115 results on '"Watson NA"'
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2. T5 Respiratory particle and droplet emission during speech and exercise
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Orton, CM, primary, Symons, HE, additional, Moseley, B, additional, Archer, J, additional, Watson, NA, additional, Philip, KEJ, additional, Saccente-Kennedy, B, additional, Costello, DAE, additional, Browne, WJ, additional, Calder, JD, additional, Bzdek, BR, additional, Hull, JH, additional, Reid, JP, additional, and Shah, PL, additional
- Published
- 2021
- Full Text
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3. The aerodynamic effect of an oblique wind on helicopter recovery to the Queen Elizabeth class aircraft carrier
- Author
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Watson, NA, Kelly, MF, Owen, I, and White, MD
- Abstract
Copyright © 2019 by the Vertical Flight Society. All rights reserved. This paper describes an investigation into the air flow over the flight deck of HMS Queen Elizabeth, the UK’s new aircraft carrier, and how it could affect helicopter recovery. The twin islands on the starboard side of the ship mean that there will be turbulent air flow over the flight deck for starboard winds. The unsteady air flow over the ship was created using time-accurate Computational Fluid Dynamics for a 25kts wind coming from 25° off the starboard, i.e. a Green 25 wind over deck. As well as using the CFD results to show the expected mean velocity field and turbulence intensity over the flight deck, the time-varying velocity components have also been used to assess how the unsteady air flow will affect a helicopter by integrating the velocity components of the ship’s airwake with a flight dynamics model of a helicopter configured to represent a SH-60B Seahawk. The application of the helicopter flight dynamics model has been implemented in two different ways: first where the flight model is held stationary in the airwake to evaluate the unsteady aerodynamic loads imposed on the helicopter, and second where the airwake and the flight model are integrated into a piloted full-motion flight simulator to assess pilot workload during a series of deck landings. The results show how the turbulent air flow over the landing spots correlates with the predicted unsteady loads on the helicopter, and with the workload ratings awarded by a test pilot in the simulator.
- Published
- 2019
4. CDK1-mediated phosphorylation at H2B serine 6 is required for mitotic chromosome segregation
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Seibert, M, Kruger, M, Watson, NA, Sen, O, Daum, JR, Slotman, Johan, Braun, T, Houtsmuller, Adriaan, Gorbsky, GJ, Jacob, R, Kracht, M, Higgins, JMG, Schmitz, ML, Seibert, M, Kruger, M, Watson, NA, Sen, O, Daum, JR, Slotman, Johan, Braun, T, Houtsmuller, Adriaan, Gorbsky, GJ, Jacob, R, Kracht, M, Higgins, JMG, and Schmitz, ML
- Published
- 2019
5. Interpolymer complexation between copovidone and carbopol and its effect on drug release from matrix tablets
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Fan Meng, Zhi Yuan Wang, Feng Zhang, and Watson Na
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Pyrrolidines ,Vinyl Compounds ,Hydrochloride ,Diffusion ,Inorganic chemistry ,Acrylic Resins ,Pharmaceutical Science ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Excipients ,Matrix (chemical analysis) ,chemistry.chemical_compound ,Theophylline ,Drug Discovery ,medicine ,Dissolution ,Pharmacology ,chemistry.chemical_classification ,Aqueous solution ,Chemistry ,Organic Chemistry ,Polymer ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,Pyrrolidinones ,0104 chemical sciences ,Drug Liberation ,Kinetics ,Solubility ,Delayed-Action Preparations ,0210 nano-technology ,Glass transition ,Tablets ,medicine.drug ,Nuclear chemistry - Abstract
The interaction between copovidone and Carbopol 907 is pH dependent. When the pH of an aqueous solution fell below pH 4.5, a water-insoluble complex began to form and precipitate. This complex resulted from a hydrogen-bond-induced interaction between the carboxylic groups in Carbopol 907 and the carbonyl groups of N-vinylpyrrolidone repeat units in copovidone. Consisting of these two polymers at an approximate 1:1 weight ratio, the complex was an amorphous material with a glass transition temperature of 157 °C. The interpolymer complexation in situ was applied to modify drug release properties of Carbopol 907-based theophylline matrix tablets. The effect of copovidone on drug release was dependent on the pH of the dissolution medium. In a 0.1 N hydrochloride acid solution at pH 1.2 and 50 mM acetate buffer at pH 4.0, an insoluble tablet matrix was formed as a result of the in situ interpolymer complexation, and theophylline was released therefore via Fickian diffusion. In a 50 mM phosphate buffer at pH 6.8, drug release from the matrix tablets was still impacted by the in situ interpolymer complexation because of the low-pH microenvironment induced by Carbopol 907. As a result, drug release rate of the matrix tablet containing both polymers at pH 6.8 was slower than that of the matrix tablets containing individual polymers. We observed similar drug release rates at both pH 1.2 and pH 6.8 between tablets containing the physical blend of these two polymers and tablets containing preformed interpolymer complexes.
- Published
- 2016
6. Interpolymer Complexation Between Polyox and Carbopol, and Its Effect on Drug Release From Matrix Tablets
- Author
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Watson Na, Joseph W. Lubach, Samad Momin, and Feng Zhang
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Diffusion ,Inorganic chemistry ,Acrylic Resins ,Pharmaceutical Science ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Polyethylene Glycols ,Matrix (chemical analysis) ,chemistry.chemical_compound ,Theophylline ,Drug Interactions ,Dissolution ,Acrylic acid ,chemistry.chemical_classification ,Drug Carriers ,Ethylene oxide ,Viscosity ,Hydrogen Bonding ,Polymer ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Amorphous solid ,Drug Liberation ,chemistry ,Solubility ,Delayed-Action Preparations ,0210 nano-technology ,Glass transition ,Nuclear chemistry ,Tablets - Abstract
Interaction between Polyox N12K and Carbopol 907 was pH dependent. A hydrogen bond–induced complexation began between pH 5.0 and 6.0 in an aqueous medium, and the interpolymer complex started to precipitate when the pH fell to 4.0. This complex was amorphous with a glass transition temperature of 3.17°C. The molar ratio between ethylene oxide and acrylic acid units in the complex was 1.3:1. About 46% of the COOH groups in Carbopol 907 were H bonded to ether oxygen in Polyox. Theophylline release from tablets containing both polymers was a function of dissolution media pH, due to the pH-dependent interactions. In 0.01 N HCl, an insoluble tablet matrix formed in situ . 93% drug was released over 27 h via Fickian diffusion. In acetate buffer pH 4.0, the insoluble tablet matrix formed in situ disintegrated into tiny gel particles. Gel erosion controlled drug release at pH 4.0. These 2 polymers were unable to complex in a phosphate buffer pH 6.8. Therefore, the tablet matrix dissolved, and drug release followed the anomalous transport mechanism at pH 6.8. The release profiles in an acetate buffer pH 4.0 and phosphate buffer pH 6.8 were statistically same, and a sustained release over 12 h was achieved.
