104 results on '"Etheridge T"'
Search Results
2. Proteomic features of skeletal muscle adaptation to resistance exercise training as a function of age
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Deane, Colleen S, Phillips, BE, Willis, CRG, Wilkinson, DJ, Smith, K, Higashitani, N, Williams, JP, Szewczyk, NJ, Atherton, PJ, Higashitani, A, and Etheridge, T
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Aging ,Geriatrics and Gerontology - Abstract
Resistance exercise training (RET) can counteract negative features of muscle ageing but older age associates with reduced adaptive capacity to RET. Altered muscle protein networks likely contribute to ageing RET adaptation; therefore, associated proteome-wide responses warrant exploration. We employed quantitative sarcoplasmic proteomics to compare age-related proteome and phosphoproteome responses to RET. Thigh muscle biopsies were collected from eight young (25 ± 1.1 years) and eight older (67.5 ± 2.6 years) adults before and after 20 weeks supervised RET. Muscle sarcoplasmic fractions were pooled for each condition and analysed using Isobaric Tags for Relative and Absolute Quantification (iTRAQ) labelling, tandem mass spectrometry and network-based hub protein identification. Older adults displayed impaired RET-induced adaptations in whole-body lean mass, body fat percentage and thigh lean mass (P > 0.05). iTRAQ identified 73 differentially expressed proteins with age and/or RET. Despite possible proteomic stochasticity, RET improved ageing profiles for mitochondrial function and glucose metabolism (top hub; PYK (pyruvate kinase)) but failed to correct altered ageing expression of cytoskeletal proteins (top hub; YWHAZ (14–3-3 protein zeta/delta)). These ageing RET proteomic profiles were generally unchanged or oppositely regulated post-RET in younger muscle. Similarly, RET corrected expression of 10 phosphoproteins altered in ageing, but these responses were again different vs. younger adults. Older muscle is characterised by RET-induced metabolic protein profiles that, whilst not present in younger muscle, improve untrained age-related proteomic deficits. Combined with impaired cytoskeletal adhesion responses, these results provide a proteomic framework for understanding and optimising ageing muscle RET adaptation.
- Published
- 2022
3. St Michael's Church, Fore Street, Beer, Devon: Results of archaeological monitoring and recording
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Etheridge, T
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Archaeology ,Grey Literature - Abstract
Archaeological monitoring and recording was carried out by AC archaeology during groundworks associated with the construction of a shed within the churchyard of St Michael's Church, Fore Street, Beer, Devon. The monitored groundworks comprised the creation of a terrace measuring 12m by 6m for the new shed. It was excavated into the sloping ground to a maximum depth of 0.95m below existing levels. The monitored groundworks partially exposed a buried soil (102) representing a probable graveyard soil beneath a series of 20th century made ground deposits. Despite the exposure of the probable graveyard soil no evidence for burials was present.
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- 2022
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4. The Paddock, Back Street, Modbury, Devon: Results of an archaeological trial trench evaluation
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Etheridge, T
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Archaeology ,Grey Literature - Abstract
An archaeological trial trench evaluation was carried out ahead of a proposed residential development by AC archaeology at The Paddock, Back Street, Modbury, Devon. The trial trench evaluation comprised the machine excavation of two trenches measuring a total of 38m long with each trench 1.5m wide. These were positioned to target areas of impact from the proposed development. The trial trench evaluation exposed a single possible pit. This was dated from finds to the mid-19th century. No evidence for earlier activity was exposed and no residual finds were recovered that could be related to the medieval origins of Modbury.
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- 2022
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5. Land north of Wrigwell Lane, Ipplepen, Devon: Results of archaeological investigations
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Etheridge, T
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Archaeology ,Grey Literature - Abstract
The works comprised the stripping of an area measuring 40m long and 20m wide for the new horse arena. This area was first reduced to the development formation layer of approximately 0.3m below existing levels. Four trial trenches were then excavated within this area onto the top of the natural subsoil. The trenches each measured 20m long and 2m wide.
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- 2021
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6. BAMMsat-on-BEXUS: A Technology and Operation Demonstration of a BioCubeSat Platform on a Stratospheric Balloon Flight Educational Program
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Shamsul, Aqeel, Sinclair, Giovanni, Bolliand, Adrien, Chabi, Amin, Martinez de Bujo, Miguel, Zalasiewicz, Mateusz, Cullen, David C., Cooke, Mike, and Etheridge, T.
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bammsat ,operation ,stratospheric ,flight ,platform ,biocubesat ,demonstration ,technology ,program ,ballon ,educational - Abstract
This paper reports the current use of the REXUS/BEXUS educational program. The program allows university students across Europe to carry out scientific and technology experiments on research sounding rockets and balloons. BAMMsat-on-BEXUS (BoB) is an experiment from Cranfield University and University of Exeter performing a technology and operation demonstration of a bioCubeSat on a stratospheric balloon at an altitude of ~30km above the ground. BEXUS stands for Balloon Experiments for University Students and is realized under an agreement between the German Aerospace Centre (DLR), Swedish National Space Agency (SNSA), European Space Agency (ESA), and EuroLaunch. The term bioCubeSat could be used to refer to a nanosatellite in a CubeSat format with a biological experiment on-board. Over the last decade, a series of six bioCubeSats have been launched into orbit by NASA and a private company, SpacePharma, i.e., GeneSat, PharmaSat, O/OREOS, SporeSat, Dido-2, and EcAMSat. The BAMMsat concept (Bioscience, Astrobiology, Medicine and Material science on CubeSat) is a bioscience hardware platform which aims to advance the current state of the art technology, under development at Cranfield University, for application in LEO and beyond LEO. This generic platform can be flown as a free-flying CubeSat or hosted as a payload on a larger spacecraft. BAMMsat utilizes COTS sensors, actuators, and fluidic components to enable bioscience experiments by reproducing the features in a traditional laboratory into a miniaturized “laboratory.” It is designed to be compatible with the mass, volume, and power budget of a CubeSat payload and flexible for a broad range of applications and biological systems such as microorganisms, nematode worms, and mammalian cells cultures, including human cell cultures. The core features of BAMMsat are the ability to (i) house multiple samples, (ii) maintain samples in an appropriate local environment (ii) perturb sample fluidically, and (iv) monitor samples. BoB aims to perform a technology and operation demonstration of the BAMMsat bioCubeSat payload in an extreme environment such as the stratosphere. The experiment is to be flown on the BEXUS30 flight campaign in October 2020 from ESRANGE Space Centre, Sweden. The stratosphere can be used as an analog of some aspect of a relevant spaceflight physical environment such as reduced pressure (near-vacuum; ~11 mbar), and temperature (-50°C). The BEXUS flight campaign could also be used as an analog of pre-flight, flight and post-flight operation similar to orbital launch campaign. For bioscience experiments, the biological samples often imposed additional requirement during pre-flight to ensure its viability. BoB will house C. elegans in a 2U pressure vessel to demonstrate its functionality to provide a controlled thermal and fluidic environment with appropriate housekeeping control. This functionality reflects the hardware capability to maintain a viable biological sample. BoB has a 3U CubeSat form factor with 2U allocated for the BAMMsat hardware and 1U allocated as the BAMMsat-on-BEXUS bus. This paper reports progress at four months before flight campaign. The paper also discusses an overview of the experiment objectives and systems design, to build a representative CubeSat that is translatable into a free-flying orbital CubeSat.
- Published
- 2020
7. Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism
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Wilkinson, D. J., Hossain, T., Hill, D. S., Phillips, B. E., Crossland, H., Williams, J., Loughna, P., Churchward-Venne, T. A., Breen, L., Phillips, S. M., Etheridge, T., Rathmacher, J. A., Smith, K., Szewczyk, N. J., and Atherton, P. J.
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- 2013
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8. Commercial access for UK/ESA student experiments on board the ISS
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Gaffney, C. J., primary, Nartallo, R., additional, Neri, G., additional, Ellwood, R. A., additional, Cooke, M., additional, Gharahdaghi, N., additional, Torregrossa, R., additional, Piasecki, M., additional, Deane, C. S.,, additional, Whiteman, M., additional, Etheridge, T., additional, Phillips, B., additional, Zolesi, D., additional, and Szewczyk, N. J., additional
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- 2020
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9. Electricity Cable Installation, West Street to Frog Street, Exeter, Devon: Results of Archaeological Monitoring and Recording
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Etheridge, T.
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Archaeology ,Grey Literature - Abstract
Archaeological monitoring and recording was carried out by AC archaeology during groundworks associated with the installation of an electricity cable between Frog Street and West Street, Exeter, Devon. The route of the new cable extended southeast from an electricity sub-station on West Street and continued southwest adjacent to the remains of the West Gate, with this then linking to a plot occupied by student accommodation on the north side of Frog Street.
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- 2018
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10. Food texture: A potential dietary consideration for obesity prevention?
