44 results on '"Sherry Liu"'
Search Results
2. Galectins-1 and-3 Increase in Equine Post-traumatic Osteoarthritis
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Heidi L. Reesink, Alan J. Nixon, Jin Su, Sherry Liu, Ryan M. Sutton, Sabine Mann, Ashlee E. Watts, and Ryan P. Peterson
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inflammatory arthritis ,cartilage ,synovium ,chondrocyte ,synoviocyte ,horse ,Veterinary medicine ,SF600-1100 - Abstract
Galectins are potent regulators of cell adhesion, growth and apoptosis in diverse cell types, including chondrocytes and synovial fibroblasts. Elevations in synovial fluid galectin-3 have been observed in rheumatoid arthritis, juvenile idiopathic arthritis and experimental inflammatory arthritis in animal models, whereas galectin-1 is thought to be protective. Less is known about galectins-1 and-3 in osteoarthritis (OA). Therefore, the purpose of this study was: (1) to determine whether galectin-1 and-3 synovial fluid concentrations and synovial membrane and cartilage histochemical staining were altered following osteochondral injury in an experimental equine osteoarthritis (OA) model and (2) to measure galectin-1 and-3 mRNA expression and synovial fluid concentrations in naturally occurring equine carpal OA. Synovial fluid galectin-1 and-3 concentrations were quantified using custom ELISAs in two research horse cohorts undergoing experimental OA induction (n = 5 and 4) and in a cohort of horses with naturally occurring carpal OA (n = 57). Galectin mRNA expression in synovial membrane and cartilage tissue obtained from carpal joints of horses with naturally occurring OA was measured using RT-qPCR, and galectin immunostaining was assessed in synovial membrane and osteochondral tissues in the experimental model (n = 5). Synovial fluid galectin-1 and-3 concentrations increased following experimental carpal osteochondral fragmentation. Cartilage galectin-1 mRNA expression increased with OA severity in naturally occurring disease. The superficial zone of healthy articular cartilage stained intensely for galectin-3 in sham-operated joints, whereas galectin-1 staining was nearly absent. Chondrocyte galectin-1 and-3 immunoreactivity increased following cartilage injury, particularly in galectin-1 positive chondrones. Galectins-1 and-3 are present in healthy equine synovial fluid and increase following post-traumatic OA. Healthy superficial zone chondrocytes express galectin-3, whereas galectin-1 chondrocyte staining is limited predominantly to chondrones and injured cartilage. Further work is needed to clarify the functions of galectins-1 and-3 in healthy and OA joints.
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- 2018
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3. Relationship between esomeprazole dose and timing to heartburn resolution in selected patients with gastroesophageal reflux disease
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Roy C Orlando, Sherry Liu, and Marta Illueca
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Roy C Orlando1, Sherry Liu2, Marta Illueca31Department of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA, 2Department of Statistics and Informatics, 3Department of Clinical Development, AstraZeneca LP, Wilmington, DE, USAObjective: To increase response rates to therapy by increasing the dosage of proton pump inhibitor (PPI) therapy in patients with gastroesophageal reflux disease (GERD) whose symptoms are predominantly associated with acid reflux.Methods: In this double-blind, randomized, proof-of-concept study, 369 patients with GERD and moderate heartburn lasting ≥three days/week, a history of response to antacids/acid suppression therapy, and a positive esophageal acid perfusion test result were randomized to esomeprazole 20 or 40 mg once daily, or to 40 mg twice daily for four weeks. Heartburn symptom relief/resolution was subsequently evaluated.Results: In this study population, no relationship was apparent between esomeprazole dosage and efficacy variables for sustained heartburn resolution (seven days without symptoms) at week 4 (48.0%, 44.0%, and 41.4% for esomeprazole 20 mg once daily, 40 mg once daily, and 40 mg twice daily, respectively). Nocturnal heartburn resolution with esomeprazole 40 mg twice daily showed a numeric improvement trend versus esomeprazole 20 and 40 mg once daily, but this was not statistically significant.Conclusions: Heartburn resolution rates at four weeks were similar for all esomeprazole dosages and comparable with rates reported previously, suggesting a plateau effect in terms of clinical response to acid suppression with PPI therapy in this population of selected GERD patients.Keywords: acid suppressive therapy, GERD, proton pump inhibitor