- Published
- 2016
7. Regional Analgesia After Total Knee Replacement
- Author
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Ganapathy, S., primary, Watson, &NA; J., additional, Wasserman, &NA; R., additional, Armstrong, DABA K., additional, and Chess, &NA; D. G., additional
- Published
- 2000
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8. Sensory Receptors and Epidermal Structures of a Meiofaunal Turbellarian (Proseriata, Monocelididae, Minoninae)
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Rohde, K, primary and Watson, NA, additional
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- 1995
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9. Sandy beach meiofauna of eastern Australia (southern Queensland and New South Wales). II. Luriculus australiensis, gen. et. sp. nov. (Luridae : Dalyelliida : Platyhelminthes)
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Faubel, A, primary, Rohde, K, additional, and Watson, NA, additional
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- 1994
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10. Ultrastructure of the Epidermis and Protonephridium of an Undescribed Species of Luridae (Platyhelminthes, Rhabdocoela)
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Rohde, K, primary, Watson, NA, additional, and Faubel, A, additional
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- 1993
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11. Ultrastructure of Sensory Receptors of an Undescribed Species of Luridae (Platyhelminthes, Rhabdocoela)
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Rohde, K, primary and Watson, NA, additional
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- 1993
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12. Ultrastructure of the Statocyst in an Undescribed Species of Luridae (Platyhelminthes, Rhabdocoela, Luridae)
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Rohde, K, primary, Watson, NA, additional, and Faubel, A, additional
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- 1993
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13. Ultrastructure of Spermiogenesis and Sperm of an Undescribed Species of Luridae (Platyhelminthes, Rhabdocoela)
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Rohde, K, primary and Watson, NA, additional
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- 1993
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14. Ultrastructure of Spermatogenesis of Syndisyrinx-Punicea (Hickman, 1956) (Platyhelminthes, Rhabdocoela, Umagillidae)
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Li, MM, primary, Watson, NA, additional, and Rohde, K, additional
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- 1992
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15. Ultrastructure of the Protonephridia of Syndisyrinx-Punicea (Hickman, 1956) (Rhabdocoela, Umagillidae) and Pterastericola-Pellucida Jondelius, 1989 (Rhabdocoela, Pterastericolidae)
- Author
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Rohde, K, primary, Watson, NA, additional, and Jondelius, U, additional
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- 1992
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16. Ultrastructure of Sperm and Spermatogenesis of Artioposthia Sp (Platyhelminthes, Tricladida, Terricola)
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Minmin, L, primary, Watson, NA, additional, and Rohde, K, additional
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- 1992
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17. Mentoring today -- the students' views. An investigative case study of pre-registration nursing students' experiences and perceptions of mentoring in one theory/practice module of the Common Foundation Programme on a Project 2000 course.
- Author
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Watson NA
- Abstract
The study reported in this paper investigated the mentoring experiences and perceptions of pre-registration nursing students in one organization, on a theory/practice nursing module. It considered the extent to which students' understanding and expectations matched their actual experiences. Interviews were conducted with 35 students on a Common Foundation Programme, and 15 allocated mentors, using a semi-structured interview guide. These were done within the clinical setting of the wards on which the students were placed as part of their requirements for completion of the module. A distortion of the actual meaning of mentoring appears to be present because of the lack of clarity provided, both internally by organizations and by the English National Board (ENB) who have provided loose guidelines. The implications of this distortion are discussed. The application of a mentoring role in practice needs to be re-examined, with the provision of a clear structured guide internally and externally, with regard to the needs of students and staff who are expected to act as mentors. The study was small scale and cannot be generalized. Mentoring, however, is now widely used within pre-registration nursing education, even though it is generally considered that its use may not be appropriate. Follow-up studies need to be undertaken on an ongoing basis, to examine what actually happens in practice, and to consider ways of ensuring that the benefits for staff and students are enhanced. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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18. Sandy beach meiofauna of eastern Australia (southern Queensland and New South Wales). II. Luriculus australiensis, gen. et. sp. nov. (Luridae : Dalyelliida : Platyhelminthes)
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Faubel, A, Rohde, K, and Watson, NA
- Abstract
Luriculus australiensis, gen. et sp, nov., from a sandy, exposed ocean beach at Arrawarra Headland, north of Coffs Harbour, NSW, Australia, is described on the basis of light and electron microscopic investigations. The establishment of the new genus Luriculus is based on the presence of germovitellaria, rather than discrete organs. Lurus castor Sterrer & Rieger, 1990, Lurus tyndareus Sterrer & Rieger, 1990, and Lurus minos Sterrer, 1992, are transferred to this genus.
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- 1994
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19. Ultrastructure of Epidermis and Sperm of the Turbellarian Syndisyrinx-Punicea (Hickman, 1956) (Rhabdocoela, Umagillidae)
- Author
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Rohde, K and Watson, NA
- Abstract
Syndisyrinx punicea has an epidermis with intraepidermal nuclei, a thick basal lamina, and microvilli containing an array of densely packed filaments and, in the widened tips, an electron-dense cap. The epidermal cilia posess a widened cytoplasmic portion close to the base and vertical and horizontal cross-striated rootlets; the latter are anchored in the adjacent matrix by means of transverse bars. Basal bodies have a distinct spike opposite the horizontal rootlet. In the tips of epidermal cilia, one of the microtubules disappears first in doublets 7-9 and 1, and gradually all peripheral doublets disappear; there is no electron-dense rod along the central microtubules, but cilia have a terminal electron-dense cap. Spermatozoa have two flagella, much shorter than the sperm (and not incorporated in it); axonemes are of the 9+'1' type; an elongate nucleus, numerous small mitochondria and electron-dense bodies are surrounded by a single peripheral row of microtubules in the thicker parts of the sperm, in the thinner parts (apparently close to the ends) microtubules are also found in the interior; some electron- dense bodies were also seen free between sperm, indicating their secretory function. Ultrastructural evidence does not support the view that Umagillidae (as well as Temnocephalida) are particularly closely related to the Neodermata, the major parasitic groups of Platyhelminthes.
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- 1988
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20. Medicinal herb use among asthmatic patients attending a specialty care facility in Trinidad
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Mohammed Rochelle, Watson Nadya, Chase Ronald, Aranda Derick, Williams Arlene F, Clement Yuri N, Stubbs Odia, and Williamson Deneil
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Other systems of medicine ,RZ201-999 - Abstract
Abstract Background There is an increasing prevalence of asthma in the Caribbean and patients remain non-compliant to therapy despite the development of guidelines for management and prevention. Some patients may self-medicate with medicinal herbs for symptomatic relief, as there is a long tradition of use for a variety of ailments. The study assessed the prevalence of use and the factors affecting the decision to use herbs in asthmatic patients attending a public specialty care clinic in Trinidad. Methods A descriptive, cross-sectional study was conducted at the Chest Clinic in Trinidad using a de novo, pilot-tested, researcher-administered questionnaire between June and July 2003. Results Fifty-eight out of 191 patients (30.4%) reported using herbal remedies for symptomatic relief. Gender, age, ethnicity, and asthma severity did not influence the decision to use herbs; however, 62.5% of patients with tertiary level schooling used herbs, p = 0.025. Thirty-four of these 58 patients (58.6%) obtained herbs from their backyards or the supermarket; only 14 patients (24.1%) obtained herbs from an herbalist, herbal shop or pharmacy. Relatives and friends were the sole source of information for most patients (70.7%), and only 10.3% consulted an herbalist. Ginger, garlic, aloes, shandileer, wild onion, pepper and black sage were the most commonly used herbs. Conclusions Among patients attending the Chest Clinic in Trinidad the use of herbal remedies in asthma is relatively common on the advice of relatives and friends. It is therefore becoming imperative for healthcare providers to become more knowledgeable on this modality and to keep abreast with the latest developments.
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- 2005
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21. Emergency casebooks. Diagnosis of femoral shaft fracture in pregnancy by ultrasound.
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Watson NA and Ferrier GM
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- 1999
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22. Relationship between Exhaled Aerosol and Carbon Dioxide Emission Across Respiratory Activities.
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Moseley B, Archer J, Orton CM, Symons HE, Watson NA, Saccente-Kennedy B, Philip KEJ, Hull JH, Costello D, Calder JD, Shah PL, Bzdek BR, and Reid JP
- Abstract
Respiratory particles produced during vocalized and nonvocalized activities such as breathing, speaking, and singing serve as a major route for respiratory pathogen transmission. This work reports concomitant measurements of exhaled carbon dioxide volume (VCO
2 ) and minute ventilation (VE), along with exhaled respiratory particles during breathing, exercising, speaking, and singing. Exhaled CO2 and VE measured across healthy adult participants follow a similar trend to particle number concentration during the nonvocalized exercise activities (breathing at rest, vigorous exercise, and very vigorous exercise). Exhaled CO2 is strongly correlated with mean particle number ( r = 0.81) and mass ( r = 0.84) emission rates for the nonvocalized exercise activities. However, exhaled CO2 is poorly correlated with mean particle number ( r = 0.34) and mass ( r = 0.12) emission rates during activities requiring vocalization. These results demonstrate that in most real-world environments vocalization loudness is the main factor controlling respiratory particle emission and exhaled CO2 is a poor surrogate measure for estimating particle emission during vocalization. Although measurements of indoor CO2 concentrations provide valuable information about room ventilation, such measurements are poor indicators of respiratory particle concentrations and may significantly underestimate respiratory particle concentrations and disease transmission risk.- Published
- 2024
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23. Combined rituximab and belimumab to treat recalcitrant epidermolysis bullosa aquisita associated with systemic lupus erythematosus.
