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Item A Flexible Near-Field Biosensor for Multisite Arterial Blood Flow Detection(MDPI, 2022-11-01) Mohammed, Noor; Cluff, Kim; Sutton, Mark; Villafana-Ibarra, Bernardo; Loflin, Benjamin E.; Griffith, Jacob L.; Becker, Ryan; Bhandari, Subash; Alruwaili, Fayez; Desai, Jaydip; Orthopaedic Surgery, School of MedicineModern wearable devices show promising results in terms of detecting vital bodily signs from the wrist. However, there remains a considerable need for a device that can conform to the human body's variable geometry to accurately detect those vital signs and to understand health better. Flexible radio frequency (RF) resonators are well poised to address this need by providing conformable bio-interfaces suitable for different anatomical locations. In this work, we develop a compact wearable RF biosensor that detects multisite hemodynamic events due to pulsatile blood flow through noninvasive tissue-electromagnetic (EM) field interaction. The sensor consists of a skin patch spiral resonator and a wearable transceiver. During resonance, the resonator establishes a strong capacitive coupling with layered dielectric tissues due to impedance matching. Therefore, any variation in the dielectric properties within the near-field of the coupled system will result in field perturbation. This perturbation also results in RF carrier modulation, transduced via a demodulator in the transceiver unit. The main elements of the transceiver consist of a direct digital synthesizer for RF carrier generation and a demodulator unit comprised of a resistive bridge coupled with an envelope detector, a filter, and an amplifier. In this work, we build and study the sensor at the radial artery, thorax, carotid artery, and supraorbital locations of a healthy human subject, which hold clinical significance in evaluating cardiovascular health. The carrier frequency is tuned at the resonance of the spiral resonator, which is 34.5 ± 1.5 MHz. The resulting transient waveforms from the demodulator indicate the presence of hemodynamic events, i.e., systolic upstroke, systolic peak, dicrotic notch, and diastolic downstroke. The preliminary results also confirm the sensor's ability to detect multisite blood flow events noninvasively on a single wearable platform.Item The AAHKS Clinical Research Award: Extended Oral Antibiotics Prevent Periprosthetic Joint Infection in High-Risk Cases: 3855 Patients With 1-Year Follow-Up(Elsevier, 2021) Kheir, Michael M.; Dilley, Julian E.; Ziemba-Davis, Mary; Meneghini, R. Michael; Orthopaedic Surgery, School of MedicineBackground: Surgical and host factors predispose patients to periprosthetic joint infection (PJI) after primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). While surgical factors are modifiable, host factors can be challenging, and there are limited data demonstrating that preoperative patient optimization decreases risk of PJI. The goal of this study was to evaluate whether extended oral antibiotic prophylaxis reduces the one-year infection rate in high-risk patients. Methods: A total of 3855 consecutive primary THAs and TKAs performed between 2011 and 2019 at a suburban academic hospital with modern perioperative and infection-prevention protocols were retrospectively reviewed. Beginning in January 2015, a 7-day oral antibiotic prophylaxis protocol was implemented after discharge for patients at high risk for PJI. The percentage of high-risk patients diagnosed with PJI within 1 year was compared between groups that did and did not receive extended antibiotic prophylaxis. Univariate and logistic regression analyses were performed, with P ≤ .05 denoting statistical significance. Results: Overall 1-year infection rates were 2.26% and 0.85% after THA and TKA, respectively. High-risk patients with extended antibiotic prophylaxis had a significantly lower rate of PJI than high-risk patients without extended antibiotic prophylaxis (0.89% vs 2.64%, respectively; P < .001). There was no difference in the infection rate between high-risk patients who received antibiotics and low-risk patients (0.89% vs 1.29%, respectively; P = .348) with numbers available. Conclusion: Extended postoperative oral antibiotic prophylaxis for 7 days led to a statistically significant and clinically meaningful reduction in 1-year infection rates of patients at high risk for infection. In fact, the PJI rate in high-risk patients who received antibiotics was less than the rate seen in low-risk patients. Thus, extended oral antibiotic prophylaxis may be a simple measure to effectively counteract poor host factors. Moreover, the findings of this study may mitigate the incentive to select healthier patients in outcome-based reimbursement models. Further study with a multicenter randomized control trial is needed to further validate this protocol.Item Adverse Local Tissue Reaction due to Acetabular Corrosion in Modular Dual-Mobility Constructs(Elsevier, 2020-12) Sonn, Kevin