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Etheridge, T., primary and Atherton, P. J., additional
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- 2018
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11. The conserved Fanconi anemia nuclease Fan1 and the SUMO E3 ligase Pli1 act in two novel Pso2-independent pathways of DNA interstrand crosslink repair in yeast
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Fontebasso, Y, Etheridge, T J, Oliver, A W, Murray, J M, and Carr, A M
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Models, Molecular ,DNA Repair ,Ubiquitin-Protein Ligases ,Sequence Homology ,Genetic screen ,Biochemistry ,Article ,Evolution, Molecular ,Ligases ,Synthetic array ,Mutation Rate ,Schizosaccharomyces ,Molecular Biology ,Recombination, Genetic ,Endodeoxyribonucleases ,Esterases ,Cell Biology ,R1 ,ICL ,High-Throughput Screening Assays ,Protein Structure, Tertiary ,Schizosaccharomyces pombe ,Epistasis ,Schizosaccharomyces pombe Proteins ,Cisplatin ,Corrigendum ,DNA Damage ,Signal Transduction - Abstract
Highlights • Characterization of FANCD2/FANCI-associated nuclease 1 (Fan1) in the model organism Schizosaccharomyces pombe. • Fan1 is a key component of a previously unidentified ICL resolution pathway in Schizosaccharomyces pombe acting in parallel to Pso2 • Demonstrate the existence of a third sub-pathway of ICL repair dependent on the SUMO E3 ligase Pli1. • The nuclease and SAP DNA binding domains are essential for Fan1 activity in ICL repair., DNA interstrand cross-links (ICLs) represent a physical barrier to the progression of cellular machinery involved in DNA metabolism. Thus, this type of adduct represents a serious threat to genomic stability and as such, several DNA repair pathways have evolved in both higher and lower eukaryotes to identify this type of damage and restore the integrity of the genetic material. Human cells possess a specialized ICL-repair system, the Fanconi anemia (FA) pathway. Conversely yeasts rely on the concerted action of several DNA repair systems. Recent work in higher eukaryotes identified and characterized a novel conserved FA component, FAN1 (Fanconi anemia-associated nuclease 1, or FANCD2/FANCI-associated nuclease 1). In this study, we characterize Fan1 in the yeast Schizosaccharomyces pombe. Using standard genetics, we demonstrate that Fan1 is a key component of a previously unidentified ICL-resolution pathway. Using high-throughput synthetic genetic arrays, we also demonstrate the existence of a third pathway of ICL repair, dependent on the SUMO E3 ligase Pli1. Finally, using sequence-threaded homology models, we predict and validate key residues essential for Fan1 activity in ICL repair.
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- 2013
12. Effects of leucine and its metabolite ?-hydroxy-?-methylbutyrate on human skeletal muscle protein metabolism
- Author
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Wilkinson, D.J., Hossain, T., Hill, D.S., Phillips, B.E., Crossland, H., Williams, J., Loughna, P., Churchward-Venne, T.A., Breen, L., Phillips, S.M., Etheridge, T., Rathmacher, J.A., Smith, K., Szewczyk, N.J., and Atherton, P.J.
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skin and connective tissue diseases ,human activities - Abstract
Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses–fed gains) in protein turnover. Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is ‘sensed’ have been the subject of great scrutiny, as a branched-chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2-13C2]Leu and [2H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by arteriovenous (A–V) dilution). Orally consumed 3.42 g free-acid (FA-HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated muscle protein synthesis (MPS; HMB +70%vs. Leu +110%). While HMB and Leu both increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e. p70S6K1 signalling ≤90 min vs. ≤30 min for HMB). HMB consumption also attenuated muscle protein breakdown (MPB; −57%) in an insulin-independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu.
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- 2013
13. A single protein meal increases recovery of muscle function following an acute eccentric exercise bout.
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Etheridge T, Philp A, and Watt PW
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- 2008
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14. Mitochondria-targeting hydrogen sulfide donors prolong healthspan: lifespan ratio in Caenorhabditis elegans.
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Etheridge, T., Gaffney, C., Szewczyk, N. J., Torregrossa, R., Wood, M., and Whiteman, M.
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MITOCHONDRIA , *ENDOGENOUS hydrogen sulfide , *CAENORHABDITIS elegans - Published
- 2017
15. Assessing mitochondrial structure and function in C. elegans muscle.
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Pollard, A., Gaffney, C., Hewitt, J., Vanapalli, S., Constantin-Teodosiu, D., Greenhaff, P., Etheridge, T., and Szewczyk, N. J.
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MITOCHONDRIA ,CAENORHABDITIS elegans ,GENE silencing - Published
- 2017
16. COMMENTARY RESPONSE TO VIEWPOINT: "WHAT IS THE RELATIONSHIP BETWEEN ACUTE MEASURES OF MUSCLE PROTEIN SYNTHESIS AND CHANGES IN MUSCLE MASS?".
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Atherton, Philip J., Phillips, B. E., Brook, M. S., Wilkinson, D. J., Smith, K., and Etheridge, T. E.
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PROTEIN synthesis ,MUSCLE proteins ,MUSCLE physiology - Abstract
A letter to the editor is presented in response to the article "What Is the Relationship Between an Acute Muscle Protein Synthetic Response and Changes in Muscle Mass?" by C. J. Mitchell and colleagues published in the journal in 2015.
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- 2015
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17. Environmental field days.
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Etheridge, T.
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AGRICULTURE - Abstract
Discusses the environmental field days for fourth-grade students sponsored by the Beaufort Soil and Water Conservation District and Goose Creek State Park (N.C.). Lessons about North Carolina's wetlands, marine fisheries and forests; Soil Conservation Service.
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- 1990
18. Education in the Republic of Texas
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Etheridge, T. H. (Truman Harrison), 1890-1962
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- Education, Texas, History, Texas Republic, 1836-1846
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- 1942
19. Consolidating multiple evolutionary theories of ageing suggests a need for new approaches to study genetic contributions to ageing decline.
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Slade L, Etheridge T, and Szewczyk NJ
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- Animals, Humans, Longevity genetics, Selection, Genetic, Aging genetics, Aging physiology, Biological Evolution, Caenorhabditis elegans genetics
- Abstract
Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with progressive declines in biochemical and molecular processes resulting from damage accumulation, yet the role of continued developmental gene activation is less appreciated. Natural selection pressures are at their highest in youthful periods to modify gene expression towards maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene functions that were once beneficial for developmental growth but become pathogenic later in life. Due to this selective 'shadowing' in ageing, mechanisms to counter such hyper/hypofunctional genes are unlikely to evolve. Interventions aimed at targeting gene hyper/hypofunction during ageing might, therefore, represent an attractive therapeutic strategy. The nematode Caenorhabditis elegans offers a strong model for post-reproductive mechanistic and therapeutic investigations, yet studies examining the mechanisms of, and countermeasures against, ageing decline largely intervene from larval stages onwards. Importantly, however, lifespan extending conditions frequently impair early-life fitness and fail to correspondingly increase healthspan. Here, we consolidate multiple evolutionary theories of ageing and discuss data supporting hyper/hypofunctional changes at a global molecular and functional level in C. elegans, and how classical lifespan-extension mutations alter these dynamics. The relevance of such mutant models for exploring mechanisms of ageing are discussed, highlighting that post-reproductive gene optimisation represents a more translatable approach for C. elegans research that is not constrained by evolutionary trade-offs. Where some genetic mutations in C. elegans that promote late-life health map accordingly with healthy ageing in humans, other widely used genetic mutations that extend worm lifespan are associated with life-limiting pathologies in people. Lifespan has also become the gold standard for quantifying 'ageing', but we argue that gerospan compression (i.e., 'healthier' ageing) is an appropriate goal for anti-ageing research, the mechanisms of which appear distinct from those regulating lifespan alone. There is, therefore, an evident need to re-evaluate experimental approaches to study the role of hyper/hypofunctional genes in ageing in C. elegans., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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20. Use of Intracameral Tissue Plasminogen Activator During Uveitic Cataract Surgery.
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Hu WF, Etheridge T, and Larochelle MB
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- Humans, Male, Retrospective Studies, Female, Middle Aged, Aged, Adult, Anterior Chamber drug effects, Cataract Extraction, Aged, 80 and over, Tissue Plasminogen Activator administration & dosage, Tissue Plasminogen Activator therapeutic use, Visual Acuity physiology, Fibrinolytic Agents therapeutic use, Fibrinolytic Agents administration & dosage, Uveitis drug therapy
- Abstract
Purpose: To report the outcomes of intracameral tissue plasminogen activator (tPA) use during uveitic cataract surgery., Design: Retrospective case series from a single United States tertiary center of 36 eyes from 31 consecutive patients with established uveitis who received intraoperative intracameral tPA during cataract surgery between 2016 and 2020., Results: Mean visual acuity (VA) improved from logMAR 1.0 ± 0.7 preoperatively to logMAR 0.7 ± 0.8 by POM12. VA improved from baseline postoperatively (POM1 p = 0.0002, POM6 p = 0.006 and POM12 p = 0.007). Minimal to no anterior chamber inflammation was achieved in 47.2% of the eyes by POW1 and 80.0% of the eyes by POM1. Mean clock-hours of posterior synechiae improved from 8.2 ± 3.8 preoperatively to 0.1 ± 0.6 by POM12. Six eyes developed hyphema and/or vitreous hemorrhage, four of which resolved spontaneously., Conclusions: Adjunctive intracameral tPA during uveitic cataract surgery improves VA and intraocular inflammation, but risks postoperative hemorrhage. Intraoperative tPA as adjunctive anti-inflammatory therapy warrants randomized prospective studies.