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Tull TJ, Benton EC, Semkova K, Watson NA, Mee JB, Lopez B, Setterfield J, Carey B, Ahmad S, Robbie SJ, Groves RW, Sanna G, and D'Cruz DP
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- Humans, Female, Treatment Outcome, Epidermolysis Bullosa drug therapy, Epidermolysis Bullosa complications, Immunosuppressive Agents therapeutic use, Immunosuppressive Agents administration & dosage, Adult, Rituximab administration & dosage, Rituximab therapeutic use, Lupus Erythematosus, Systemic drug therapy, Lupus Erythematosus, Systemic complications, Antibodies, Monoclonal, Humanized therapeutic use, Drug Therapy, Combination methods
- Abstract
Competing Interests: Conflicts of interest The authors declare no conflicts of interest.
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- 2024
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24. In Silico Study of the Early Stages of Aggregation of β-Sheet Forming Antimicrobial Peptide GL13K.
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Hamidabad MN, Watson NA, Wright LN, and Mansbach RA
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- Amino Acid Sequence, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents chemical synthesis, Antimicrobial Cationic Peptides chemistry, Antimicrobial Cationic Peptides pharmacology, Molecular Dynamics Simulation, Protein Aggregates drug effects, Protein Conformation, beta-Strand, Thermodynamics, Antimicrobial Peptides chemistry, Antimicrobial Peptides pharmacology, Antimicrobial Peptides chemical synthesis
- Abstract
Antimicrobial peptides (AMPs) are of growing interest as potential candidates that may offer more resilience against antimicrobial resistance than traditional antibiotic agents. In this article, we perform the first in silico study of the synthetic ß sheet-forming AMP GL13K. Through atomistic simulations of single and multi-peptide systems under different conditions, we are able to shine a light on the short timescales of early aggregation. We find that isolated peptide conformations are primarily dictated by sequence rather than charge, whereas changing charge has a significant impact on the conformational free energy landscape of multi-peptide systems. We demonstrate that the loss of charge-charge repulsion is a sufficient minimal model for experimentally observed aggregation. Overall, our work explores the molecular biophysical underpinnings of the first stages of aggregation of a unique AMP, laying necessary groundwork for its further development as an antibiotic candidate., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)
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- 2024
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25. Mitigation of Respirable Aerosol Particles from Speech and Language Therapy Exercises.
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Saccente-Kennedy B, Szczepanska A, Harrison J, Archer J, Watson NA, Orton CM, Costello D, Calder JD, Shah PL, Reid JP, Bzdek BR, and Epstein R
- Abstract
Introduction: Phonation and speech are known sources of respirable aerosol in humans. Voice assessment and treatment manipulate all the subsystems of voice production, and previous work (Saccente-Kennedy et al., 2022) has demonstrated such activities can generate >10 times more aerosol than conversational speech and 30 times more aerosol than breathing. Aspects of voice therapy may therefore be considered aerosol generating procedures and pose a greater risk of potential airborne pathogen (eg, SARS-CoV-2) transmission than typical speech. Effective mitigation measures may be required to ensure safe service delivery for therapist and patient., Objective: To assess the effectiveness of mitigation measures in reducing detectable respirable aerosol produced by voice assessment/therapy., Methods: We recruited 15 healthy participants (8 cis-males, 7 cis-females), 9 of whom were voice-specialist speech-language pathologists. Optical Particle Sizers (OPS) (Model 3330, TSI) were used to measure the number concentration of respirable aerosol particles (0.3 µm-10 µm) generated during a selection of voice assessment/therapy tasks, both with and without mitigation measures in place. Measurements were performed in a laminar flow operating theatre, with near-zero background aerosol concentration, allowing us to quantify the number concentration of respiratory aerosol particles produced. Mitigation measures included the wearing of Type IIR fluid resistant surgical masks, wrapping the same masks around the end of straws, and the use of heat and moisture exchange microbiological filters (HMEFs) for a water resistance therapy (WRT) task., Results: All unmitigated therapy tasks produced more aerosol than unmasked breathing or speaking. Mitigation strategies reduced detectable aerosol from all tasks to a level significantly below, or no different to, that of unmasked breathing. Pooled filtration efficiencies determined that Type IIR surgical masks reduced detectable aerosol by 90%. Surgical masks wrapped around straws reduced detectable aerosol by 96%. HMEF filters were 100% effective in mitigating the aerosol from WRT, the exercise that generated more aerosol than any other task in the unmitigated condition., Conclusions: Voice therapy and assessment causes the release of significant quantities of respirable aerosol. However, simple mitigation strategies can reduce emitted aerosol concentrations to levels comparable to unmasked breathing., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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26. Inferring Pathways of Oxidative Folding from Prefolding Free Energy Landscapes of Disulfide-Rich Toxins.
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Mansbach RA, Patel LA, Watson NA, Kubicek-Sutherland JZ, and Gnanakaran S
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- Amino Acid Sequence, Cysteine chemistry, Hirudins metabolism, Peptides chemistry, Oxidative Stress, Protein Folding, Disulfides chemistry, Conotoxins chemistry
- Abstract
Short, cysteine-rich peptides can exist in stable or metastable structural ensembles due to the number of possible patterns of formation of their disulfide bonds. One interesting subset of this peptide group is the conotoxins, which are produced by aquatic snails in the family Conidae . The μ conotoxins, which are antagonists and blockers of the voltage-gated sodium channel, exist in a folding spectrum: on one end of the spectrum are more hirudin-like folders, which form disulfide bonds and then reshuffle them, leading to an ensemble of kinetically trapped isomers, and on the other end are more BPTI-like folders, which form the native disulfide bonds one by one in a particular order, leading to a preponderance of conformations existing in a single stable state. In this Article, we employ the composite diffusion map approach to study the unified free energy surface of prefolding μ-conotoxin equilibrium. We identify the two most important nonlinear collective modes of the unified folding landscape and demonstrate that in the absence of their disulfides, the conotoxins can be thought of as largely disordered polymers. A small increase in the number of hydrophobic residues in the protein shifts the free energy landscape toward hydrophobically collapsed coil conformations responsible for cysteine proximity in hirudin-like folders, compared to semiextended coil conformations with more distal cysteines in BPTI-like folders. Overall, this work sheds important light on the folding processes and free energy landscapes of cysteine-rich peptides and demonstrates the extent to which sequence and length contribute to these landscapes.
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- 2023
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27. Quantification of Respirable Aerosol Particles from Speech and Language Therapy Exercises.
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Saccente-Kennedy B, Archer J, Symons HE, Watson NA, Orton CM, Browne WJ, Harrison J, Calder JD, Shah PL, Costello D, Reid JP, Bzdek BR, and Epstein R
- Abstract
Introduction: Voice assessment and treatment involve the manipulation of all the subsystems of voice production, and may lead to production of respirable aerosol particles that pose a greater risk of potential viral transmission via inhalation of respirable pathogens (eg, SARS-CoV-2) than quiet breathing or conversational speech., Objective: To characterise the production of respirable aerosol particles during a selection of voice assessment therapy tasks., Methods: We recruited 23 healthy adult participants (12 males, 11 females), 11 of whom were speech-language pathologists specialising in voice disorders. We used an aerodynamic and an optical particle sizer to measure the number concentration and particle size distributions of respirable aerosols generated during a variety of voice assessment and therapy tasks. The measurements were carried out in a laminar flow operating theatre, with a near-zero background aerosol concentration, allowing us to quantify the number concentration and size distributions of respirable aerosol particles produced from assessment/therapy tasks studied., Results: Aerosol number concentrations generated while performing assessment/therapy tasks were log-normally distributed among individuals with no significant differences between professionals (speech-language pathologists) and non-professionals or between males and females. Activities produced up to 32 times the aerosol number concentration of breathing and 24 times that of speech at 70-80 dBA. In terms of aerosol mass, activities produced up to 163 times the mass concentration of breathing and up to 36 times the mass concentration of speech. Voicing was a significant factor in aerosol production; aerosol number/mass concentrations generated during the voiced activities were 1.1-5 times higher than their unvoiced counterpart activities. Additionally, voiced activities produced bigger respirable aerosol particles than their unvoiced variants except the trills. Humming generated higher aerosol concentrations than sustained /a/, fricatives, speaking (70-80 dBA), and breathing. Oscillatory semi-occluded vocal tract exercises (SOVTEs) generated higher aerosol number/mass concentrations than the activities without oscillation. Water resistance therapy (WRT) generated the most aerosol of all activities, ∼10 times higher than speaking at 70-80 dBA and >30 times higher than breathing., Conclusions: All activities generated more aerosol than breathing, although a sizeable minority were no different to speaking. Larger number concentrations and larger particle sizes appear to be generated by activities with higher suspected airflows, with the greatest involving intraoral pressure oscillation and/or an oscillating oral articulation (WRT or trilling)., Competing Interests: Competing interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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28. Biomechanical assessment of the effect of sublaminar band tensioning on lumbar motion.