A.; Meneghini, Michael; Orthopaedic Surgery, School of MedicineDual-mobility (DM) bearings in total hip arthroplasty (THA) have been reported to reduce dislocation rates, especially in high-risk patients, and are being rapidly adopted in primary and revision THAs. However, this technology introduces additional interfaces that have the potential to result in unforeseen complications. We present a series of 3 patients with mechanically assisted crevice corrosion at the acetabular component–metal dual-mobility liner interface. Consequently, we urge judicious use and close clinical observation of this new, effective technology in THA.Item Age-related Cellular and Microstructural Changes in the Rotator Cuff Enthesis(Wiley, 2022) Long, Zeling; Nakagawa, Koichi; Wang, Zhanwen; Amadio, Peter C.; Zhao, Chunfeng; Gingery, Anne; Orthopaedic Surgery, School of MedicineRotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age-related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age-related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased non-mineralized zone. Proliferation, migration, and colony forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and highlights the importance of using age appropriate models, as well as provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.Item Aging negatively impacts the ability of megakaryocytes to stimulate osteoblast proliferation and bone mass(Elsevier, 2019) Maupin, Kevin A.; Himes, Evan R.; Plett, Artur P.; Chua, Hui Lin; Singh, Pratibha; Ghosh, Joydeep; Mohamad, Safa F.; Abeysekera, Irushi; Fisher, Alexa; Sampson, Carol; Hong, Jung-Min; Childress, Paul; Alvarez, Marta; Srour, Edward F.; Bruzzaniti, Angela; Pelus, Louis M.; Orschell, Christie M.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineOsteoblast number and activity decreases with aging, contributing to the age-associated decline of bone mass, but the mechanisms underlying changes in osteoblast activity are not well understood. Here, we show that the age-associated bone loss critically depends on impairment of the ability of megakaryocytes (MKs) to support osteoblast proliferation. Co-culture of osteoblast precursors with young MKs is known to increase osteoblast proliferation and bone formation. However, co-culture of osteoblast precursors with aged MKs resulted in significantly fewer osteoblasts compared to co-culture with young MKs, and this was associated with the downregulation of transforming growth factor beta. In addition, the ability of MKs to increase bone mass was attenuated during aging as transplantation of GATA1low/low hematopoietic donor cells (which have elevated MKs/MK precursors) from young mice resulted in an increase in bone mass of recipient mice compared to transplantation of young wild-type donor cells, whereas transplantation of GATA1low/low donor cells from old mice failed to enhance bone mass in recipient mice compared to transplantation of old wild-type donor cells. These findings suggest that the preservation or restoration of the MK-mediated induction of osteoblast proliferation during aging may hold the potential to prevent age-associated bone loss and resulting fractures.Item Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro(BMC, 2018-04-27) Natoli, Roman M.; Yu, Henry; Meislin, Megan Conti-Mica; Abbasnia, Pegah; Roper, Philip; Vuchkovska, Aleksandra; Xiao, Xianghui; Stock, Stuart R.; Callaci, John J.; Orthopaedic Surgery, School of MedicineBACKGROUND: Alcohol consumption is a risk factor for impaired fracture healing, though the mechanism(s) by which this occurs are not well understood. Our laboratory has previously shown that episodic alcohol exposure of rodents negatively affects fracture callus development, callus biomechanics, and cellular signaling which regulates stem cell differentiation. Here, we examine whether alcohol alters chemokine expression and/or signaling activity in the mouse fracture callus during early fracture healing. METHODS: A mouse model for alcohol-impaired tibia fracture healing was utilized. Early fracture callus was examined for alcohol-effects on tissue composition, expression of chemokines involved in MSC migration to the fracture site, and biomechanics. The effects of alcohol on MSC migration and cell adhesion receptors were examined in an in vitro system. RESULTS: Mice exposed to alcohol showed decreased evidence of external callus formation, decreased callus-related osteopontin (OPN) expression levels, and decreased biomechanical stiffness. Alcohol exposure decreased rOPN-mediated MSC migration and integrin β1 receptor expression in vitro. CONCLUSIONS: The effects of alcohol exposure demonstrated here on fracture callus-associated OPN expression, rOPN-mediated MSC migration in vitro, and MSC integrin β1 receptor expression in vitro have not been previously reported. Understanding the effects of alcohol exposure on the early stages of fracture repair may allow timely initiation of treatment to mitigate the long-term complications of delayed healing and/or fracture non-union.Item Alterations to maternal cortical and trabecular bone in multiparous middle-aged mice(Hylonome, 2017-12-01) Gu, A.; Sellamuthu, R.; Himes, E.; Childress, P.J.; Pelus, L.M.; Orschell, C.M.