Pauloski BR, Rademaker AW, Kahrilas PJ. Oropharyngeal swallow in younger and older women: videofluoroscopic analysis. J Speech Lang Hear Res. 2002;45:434–45. [PubMed: 12068997] Peters M. D. J., Godfrey C, McInerney P, Munn Z, Tricco AC, Khalil, H. Chapter 11: Scoping Reviews (2020 version). In: Aromataris E, Munn Z (Editors). JBI Manual for Evidence Synthesis, JBI, 2020. Available from https://synthesismanual.jbi.global . https://doi.org/10.46658/JBIMES-20-12 Peters, M. D. J., Godfrey, C. M., Khalil, H., McInerney, P., Parker, D., &amp; Soares, C. B. (2015). Guidance for conducting systematic scoping reviews. International Journal of Evidence-Based Healthcare, 13(3), 141–146. https://doi.org/10.1097/XEB.0000000000000050 Steele C. M. (2012). Exercise-based approaches to dysphagia rehabilitation. Nestle Nutrition Institute workshop series, 72, 109–117. https://doi.org/10.1159/000339999 Tricco, A. C., Lillie, E., Zarin, W., O'Brien, K. K., Colquhoun, H., Levac, D., Moher, D., Peters, M., Horsley, T., Weeks, L., Hempel, S., Akl, E. A., Chang, C., McGowan, J., Stewart, L., Hartling, L., Aldcroft, A., Wilson, M. G., Garritty, C., Lewin, S., … Straus, S. E. (2018). PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Annals of internal medicine, 169(7), 467–473. https://doi.org/10.7326/M18-0850 Troche, M. S., Okun, M. S., Rosenbek, J. C., Musson, N., Fernandez, H. H., Rodriguez, R., Romrell, J., Pitts, T., Wheeler-Hegland, K. M., &amp; Sapienza, C. M. (2010). Aspiration and swallowing in Parkinson disease and rehabilitation with EMST: a randomized trial. Neurology, 75(21), 1912–1919. https://doi.org/10.1212/WNL.0b013e3181fef115 Vose, A., &amp; Humbert, I. (2019). "Hidden in Plain Sight": A Descriptive Review of Laryngeal Vestibule Closure. Dysphagia, 34(3), 281–289. https://doi.org/10.1007/s00455-018-9928-

Evaluation Tools and Outcome Measures used to assess Dysphagia in adults with Disorders of Consciousness secondary to Acquired Brain Injury: A Scoping Review protocol

1 Title Evaluation Tools and Outcome Measures used to assess dysphagia in adults with Disorders of consciousness secondary to Acquired brain injury: A Scoping Review protocol. Scoping review question: “What tools (validated or non-validated) and what outcome measures are used by speech and language therapists during dysphagia screening and assessment in adults with DoC associated with ABI?” 2 Introduction Disorders of consciousness (DoC) are a wide range of conditions whereby patients don't have the ability to interact with the environment(Young, 2012). To be conscious, arousal and awareness must be present and interact with each other, when one of these systems is disrupted, consciousness is impaired (Gosseries et al., 2011). DoC can result from Acquired Brain Injury (ABI) (Young, 2012): a damage to the brain that occurs after birth, not related to congenital disorders, developmental disabilities, or progressive conditions (Eskildsen et al., 2019). Dysphagia is frequent in this population (Mackay et al., 1999) and some components of swallowing impairments are particularly related to consciousness (Bremare et al., 2016; Mélotte et al., 2021). The existence of cognitive and behavioural disabilities in this population has a significant impact on the evaluation (Terré &amp; Mearin, 2007). Therefore, the importance of having an overview of the formal and informal assessment outcome measures and tools used to evaluate deglutition disorders in this population. A preliminary search for existing scoping reviews and systematic reviews on the topic has been conducted in November 2021 in JBI Evidence Synthesis, Cochrane Database of Systematic Reviews, PubMed and Prospero. The aim of the project is to outline and categorize the existing evidence regarding the informal and formal assessment tools and outcome measures useful for speech and language therapists’ management of dysphagia with specific emphasis both in screening and in clinical swallow evaluation in patients with DoC secondary to ABI. The comprehensive overview of the literature may offer useful support for speech and language therapists (SLT) since it would provide an insight of the availability of the tools and measures to choose from when assessing dysphagia in DoC patients after ABI. Additionally, this scoping review may also lay the foundations for a future systematic review to identify the methodological quality of the psychometric properties of the tools and outcome measures identified, and to select the most appropriate ones to include in a core outcome set. 3 Eligibility criteria Inclusion criteria Population Patients with DoC arising from moderate, severe, or very severe acquired damage of the brain. Papers should include DOC and patients with moderate severe, or very severe ABI . In the scenario where consciousness is