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Park BJ, Gold CJ, Christianson D, DeVries Watson NA, Nourski KV, Woodroffe RW, and Hitchon PW
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- Humans, Biomechanical Phenomena, Cadaver, Lumbar Vertebrae surgery, Lumbar Vertebrae physiology, Range of Motion, Articular physiology, Rotation, Spinal Fusion
- Abstract
Objective: Adjacent-segment disease (ASD) proximal to lumbosacral fusion is assumed to result from increased stress and motion that extends above or below the fusion construct. Sublaminar bands (SBs) have been shown to potentially mitigate stresses in deformity constructs. A similar application of SBs in lumbar fusions is not well described yet may potentially mitigate against ASD., Methods: Eight fresh-frozen human cadaveric spine specimens were instrumented with transforaminal lumbar interbody fusion (TLIF) cages at L3-4 and L4-5, and pedicle screws from L3 to S1. Bilateral SBs were applied at L2 and tightened around the rods extending above the L3 pedicle screws. After being mounted on a testing frame, the spines were loaded at L1 to 6 Nm in all 3 planes, i.e., flexion/extension, right and left lateral bending, and right and left axial rotation. Motion and intradiscal pressures (IDPs) at L2-3 were measured for 5 conditions: intact, instrumentation (L3-S1), band tension (BT) 30%, BT 50%, and BT 100%., Results: There was significant increase in motion at L2-3 with L3-S1 instrumentation compared with the intact spine in flexion/extension (median 8.78°, range 4.07°-10.81°, vs median 7.27°, range 1.63°-9.66°; p = 0.016). When compared with instrumentation, BT 100% reduced motion at L2-3 in flexion/extension (median 8.78°, range 4.07°-10.81°, vs median 3.61°, range 1.11°-9.39°; p < 0.001) and lateral bending (median 6.58°, range 3.67°-8.59°, vs median 5.62°, range 3.28°-6.74°; p = 0.001). BT 50% reduced motion at L2-3 only in flexion/extension when compared with instrumentation (median 8.78°, range 4.07°-10.81°, vs median 5.91°, range 2.54°-10.59°; p = 0.027). There was no significant increase of motion at L1-2 with banding when compared with instrumentation, although an increase was seen from the intact spine with BT 100% in flexion/extension (median 5.14°, range 2.47°-9.73°, vs median 7.34°, range 4.22°-9.89°; p = 0.005). BT 100% significantly reduced IDP at L2-3 from 25.07 psi (range 2.41-48.08 psi) before tensioning to 19.46 psi (range -2.35 to 29.55 psi) after tensioning (p = 0.016)., Conclusions: In this model, the addition of L2 SBs reduced motion and IDP at L2-3 after the L3-S1 instrumentation. There was no significant increase in motion at L1-2 in response to band tensioning compared with instrumentation alone. The application of SBs may have a clinical application in reducing the incidence of ASD.
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- 2022
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29. Providing evidence from practice: Evaluating 4.5 years of implementing diabetes education support program in carbohydrate management.
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Mergelsberg ELP, Olson JL, Moore S, Jensen JF, Seivwright H, Norman R, and Watson NA
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- Australia, Carbohydrates, Health Education, Humans, Diabetes Mellitus therapy, Self-Management
- Abstract
Objective: To evaluate personal and economical outcomes of CarbSmart, a 3-hour person-centered, theory-based program implemented throughout Australia, targeting optimal dietary carbohydrate management., Methods: More than 500 CarbSmart programs were implemented over 4.5 years. Pre-, post-, (N = 4656) and 3-month follow-up assessments (N = 188) of knowledge, empowerment, confidence, and patient activation were collected from people with diabetes. Participant satisfaction and potential annual cost-savings were calculated., Findings: Repeated measures ANCOVAs showed large improvements pre- to post-program in all outcome variables (d = 0.80-1.68), which were maintained at 3-month follow-up in a sub-sample. Participant satisfaction was high (Net Promoter Score = 72.3). Potential annual cost-savings nation-wide were estimated at US$512million., Conclusion: This paper provides evidence that CarbSmart is effective in improving behavioral indicators of self-management outcomes in Australians living with diabetes., Practice Implications: CarbSmart has the potential to prevent diabetes-related complications. However, not engaging people living with diabetes with lower levels of patient activation at baseline was recognized as a future opportunity to improve the impact of our service. Strategies are needed to engage people with lower activation levels to improve outcomes in vulnerable and at-risk populations., Funding: The development of CarbSmart was funded by Diabetes WA, the national implementation of CarbSmart by the National Diabetes Services Scheme, an initiative of the Australian Government., (Copyright © 2022. Published by Elsevier B.V.)
- Published
- 2022
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30. Dissecting the roles of Haspin and VRK1 in histone H3 phosphorylation during mitosis.
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Cartwright TN, Harris RJ, Meyer SK, Mon AM, Watson NA, Tan C, Marcelot A, Wang F, Zinn-Justin S, Traktman P, and Higgins JMG
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- Intracellular Signaling Peptides and Proteins, Phosphorylation, Protein Serine-Threonine Kinases, Threonine metabolism, Histones metabolism, Mitosis
- Abstract
Protein kinases that phosphorylate histones are ideally-placed to influence the behavior of chromosomes during cell division. Indeed, a number of conserved histone phosphorylation events occur prominently during mitosis and meiosis in most eukaryotes, including on histone H3 at threonine-3 (H3T3ph). At least two kinases, Haspin and VRK1 (NHK-1/ballchen in Drosophila), have been proposed to carry out this modification. Phosphorylation of H3 by Haspin has defined roles in mitosis, but the significance of VRK1 activity towards histones in dividing cells has been unclear. Here, using in vitro kinase assays, KiPIK screening, RNA interference, and CRISPR/Cas9 approaches, we were unable to substantiate a direct role for VRK1, or its paralogue VRK2, in the phosphorylation of threonine-3 or serine-10 of Histone H3 in mitosis, although loss of VRK1 did slow cell proliferation. We conclude that the role of VRKs, and their more recently identified association with neuromuscular disease and importance in cancers of the nervous system, are unlikely to involve mitotic histone kinase activity. In contrast, Haspin is required to generate H3T3ph during mitosis., (© 2022. The Author(s).)
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- 2022
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31. A comparison of respiratory particle emission rates at rest and while speaking or exercising.