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- 2024
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21. ACUTE POST-TRAUMATIC ENDOPHTHALMITIS SECONDARY TO BACILLUS PUMILUS / SAFENSIS.
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Etheridge T, Swiston C, Harrie RP, and Bernstein PS
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- Humans, Male, Middle Aged, Corneal Injuries microbiology, Anti-Bacterial Agents therapeutic use, Acute Disease, Eye Injuries, Penetrating complications, Eye Injuries, Penetrating microbiology, Eye Injuries, Penetrating diagnosis, Bacillus isolation & purification, Vitrectomy, Bacillaceae Infections microbiology, Bacillaceae Infections diagnosis, Eye Injuries complications, Endophthalmitis microbiology, Endophthalmitis diagnosis, Endophthalmitis etiology, Eye Infections, Bacterial microbiology, Eye Infections, Bacterial diagnosis, Eye Infections, Bacterial etiology, Bacillus pumilus isolation & purification
- Abstract
Purpose: To report a case of post-traumatic endophthalmitis secondary to Bacillus pumilus/safensis ., Methods: Observational case report of a single patient., Results: A 62-year-old man presented with a traumatic corneal laceration because of baling wire while working on a sheep farm. Appropriate corneal laceration repair with injection of intravitreal antibiotics (ceftazidime, clindamycin, and vancomycin) was performed. A single organism, identified as B. pumilus or Bacillus safensis, was isolated from the vitreous aspirate. A subsequent pars plana vitrectomy, pars plana lensectomy, anterior capsulotomy, and fluid-air exchange was required because of severe inflammatory reaction from retained lens material, retinal edema, and vitreous opacities. Vision improved from hand motion to 20/60 at the three-month follow-up visit., Conclusion: We describe a case of acute post-traumatic endophthalmitis secondary to B. pumilus/safensis.
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- 2024
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22. Hydrogen sulfide supplementation as a potential treatment for primary mitochondrial diseases.
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Slade L, Deane CS, Szewczyk NJ, Etheridge T, and Whiteman M
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- Humans, Animals, Dietary Supplements, Signal Transduction drug effects, Hydrogen Sulfide metabolism, Hydrogen Sulfide therapeutic use, Mitochondrial Diseases drug therapy, Mitochondrial Diseases metabolism, Mitochondria metabolism, Mitochondria drug effects
- Abstract
Primary mitochondrial diseases (PMD) are amongst the most common inborn errors of metabolism causing fatal outcomes within the first decade of life. With marked heterogeneity in both inheritance patterns and physiological manifestations, these conditions present distinct challenges for targeted drug therapy, where effective therapeutic countermeasures remain elusive within the clinic. Hydrogen sulfide (H
2 S)-based therapeutics may offer a new option for patient treatment, having been proposed as a conserved mitochondrial substrate and post-translational regulator across species, displaying therapeutic effects in age-related mitochondrial dysfunction and neurodegenerative models of mitochondrial disease. H2 S can stimulate mitochondrial respiration at sites downstream of common PMD-defective subunits, augmenting energy production, mitochondrial function and reducing cell death. Here, we highlight the primary signalling mechanisms of H2 S in mitochondria relevant for PMD and outline key cytoprotective proteins/pathways amenable to post-translational restoration via H2 S-mediated persulfidation. The mechanisms proposed here, combined with the advent of potent mitochondria-targeted sulfide delivery molecules, could provide a framework for H2 S as a countermeasure for PMD disease progression., Competing Interests: Declaration of Competing Interest M.W. has intellectual property (patents awarded and pending) on slow-release sulfide-generating molecules and their therapeutic use. M.W. is CSO of MitoRx Therapeutics, Oxford, U.K, developing organelle-targeted molecules for clinical use. L.S, C.S.D, N.J.S and T.E declare no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)- Published
- 2024
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23. Ophthalmic Artery Obstruction With Focal Cerebral Arteriopathy of Childhood.
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Etheridge T, Jones J, Caskey E, Zielinski BA, Seay MD, and Warner JEA
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- Humans, Ophthalmic Artery diagnostic imaging, Cerebral Angiography, Cerebrovascular Disorders, Cerebral Arterial Diseases complications, Cerebral Arterial Diseases diagnosis, Stroke
- Abstract
Competing Interests: The authors report no conflicts of interest.
- Published
- 2024
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24. The Environmental Impacts of Electronic Medical Records Versus Paper Records at a Large Eye Hospital in India: Life Cycle Assessment Study.
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Kwon C, Essayei L, Spencer M, Etheridge T, Venkatesh R, Vengadesan N, and Thiel CL
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- Climate, Software, Environment, India, Ophthalmology, Health Care Sector, Climate Change, Electronic Health Records, Paper, Medical Records, Hospitals, Special, Carbon Footprint
- Abstract
Background: Health care providers worldwide are rapidly adopting electronic medical record (EMR) systems, replacing paper record-keeping systems. Despite numerous benefits to EMRs, the environmental emissions associated with medical record-keeping are unknown. Given the need for urgent climate action, understanding the carbon footprint of EMRs will assist in decarbonizing their adoption and use., Objective: We aimed to estimate and compare the environmental emissions associated with paper medical record-keeping and its replacement EMR system at a high-volume eye care facility in southern India., Methods: We conducted the life cycle assessment methodology per the ISO (International Organization for Standardization) 14040 standard, with primary data supplied by the eye care facility. Data on the paper record-keeping system include the production, use, and disposal of paper and writing utensils in 2016. The EMR system was adopted at this location in 2018. Data on the EMR system include the allocated production and disposal of capital equipment (such as computers and routers); the production, use, and disposal of consumable goods like paper and writing utensils; and the electricity required to run the EMR system. We excluded built infrastructure and cooling loads (eg. buildings and ventilation) from both systems. We used sensitivity analyses to model the effects of practice variation and data uncertainty and Monte Carlo assessments to statistically compare the 2 systems, with and without renewable electricity sources., Results: This location's EMR system was found to emit substantially more greenhouse gases (GHGs) than their paper medical record system (195,000 kg carbon dioxide equivalents [CO
2 e] per year or 0.361 kg CO2 e per patient visit compared with 20,800 kg CO2 e per year or 0.037 kg CO2 e per patient). However, sensitivity analyses show that the effect of electricity sources is a major factor in determining which record-keeping system emits fewer GHGs. If the study hospital sourced all electricity from renewable sources such as solar or wind power rather than the Indian electric grid, their EMR emissions would drop to 24,900 kg CO2 e (0.046 kg CO2 e per patient), a level comparable to the paper record-keeping system. Energy-efficient EMR equipment (such as computers and monitors) is the next largest factor impacting emissions, followed by equipment life spans. Multimedia Appendix 1 includes other emissions impact categories., Conclusions: The climate-changing emissions associated with an EMR system are heavily dependent on the sources of electricity. With a decarbonized electricity source, the EMR system's GHG emissions are on par with paper medical record-keeping, and decarbonized grids would likely have a much broader benefit to society. Though we found that the EMR system produced more emissions than a paper record-keeping system, this study does not account for potential expanded environmental gains from EMRs, including expanding access to care while reducing patient travel and operational efficiencies that can reduce unnecessary or redundant care., (©Cordelia Kwon, Lernik Essayei, Michael Spencer, Tom Etheridge, Rengaraj Venkatesh, Natrajan Vengadesan, Cassandra L Thiel. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.02.2024.)- Published
- 2024
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25. Bisphosphonates attenuate age-related muscle decline in Caenorhabditis elegans.