not explicitly mentioned, scales to assess cognitive and behavioural patterns in patients emerging from a coma (e.g. Rancho Los Amigos Level of Cognitive Functioning Scale) or a description of the level of consciousness (LoC) of the patients has to be present. If information about the LoC is missing, the full text will be examined. Patients with tracheostomy are included in the study since it is frequently a necessary procedure in the ICU, especially in patients with TBI (Robba et al., 2020). Excluding patients requiring tracheostomy would dismiss severe/very severe ABI patients limiting the number of eligible papers and foremost the population of interest. However, it is recognised that some features of the dysphagia in the patients may be caused by the presence of the tracheostomy(Skoretz et al., 2020). Exclusion criteria Population Patients with mild ABI (Glasgow Coma Scale 13-15, post-traumatic amnesia &lt;1 hour and loss of consciousness &lt;15 minutes) Inclusion Criteria Concept Any instrumental and non-instrumental assessment measure or assessment tool to evaluate dysphagia must be mentioned. Exclusion criteria Concept Holistic scales evaluating neurobehavioral measures that contain dysphagia as a collateral item will not be included in the study. Context There is no restriction on setting (i.e., hospital settings, post-acute care and in the community acute care, primary health care or the community) and language in order to avoid the exclusion of relevant studies, and therefore overcome recruitment bias. Types of evidence sources In accordance with “PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation” (Tricco et al., 2018), no restrictions are imposed on study design or quality. Research designs such as primary research studies, systematic reviews, meta-analyses, guidelines, experimental designs, single case studies and retrospective reviews will be included. 4 Search strategy The research string consists in a branch related to consciousness and brain injuries and a second one related to dysphagia. The consciousness branch has entry terms related to behavioural scales (e.g Rancho Los Amigos Level of Cognitive Functioning Scale) to capture studies that reported assessment scales for DoC, but that did not specify DoC in the title/abstract. The combination of the terms of the branch dealing with consciousness, behavioural scales, and brain injuries should strike a balance between the strategy itself and its potential limitation. To limit the possibility of excluding relevant studies the search of the reference list of relevant articles is carried out. If further information on certain papers is needed the authors will be contacted to request the data. If there will not be an answer, the paper will be excluded. Following the suggestion of the Subject Librarian, the following electronic bibliographic databases are considered: MEDLINE (PubMed); EMBASE (Ovid); CINAHL (EBSCO); Web of Science. Grey literature will be included. The grey literature research was developed following the approach proposed in “Grey Matters: a practical tool for searching health-related grey literature” (Canadian Agency for Drugs and Technologies in Health, 2015) . 5 Source of evidence selection The study selection phase will consist of the elimination of duplicates, screening of title, abstracts, and full text according to the eligibility criteria (Table 4), using Covidence systematic review online software, Veritas Health Innovation, Melbourne, Australia. The criteria will be tested on a sample of 25 abstracts before the review process to ensure that they were sufficiently robust in capturing relevant studies and excluding non-eligible studies. The team will start screening when 75% agreement is achieved. Two reviewers will conduct the process independently (Levac et al., 2010), ruling in or out according to inclusion and exclusion criteria. The third reviewer will handle the disagreements (3rd independent rater). PRISMA guidelines extensions for ScR will be used throughout the progression of the study (Tricco et al., 2018). 6 Data extraction The data extraction sheet contains author/year, publication date, country of origin, demographic data, study design, objective/s of the paper, setting, cause of ABI, type of ABI (moderate or severe), level of consciousness/scale used to assess consciousness, the dysphagia assessment tools/measures used (Levac et al., 2010; Peters et al., 2015). The charting form will be developed by the first author. To improve reliability, the first and second author will then meet to ensure common understanding of the form. The first and second author will collect the data and update the data charting form in an iterative process (Levac et al., 2010). The sheet will be modified to allow essential information to be charted. The data extraction sheet will be blindly and independently piloted on five studies by the first and second author to assess inter-rater reliability. Disagreements will be settled through discussion with the supervisor. 