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Orton CM, Symons HE, Moseley B, Archer J, Watson NA, Philip KEJ, Sheikh S, Saccente-Kennedy B, Costello D, Browne WJ, Calder JD, Bzdek BR, Hull JH, Reid JP, and Shah PL
- Abstract
Background: The coronavirus disease-19 (COVID-19) pandemic led to the prohibition of group-based exercise and the cancellation of sporting events. Evaluation of respiratory aerosol emissions is necessary to quantify exercise-related transmission risk and inform mitigation strategies., Methods: Aerosol mass emission rates are calculated from concurrent aerosol and ventilation data, enabling absolute comparison. An aerodynamic particle sizer (0.54-20 μm diameter) samples exhalate from within a cardiopulmonary exercise testing mask, at rest, while speaking and during cycle ergometer-based exercise. Exercise challenge testing is performed to replicate typical gym-based exercise and very vigorous exercise, as determined by a preceding maximally exhaustive exercise test., Results: We present data from 25 healthy participants (13 males, 12 females; 36.4 years). The size of aerosol particles generated at rest and during exercise is similar (unimodal ~0.57-0.71 µm), whereas vocalization also generated aerosol particles of larger size (i.e. was bimodal ~0.69 and ~1.74 µm). The aerosol mass emission rate during speaking (0.092 ng s
-1 ; minute ventilation (VE) 15.1 L min-1 ) and vigorous exercise (0.207 ng s-1 , p = 0.726; VE 62.6 L min-1 ) is similar, but lower than during very vigorous exercise (0.682 ng s-1 , p < 0.001; VE 113.6 L min-1 )., Conclusions: Vocalisation drives greater aerosol mass emission rates, compared to breathing at rest. Aerosol mass emission rates in exercise rise with intensity. Aerosol mass emission rates during vigorous exercise are no different from speaking at a conversational level. Mitigation strategies for airborne pathogens for non-exercise-based social interactions incorporating vocalisation, may be suitable for the majority of exercise settings. However, the use of facemasks when exercising may be less effective, given the smaller size of particles produced., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)- Published
- 2022
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32. Fifteen-minute consultation: Guide to paediatric voice disorders.
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Watson NA, Orton KA, and Hall A
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- Adult, Child, Humans, Referral and Consultation, Deglutition Disorders diagnosis, Dysphonia diagnosis, Dysphonia etiology, Larynx
- Abstract
Paediatric voice disorders in the normal paediatric population ranges from 6% to 20%. We outline the important features in the initial evaluation of a persistent altered cry or voice in children and highlight the subsequent management currently used by ear, nose and throat (ENT) surgeons and speech and language therapists (SLTs). It is important to appreciate that there are stark differences between a child and adult larynx due to anatomical and physiological changes during development. The voice history elicited from both child and parent includes birth and developmental history, hearing, early feeding and respiratory function. Red flag symptoms or signs presenting with dysphonia include stridor, dysphagia, failure to thrive and recurrent chest infections. The most likely cause for dysphonia in children presenting to general paediatric practice and primary care will be secondary to laryngitis, hyperfunction and vocal cord nodules, and laryngopharyngeal reflux. Regarding treatment, in most cases a non-surgical option is preferred with voice therapy preferably delivered by a specialist paediatric voice SLT. The maximum effectiveness of behavioural or direct therapy is to children over 7 years, for in excess of 8 weeks with additional rigorous home rehearsal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
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33. Comparing aerosol number and mass exhalation rates from children and adults during breathing, speaking and singing.
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Archer J, McCarthy LP, Symons HE, Watson NA, Orton CM, Browne WJ, Harrison J, Moseley B, Philip KEJ, Calder JD, Shah PL, Bzdek BR, Costello D, and Reid JP
- Abstract
Aerosol particles of respirable size are exhaled when individuals breathe, speak and sing and can transmit respiratory pathogens between infected and susceptible individuals. The COVID-19 pandemic has brought into focus the need to improve the quantification of the particle number and mass exhalation rates as one route to provide estimates of viral shedding and the potential risk of transmission of viruses. Most previous studies have reported the number and mass concentrations of aerosol particles in an exhaled plume. We provide a robust assessment of the absolute particle number and mass exhalation rates from measurements of minute ventilation using a non-invasive Vyntus Hans Rudolf mask kit with straps housing a rotating vane spirometer along with measurements of the exhaled particle number concentrations and size distributions. Specifically, we report comparisons of the number and mass exhalation rates for children (12-14 years old) and adults (19-72 years old) when breathing, speaking and singing, which indicate that child and adult cohorts generate similar amounts of aerosol when performing the same activity. Mass exhalation rates are typically 0.002-0.02 ng s
-1 from breathing, 0.07-0.2 ng s-1 from speaking (at 70-80 dBA) and 0.1-0.7 ng s-1 from singing (at 70-80 dBA). The aerosol exhalation rate increases with increasing sound volume for both children and adults when both speaking and singing., (© 2022 The Authors.)- Published
- 2022
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34. Effects of coronavirus disease-2019 on voice: our experience of laryngeal complications following mechanical ventilation in severe coronavirus disease-2019 pneumonitis and review of current literature.
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Watson NA, Karagama Y, Burnay V, Boztepe S, Warner S, and Chevretton EB
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- Humans, Respiration, Artificial adverse effects, SARS-CoV-2, Treatment Outcome, COVID-19, Dysphonia etiology, Dysphonia therapy, Larynx
- Abstract
Purpose of Review: Dysphonia has been described as a major symptom of coronavirus disease-2019 (COVID-19). A literature review examining this topic was undertaken and is presented here, combined with insights from our experience in managing patients with laryngeal complications following mechanical ventilation for severe COVID-19 pneumonitis., Recent Findings: Naunheim et al. reported that patients who are most at risk of needing intubation with COVID-19 disease are those with patient-specific risk factors and these are at an increased risk for subsequent laryngotracheal injury following intubation (1). In our cohort of 105 patients referred with laryngological symptoms postintubation for COVID-19 pneumonitis, 40% presented as urgent reviews, of which almost half had severe postintubation complications requiring surgery. Perceptual voice ratings and patient-reported voice ratings varied widely, but there was no significant change in voice scores postoperatively. The reflux symptom index (RSI) scores did improve significantly (p = 0.0266). The need for surgery was associated with the presence of comorbidities for instance hypertension, diabetes and obesity in our cohort. This is in support of reported association of comorbidity as a risk factor for intubation and subsequent development of postintubation airway complications., Summary: Dysphonia following COVID-19 infection may have multiple causes. Literature reports demonstrate intubation injury, sensory neuropathy, and postviral neuropathy are associated with voice changes. Our personal experience has confirmed postintubation injury markedly affects glottic function with resultant dysphonia attributable to scar formation, posterior glottic stenosis, granulation and subglottic stenosis. Frequent surgical intervention is required for airway patency and may have short-term further deleterious effects on phonation, although in our cohort this is not statistically significant analysing Grade, Roughness, Breathiness, Asthenia, Strain, Voice Handicap Index-10 or Airway, Voice, Swallow scores. Maximal antireflux medications and advice statistically improved RSI scores postoperatively., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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35. Non-aesthetic uses of botulinum toxin in the head and neck.
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Watson NA, Siddiqui Z, Miller BJ, Karagama Y, and Gibbins N
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- Head, Humans, Neck, Botulinum Toxins, Type A, Pharyngeal Diseases, Sweating, Gustatory
- Abstract
Introduction: The use of botulinum toxin in the specialty of aesthetic surgery in the head and neck is well known. However, it has also been used for other conditions affecting the head and neck, and in recent years its use, as well as the number of relevant applications, has expanded enormously., Review: This article presents a summary of the current range of uses in the laryngeal, pharyngeal, cervical, oromandibular and facial muscles and salivary glands. We highlight particular conditions focusing on dystonia (laryngeal, craniocervical, oromandibular and cervical), multiple system atrophy, migraines, facial nerve palsy, post-laryngectomy, cricopharyngeal dysphagia, Zenker's diverticulum, retrograde cricopharyngeal dysfunction disorder, sialorrhea and gustatory sweating (Frey's syndrome)., Conclusion: This article should aid the ear, nose and throat surgeon garner knowledge about the range of uses for botulinum toxin in the head and neck., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2021
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36. Breathing dystonia in Meige syndrome.
