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Item Fixed lateral unicompartmental knee replacement is a reliable treatment for lateral compartment osteoarthritis after mobile-bearing medial unicompartmental replacement(Springer, 2023-09-28) Lazzara, Joseph T.; Arthur, Lachlan W.; Jenkins, Cathy; Dodd, Christopher A. F.; Mellon, Stephen J.; Murray, David W.Purpose: Lateral osteoarthritis following medial unicompartmental knee replacement (UKR) is usually treated with total knee replacement, however, lateral UKR is a less invasive option that preserves a well-functioning medial UKR. This study aimed to determine the 5-year outcome of the cemented Fixed Lateral Oxford UKR (FLO) when used for the treatment of severe lateral disease after medial Oxford unicompartmental knee replacement. Methods: Forty-four knees with lateral bone-on-bone osteoarthritis (n = 43) and avascular necrosis (n = 1) treated with the FLO following medial Oxford UKR were followed up prospectively. The Oxford Knee Score (OKS) and Tegner Activity Score (TAS) were collected pre- and post-operatively. Life-table analysis was used to determine survival rates. Results: The mean patient age at the time of FLO surgery was 74.4 years with a mean time of 12.1 years between the primary medial UKR and the conversion to a bi-UKR with a FLO. Mean follow-up of the FLO was 3.5 years. After FLO no intra-operative or medical complications, re-admissions, or mortality occurred. There was one reoperation in which a bearing was exchanged for a medial bearing dislocation. There were no revisions of the FLO, so the FLO survival rate at 5 years was 100% (24 at risk). The mean pre-operative OKS was 22, which significantly (p < 0.0001) improved to a mean of 42, 42, and 40 at 1, 2, and 5 years, respectively. The median TAS had a non-significant improvement from 2.5 (Range 0-8) pre-operatively to 2 (Range 1-6) at 5 years postoperatively. Conclusion: The FLO is a reliable treatment for lateral osteoarthritis following medial UKR. At 5 years there was a 100% survival of the FLO with a mean OKS of 40.Item Osteoclast-mediated bone loss observed in a COVID-19 mouse model(2021-10-02) Awosanya, Olatundun D.; Dalloul, Christopher E.; Blosser, Rachel J.; Dadwal, Ushashi C.; Carozza, Mariel; Boschen, Karen; Klemsz, Michael J.; Johnston, Nancy A.; Bruzzaniti, Angela; Robinson, Christopher M.; Srour, Edward F.; Kacena, Melissa A.The consequences of SARS-CoV-2 infection on the musculoskeletal system represent a dangerous knowledge gap. Aging patients are at added risk for SARS-CoV-2 infection; therefore, a greater understanding of the resulting musculoskeletal sequelae of SARS-CoV-2 infection may help guide clinical strategies. This study examined fundamental bone parameters among mice treated with escalating viral loads. Male C57BL/6J (WT, n = 17) and B6.Cg-Tg(K18-ACE2)2Prlmn/J mice (K18-hACE2 transgenic mice, n = 21) expressing human ACE2 (TG) were divided into eight groups (n = 4-6/group) and subjected to intranasal dosing of 0, 1 × 103, 1 × 104, and 1 × 105 PFU (plaque forming units) of human SARS-CoV-2. Animal health was assessed daily by veterinary staff using established and validated scoring criteria (activity, posture, body condition scores and body weight). We report here that mock and WT infected mice were healthy and completed the study, surviving until 12-14 days post infection (dpi). In contrast, the TG mice infected with 1 × 105 PFU all experienced severe health declines that necessitated early euthanasia (6-7 dpi). For TG mice infected with 1 × 104 PFU, 2 mice were also euthanized after 7 dpi, while 3 mice showed signs of moderate disease at day 6 dpi, but recovered fully by day 11 dpi. Four of the 5 TG mice that were infected with 1 × 103 PFU remained healthy throughout the study. This suggests that our study mimics what is seen during human disease, where some patients develop severe disease resulting in death, while others have moderate to severe disease but recover, and others are asymptomatic. At necropsy, femurs were extracted and analyzed by μCT. No difference was found in μCT determined bone parameters among the WT groups. There was, however, a significant 24.4% decrease in trabecular bone volume fraction (p = 0.0009), 19.0% decrease in trabecular number (p = 0.004), 6.2% decrease in trabecular thickness (p = 0.04), and a 9.8% increase in trabecular separation (p = 0.04) among surviving TG mice receiving any viral load compared to non-infected controls. No differences in cortical bone parameters were detected. TRAP staining revealed surviving infected mice had a significant 64% increase in osteoclast number, a 27% increase in osteoclast surface, and a 38% increase in osteoclasts per bone surface. While more studies are needed to investigate the long-term consequences of SARS-CoV-2 infection on skeletal health, this study demonstrates a significant reduction in several bone parameters and corresponding robust increases in osteoclast number observed within 2 weeks post-infection in surviving asymptomatic and moderately affected mice.Item Trans-omic knowledge transfer modeling infers gut microbiome biomarkers of anti-TNF resistance in ulcerative colitis(World Scientific, 2023) Trinh, Alan; Ran, Ran; Brubaker, Douglas KA critical challenge in analyzing multi-omics data from clinical cohorts is the re-use of these valuable datasets to answer biological questions beyond the scope of the original study. Transfer Learning and Knowledge Transfer approaches are machine learning methods that leverage knowledge gained in one domain to solve a problem in another. Here, we address the challenge of developing Knowledge Transfer approaches to map trans-omic information from a multi-omic clinical cohort to another cohort in which a novel phenotype is measured. Our test case is that of predicting gut microbiome and gut metabolite biomarkers of resistance to anti-TNF therapy in Ulcerative Colitis patients. Three approaches are proposed for Trans-omic Knowledge Transfer, and the resulting performance and downstream inferred biomarkers are compared to identify efficacious methods. We find that multiple approaches reveal similar metabolite and microbial biomarkers of anti-TNF resistance and that these commonly implicated biomarkers can be validated in literature analysis. Overall, we demonstrate a promising approach to maximize the value of the investment in large clinical multi-omics studies by re-using these data to answer biological and clinical questions not posed in the original study.Item Machine embroidery of light-emitting textiles with multicolor electroluminescent threads(Science Advances, 2024-01-03) Cho, Seungse; Chang, Taehoo; Yu, Tianhao; Gong, Sunland L.; Lee, Chi HwanAdvances in electroluminescent threads, suitable for weaving or knitting, have opened doors for the development of light-emitting textiles, driving growth in the market for flexible and wearable displays. Although direct embroidery of these textiles with custom designs and patterns could offer substantial benefits, the rigorous demands of machine embroidery challenge the integrity of these threads. Here, we present embroiderable multicolor electroluminescent threads-in blue, green, and yellow-that are compatible with standard embroidery machines. These threads can be used to stitch decorative designs onto various consumer fabrics without compromising their wear resistance or light-emitting capabilities. Demonstrations include illuminating specific messages or designs on consumer products and delivering emergency alerts on helmet liners for physical hazards. Our research delivers a comprehensive toolkit for integrating light-emitting textiles into trendy, customized crafts tailored to the unique requirements of diverse flexible and wearable displays.Item Quantification of murine myocardial infarct size using 2-D and 4-D high-frequency ultrasound(American Physiological Society, 2022) Dann, Melissa M.; Clark, Sydney Q.; Trzaskalski, Natasha A.; Earl, Conner C.; Schepers, Luke E.; Pulente, Selena M.; Lennord, Ebonee N.; Annamalai, Karthik; Gruber, Joseph M.; Cox, Abigail D.; Lorenzen-Schmidt, Ilka; Seymour, Richard; Kim, Kyoung-Han; Goergen, Craig J.; Mulvihill, Erin E.; Medicine, School of MedicineIschemic heart disease is the leading cause of death in the United States, Canada, and worldwide. Severe disease is characterized by coronary artery occlusion, loss of blood flow to the myocardium, and necrosis of