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineOBJECTIVES: During the reproductive cycle, altered calcium homeostasis is observed due to variable demand for mineral requirements. This results in increased bone resorption during the time period leading up to parturition and subsequent lactation. During lactation, women will lose 1-3% of bone mineral density per month, which is comparable to the loss experienced on an annual basis post-menopausal. The purpose of this study was to determine the effect of parity on bone formation in middle-aged mice. METHODS: Mice were mated and grouped by number of parity and compared with age matched nulliparous controls. Measurements were taken of femoral trabecular and cortical bone. Calcium, protein and alkaline phosphatase levels were also measured. RESULTS: An increase in trabecular bone mineral density was observed when comparing mice that had undergone parity once to the nulliparous control. An overall decrease in trabecular bone mineral density was observed as parity increased from 1 to 5 pregnancies. No alteration was seen in cortical bone formation. No difference was observed when calcium, protein and alkaline phosphatase levels were assessed. CONCLUSIONS: This study demonstrates that number of parity has an impact on trabecular bone formation in middle-aged mice, with substantial changes in bone density seen among the parous groups.Item Alterations to maternal cortical and trabecular bone in multiparous middle-aged mice(Hylonome, 2017-11) Gu, Alex; Sellamuthu, Rajendran; Himes, Evan; Childress, Paul J.; Pelus, Louis M.; Orschell, Christie M.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineObjectives: During the reproductive cycle, altered calcium homeostasis is observed due to variable demand for mineral requirements. This results in increased bone resorption during the time period leading up to parturition and subsequent lactation. During lactation, women will lose 1-3% of bone mineral density per month, which is comparable to the loss experienced on an annual basis post-menopausal. The purpose of this study was to determine the effect of parity on bone formation in middle-aged mice. Methods: Mice were mated and grouped by number of parity and compared with age matched nulliparous controls. Measurements were taken of femoral trabecular and cortical bone. Calcium, protein and alkaline phosphatase levels were also measured. Results: An increase in trabecular bone mineral density was observed when comparing mice that had undergone parity once to the nulliparous control. An overall decrease in trabecular bone mineral density was observed as parity increased from 1 to 5 pregnancies. No alteration was seen in cortical bone formation. No difference was observed when calcium, protein and alkaline phosphatase levels were assessed. Conclusions: This study demonstrates that number of parity has an impact on trabecular bone formation in middle-aged mice, with substantial changes in bone density seen among the parous groups.Item The American Association of Hip and Knee Surgeons, Hip Society, Knee Society, and American Academy of Orthopaedic Surgeons Position Statement on Outpatient Joint Replacement(Elsevier, 2018-12) Meneghini, R.; Gibson, Wilford; Halsey, David; Padgett, Douglas; Berend, Keith; Della Valle, Craig J.; Orthopaedic Surgery, School of MedicineItem Analysis of the effects of spaceflight and local administration of thrombopoietin to a femoral defect injury on distal skeletal sites(Springer Nature, 2021-03-26) Zamarioli, Ariane; Campbell, Zachery R.; Maupin, Kevin A.; Childress, Paul J.; Ximenez, Joao P.B.; Adam, Gremah; Chakraborty, Nabarun; Gautam, Aarti; Hammamieh, Rasha; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineWith increased human presence in space, bone loss and fractures will occur. Thrombopoietin (TPO) is a recently patented bone healing agent. Here, we investigated the systemic effects of TPO on mice subjected to spaceflight and sustaining a bone fracture. Forty, 9-week-old, male, C57BL/6 J were divided into 4 groups: (1) Saline+Earth; (2) TPO + Earth; (3) Saline+Flight; and (4) TPO + Flight (n = 10/group). Saline- and TPO-treated mice underwent a femoral defect surgery, and 20 mice were housed in space ("Flight") and 20 mice on Earth for approximately 4 weeks. With the exception of the calvarium and incisor, positive changes were observed in TPO-treated, spaceflight bones, suggesting TPO may improve osteogenesis in the absence of mechanical loading. Thus, TPO, may serve as a new bone healing agent, and may also improve some skeletal properties of astronauts, which might be extrapolated for patients on Earth with restraint mobilization and/or are incapable of bearing weight on their bones.