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Slade L, Bollen SE, Bass JJ, Phillips BE, Smith K, Wilkinson DJ, Szewczyk NJ, Atherton PJ, and Etheridge T
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- Animals, Caenorhabditis elegans genetics, Diphosphonates pharmacology, Diphosphonates therapeutic use, Quality of Life, Muscles, Caenorhabditis elegans Proteins genetics, Sarcopenia
- Abstract
Background: Age-related muscle decline (sarcopenia) associates with numerous health risk factors and poor quality of life. Drugs that counter sarcopenia without harmful side effects are lacking, and repurposing existing pharmaceuticals could expedite realistic clinical options. Recent studies suggest bisphosphonates promote muscle health; however, the efficacy of bisphosphonates as an anti-sarcopenic therapy is currently unclear., Methods: Using Caenorhabditis elegans as a sarcopenia model, we treated animals with 100 nM, 1, 10, 100 and 500 μM zoledronic acid (ZA) and assessed lifespan and healthspan (movement rates) using a microfluidic chip device. The effects of ZA on sarcopenia were examined using GFP-tagged myofibres or mitochondria at days 0, 4 and 6 post-adulthood. Mechanisms of ZA-mediated healthspan extension were determined using combined ZA and targeted RNAi gene knockdown across the life-course., Results: We found 100 nM and 1 μM ZA increased lifespan (P < 0.001) and healthspan [954 ± 53 (100 nM) and 963 ± 48 (1 μM) vs. 834 ± 59% (untreated) population activity AUC, P < 0.05]. 10 μM ZA shortened lifespan (P < 0.0001) but not healthspan (758.9 ± 37 vs. 834 ± 59, P > 0.05), whereas 100 and 500 μM ZA were larval lethal. ZA (1 μM) significantly improved myofibrillar structure on days 4 and 6 post-adulthood (83 and 71% well-organized myofibres, respectively, vs. 56 and 34% controls, P < 0.0001) and increased well-networked mitochondria at day 6 (47 vs. 16% in controls, P < 0.01). Genes required for ZA-mediated healthspan extension included fdps-1/FDPS-1 (278 ± 9 vs. 894 ± 17% population activity AUC in knockdown + 1 μM ZA vs. untreated controls, respectively, P < 0.0001), daf-16/FOXO (680 ± 16 vs. 894 ± 17%, P < 0.01) and agxt-2/BAIBA (531 ± 23 vs. 552 ± 8%, P > 0.05). Life/healthspan was extended through knockdown of igdb-1/FNDC5 (635 ± 10 vs. 523 ± 10% population activity AUC in gene knockdown vs. untreated controls, P < 0.01) and sir-2.3/SIRT-4 (586 ± 10 vs. 523 ± 10%, P < 0.05), with no synergistic improvements in ZA co-treatment vs. knockdown alone [651 ± 12 vs. 635 ± 10% (igdb-1/FNDC5) and 583 ± 9 vs. 586 ± 10% (sir-2.3/SIRT-4), both P > 0.05]. Conversely, let-756/FGF21 and sir-2.2/SIRT-4 were dispensable for ZA-induced healthspan [630 ± 6 vs. 523 ± 10% population activity AUC in knockdown + 1 μM ZA vs. untreated controls, P < 0.01 (let-756/FGF21) and 568 ± 9 vs. 523 ± 10%, P < 0.05 (sir-2.2/SIRT-4)]., Conclusions: Despite lacking an endoskeleton, ZA delays Caenorhabditis elegans sarcopenia, which translates to improved neuromuscular function across the life course. Bisphosphonates might, therefore, be an immediately exploitable anti-sarcopenia therapy., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)
- Published
- 2023
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26. Adaptability to eccentric exercise training is diminished with age in female mice.
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Baumann CW, Deane CS, Etheridge T, Szewczyk NJ, Willis CRG, and Lowe DA
- Subjects
- Female, Animals, Mice, Torque, Muscle, Skeletal physiology
- Abstract
The ability of skeletal muscle to adapt to eccentric contractions has been suggested to be blunted in older muscle. If eccentric exercise is to be a safe and efficient training mode for older adults, preclinical studies need to establish if older muscle can effectively adapt and if not, determine the molecular signatures that are causing this impairment. The purpose of this study was to quantify the extent age impacts functional adaptations of muscle and identify genetic signatures associated with adaptation (or lack thereof). The anterior crural muscles of young (4 mo) and older (28 mo) female mice performed repeated bouts of eccentric contractions in vivo (50 contractions/wk for 5 wk) and isometric torque was measured across the initial and final bouts. Transcriptomics was completed by RNA-sequencing 1 wk following the fifth bout to identify common and differentially regulated genes. When torques post eccentric contractions were compared after the first and fifth bouts, young muscle exhibited a robust ability to adapt, increasing isometric torque 20%-36%, whereas isometric torque of older muscle decreased up to 18% ( P ≤ 0.047). Using differential gene expression, young and older muscles shared some common transcriptional changes in response to eccentric exercise training, whereas other transcripts appeared to be age dependent. That is, the ability to express particular genes after repeated bouts of eccentric contractions was not the same between ages. These molecular signatures may reveal, in part, why older muscles do not appear to be as adaptive to exercise training as young muscles. NEW & NOTEWORTHY The ability to adapt to exercise training may help prevent and combat sarcopenia. Here, we demonstrate young mouse muscles get stronger whereas older mouse muscles become weaker after repeated bouts of eccentric contractions, and that numerous genes were differentially expressed between age groups following training. These results highlight that molecular and functional plasticity is not fixed in skeletal muscle with advancing age, and the ability to handle or cope with physical stress may be impaired.
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- 2023
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27. Spaceflight Induces Strength Decline in Caenorhabditis elegans .
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Soni P, Edwards H, Anupom T, Rahman M, Lesanpezeshki L, Blawzdziewicz J, Cope H, Gharahdaghi N, Scott D, Toh LS, Williams PM, Etheridge T, Szewczyk N, Willis CRG, and Vanapalli SA
- Subjects
- Humans, Animals, Caenorhabditis elegans metabolism, Acetylcholine metabolism, Calcium metabolism, Dystrophin genetics, Space Flight, Caenorhabditis elegans Proteins genetics, Caenorhabditis elegans Proteins metabolism
- Abstract
Background: Understanding and countering the well-established negative health consequences of spaceflight remains a primary challenge preventing safe deep space exploration. Targeted/personalized therapeutics are at the forefront of space medicine strategies, and cross-species molecular signatures now define the 'typical' spaceflight response. However, a lack of direct genotype-phenotype associations currently limits the robustness and, therefore, the therapeutic utility of putative mechanisms underpinning pathological changes in flight. Methods: We employed the worm Caenorhabditis elegans as a validated model of space biology, combined with 'NemaFlex-S' microfluidic devices for assessing animal strength production as one of the most reproducible physiological responses to spaceflight. Wild-type and dys-1 (BZ33) strains (a Duchenne muscular dystrophy (DMD) model for comparing predisposed muscle weak animals) were cultured on the International Space Station in chemically defined media before loading second-generation gravid adults into NemaFlex-S devices to assess individual animal strength. These same cultures were then frozen on orbit before returning to Earth for next-generation sequencing transcriptomic analysis. Results: Neuromuscular strength was lower in flight versus ground controls (16.6% decline, p < 0.05), with dys-1 significantly more (23% less strength, p < 0.01) affected than wild types. The transcriptional gene ontology signatures characterizing both strains of weaker animals in flight strongly corroborate previous results across species, enriched for upregulated stress response pathways and downregulated mitochondrial and cytoskeletal processes. Functional gene cluster analysis extended this to implicate decreased neuronal function, including abnormal calcium handling and acetylcholine signaling, in space-induced strength declines under the predicted control of UNC-89 and DAF-19 transcription factors. Finally, gene modules specifically altered in dys-1 animals in flight again cluster to neuronal/neuromuscular pathways, suggesting strength loss in DMD comprises a strong neuronal component that predisposes these animals to exacerbated strength loss in space. Conclusions: Highly reproducible gene signatures are strongly associated with space-induced neuromuscular strength loss across species and neuronal changes in calcium/acetylcholine signaling require further study. These results promote targeted medical efforts towards and provide an in vivo model for safely sending animals and people into deep space in the near future.
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- 2023
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28. Association of macular pigment optical density with retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma.
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Lawler T, Mares JA, Liu Z, Thuruthumaly C, Etheridge T, Vajaranant TS, Domalpally A, Hammond BR, Wallace RB, Tinker LF, Nalbandyan M, Klein BEK, and Liu Y
- Subjects
- Humans, Retinal Ganglion Cells, Intraocular Pressure, Tomography, Optical Coherence methods, Macular Pigment, Glaucoma, Open-Angle diagnostic imaging, Macula Lutea diagnostic imaging
- Abstract
Objective: To investigate associations between baseline macular pigment optical density (MPOD) and retinal layer thicknesses in eyes with and without manifest primary open-angle glaucoma (POAG) in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2)., Methods and Analysis: MPOD was measured at CAREDS baseline (2001-2004) via heterochromatic flicker photometry (0.5° from foveal centre). Peripapillary retinal nerve fibre layer (RNFL), macular ganglion cell complex (GCC), ganglion cell layer (GCL), inner plexiform layer (IPL), and RNFL thicknesses were measured at CAREDS2 (2016-2019) via spectral-domain optical coherence tomography. Associations between MPOD and retinal thickness were assessed using multivariable linear regression., Results: Among 742 eyes (379 participants), manifest POAG was identified in 50 eyes (32 participants). In eyes without manifest POAG, MPOD was positively associated with macular GCC, GCL and IPL thicknesses in the central subfield (P-trend ≤0.01), but not the inner or outer subfields. Among eyes with manifest POAG, MPOD was positively associated with macular GCC, GCL, IPL and RNFL in the central subfield (P-trend ≤0.03), but not the inner or outer subfields, and was positively associated with peripapillary RNFL thickness in the superior and temporal quadrants (P-trend≤0.006)., Conclusion: We observed a positive association between MPOD and central subfield GCC thickness 15 years later. MPOD was positively associated with peripapillary RNFL superior and temporal quadrant thicknesses among eyes with manifest POAG. Our results linking low MPOD to retinal layers that are structural indicators of early glaucoma provide further evidence that carotenoids may be protective against manifest POAG., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)
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- 2023
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29. Comparative Analysis of Muscle Atrophy During Spaceflight, Nutritional Deficiency and Disuse in the Nematode Caenorhabditis elegans .