tissue, with subsequent remodeling of the heart wall, including fibrotic scarring. The current study aims to demonstrate the efficacy of quantitating infarct size via two-dimensional (2-D) echocardiographic akinetic length and four-dimensional (4-D) echocardiographic infarct volume and surface area as in vivo analysis techniques. We further describe and evaluate a new surface area strain analysis technique for estimating myocardial infarction (MI) size after ischemic injury. Experimental MI was induced in mice via left coronary artery ligation. Ejection fraction and infarct size were measured through 2-D and 4-D echocardiography. Infarct size established via histology was compared with ultrasound-based metrics via linear regression analysis. Two-dimensional echocardiographic akinetic length (r = 0.76, P = 0.03), 4-D echocardiographic infarct volume (r = 0.85, P = 0.008), and surface area (r = 0.90, P = 0.002) correlate well with histology. Although both 2-D and 4-D echocardiography were reliable measurement techniques to assess infarct, 4-D analysis is superior in assessing asymmetry of the left ventricle and the infarct. Strain analysis performed on 4-D data also provides additional infarct sizing techniques, which correlate with histology (surface strain: r = 0.94, P < 0.001, transmural thickness: r = 0.76, P = 0.001). Two-dimensional echocardiographic akinetic length, 4-D echocardiography ultrasound, and strain provide effective in vivo methods for measuring fibrotic scarring after MI. NEW & NOTEWORTHY: Our study supports that both 2-D and 4-D echocardiographic analysis techniques are reliable in quantifying infarct size though 4-D ultrasound provides a more holistic image of LV function and structure, especially after myocardial infarction. Furthermore, 4-D strain analysis correctly identifies infarct size and regional LV dysfunction after MI. Therefore, these techniques can improve functional insight into the impact of pharmacological interventions on the pathophysiology of cardiac disease.Item In situ efficacy of an experimental toothpaste on enamel rehardening and prevention of demineralisation: a randomised, controlled trial(BMC, 2020) Creeth, Jonathan E.; Burnett, Gary R.; Souverain, Audrey; Gomez-Pereira, Paola; Zero, Domenick T.; Lippert, Frank; Hara, Anderson T.; Cariology, Operative Dentistry and Dental Public Health, School of DentistryBackground A novel sodium fluoride toothpaste containing lactate ion and polyvinylmethylether-maleic anhydride has been developed to promote enamel remineralisation and resistance to demineralisation. In this in situ study, we compared this toothpaste (‘Test’) with a stannous fluoride-zinc citrate (SnF2-Zn) toothpaste (‘Reference’) (both 1100–1150 ppm fluoride) and a fluoride-free toothpaste (‘Placebo’) using an enamel dental erosion-rehardening model. Methods In each phase of this randomised, investigator-blind, crossover study, participants wore palatal appliances holding bovine enamel specimens with erosive lesions. They brushed their natural teeth with either the Test, Reference or Placebo toothpastes, then swished the resultant slurry. Specimens were removed at 2 h and 4 h post-brushing and exposed to an in vitro acid challenge. Surface microhardness was measured at each stage; enamel fluoride uptake was measured after in situ rehardening. Surface microhardness recovery, relative erosion resistance, enamel fluoride uptake and acid resistance ratio were calculated at both timepoints. Results Sixty two randomised participants completed the study. Test toothpaste treatment yielded significantly greater surface microhardness recovery, relative erosion resistance and enamel fluoride uptake values than either Reference or Placebo toothpastes after 2 and 4 h. The acid resistance ratio value for Test toothpaste was significantly greater than either of the other treatments after 2 h; after 4 h, it was significantly greater versus Placebo only. No treatment-related adverse events were reported. Conclusions In this in situ model, the novel-formulation sodium fluoride toothpaste enhanced enamel rehardening and overall protection against demineralisation compared with a fluoride-free toothpaste and a marketed SnF2-Zn toothpaste.