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- 2010
4. Systematic review: Can non-mydriatic cameras accurately detect diabetic retinopathy?
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Bedard, Chloe, (Sherry) Liu, Siying, Patterson, Christopher, Gerstein, Hertzel, and Griffith, Lauren
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- 2017
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5. Ordinary Differential Equations and Boundary Value Problems: Volume II: Boundary Value Problems
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John R Graef, Johnny Henderson, Lingju Kong, Xueyan Sherry Liu, John R Graef, Johnny Henderson, Lingju Kong, and Xueyan Sherry Liu
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- 2018
6. Ordinary Differential Equations and Boundary Value Problems: Volume I: Advanced Ordinary Differential Equations
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John R Graef, Johnny Henderson, Lingju Kong, Xueyan Sherry Liu, John R Graef, Johnny Henderson, Lingju Kong, and Xueyan Sherry Liu
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- 2018
7. Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss
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Yu, Wei, Zhong, Leilei, Yao, Lutian, Wei, Yulong, Gui, Tao, Li, Ziqing, Kim, Hyunsoo, Holdreith, Nicholas, Jiang, Xi, Tong, Wei, Dyment, Nathaniel, X. Sherry, Liu, Yang, Shuying, Choi, Yongwon, Ahn, Jaimo, and Qin, Ling
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Medical research ,Medicine, Experimental ,Hematopoietic stem cells -- Physiological aspects -- Health aspects ,Osteoclasts (Biology) -- Health aspects -- Physiological aspects ,Fat cells -- Physiological aspects -- Health aspects ,Bone remodeling -- Research ,Health care industry - Abstract
Bone is maintained by coupled activities of bone-forming osteoblasts/osteocytes and bone-resorbing osteoclasts. Alterations in this relationship can lead to pathologic bone loss such as osteoporosis. It is well known that osteogenic cells support osteoclastogenesis via production of RANKL. Interestingly, our recently identified bone marrow mesenchymal cell population--marrow adipogenic lineage precursors (MALPs) that form a multidimensional cell network in bone--was computationally demonstrated to be the most interactive with monocyte-macrophage lineage cells through high and specific expression of several osteoclast regulatory factors, including RANKL. Using an adipocyte-specific Adipoq-Cre to label MALPs, we demonstrated that mice with RANKL deficiency in MALPs have a drastic increase in trabecular bone mass in long bones and vertebrae starting from 1 month of age, while their cortical bone appears normal. This phenotype was accompanied by diminished osteoclast number and attenuated bone formation at the trabecular bone surface. Reduced RANKL signaling in calvarial MALPs abolished osteolytic lesions after LPS injections. Furthermore, in ovariectomized mice, elevated bone resorption was partially attenuated by RANKL deficiency in MALPs. In summary, our studies identified MALPs as a critical player in controlling bone remodeling during normal bone metabolism and pathological bone loss in a RANKL-dependent fashion., Introduction Bone is a dynamic tissue, constantly undergoing remodeling through coupled activities of bone-resorbing osteoclasts and bone-forming osteoblasts/osteocytes. A shift in the balance of these 2 actions toward resorption leads [...]
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- 2021
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8. Dependence of mechanical properties of trabecular bone on plate–rod microstructure determined by individual trabecula segmentation (ITS)
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Zhou, Bin, Sherry Liu, X., Wang, Ji, Lucas Lu, X., Fields, Aaron J., and Edward Guo, X.
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- 2014
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9. Type and orientation of yielded trabeculae during overloading of trabecular bone along orthogonal directions
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Shi, Xiutao, Sherry Liu, X., Wang, Xiang, Edward Guo, X., and Niebur, Glen L.