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Kim BS, Alcantara AV Jr, Moon JH, Higashitani A, Higashitani N, Etheridge T, Szewczyk NJ, Deane CS, Gaffney CJ, Higashibata A, Hashizume T, Yoon KH, and Lee JI
- Subjects
- Humans, Animals, Caenorhabditis elegans genetics, Muscular Atrophy etiology, Malnutrition, Space Flight, Starvation
- Abstract
While spaceflight is becoming more common than before, the hazards spaceflight and space microgravity pose to the human body remain relatively unexplored. Astronauts experience muscle atrophy after spaceflight, but the exact reasons for this and solutions are unknown. Here, we take advantage of the nematode C. elegans to understand the effects of space microgravity on worm body wall muscle. We found that space microgravity induces muscle atrophy in C. elegans from two independent spaceflight missions. As a comparison to spaceflight-induced muscle atrophy, we assessed the effects of acute nutritional deprivation and muscle disuse on C. elegans muscle cells. We found that these two factors also induce muscle atrophy in the nematode. Finally, we identified clp-4 , which encodes a calpain protease that promotes muscle atrophy. Mutants of clp-4 suppress starvation-induced muscle atrophy. Such comparative analyses of different factors causing muscle atrophy in C. elegans could provide a way to identify novel genetic factors regulating space microgravity-induced muscle atrophy.
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- 2023
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30. Mitochondrial sulfide promotes life span and health span through distinct mechanisms in developing versus adult treated Caenorhabditis elegans .
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Vintila AR, Slade L, Cooke M, Willis CRG, Torregrossa R, Rahman M, Anupom T, Vanapalli SA, Gaffney CJ, Gharahdaghi N, Szabo C, Szewczyk NJ, Whiteman M, and Etheridge T
- Subjects
- Animals, Caenorhabditis elegans metabolism, Longevity, Sulfides metabolism, Mitochondria metabolism, Oxidative Stress, GATA Transcription Factors metabolism, Caenorhabditis elegans Proteins genetics, Caenorhabditis elegans Proteins metabolism, Hydrogen Sulfide metabolism
- Abstract
Living longer without simultaneously extending years spent in good health ("health span") is an increasing societal burden, demanding new therapeutic strategies. Hydrogen sulfide (H
2 S) can correct disease-related mitochondrial metabolic deficiencies, and supraphysiological H2 S concentrations can pro health span. However, the efficacy and mechanisms of mitochondrion-targeted sulfide delivery molecules (mtH2 S) administered across the adult life course are unknown. Using a Caenorhabditis elegans aging model, we compared untargeted H2 S (NaGYY4137, 100 µM and 100 nM) and mtH2 S (AP39, 100 nM) donor effects on life span, neuromuscular health span, and mitochondrial integrity. H2 S donors were administered from birth or in young/middle-aged animals (day 0, 2, or 4 postadulthood). RNAi pharmacogenetic interventions and transcriptomics/network analysis explored molecular events governing mtH2 S donor-mediated health span. Developmentally administered mtH2 S (100 nM) improved life/health span vs. equivalent untargeted H2 S doses. mtH2 S preserved aging mitochondrial structure, content (citrate synthase activity) and neuromuscular strength. Knockdown of H2 S metabolism enzymes and FoxO/ daf-16 prevented the positive health span effects of mtH2 S, whereas DCAF11/ wdr-23 - Nrf2/ skn-1 oxidative stress protection pathways were dispensable. Health span, but not life span, increased with all adult-onset mtH2 S treatments. Adult mtH2 S treatment also rejuvenated aging transcriptomes by minimizing expression declines of mitochondria and cytoskeletal components, and peroxisome metabolism hub components, under mechanistic control by the elt-6 / elt-3 transcription factor circuit. H2 S health span extension likely acts at the mitochondrial level, the mechanisms of which dissociate from life span across adult vs. developmental treatment timings. The small mtH2 S doses required for health span extension, combined with efficacy in adult animals, suggest mtH2 S is a potential healthy aging therapeutic.- Published
- 2023
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31. Enhancing European capabilities for application of multi-omics studies in biology and biomedicine space research.
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Manzano A, Weging S, Bezdan D, Borg J, Cahill T, Carnero-Diaz E, Cope H, Deane CS, Etheridge T, Giacomello S, Hardiman G, Leys N, Madrigal P, Mastroleo F, Medina FJ, Mieczkowski J, Fernandez-Rojo MA, Siew K, Szewczyk NJ, Walsh SB, da Silveira WA, and Herranz R
- Abstract
Following on from the NASA twins' study, there has been a tremendous interest in the use of omics techniques in spaceflight. Individual space agencies, NASA's GeneLab, JAXA's ibSLS, and the ESA-funded Space Omics Topical Team and the International Standards for Space Omics Processing (ISSOP) groups have established several initiatives to support this growth. Here, we present recommendations from the Space Omics Topical Team to promote standard application of space omics in Europe. We focus on four main themes: i) continued participation in and coordination with international omics endeavors, ii) strengthening of the European space omics infrastructure including workforce and facilities, iii) capitalizing on the emerging opportunities in the commercial space sector, and iv) capitalizing on the emerging opportunities in human subjects research., Competing Interests: F.M. is CEO/Co-Founder at Genegoggle, D.B. is a cofounder of Poppy Health, Inc. and CSO of Yuri Gravity GmbH and declares affiliations at the NGS Competence Center Tübingen (NCCT), University of Tübingen, Tübingen and Yuri Gravity, Meckenbeuren, Germany. M.F.R. declares additional affiliation at Diamantina Institute, The University of Queensland, St Lucia, Queensland 4072, Australia. S.G. is a scientific consultant of 10x Genomics., (© 2023 The Authors.)
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- 2023
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32. Caenorhabditis elegans in microgravity: An omics perspective.
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Scott A, Willis CRG, Muratani M, Higashitani A, Etheridge T, Szewczyk NJ, and Deane CS
- Abstract
The application of omics to study Caenorhabditis elegans ( C. elegans ) in the context of spaceflight is increasing, illuminating the wide-ranging biological impacts of spaceflight on physiology. In this review, we highlight the application of omics, including transcriptomics, genomics, proteomics, multi-omics, and integrated omics in the study of spaceflown C. elegans , and discuss the impact, use, and future direction of this branch of research. We highlight the variety of molecular alterations that occur in response to spaceflight, most notably changes in metabolic and neuromuscular gene regulation. These transcriptional features are reproducible and evident across many spaceflown species (e.g., mice and astronauts), supporting the use of C. elegans as a model organism to study spaceflight physiology with translational capital. Integrating tissue-specific, spatial, and multi-omics approaches, which quantitatively link molecular responses to phenotypic adaptations, will facilitate the identification of candidate regulatory molecules for therapeutic intervention and thus represents the next frontiers in C. elegans space omics research., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors.)
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- 2023
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33. Proteomic features of skeletal muscle adaptation to resistance exercise training as a function of age.
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Deane CS, Phillips BE, Willis CRG, Wilkinson DJ, Smith K, Higashitani N, Williams JP, Szewczyk NJ, Atherton PJ, Higashitani A, and Etheridge T
- Subjects
- Humans, Aged, Proteome metabolism, Proteomics, Muscle, Skeletal metabolism, Aging physiology, Resistance Training methods
- Abstract
Resistance exercise training (RET) can counteract negative features of muscle ageing but older age associates with reduced adaptive capacity to RET. Altered muscle protein networks likely contribute to ageing RET adaptation; therefore, associated proteome-wide responses warrant exploration. We employed quantitative sarcoplasmic proteomics to compare age-related proteome and phosphoproteome responses to RET. Thigh muscle biopsies were collected from eight young (25 ± 1.1 years) and eight older (67.5 ± 2.6 years) adults before and after 20 weeks supervised RET. Muscle sarcoplasmic fractions were pooled for each condition and analysed using Isobaric Tags for Relative and Absolute Quantification (iTRAQ) labelling, tandem mass spectrometry and network-based hub protein identification. Older adults displayed impaired RET-induced adaptations in whole-body lean mass, body fat percentage and thigh lean mass (P > 0.05). iTRAQ identified 73 differentially expressed proteins with age and/or RET. Despite possible proteomic stochasticity, RET improved ageing profiles for mitochondrial function and glucose metabolism (top hub; PYK (pyruvate kinase)) but failed to correct altered ageing expression of cytoskeletal proteins (top hub; YWHAZ (14-3-3 protein zeta/delta)). These ageing RET proteomic profiles were generally unchanged or oppositely regulated post-RET in younger muscle. Similarly, RET corrected expression of 10 phosphoproteins altered in ageing, but these responses were again different vs. younger adults. Older muscle is characterised by RET-induced metabolic protein profiles that, whilst not present in younger muscle, improve untrained age-related proteomic deficits. Combined with impaired cytoskeletal adhesion responses, these results provide a proteomic framework for understanding and optimising ageing muscle RET adaptation., (© 2022. The Author(s).)