7 Analysis of the evidence The analysis will include quantitative descriptive numerical summaries analysis of data: frequency counts of concepts, populations, characteristics, as well as qualitative descriptive analysis (Aromataris &amp; Munn, 2020) to identify themes from published research. The results will be reported considering the meaning of the findings concerning the overall research purpose (Levac et al., 2010) to outline and categorize the existing evidence regarding the dysphagia assessment used by SLTs with specific emphasis in patients with DoC secondary to ABI. 8 Presentation of the results The results will be presented both in tabular form and in a descriptive format. The tables and charts will include distribution of sources of evidence by year, countries of origin, research methods. The results were classified under main conceptual categories such as: “level of consciousness of the population”, “type of assessment” (screening, bedside swallow evaluation, instrumental), "type of ABI", “presence of tracheostomy”. The analyses and presentation of the results will be independently carried out by the first author. Bibliography Aromataris, E., &amp; Munn, Z. (2020). JBI Manual for Evidence Synthesis. https://synt.hesismanual.jbi.global. https://doi.org/10.46658/JBIMES-20-01 Bremare, A., Rapin, A., Veber, B., Beuret Blanquart, F., &amp; Verin, E. (2016). Swallowing disorders in severe brain injury in the arousal phase [Conference Abstract]. Dysphagia, 31(2), 283. https://doi.org/10.1007/s00455-016-9698-6 Eskildsen, S. J., Jakobsen, D., Riberholt, C. G., Poulsen, I., &amp; Curtis, D. J. (2019). Protocol for a scoping review study to identify and map treatments for dysphagia following moderate to severe acquired brain injury. BMJ Open, 9(7), e029061. https://doi.org/10.1136/bmjopen-2019-029061 Gosseries, O., Vanhaudenhuyse, A., Bruno, M.-A., Demertzi, A., Schnakers, C., Boly, M. M., Maudoux, A., Moonen, G., &amp; Laureys, S. (2011). Disorders of Consciousness: Coma, Vegetative and Minimally Conscious States. In (pp. 29-55). Springer Berlin Heidelberg. https://doi.org/10.1007/978-3-642-18047-7_2 Grey matters: A practical tool for searching health-related grey literature - cadth.ca. CADTH evidence driven (2022, February 9). Retrieved February 9, 2022, from https://www.cadth.ca/grey-matters-practical-tool-searching-health-related-grey-literature-0 Levac, D., Colquhoun, H., &amp; O'Brien, K. K. (2010). Scoping studies: advancing the methodology. Implement Sci, 5, 69. https://doi.org/10.1186/1748-5908-5-69 Mackay, L. E., Morgan, A. S., &amp; Bernstein, B. A. (1999). Swallowing disorders in severe brain injury: Risk factors affecting return to oral intake. Archives of Physical Medicine and Rehabilitation, 80(4), 365-371. https://doi.org/10.1016/s0003-9993(99)90271-x Mélotte, E., Maudoux, A., Delhalle, S., Lagier, A., Thibaut, A., Aubinet, C., Kaux, J.-F., Vanhaudenhuyse, A., Ledoux, D., Laureys, S., &amp; Gosseries, O. (2021). Swallowing in individuals with disorders of consciousness: A cohort study. Annals of Physical and Rehabilitation Medicine, 64(4), 101403. https://doi.org/10.1016/j.rehab.2020.04.008 Peters, M. D., Godfrey, C. M., Khalil, H., McInerney, P., Parker, D., &amp; Soares, C. B. (2015). Guidance for conducting systematic scoping reviews. Int J Evid Based Healthc, 13(3), 141-146. https://doi.org/10.1097/XEB.0000000000000050 Robba, C., Galimberti, S., Graziano, F., Wiegers, E. J. A., Lingsma, H. F., Iaquaniello, C., Stocchetti, N., Menon, D., &amp; Citerio, G. (2020). Tracheostomy practice and timing in traumatic brain-injured patients: a CENTER-TBI study. Intensive Care Medicine, 46(5), 983-994. https://doi.org/10.1007/s00134-020-05935-5 Skoretz, S. A., Anger, N., Wellman, L., Takai, O., &amp; Empey, A. (2020). A Systematic Review of Tracheostomy Modifications and Swallowing in Adults. Dysphagia, 35(6), 935-947. https://doi.org/10.1007/s00455-020-10115-0 Terré, R., &amp; Mearin, F. (2007). Prospective evaluation of oro-pharyngeal dysphagia after severe traumatic brain injury. Brain Injury, 21(13-14), 1411-1417. https://doi.org/10.1080/02699050701785096 Tricco, A. C., Lillie, E., Zarin, W., O'Brien, K. K., Colquhoun, H., Levac, D., Moher, D., Peters, M. D. J., Horsley, T., Weeks, L., Hempel, S., Akl, E. A., Chang, C., McGowan, J., Stewart, L., Hartling, L., Aldcroft, A., Wilson, M. G., Garritty, C., . . . Straus, S. E. (2018). PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med, 169(7), 467-473. https://doi.org/10.7326/M18-0850 Young, G., B. (2012). Disorders of Consciousness (Saunders, Ed. 1st ed., Vol. 29)