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- 2010
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10. Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss
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Hyunsoo Kim, Wei Yu, Yulong Wei, X. Sherry Liu, Shuying Yang, Yongwon Choi, Lutian Yao, Nathaniel A. Dyment, Ziqing Li, Xi Jiang, Wei Tong, Leilei Zhong, Tao Gui, Nicholas Holdreith, Jaimo Ahn, and Ling Qin
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0301 basic medicine ,musculoskeletal diseases ,medicine.medical_specialty ,biology ,Chemistry ,Osteoporosis ,General Medicine ,medicine.disease ,Bone resorption ,Bone remodeling ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Endocrinology ,RANKL ,Osteoclast ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,biology.protein ,Ovariectomized rat ,Cortical bone ,Bone marrow ,Research Article - Abstract
Bone is maintained by coupled activities of bone-forming osteoblasts/osteocytes and bone-resorbing osteoclasts. Alterations in this relationship can lead to pathologic bone loss such as osteoporosis. It is well known that osteogenic cells support osteoclastogenesis via production of RANKL. Interestingly, our recently identified bone marrow mesenchymal cell population-marrow adipogenic lineage precursors (MALPs) that form a multidimensional cell network in bone-was computationally demonstrated to be the most interactive with monocyte-macrophage lineage cells through high and specific expression of several osteoclast regulatory factors, including RANKL. Using an adipocyte-specific Adipoq-Cre to label MALPs, we demonstrated that mice with RANKL deficiency in MALPs have a drastic increase in trabecular bone mass in long bones and vertebrae starting from 1 month of age, while their cortical bone appears normal. This phenotype was accompanied by diminished osteoclast number and attenuated bone formation at the trabecular bone surface. Reduced RANKL signaling in calvarial MALPs abolished osteolytic lesions after LPS injections. Furthermore, in ovariectomized mice, elevated bone resorption was partially attenuated by RANKL deficiency in MALPs. In summary, our studies identified MALPs as a critical player in controlling bone remodeling during normal bone metabolism and pathological bone loss in a RANKL-dependent fashion.
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- 2021
11. Infected macrophages engage alveolar epithelium to metabolically reprogram myeloid cells and promote antibacterial inflammation
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Alicia M. Holmgren, Sunny Shin, Mark A. Boyer, and Xiaowei Sherry Liu
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0303 health sciences ,medicine.medical_treatment ,Alveolar Epithelium ,Inflammation ,Translation (biology) ,Biology ,respiratory system ,biology.organism_classification ,Legionella pneumophila ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cytokine ,Immunology ,medicine ,Bystander effect ,Macrophage ,medicine.symptom ,030304 developmental biology ,030215 immunology - Abstract
Alveolar macrophages are the primary immune cells that first detect lung infection. However, only one macrophage patrols every three alveoli. How this limited number of macrophages provides protection is unclear, as numerous pathogens block cell-intrinsic immune responses. The intracellular pathogenLegionella pneumophilainhibits host translation, thereby impairing the ability of infected macrophages to produce critical cytokines. Nevertheless, infected macrophages induce an IL-1-dependent inflammatory response by recruited myeloid cells that controls infection. Here, we show that collaboration with the alveolar epithelium is critical, in that IL-1 instructs the alveolar epithelium to produce GM-CSF. Intriguingly, GM-CSF drives maximal cytokine production in bystander myeloid cells by enhancing PRR-induced glycolysis. Our findings reveal that alveolar macrophages engage alveolar epithelial signals to metabolically reprogram myeloid cells and amplify antibacterial inflammation.One Sentence SummaryThe alveolar epithelium is a central signal relay between infected and bystander myeloid cells that orchestrates antibacterial defense.
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- 2020
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12. Trabecular Bone Deficit and Enhanced Anabolic Response to Re-Ambulation after Disuse in Perlecan-Deficient Skeleton
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Hongbo Zhao, Shaopeng Pei, X. Lucas Lu, Jerahme R. Martinez, Ashutosh Parajuli, Mary C. Farach-Carson, Liyun Wang, Catherine B. Kirn-Safran, and X. Sherry Liu