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- 2023
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34. Incidence and severity of asymptomatic ocular injury in adult and pediatric orbital fractures.
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Etheridge T, Brintz BJ, Jensen MS, Peralta E, Ayesha A, Jebaraj A, and Marx DP
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- Humans, Adult, Male, Child, Young Adult, Middle Aged, Female, Incidence, Retrospective Studies, Visual Acuity, Orbital Fractures epidemiology, Orbital Fractures complications, Eye Injuries epidemiology, Eye Injuries etiology
- Abstract
Purpose: To evaluate the incidence of severe ocular injury requiring emergent ophthalmic evaluation in visually asymptomatic patients presenting with orbital fractures., Methods: We performed a retrospective chart review of all adult and pediatric orbital fractures between 2012-2022 at a level 1 trauma center. Ocular injuries were categorized into severe, moderate, and mild. We evaluated symptoms, mechanism of injury, visual acuity (VA), and severity of injuries using the Cochran-Armitage and linear-by-linear tests., Results: Of the 2495 cases, 1534 had ophthalmology evaluation. The mean ± standard deviation age was 40.4 ± 20.4 years. Most patients were male (73.1%) and Caucasian (75.9%). The mean time to evaluation was 0.6 ± 2.5 days. 486 (31.7%) were visually symptomatic, 760 (49.5%) were asymptomatic, and 288 (18.8%) were unknown. Of the symptomatic, 135 (27.8%) had severe injuries, 108 (22.2%) had moderate injuries, 216 (44.4%) had mild injuries, and 27 (5.6%) had no injuries. Of the asymptomatic, 67 (8.8%) had severe injuries, 183 (24.1%) had moderate injuries, 468 (61.6%) had mild injuries, and 42 (5.5%) had no injuries. Symptoms correlated with injury severity ( p -value <.001). The most common mechanism of injury were falls (24.0%), assaults (22.2%), and motor vehicle accidents (14.8%)., Conclusions: Visually asymptomatic orbital fractures were less likely to have severe ocular injuries; however, many patients were unable to express symptoms. Emergent ophthalmology evaluation should be considered in all patients presenting with orbital fractures, especially patients with visual symptoms or are unable to report symptoms.
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- 2023
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35. An evaluation of the role of miR-361-5p in senescence and systemic ageing.
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Manni E, Jeffery N, Chambers D, Slade L, Etheridge T, and Harries LW
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- Animals, Humans, Caenorhabditis elegans genetics, Cellular Senescence genetics, RNA Interference, Endothelial Cells, MicroRNAs genetics
- Abstract
Senescent cells are key regulators of ageing and age-associated disease. MicroRNAs (miRs) are a key component of the molecular machinery governing cellular senescence, with several known to regulate important genes associated with this process. We sought to identify miRs associated with both senescence and reversal by pinpointing those showing opposing directionality of effect in senescence and in response to senotherapy. Cellular senescence phenotypes were assessed in primary human endothelial cells following targeted manipulation of emergent miRNAs. Finally, the effect of conserved target gene knockdown on lifespan and healthspan was assessed in a C. elegans system in vivo. Three miRNAs (miR-5787, miR-3665 and miR-361-5p) demonstrated associations with both senescence and rejuvenation, but miR-361-5p alone demonstrated opposing effects in senescence and rescue. Treatment of late passage human endothelial cells with a miR-361-5p mimic caused a 14 % decrease in the senescent load of the culture. RNAi gene knockdown of conserved miR-361-5p target genes in a C. elegans model however resulted in adverse effects on healthspan and/or lifespan. Although miR-361-5p may attenuate aspects of the senescence phenotype in human primary endothelial cells, many of its validated target genes also play essential roles in the regulation or formation of the cytoskeletal network, or its interaction with the extracellular matrix. These processes are essential for cell survival and cell function. Targeting miR-361-5p alone may not represent a promising target for future senotherapy; more sophisticated approaches to attenuate its interaction with specific targets without roles in essential cell processes would be required., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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36. STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS: NOVEL FINDINGS AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY ANALYSIS.
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Schildroth KR, Mititelu M, Etheridge T, Holman I, and Chang JS
- Subjects
- Humans, Female, Male, Tomography, Optical Coherence methods, Bevacizumab, Retrospective Studies, Fluorescein Angiography methods, Retinoschisis
- Abstract
Purpose: To present novel findings in stellate nonhereditary idiopathic foveomacular retinoschisis, including the largest series of optical coherence tomography angiography findings to date., Methods: A retrospective case series with multimodal imaging was obtained and reviewed., Results: All three patients were women, aged 59-63. Two cases were unilateral, and one was bilateral. Vision ranged from 20/20 to 20/60 in the affected eyes. Peripheral retinoschisis was observed in all three patients. All patients were followed for a minimum of 1 year. In one case, progressive macular retinoschisis leading to foveal involvement was observed over two years, with an associated vision decline from 20/25 to 20/60. Attempted interventions included topical dorzolamide in all cases and intravitreal bevacizumab in one patient; however, no treatment effect was observed. The foveal avascular zone size was within normal limits (mean 280 µ m). In all stellate nonhereditary idiopathic foveomacular retinoschisis eyes, the retinoschisis cavities were nonvascular., Conclusion: Novel findings regarding stellate nonhereditary idiopathic foveomacular retinoschisis include the progressive nature of foveal involvement and the lack of response to topical dorzolamide and intravitreal bevacizumab. Foveal avascular zone was normal in all eyes, consistent with the relatively preserved vision in these cases. Retinoschisis cavities were nonvascular in all eyes, a finding which may give insight into the mechanism of this disease.
- Published
- 2023
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37. Implantation Cyst of Anterior Chamber: A Case Report.
- Author
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Peralta E, Etheridge T, Harrie R, and Lin A
- Abstract
This clinical case report describes a single case of a progressively enlarging anterior chamber cyst arising in a patient with prior cataract surgery. We detail findings of a large implantation cyst within the anterior chamber, confirmed on ultrasound biomicroscopy. The patient was successfully treated with needle aspiration and injection of 5-fluorouracil without recurrence at 5 months. Anterior chamber cysts are a rare side effect of cataract surgery caused by intrusion of epithelial cells during surgery. Patients may present with a progressively enlarging mass requiring surgical intervention. Aspiration and injection of a cytodestructive chemical agent is one conservative approach in the management of an implantation cyst, with our patient exhibiting favorable visual outcomes., Competing Interests: The following authors have no financial disclosures: Esteban Peralta, Tyler Etheridge, Roger Harrie, and Amy Lin., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2022
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38. Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy.
- Author
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Ellwood RA, Slade L, Lewis J, Torregrossa R, Sudevan S, Piasecki M, Whiteman M, Etheridge T, and Szewczyk NJ
- Subjects
- Animals, Caenorhabditis elegans genetics, Sulfur, Cysteine, Dietary Supplements, Muscular Dystrophy, Duchenne drug therapy, Muscular Dystrophy, Duchenne genetics
- Abstract
Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), a common muscle disease that manifests with muscle weakness, wasting, and degeneration. An emerging theme in DMD pathophysiology is an intramuscular deficit in the gasotransmitter hydrogen sulfide (H
2 S). Here we show that the C. elegans DMD model displays reduced levels of H2 S and expression of genes required for sulfur metabolism. These reductions can be offset by increasing bioavailability of sulfur containing amino acids (L-methionine, L-homocysteine, L-cysteine, L-glutathione, and L-taurine), augmenting healthspan primarily via improved calcium regulation, mitochondrial structure and delayed muscle cell death. Additionally, we show distinct differences in preservation mechanisms between sulfur amino acid vs H2 S administration, despite similarities in required health-preserving pathways. Our results suggest that the H2 S deficit in DMD is likely caused by altered sulfur metabolism and that modulation of this pathway may improve DMD muscle health via multiple evolutionarily conserved mechanisms., (© 2022. The Author(s).)- Published
- 2022
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39. Cognitive enhancing supplements and medications in United States Resident Physicians.