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Watson NA, Hicklin LA, and Marion MH
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Background: Dyspnoea is rarely mentioned in the clinical description of adult-onset isolated dystonia. In this study, we present the clinical features of 13 patients with Meige syndrome (cranio-cervical dystonia) with breathing difficulties., Methods: A retrospective case note review was performed of patients presenting with Meige syndrome and shortness of breath, to a neuro-laryngology MDT clinic., Results: Some patients were severely limited by their breathlessness, but others did not volunteer these symptoms. The majority of patients were referred with the assumption that the larynx was the cause of the problem; however half the patients did not have evidence of laryngeal involvement. Of the patients who had laryngeal involvement, injecting the larynx alone did not always relieve the dyspnoea. The majority of our patients responded to injection of the suprahyoid muscles, including genioglossus, digastric and mylohyoid., Conclusion: We recommend routinely establishing if the patient with Meige syndrome has signs or symptoms of breathlessness, and establishing the level of the problem, as this can be treated successfully., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)
- Published
- 2021
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37. Ovine Hemisection Model of Spinal Cord Injury.
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Wilson S, Fredericks DC, Safayi S, DeVries-Watson NA, Holland MT, Nagel SJ, Gillies GT, and Howard MA 3rd
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- Animals, Disease Models, Animal, Gait, Sheep, Spinal Cord, Spinal Cord Injuries
- Abstract
Introduction: We are developing ovine models of spinal cord injury to test novel neuromodulation-based methods on spasticity. The hemisection has been reported in a number of large animal studies. Our aim is to duplicate a hemisection injury in the sheep. Our effort is explored here. Methods and Results : Three sheep underwent hemi-sectioning of the spinal cord. Quantitative gait analysis was completed both pre- and post-injury. While measurable differences in most of the 20 gait metrics were observed, relatively few were above the predicted thresholds based on error levels expected from the data. Variations in severity of injury across the three sheep were observed. Conclusions : The hemisection ovine model of spinal cord injury shows promise as a large-animal platform for developing new therapies for treating spinal cord injuries. While variability in injury severity was observed across animals, as has been observed with weight drop-based SCI models, the hemi-section approach has the advantages of procedural ease and reduced technical complexity.
- Published
- 2021
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38. Ultrasound Study to Validate the Anterior Cervical Approach to the Longus Colli Muscle Using Electromyography Control Alone.
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Hicklin LA, Kocer S, Watson NA, and Marion MH
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- Adult, Electromyography, Humans, Injections, Intramuscular adverse effects, Neck Muscles diagnostic imaging, Torticollis diagnostic imaging, Ultrasonography, Injections, Intramuscular methods, Neck Muscles drug effects, Neuromuscular Agents administration & dosage, Torticollis drug therapy
- Abstract
Background: One of the main difficulties in the treatment of dystonic anterocollis is the injection of the deep flexor muscles of the neck such as Longus Colli (LCo). The injection of the LCo has been regarded as difficult and potentially dangerous; since we published our anterior median approach, a number of questions about the precision and the safety of our technique have been raised by colleagues., Methods: 7 patients with anterocollis were injected, using our injection technique and when the needle was deemed to be in place, we used the ultrasound probe to determine what the needle had passed through, the depth of the tip of the needle and if the identified muscle was indeed LCo., Results: On the ultrasound section the LCo muscle is between 24 and 28 mm deep in the patients examined in this study. The location of the needle was confirmed by ultrasound and in most cases the needle was placed in the right axis but sometimes not deep enough. The EMG control made it possible to correct the depth in all cases. In most of the injections the needle traversed the thyroid. No acute incident occurred by this route of injection. Injections were performed between 22 and 28 mm deep., Discussion: From this study and based on a review of complications over 9 years experience with injecting LCo under EMG control using an anterior approach, we conclude that this technique is precise, safe and well tolerated., Summary Highlights: The injection of the Longus Coli muscle for anterocollis has been regarded as difficult and potentially dangerous. This study showed, using ultrasound to determine the needle trajectory, that the anterior approach using EMG control is a precise, safe and well tolerated technique., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)
- Published
- 2020
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39. Kinase inhibition profiles as a tool to identify kinases for specific phosphorylation sites.
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Watson NA, Cartwright TN, Lawless C, Cámara-Donoso M, Sen O, Sako K, Hirota T, Kimura H, and Higgins JMG
- Subjects
- Chromosomal Proteins, Non-Histone metabolism, DNA-Binding Proteins metabolism, Enzyme Assays, HeLa Cells, Humans, Mitosis, Phosphorylation drug effects, Recombinant Proteins metabolism, Transcription Factors metabolism, Genetic Testing methods, High-Throughput Screening Assays methods, Protein Kinase Inhibitors pharmacology, Protein Kinases metabolism
- Abstract
There are thousands of known cellular phosphorylation sites, but the paucity of ways to identify kinases for particular phosphorylation events remains a major roadblock for understanding kinase signaling. To address this, we here develop a generally applicable method that exploits the large number of kinase inhibitors that have been profiled on near-kinome-wide panels of protein kinases. The inhibition profile for each kinase provides a fingerprint that allows identification of unknown kinases acting on target phosphosites in cell extracts. We validate the method on diverse known kinase-phosphosite pairs, including histone kinases, EGFR autophosphorylation, and Integrin β1 phosphorylation by Src-family kinases. We also use our approach to identify the previously unknown kinases responsible for phosphorylation of INCENP at a site within a commonly phosphorylated motif in mitosis (a non-canonical target of Cyclin B-Cdk1), and of BCL9L at S915 (PKA). We show that the method has clear advantages over in silico and genetic screening.
- Published
- 2020
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40. The Hemisection Approach in Large Animal Models of Spinal Cord Injury: Overview of Methods and Applications.
- Author
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Wilson S, Nagel SJ, Frizon LA, Fredericks DC, DeVries-Watson NA, Gillies GT, and Howard MA 3rd
- Subjects
- Animals, Body Size, Cats, Cattle, Dogs, Humans, Macaca, Rabbits, Sheep, Spinal Cord physiopathology, Spinal Cord Injuries physiopathology, Swine, Disease Models, Animal, Dissection methods, Spinal Cord surgery, Spinal Cord Injuries etiology
- Abstract
Introduction : Translating basic science research into a safe and effective therapy for spinal cord injury (SCI) requires suitable large animal models for testing both implantable devices and biologic approaches to better approximate human anatomy and function. Hemisection lesions, routinely used for investigational purposes in small animals, are less frequently described in large animals that might be appropriate for translational studies. Size constraints of small animals (mice and rats) limits the predictability of the findings when scaled up. Our goal is to review the status of hemisection SCI in large animals across species and time to prepare for the testing of a novel intradural spinal cord stimulation device for control of spasticity in an ovine model. Methods and Results : We surveyed the literature on hemisection in quadrupeds and nonhuman primates, and catalogued the species, protocols and outcomes of the experimental work in this field. Feline, lapine, canine, simian, porcine, ovine and bovine models were the primary focal points. There is a consistent body of literature reporting use of the hemisection approach in large animals, but with differences in surgical technique depending on the goals and nature of the individual studies. While the injuries are not always consistent, the experimental variability is generally lower than that of the contusion-based approach. In general, as the body size of the animal increases, animal care requirements and the associated costs follow. In most cases, this is inversely correlated with the number of animals used in hemisection models. Conclusions : The hemisection approach to modeling SCI is straightforward compared with other methods such as the contusive impact and enables the transection of isolated ascending and descending tracts and segment specific cell bodies. This has certain advantages in models investigating post-injury axonal regrowth. However, this approach is not generally in line with the patho-physiologies encountered in SCI patients. Even so, the ability to achieve more control over the level of injury makes it a useful adjunct to contusive and ischemic approaches, and suggests a useful role in future translational studies.
- Published
- 2020
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41. Preconception Counseling for Women With Diabetes.
- Author
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Hubberd AL, Watson NA, Cobb E, Wardian JL, Morrow CC, and Sauerwein TJ
- Abstract
"Quality Improvement Success Stories" are published by the American Diabetes Association in collaboration with the American College of Physicians, Inc., and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes . The following article describes the efforts of a U.S. Airforce diabetes specialty clinic to improve the delivery of preconception counseling to women with diabetes who are of childbearing potential., (© 2019 by the American Diabetes Association.)
- Published
- 2020
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42. CDK1-mediated phosphorylation at H2B serine 6 is required for mitotic chromosome segregation.