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Male ,0301 basic medicine ,Osteoporosis ,lcsh:QR1-502 ,Osteoclasts ,Walking ,Mechanotransduction, Cellular ,Biochemistry ,lcsh:Microbiology ,Extracellular matrix ,Mice ,0302 clinical medicine ,Osteogenesis ,Risk Factors ,Femur ,micro-computed tomography ,biology ,Chemistry ,Phenotype ,medicine.anatomical_structure ,trabecular bone ,Cancellous Bone ,hindlimb suspension ,medicine.medical_specialty ,schwartz-jampel syndrome ,Schwartz–Jampel syndrome ,030209 endocrinology & metabolism ,Perlecan ,Osteocytes ,Article ,03 medical and health sciences ,Osteoclast ,Internal medicine ,medicine ,Animals ,Kyphosis ,Molecular Biology ,Endochondral ossification ,osteoclastogenesis ,Basement membrane ,re-ambulation ,X-Ray Microtomography ,Hematopoietic Stem Cells ,medicine.disease ,osteoporosis ,Mice, Inbred C57BL ,perlecan ,Metabolism ,030104 developmental biology ,Endocrinology ,biology.protein ,Cortical bone ,Stress, Mechanical ,Heparan Sulfate Proteoglycans - Abstract
Perlecan/Hspg2, a large monomeric heparan sulfate proteoglycan, is found in the basement membrane and extracellular matrix, where it acts as a matrix scaffold, growth factor depot, and tissue barrier. Perlecan deficiency leads to skeletal dysplasia in Schwartz-Jampel Syndrome (SJS) and is a risk factor for osteoporosis. In the SJS-mimicking murine model (Hypo), inferior cortical bone quality and impaired mechanotransduction in osteocytes were reported. This study focused on trabecular bone, where perlecan deficiency was hypothesized to result in structural deficit and altered response to disuse and re-loading. We compared the Hypo versus WT trabecular bone in both axial and appendicular skeletons of 8-38-week-old male mice, and observed severe trabecular deficit in Hypo mice, approximately 50% reduction of Tb.BV/TV regardless of skeletal site and animal age. Defects in endochondral ossification (e.g., accelerated mineralization), increases in osteoclast activity, and altered differentiation of bone progenitor cells in marrow contributed to the Hypo phenotype. The Hypo trabecular bone deteriorated further under three-week hindlimb suspension as did the WT. Re-ambulation partially recovered the lost trabecular bone in Hypo, but not in WT mice. The novel finding that low-impact loading could counter detrimental disuse effects in the perlecan-deficient skeleton suggests a strategy to maintain skeletal health in SJS patients.
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- 2020
13. Emerging Scholar Profile.
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Xuerui (Sherry) Liu
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- 2022
14. Reproducibility and Radiation Effect of High-Resolution In Vivo Micro Computed Tomography Imaging of the Mouse Lumbar Vertebra and Long Bone
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Liu Yang, Linhong Deng, Rebecca Chung, X. Sherry Liu, Wei Ju Tseng, Priyanka Ghosh, Youwen Yang, Chih-Chiang Chang, Hongbo Zhao, and Chantal M.J. de Bakker
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Lumbar Vertebrae ,Tibia ,business.industry ,Long bone ,Biomedical Engineering ,Reproducibility of Results ,Osteoblast ,Lumbar vertebrae ,X-Ray Microtomography ,Radiation effect ,Article ,Vertebra ,Mice, Inbred C57BL ,medicine.anatomical_structure ,In vivo ,medicine ,Animals ,Femur ,Female ,business ,Biomedical engineering - Abstract
A moderate radiation dose, in vivo μCT scanning protocol was developed and validated for long-term monitoring of multiple skeletal sites (femur, tibia, vertebra) in mice. A customized, 3D printed mouse holder was designed and utilized to minimize error associated with animal repositioning, resulting in good to excellent reproducibility in most cortical and trabecular bone microarchitecture and density parameters except for connectivity density. Repeated in vivo μCT scans of mice were performed at the right distal femur and the 4(th) lumbar vertebra every 3 weeks until sacrifice at 9 weeks after the baseline scan. Comparing to the non-radiated counterparts, no radiation effect was found on trabecular bone volume fraction, osteoblast and osteoblast number/surface, or bone formation rate at any skeletal site. However, trabecular number, thickness, and separation, and structure model index were sensitive to ionizing radiation associated with the μCT scans, resulting in subtle but significant changes over multiple scans. Although the extent of radiation damage on most trabecular bone microarchitecture measures are comparable or far less than the age-related changes during the monitoring period, additional considerations need to be taken to minimize the confounding radiation factors when designing experiments using in vivo μCT imaging for long-term monitoring of mouse bone.