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Etheridge T, Kennedy B, Millar MM, Brintz BJ, Wu C, and Pettey J
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- Adult, Child, Male, United States, Humans, Female, Pilot Projects, Surveys and Questionnaires, Cognition, Internship and Residency, Physicians psychology
- Abstract
Background: The use of cognitive-enhancing medications and supplements among healthy adults continues to rise. Limited data exists on their use among resident physicians. Given their highly competitive and stressful lifestyle, we sought to evaluate the prevalence, motivations, and side effects of using cognitive-enhancing supplements and medications among resident physicians at a large United States academic institution., Methods: An anonymous web-based survey was circulated to resident physicians inquiring about using cognitive-enhancing supplements and medications, as well as personal characteristics such as gender, marital and parental status, medical diagnoses, and medical specialty. Before circulation, we performed a pilot study. Weighted logistic regression analyses estimated the impact of personal characteristics on the probability of using both supplements and medications., Results: Survey response rate was 46.4%. Of respondents, 48.6% were female, 45.9% were married, 70.9% were without children, and 67.2% were in a non-surgical medical specialty. Few respondents had a related medical diagnosis, with attention deficit hyperactivity disorder being the most common (7.1%). Male, non-married, surgical residents were more likely to take supplements (odds ratio (OR) = 1.06, 1.05, and 1.05). Males, without children, and those who felt pressure to perform well, were afraid of being left behind, felt pressure because colleagues take them, or felt they could not reach their current level of training without medications were more likely to take medications (OR = 1.11, 1.04, 1.05, and 1.08). Adverse effects with medications were common., Conclusion: Supplement and medication use for cognitive enhancement was high among resident physicians at a single institution despite few having a related medical diagnosis. This study raises awareness of the growing pressure in competitive residency environments to use cognitive enhancement regardless of the potential side effects., (© 2022. The Author(s).)
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- 2022
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40. Bilateral Posterior Cerebral Artery Stroke from COVID-Related Multisystem Inflammatory Syndrome in a Child.
- Author
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Wilkinson SW, Etheridge T, Swiston CJ, Vegunta S, Wiggins RH, and Warner JEA
- Subjects
- Child, Humans, Systemic Inflammatory Response Syndrome, COVID-19 complications, Infarction, Posterior Cerebral Artery
- Abstract
Competing Interests: The authors report no conflicts of interest.
- Published
- 2022
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41. Routine omics collection is a golden opportunity for European human research in space and analog environments.
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Cope H, Willis CRG, MacKay MJ, Rutter LA, Toh LS, Williams PM, Herranz R, Borg J, Bezdan D, Giacomello S, Muratani M, Mason CE, Etheridge T, and Szewczyk NJ
- Abstract
Widespread generation and analysis of omics data have revolutionized molecular medicine on Earth, yet its power to yield new mechanistic insights and improve occupational health during spaceflight is still to be fully realized in humans. Nevertheless, rapid technological advancements and ever-regular spaceflight programs mean that longitudinal, standardized, and cost-effective collection of human space omics data are firmly within reach. Here, we consider the practicality and scientific return of different sampling methods and omic types in the context of human spaceflight. We also appraise ethical and legal considerations pertinent to omics data derived from European astronauts and spaceflight participants (SFPs). Ultimately, we propose that a routine omics collection program in spaceflight and analog environments presents a golden opportunity. Unlocking this bright future of artificial intelligence (AI)-driven analyses and personalized medicine approaches will require further investigation into best practices, including policy design and standardization of omics data, metadata, and sampling methods., (© 2022 The Authors.)
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- 2022
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42. Editorial: Integrative Physiology of Common Chronic Musculoskeletal Disorders.
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Clark BC, Grooms DR, Etheridge T, Wilkinson DJ, Zhu S, Arnold WD, and Szewczyk NJ
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2022
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43. Barriers to Physiotherapists' Use of Professional Development Tools for Chronic Pain: A Knowledge Translation Study.
- Author
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Etheridge T, Bostick GP, Hoens AM, Holly J, Ippersiel P, Bobos P, Arumugam V, Woods S, Gielen S, Woznowski-Vu A, and Campbell N
- Abstract
Purpose: The Pain Science Division (PSD) is a special interest group of the Canadian Physiotherapy Association that serves physiotherapists who have an interest in better understanding and managing patients' pain. The PSD developed evidence-based resources for its members with the goal of improving patient care by supporting professional development. However, online metrics tracking access to these resources indicated that access was low. The purpose of this study was to identify the barriers PSD members encountered to the use of PSD resources and to recommend interventions to address these barriers guided by the Theory and Techniques Tool (TTT). Method: We distributed an online survey to PSD members across Canada. We used the TTT, a knowledge translation tool, to guide the design of the questionnaire and identify actionable findings. Results: Response rates from 621 non-student members and 1,470 student members were 26.9% and 1.4%, respectively. Based on the frequency of practising physiotherapists' ( n = 167) agreement with items in the TTT, the primary barriers to use of the PSD resources were forgetting that the resources were available and forgetting to use them. Conclusions: The TTT can be used to identify barriers to use of professional development tools., (© Canadian Physiotherapy Association.)
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- 2022
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44. Chronic postoperative Cutibacterium acnes endophthalmitis with implantable collamer lens.
- Author
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Wilkinson S, Etheridge T, Monson BK, and Larochelle MB
- Abstract
Purpose: We report a case of chronic post-operative endophthalmitis secondary to Cutibacterium acnes ( C. acnes ) in a patient with an implantable collamer lens (ICL)., Observations: A 45-year-old male presented three months after ICL implantation of the right eye with blurry vision, redness, and ocular pain in the setting of prolonged post-operative anterior chamber (AC) cell. Reduced visual acuity (VA) at 20/30-1, keratic precipitates, 1+ AC cell, and white ICL precipitates were concerning for chronic post-operative endophthalmitis. Anaerobic cultures from a vitreous tap grew C. acnes . Multiple intravitreal and intracameral injections with topical steroids were required to maintain a stable VA at 20/30; however, inflammation persisted and removal of the ICL and his native lens was ultimately required., Conclusions and Importance: Chronic post-operative inflammation and white plaque after ICL implantation should raise high suspicion for endophthalmitis secondary to C. acnes . Anaerobic vitreous cultures can confirm the diagnosis. Removal of the ICL implant is often necessary for treatment. More research is needed to best manage this vision threatening condition., Competing Interests: The following authors have no financial disclosures: SW, TE, MBL., (© 2022 Published by Elsevier Inc.)
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- 2022
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45. Loss of physical contact in space alters the dopamine system in C. elegans .
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Sudevan S, Muto K, Higashitani N, Hashizume T, Higashibata A, Ellwood RA, Deane CS, Rahman M, Vanapalli SA, Etheridge T, Szewczyk NJ, and Higashitani A
- Abstract
Progressive neuromuscular decline in microgravity is a prominent health concern preventing interplanetary human habitation. We establish functional dopamine-mediated impairments as a consistent feature across multiple spaceflight exposures and during simulated microgravity in C. elegans . Animals grown continuously in these conditions display reduced movement and body length. Loss of mechanical contact stimuli in microgravity elicits decreased endogenous dopamine and comt-4 (catechol-O-methyl transferase) expression levels. The application of exogenous dopamine reverses the movement and body length defects caused by simulated microgravity. In addition, increased physical contact made comt-4 and dopamine levels rise. It also increased muscular cytoplasmic Ca
2+ firing. In dop-3 (D2-like receptor) mutants, neither decrease in movement nor in body length were observed during simulated microgravity growth. These results strongly suggest that targeting the dopamine system through manipulation of the external environment (contact stimuli) prevents muscular changes and is a realistic and viable treatment strategy to promote safe human deep-space travel., Competing Interests: Authors declare that they have no competing interests., (© 2022 The Author(s).)- Published
- 2022
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46. Transcriptomic adaptation during skeletal muscle habituation to eccentric or concentric exercise training.
- Author
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Willis CRG, Deane CS, Ames RM, Bass JJ, Wilkinson DJ, Smith K, Phillips BE, Szewczyk NJ, Atherton PJ, and Etheridge T
- Subjects
- Adult, Humans, Male, Adaptation, Physiological, Exercise, Muscle Contraction, Muscle Proteins biosynthesis, Muscle, Skeletal metabolism, Transcriptome
- Abstract
Eccentric (ECC) and concentric (CON) contractions induce distinct muscle remodelling patterns that manifest early during exercise training, the causes of which remain unclear. We examined molecular signatures of early contraction mode-specific muscle adaptation via transcriptome-wide network and secretome analyses during 2 weeks of ECC- versus CON-specific (downhill versus uphill running) exercise training (exercise 'habituation'). Despite habituation attenuating total numbers of exercise-induced genes, functional gene-level profiles of untrained ECC or CON were largely unaltered post-habituation. Network analysis revealed 11 ECC-specific modules, including upregulated extracellular matrix and immune profiles plus downregulated mitochondrial pathways following untrained ECC. Of 3 CON-unique modules, 2 were ribosome-related and downregulated post-habituation. Across training, 376 ECC-specific and 110 CON-specific hub genes were identified, plus 45 predicted transcription factors. Secreted factors were enriched in 3 ECC- and/or CON-responsive modules, with all 3 also being under the predicted transcriptional control of SP1 and KLF4. Of 34 candidate myokine hubs, 1 was also predicted to have elevated expression in skeletal muscle versus other tissues: THBS4, of a secretome-enriched module upregulated after untrained ECC. In conclusion, distinct untrained ECC and CON transcriptional responses are dampened after habituation without substantially shifting molecular functional profiles, providing new mechanistic candidates into contraction-mode specific muscle regulation., (© 2021. The Author(s).)