- Author
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Seibert M, Krüger M, Watson NA, Sen O, Daum JR, Slotman JA, Braun T, Houtsmuller AB, Gorbsky GJ, Jacob R, Kracht M, Higgins JMG, and Schmitz ML
- Subjects
- CDC2 Protein Kinase genetics, Cell Nucleus genetics, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Female, Genomic Instability, HCT116 Cells, HEK293 Cells, HeLa Cells, Histone Chaperones genetics, Histone Chaperones metabolism, Humans, Neoplasms enzymology, Neoplasms genetics, Phosphorylation, Protein Binding, Retinal Pigment Epithelium enzymology, Serine, Signal Transduction, CDC2 Protein Kinase metabolism, Cell Nucleus enzymology, Chromosome Segregation, Chromosomes, Human, Histones metabolism, Mitosis
- Abstract
Faithful mitotic chromosome segregation is required for the maintenance of genomic stability. We discovered the phosphorylation of histone H2B at serine 6 (H2B S6ph) as a new chromatin modification site and found that this modification occurs during the early mitotic phases at inner centromeres and pericentromeric heterochromatin. This modification is directly mediated by cyclin B1-associated CDK1, and indirectly by Aurora B, and is antagonized by PP1-mediated dephosphorylation. H2B S6ph impairs chromatin binding of the histone chaperone SET (I2PP2A), which is important for mitotic fidelity. Injection of phosphorylation-specific H2B S6 antibodies in mitotic cells caused anaphase defects with impaired chromosome segregation and incomplete cytokinesis. As H2B S6ph is important for faithful chromosome separation, this modification may contribute to the prevention chromosomal instability and aneuploidy which frequently occur in cancer cells., (© 2019 Seibert et al.)
- Published
- 2019
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43. Striking lung cancer response to self-administration of cannabidiol: A case report and literature review.
- Author
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Sulé-Suso J, Watson NA, van Pittius DG, and Jegannathen A
- Abstract
In spite of new drugs, lung cancer is associated with a very poor prognosis. While targeted therapies are improving outcomes, it is not uncommon for many patients to have only a partial response, and relapse during follow-up. Thus, new drugs or re-evaluation of existing therapies used to treat other non-malignant diseases (drug repurposing) are still needed. While this research both in vitro and in vivo is being carried out, it is important to be attentive to patients where the disease responds to treatments not considered standard in clinical practice. We report here a patient with adenocarcinoma of the lung who, after declining chemotherapy and radiotherapy, presented with tumour response following self-administration of cannabidiol, a non-psychoactive compound present in Cannabis sativa . Prior work has shown that cannabidiol may have anti-neoplastic properties and enhance the immune response to cancer. The data presented here indicate that cannabidiol might have led to a striking response in a patient with lung cancer., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2019
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44. Biomechanical assessment of proximal junctional semi-rigid fixation in long-segment thoracolumbar constructs.
- Author
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Viswanathan VK, Ganguly R, Minnema AJ, DeVries Watson NA, Grosland NM, Fredericks DC, Grossbach AJ, Viljoen SV, and Farhadi HF
- Subjects
- Adult, Aged, Biomechanical Phenomena physiology, Female, Humans, Male, Middle Aged, Pedicle Screws, Range of Motion, Articular physiology, Risk Factors, Spinal Fusion methods, Kyphosis surgery, Lumbar Vertebrae surgery, Postoperative Complications surgery, Thoracic Vertebrae surgery
- Abstract
OBJECTIVEProximal junctional kyphosis (PJK) and failure (PJF) are potentially catastrophic complications that result from abrupt changes in stress across rigid instrumented and mobile non-fused segments of the spine (transition zone) after adult spinal deformity surgery. Recently, data have indicated that extension (widening) of the transitional zone via use of proximal junctional (PJ) semi-rigid fixation can mitigate this complication. To assess the biomechanical effectiveness of 3 semi-rigid fixation constructs (compared to pedicle screw fixation alone), the authors performed cadaveric studies that measured the extent of PJ motion and intradiscal pressure changes (ΔIDP).METHODSTo measure flexibility and ΔIDP at the PJ segments, moments in flexion, extension, lateral bending (LB), and torsion were conducted in 13 fresh-frozen human cadaveric specimens. Five testing cycles were conducted, including intact (INT), T10-L2 pedicle screw-rod fixation alone (PSF), supplemental hybrid T9 Mersilene tape insertion (MT), hybrid T9 sublaminar band insertion (SLB1), and hybrid T8/T9 sublaminar band insertion (SLB2).RESULTSCompared to PSF, SLB1 significantly reduced flexibility at the level rostral to the upper-instrumented vertebral level (UIV+1) under moments in 3 directions (flexion, LB, and torsion, p ≤ 0.01). SLB2 significantly reduced motion in all directions at UIV+1 (flexion, extension, LB, torsion, p < 0.05) and at UIV+2 (LB, torsion, p ≤ 0.03). MT only reduced flexibility in extension at UIV+1 (p = 0.02). All 3 constructs revealed significant reductions in ΔIDP at UIV+1 in flexion (MT, SLB1, SLB2, p ≤ 0.02) and torsion (MT, SLB1, SLB2, p ≤ 0.05), while SLB1 and SLB2 significantly reduced ΔIDP in extension (SLB1, SLB2, p ≤ 0.02) and SLB2 reduced ΔIDP in LB (p = 0.05). At UIV+2, SLB2 similarly significantly reduced ΔIDP in extension, LB, and torsion (p ≤ 0.05).CONCLUSIONSCompared to MT, the SLB1 and SLB2 constructs significantly reduced flexibility and ΔIDP in various directions through the application of robust anteroposterior force vectors at UIV+1 and UIV+2. These findings indicate that semi-rigid sublaminar banding can most effectively expand the transition zone and mitigate stresses at the PJ levels of long-segment thoracolumbar constructs.
- Published
- 2018
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45. Volume of Brain Herniation After Decompressive Craniectomy in Patients with Traumatic Brain Injury.
- Author
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Abode-Iyamah KO, Stoner KE, Close LN, DeVries Watson NA, Flouty OE, Grosland NM, and Howard MA 3rd
- Subjects
- Adult, Aged, Aged, 80 and over, Brain Edema etiology, Decompressive Craniectomy adverse effects, Humans, Intracranial Hypertension etiology, Middle Aged, Organ Size, Surgical Flaps statistics & numerical data, Young Adult, Brain Edema diagnostic imaging, Brain Injuries, Traumatic diagnostic imaging, Brain Injuries, Traumatic surgery, Decompressive Craniectomy trends, Intracranial Hypertension diagnostic imaging, Surgical Flaps trends
- Abstract
Background: The decompressive hemicraniectomy operation is highly effective in relieving refractory intracranial hypertension. However, one limitation of this treatment strategy is the requirement to perform a subsequent cranioplasty operation to reconstruct the skull defect-an expensive procedure with high complication rates. An implant that is capable of accommodated post-hemicraniectomy brain swelling, but also provides acceptable skull defect coverage after brain swelling abates, would theoretically eliminate the need for the cranioplasty operation. In an earlier report, the concept of using a thin, moveable plate implant for this purpose was introduced., Methods: Measurements were obtained in a series of stroke patients to determine whether a plate offset from the skull by 5 mm would accommodate the observed post-hemicraniectomy brain swelling. The volume of brain swelling measured in all patients in the stroke series would be accommodated by a 5-mm offset plate. In the current report, we expanded our analysis to study brain swelling patterns in a different population of patients requiring a hemicraniectomy operation: those with traumatic brain injuries (TBI)., Results: We identified 56 patients with TBI and measured their postoperative brain herniation volumes. A moveable plate offset by 5 mm would create sufficient additional volume to accommodate the brain swelling measured in all but one patient. That patient had malignant intraoperative brain swelling and died the following day., Conclusions: These data suggest that a 5 mm offset plate will provide sufficient volume for brain expansion for almost all hemicraniectomy operations., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2018
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46. Reductions in food cravings are similar with low-fat weight loss diets differing in protein and carbohydrate in overweight and obese adults with type 2 diabetes: A randomized clinical trial.