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- 2019
15. The critical role of Hedgehog-responsive mesenchymal progenitors in meniscus development and injury repair.
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Yulong Wei, Hao Sun, Tao Gui, Lutian Yao, Leilei Zhong, Wei Yu, Su-Jin Heo, Lin Han, Dyment, Nathaniel A., Xiaowei Sherry Liu, Yejia Zhang, Eiki Koyama, Fanxin Long, Zgonis, Miltiadis H., Mauck, Robert L., Jaimo Ahn, and Ling Qin
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- 2021
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16. A 13-year-old boy with fatigue and dizziness
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Siying Sherry Liu and Mohanad Shalan Al-Gazi
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03 medical and health sciences ,Pediatrics ,medicine.medical_specialty ,0302 clinical medicine ,Text mining ,business.industry ,Pediatrics, Perinatology and Child Health ,medicine ,MEDLINE ,030204 cardiovascular system & hematology ,business ,030217 neurology & neurosurgery ,Clinician’s Corner - Published
- 2017
17. Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage
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Sherry Liu, Heidi L. Reesink, Lawrence J. Bonassar, Carolyn R. Shurer, Alan J. Nixon, Edward D. Bonnevie, and Michael J. Hollander
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0301 basic medicine ,Cartilage, Articular ,Glycosylation ,animal structures ,Galectin 3 ,Osteoarthritis ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Lubrication ,medicine ,otorhinolaryngologic diseases ,Synovial fluid ,Animals ,Humans ,Horses ,Glycomics ,Galectin ,Glycoproteins ,030203 arthritis & rheumatology ,chemistry.chemical_classification ,Multidisciplinary ,Cartilage ,medicine.disease ,Glycome ,Cell biology ,stomatognathic diseases ,Kinetics ,030104 developmental biology ,medicine.anatomical_structure ,Phenotype ,chemistry ,Biochemistry ,Galectin-3 ,Cattle ,Glycoprotein ,Protein Binding - Abstract
Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. Extensive O-linked glycosylation within lubricin’s mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis.
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- 2016
18. Influence of Vertical Trabeculae on the Compressive Strength of the Human Vertebra
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Aaron J. Fields, X. Edward Guo, Tony M. Keaveny, X. Sherry Liu, Michael G. Jekir, and Gideon L. Lee
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Male ,Materials science ,Compressive Strength ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Finite Element Analysis ,030209 endocrinology & metabolism ,OSTEOPOROSIS ,Medical and Health Sciences ,Bone and Bones ,03 medical and health sciences ,Bone volume fraction ,Engineering ,0302 clinical medicine ,80 and over ,medicine ,Cadaver ,Humans ,Orthopedics and Sports Medicine ,Compression testing ,Rachis ,030304 developmental biology ,Aged ,Aged, 80 and over ,0303 health sciences ,Biomechanics ,Anatomy ,Biological Sciences ,Middle Aged ,Anatomy & Morphology ,medicine.disease ,BIOMECHANICS ,Spine ,Vertebra ,Biomechanical Phenomena ,Compressive strength ,medicine.anatomical_structure ,FINITE-ELEMENT ANALYSIS ,Regression Analysis ,Original Article ,Female ,Tomography ,BONE STRENGTH - Abstract
Vertebral strength, a key etiologic factor of osteoporotic fracture, may be affected by the relative amount of vertically oriented trabeculae. To better understand this issue, we performed experimental compression testing, high-resolution micro–computed tomography (µCT), and micro–finite-element analysis on 16 elderly human thoracic ninth (T9) whole vertebral bodies (ages 77.5 ± 10.1 years). Individual trabeculae segmentation of the µCT images was used to classify the trabeculae by their orientation. We found that the bone volume fraction (BV/TV) of just the vertical trabeculae accounted for substantially more of the observed variation in measured vertebral strength than did the bone volume fraction of all trabeculae (r2 = 0.83 versus 0.59, p < .005). The bone volume fraction of the oblique or horizontal trabeculae was not associated with vertebral strength. Finite-element analysis indicated that removal of the cortical shell did not appreciably alter these trends; it also revealed that the major load paths occur through parallel columns of vertically oriented bone. Taken together, these findings suggest that variation in vertebral strength across individuals is due primarily to variations in the bone volume fraction of vertical trabeculae. The vertical tissue fraction, a new bone quality parameter that we introduced to reflect these findings, was both a significant predictor of vertebral strength alone (r2 = 0.81) and after accounting for variations in total bone volume fraction in multiple regression (total R2 = 0.93). We conclude that the vertical tissue fraction is a potentially powerful microarchitectural determinant of vertebral strength. © 2011 American Society for Bone and Mineral Research.