- Published
- 2021
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47. Spectral Domain OCT Predictors of Visual Acuity in the Study of COmparative Treatments for REtinal Vein Occlusion 2: SCORE 2 Report 15.
- Author
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Etheridge T, Blodi B, Oden N, Van Veldhuisen P, Scott IU, Ip MS, Mititelu M, and Domalpally A
- Subjects
- Aged, Aged, 80 and over, Bevacizumab therapeutic use, Female, Follow-Up Studies, Humans, Intravitreal Injections, Macular Edema drug therapy, Macular Edema physiopathology, Male, Middle Aged, Prospective Studies, Receptors, Vascular Endothelial Growth Factor therapeutic use, Recombinant Fusion Proteins therapeutic use, Retinal Vein Occlusion drug therapy, Retinal Vein Occlusion physiopathology, Subretinal Fluid, Angiogenesis Inhibitors therapeutic use, Macular Edema diagnostic imaging, Retinal Vein Occlusion diagnostic imaging, Tomography, Optical Coherence, Visual Acuity physiology
- Abstract
Purpose: To evaluate the association between baseline demographic and spectral domain OCT (SD-OCT) features with visual acuity (VA) in the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2) over 2 years., Design: Post hoc analysis of prospective clinical trial data., Participants: A total of 362 SCORE2 participants with macular edema secondary to central retinal (CRVO) or hemiretinal vein occlusion (HRVO)., Methods: Spectral domain OCT volume scans were assessed at the SCORE2 reading center at baseline, month 01 (M01), month 06 (M06), month 12 (M12), and month 24 (M24) for central subfield thickness (CST), subretinal fluid, intraretinal fluid, vitreoretinal interface abnormalities, disorganization of retinal inner layers (DRIL), and ellipsoid zone (EZ) within the central subfield (CSF)., Main Outcome Measures: Visual acuity at M06, M12, and M24., Results: Mean baseline age was 68.9 years. Mean VA at M01 was 63.2 letters, and CST was 299.7 μm. At M01, subretinal fluid was seen in 28.5% intraretinal fluid in 67.2%, DRIL was seen in 73.8%, mostly within the CSF, and the EZ was absent in 9.8 and patchy in 31.7%. In multivariate analysis including all M01 demographics and SD-OCT parameters and their association with VA at M06, M12, and M24, VA at M01 remained significant across all time points up to M24 (P < 0.001)., Conclusions: In this 2-year follow-up of eyes that were treated with both per protocol and off protocol for RVO, VA at M01 was an important predictor of long-term vision and change in vision. Establishing predictors of visual recovery helps identify causes for poor responders to treatment in patients with RVO., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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48. Transcriptomic links to muscle mass loss and declines in cumulative muscle protein synthesis during short-term disuse in healthy younger humans.
- Author
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Willis CRG, Gallagher IJ, Wilkinson DJ, Brook MS, Bass JJ, Phillips BE, Smith K, Etheridge T, Stokes T, McGlory C, Gorissen SHM, Szewczyk NJ, Phillips SM, and Atherton PJ
- Subjects
- Adult, Humans, Male, Muscle Strength genetics, Young Adult, Muscle Proteins genetics, Muscle, Skeletal physiology, Muscular Atrophy genetics, Muscular Diseases genetics, Protein Biosynthesis genetics, Transcriptome genetics
- Abstract
Muscle disuse leads to a rapid decline in muscle mass, with reduced muscle protein synthesis (MPS) considered the primary physiological mechanism. Here, we employed a systems biology approach to uncover molecular networks and key molecular candidates that quantitatively link to the degree of muscle atrophy and/or extent of decline in MPS during short-term disuse in humans. After consuming a bolus dose of deuterium oxide (D
2 O; 3 mL.kg-1 ), eight healthy males (22 ± 2 years) underwent 4 days of unilateral lower-limb immobilization. Bilateral muscle biopsies were obtained post-intervention for RNA sequencing and D2 O-derived measurement of MPS, with thigh lean mass quantified using dual-energy X-ray absorptiometry. Application of weighted gene co-expression network analysis identified 15 distinct gene clusters ("modules") with an expression profile regulated by disuse and/or quantitatively connected to disuse-induced muscle mass or MPS changes. Module scans for candidate targets established an experimentally tractable set of candidate regulatory molecules (242 hub genes, 31 transcriptional regulators) associated with disuse-induced maladaptation, many themselves potently tied to disuse-induced reductions in muscle mass and/or MPS and, therefore, strong physiologically relevant candidates. Notably, we implicate a putative role for muscle protein breakdown-related molecular networks in impairing MPS during short-term disuse, and further establish DEPTOR (a potent mTOR inhibitor) as a critical mechanistic candidate of disuse driven MPS suppression in humans. Overall, these findings offer a strong benchmark for accelerating mechanistic understanding of short-term muscle disuse atrophy that may help expedite development of therapeutic interventions., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)- Published
- 2021
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49. Transcriptomic meta-analysis of disuse muscle atrophy vs. resistance exercise-induced hypertrophy in young and older humans.
- Author
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Deane CS, Willis CRG, Phillips BE, Atherton PJ, Harries LW, Ames RM, Szewczyk NJ, and Etheridge T
- Subjects
- Aged, Humans, Hypertrophy, Mechanotransduction, Cellular, Muscle, Skeletal, Muscular Atrophy genetics, Transcriptome, Resistance Training
- Abstract
Background: Skeletal muscle atrophy manifests across numerous diseases; however, the extent of similarities/differences in causal mechanisms between atrophying conditions in unclear. Ageing and disuse represent two of the most prevalent and costly atrophic conditions, with resistance exercise training (RET) being the most effective lifestyle countermeasure. We employed gene-level and network-level meta-analyses to contrast transcriptomic signatures of disuse and RET, plus young and older RET to establish a consensus on the molecular features of, and therapeutic targets against, muscle atrophy in conditions of high socio-economic relevance., Methods: Integrated gene-level and network-level meta-analysis was performed on publicly available microarray data sets generated from young (18-35 years) m. vastus lateralis muscle subjected to disuse (unilateral limb immobilization or bed rest) lasting ≥7 days or RET lasting ≥3 weeks, and resistance-trained older (≥60 years) muscle., Results: Disuse and RET displayed predominantly separate transcriptional responses, and transcripts altered across conditions were mostly unidirectional. However, disuse and RET induced directly inverted expression profiles for mitochondrial function and translation regulation genes, with COX4I1, ENDOG, GOT2, MRPL12, and NDUFV2, the central hub components of altered mitochondrial networks, and ZMYND11, a hub gene of altered translation regulation. A substantial number of genes (n = 140) up-regulated post-RET in younger muscle were not similarly up-regulated in older muscle, with young muscle displaying a more pronounced extracellular matrix (ECM) and immune/inflammatory gene expression response. Both young and older muscle exhibited similar RET-induced ubiquitination/RNA processing gene signatures with associated PWP1, PSMB1, and RAF1 hub genes., Conclusions: Despite limited opposing gene profiles, transcriptional signatures of disuse are not simply the converse of RET. Thus, the mechanisms of unloading cannot be derived from studying muscle loading alone and provides a molecular basis for understanding why RET fails to target all transcriptional features of disuse. Loss of RET-induced ECM mechanotransduction and inflammatory profiles might also contribute to suboptimal ageing muscle adaptations to RET. Disuse and age-dependent molecular candidates further establish a framework for understanding and treating disuse/ageing atrophy., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)
- Published
- 2021
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50. Management of Retinal Detachment Associated with Morning Glory Disc Syndrome.
- Author
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Etheridge T, Oakey Z, and Altaweel MM
- Abstract
We report a case of morning glory disc anomaly in a young patient with tractional retinal detachment successfully repaired with complex pars plana vitrectomy, membrane peel, laser, and oil tamponade. A 19-year-old female with a history of right morning glory disc anomaly associated with PAX6 gene mutation presented with floaters, photopsia, central scotoma, and visual acuity (VA) of 1/200. A complex macula-involving tractional retinal detachment centered around the optic nerve with a morning glory disc anomaly. Retinal detachment was treated with 25-gauge pars plana vitrectomy with difficult separation of the posterior hyaloid. Fibrous preretinal membranes were peeled, a temporal relaxing retinotomy was required, subretinal fluid was drained through a superonasal retinotomy during air-fluid exchange, endolaser was applied, and tamponade was achieved with 1,000-centistoke silicone oil. The retina remained attached at 1-year follow-up, with VA count fingers throughout. Morning glory disc is a rare congenital anomaly associated with PAX6 gene mutation that most often occurs unilaterally. It is rarely associated with tractional retinal detachment. Optimization of visual outcome is imperative despite a poor visual prognosis., Competing Interests: The authors have no financial disclosures., (Copyright © 2021 by S. Karger AG, Basel.)
- Published
- 2021
- Full Text
- View/download PDF
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