- Author
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Watson NA, Dyer KA, Buckley JD, Brinkworth GD, Coates AM, Parfitt G, Howe PRC, Noakes M, and Murphy KJ
- Subjects
- Aged, Attention, Body Mass Index, Dietary Fats administration & dosage, Emotions, Energy Intake, Female, Humans, Inhibition, Psychological, Male, Middle Aged, Overweight, Satiation, Weight Loss, Craving, Diabetes Mellitus, Type 2 complications, Diet, Fat-Restricted, Diet, Reducing, Dietary Carbohydrates administration & dosage, Dietary Proteins administration & dosage, Obesity complications, Obesity diet therapy, Obesity psychology
- Abstract
Food cravings are common in type 2 diabetes (T2D). Higher-protein diets are effective in improving satiety but their effect on cravings is unclear. It was hypothesized that a high protein (HP) diet would provide greater reductions in cravings than an isocaloric higher-carbohydrate diet (HC). In a randomized controlled trial, 61 adults (54% males) with T2D (means ± SD: BMI 34.3 ± 5.1 kg/m
2 ; aged 55 ± 8 years) consumed either a HP diet (mean across study: 29% protein, 34% carbohydrate, 31% fat) or an isocaloric HC diet (21%:48%:24%) for 12-weeks each of weight loss (WL) and weight maintenance (WM). The Food Craving Inventory (FCI), measuring types of foods craved and the General Food Craving Questionnaires measuring traits (G-FCQ-T) and states (G-FCQ-S) were assessed at Weeks 0, 12 and 24. Weight changes were similar between groups (means ± SEM: WL: -7.8 ± 0.6 kg, WM: -0.6 ± 0.4 kg). No group effects or group x time interactions were found for any outcome (P ≥ .07). Independent of group, all food cravings (except carbohydrates) and G-FCQ-T subscales decreased over the 24-week study (P ≤ .04) with sweets and fast food cravings, loss of control and emotional cravings reducing following WL (P ≤ .03). Obsessive preoccupation with food decreased following both phases (WL: P = .03; WM: P = .001). Weight was associated with several FCI subscales (r ≥ 0.24, P ≤ .04). In conclusion, both the HP and HC diets provided significant reductions in food cravings after similar weight losses which were maintained when weight was stabilized., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2018
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47. Comparison of two low-fat diets, differing in protein and carbohydrate, on psychological wellbeing in adults with obesity and type 2 diabetes: a randomised clinical trial.
- Author
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Watson NA, Dyer KA, Buckley JD, Brinkworth GD, Coates AM, Parfitt G, Howe PRC, Noakes M, and Murphy KJ
- Subjects
- Aged, Exercise, Humans, Middle Aged, Surveys and Questionnaires, Weight Loss, Diabetes Mellitus, Type 2 diet therapy, Diet, Fat-Restricted psychology, Dietary Carbohydrates administration & dosage, Dietary Proteins administration & dosage, Obesity diet therapy, Quality of Life psychology
- Abstract
Background: Although higher-protein diets (HP) can assist with weight loss and glycemic control, their effect on psychological wellbeing has not been established. The objective of this study was to compare the effects of a HP and a higher-carbohydrate diet (HC), combined with regular exercise, on psychological wellbeing both during weight loss (WL) and weight maintenance phases (WM)., Methods: In a parallel RCT, 61 adults with T2D (mean ± SD: BMI 34.3 ± 5.1 kg/m
2 , aged 55 ± 8 years) consumed a HP diet (29% protein, 34% carbohydrate, 31% fat) or an isocaloric HC diet (21%:48%:24%), with moderate intensity exercise, for 12 weeks of WL and 12 weeks of WM. Secondary data evaluating psychological wellbeing was assessed using: Problems Areas in Diabetes (PAID); Diabetes-39 Quality of Life (D-39); Short Form Health Survey (SF-36); Perceived Stress Scale-10 (PSS-10) and the Leeds Sleep Evaluation Questionnaire (LSEQ) at Weeks 0, 12 and 24 and evaluated with mixed models analysis., Results: Independent of diet, improvements for PAID; D-39 diabetes control; D-39 severity of diabetes; SF-36 physical functioning and SF-36 general health were found following WL (d = 0.30 to 0.69, P ≤ 0.04 for all) which remained after 12 weeks of WM. SF-36 vitality improved more in the HP group (group x time interaction P = 0.03). Associations were seen between HbA1c and D-39 severity of diabetes rating (r = 0.30, P = 0.01) and SF-36 mental health (r = - 0.32, P = 0.003) and between weight loss and PAID (r = 0.30, P = 0.01)., Conclusion: Several improvements in diabetes-related and general psychological wellbeing were seen similarly for both diets following weight loss and a reduction in HbA1c with most of these improvements remaining when weight loss was sustained for 12 weeks. A HP diet may provide additional increases in vitality., Trial Registration: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12613000008729 ) on 4 January 2013.- Published
- 2018
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48. Diabetes Center of Excellence Hypoglycemia Emergency Preparedness Project.
- Author
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Cobb EC, Watson NA, Wardian J, Morrow CC, and Sauerwein TJ
- Abstract
IN BRIEF "Quality Improvement Success Stories" are published by the American Diabetes Association in collaboration with the American College of Physicians, Inc., and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes . The following article describes a successful effort to ensure that patients who are at risk for severe hypoglycemic events have a viable glucagon emergency plan in place.
- Published
- 2018
- Full Text
- View/download PDF
49. Topical ofloxacin use in glucose-6-phosphate dehydrogenase deficiency-safe or unsafe?
- Author
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Watson NA, Gomez Serrano M, and Selvadurai D
- Subjects
- Administration, Topical, Child, Preschool, Humans, Anemia, Hemolytic etiology, Anti-Bacterial Agents adverse effects, Glucosephosphate Dehydrogenase Deficiency complications, Middle Ear Ventilation, Ofloxacin adverse effects, Otitis Media with Effusion surgery
- Published
- 2018
- Full Text
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50. Evaluation of the Group Lifestyle Balance Program in a Military Setting: An Investment Worth Expanding.
- Author
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Wardian JL, True MW, Sauerwein TJ, Watson NA, and Hoover AM
- Subjects
- Adult, Cost-Benefit Analysis, Diabetes Mellitus, Type 2 prevention & control, Diabetes Mellitus, Type 2 therapy, Female, Humans, Male, Metabolic Syndrome prevention & control, Metabolic Syndrome therapy, Middle Aged, Military Personnel statistics & numerical data, Prediabetic State therapy, Program Evaluation economics, Retrospective Studies, Group Processes, Healthy Lifestyle, Military Personnel psychology, Program Evaluation methods
- Abstract
Introduction: The Diabetes Prevention Program (DPP) demonstrated that lifestyle intervention programs were effective in preventing or delaying the onset of diabetes. The Group Lifestyle Balance (GLB) program translated the DPP curriculum into a 12-wk group intervention for those at risk for diabetes. This retrospective evaluation examined clinical outcomes for patients in the Diabetes Center of Excellence GLB program located at Wilford Hall Ambulatory Surgical Center from 2009 to 2013. Objectives included determining rates of retention, demographic characteristics of program completers, and changes in metabolic surrogates of disease prevalence., Study Design: Adults with prediabetes or metabolic syndrome (MetS) were referred to the GLB program. Updated participant metabolic data were collected at regular intervals during their participation., Results: During the 5-yr study, 704 patients attended the initial class. Overall, 52% of all participants completed the program with the greatest decline in participation occurring by the fourth week (30%). Baseline prevalence of conditions of interest for those who completed the program was prediabetes (93.2%), obesity (56.1%), and MetS (31.5%). GLB completers were older and retired (p < 0.05). A significant number of active duty military members (44.9%, p < 0.01, n = 53) dropped out of the program before the fourth week. Furthermore, those who completed the program saw a 2.0% reduction in prediabetes prevalence (p < 0.001), obesity decreased by 8.7% (p < 0.001), and MetS decreased by 6.8% (p < 0.01). Significant differences were found for central obesity, triglycerides, and fasting blood sugar (p < 0.001)., Conclusions: The GLB program is a valuable DPP and was effective at improving clinical outcomes and reducing the incidence of prediabetes, obesity, and MetS for participants who completed the program. Every effort should be made to support and encourage GLB participants to complete the program., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
- Published
- 2018
- Full Text
- View/download PDF
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