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- 2010
19. Inhibition of gut-derived serotonin synthesis: a potential bone anabolic treatment
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Michael D. Gershon, Marc Vidal, S. Balaji, Anil K. Balapure, Patricia Ducy, Vijay K. Yadav, Gerard Karsenty, Rudraiah Medhamurthy, Zhishan Li, X. Sherry Liu, J. John Mann, X. Edward Guo, Padmanaban S. Suresh, and Xin Lu
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Serotonin ,medicine.medical_specialty ,Anabolism ,Osteoporosis ,Tryptophan Hydroxylase ,Pharmacology ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Bone resorption ,Article ,Mice ,chemistry.chemical_compound ,Serotonin Agents ,Biosynthesis ,Osteogenesis ,Oral administration ,Internal medicine ,medicine ,Animals ,Humans ,Osteoporosis, Postmenopausal ,Dose-Response Relationship, Drug ,Tryptophan ,General Medicine ,medicine.disease ,Rats ,Gastrointestinal Tract ,Mice, Inbred C57BL ,Pyrimidines ,Endocrinology ,chemistry ,Ovariectomized rat ,Female - Abstract
Osteoporosis is a disease of low bone mass most often caused by an increase in bone resorption that is not sufficiently compensated for by a corresponding increase in bone formation(1). As gut-derived serotonin (GDS) inhibits bone formation(2), we asked whether hampering its biosynthesis could treat osteoporosis through an anabolic mechanism (that is, by increasing bone formation). We synthesized and used LP533401, a small molecule inhibitor of tryptophan hydroxylase-1 (Tph-1), the initial enzyme in GDS biosynthesis. Oral administration of this small molecule once daily for up to six weeks acts prophylactically or therapeutically, in a dose-dependent manner, to treat osteoporosis in ovariectomized rodents because of an isolated increase in bone formation. These results provide a proof of principle that inhibiting GDS biosynthesis could become a new anabolic treatment for osteoporosis.
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- 2010
20. Individual Trabeculae Segmentation (ITS)–Based Morphological Analysis of High-Resolution Peripheral Quantitative Computed Tomography Images Detects Abnormal Trabecular Plate and Rod Microarchitecture in Premenopausal Women With Idiopathic Osteoporosis
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Robert R. Recker, Joan M. Lappe, Halley Rogers, X. Edward Guo, X. Sherry Liu, Elizabeth Shane, Emily M. Stein, Perry T. Yin, Donald J. McMahon, Adi Cohen, and Shannon L Kokolus
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high-resolution peripheral quantitative computed tomography ,Adult ,Bone density ,genetic structures ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Bone and Bones ,Bone Density ,individual trabeculae segmentation ,medicine ,Humans ,Orthopedics and Sports Medicine ,Tibia ,Quantitative computed tomography ,bone microstructure ,Bone mineral ,medicine.diagnostic_test ,business.industry ,Anatomy ,Middle Aged ,medicine.disease ,musculoskeletal system ,Peripheral ,Radius ,Premenopause ,Morphological analysis ,Original Article ,Female ,Tomography ,sense organs ,business ,Tomography, X-Ray Computed ,trabecular plate/rod - Abstract
Idiopathic osteoporosis (IOP) in premenopausal women is a poorly understood entity in which otherwise healthy women have low-trauma fracture or very low bone mineral density (BMD). In this study, we applied individual trabeculae segmentation (ITS)–based morphological analysis to high-resolution peripheral quantitative computed tomography (HR-pQCT) images of the distal radius and distal tibia to gain greater insight into skeletal microarchitecture in premenopausal women with IOP. HR-pQCT scans were performed for 26 normal control individuals and 31 women with IOP. A cubic subvolume was extracted from the trabecular bone compartment and subjected to ITS-based analysis. Three Young's moduli and three shear moduli were calculated by micro–finite element (µFE) analysis. ITS-based morphological analysis of HR-pQCT images detected significantly decreased trabecular plate and rod bone volume fraction and number, decreased axial bone volume fraction in the longitudinal axis, increased rod length, and decreased rod-to-rod, plate-to-rod, and plate-to-plate junction densities at the distal radius and distal tibia in women with IOP. However, trabecular plate and rod thickness did not differ. A more rod-like trabecular microstructure was found in the distal radius, but not in the distal tibia. Most ITS measurements contributed significantly to the elastic moduli of trabecular bone independent of bone volume fraction (BV/TV). At a fixed BV/TV, plate-like trabeculae contributed positively to the mechanical properties of trabecular bone. The results suggest that ITS-based morphological analysis of HR-pQCT images is a sensitive and promising clinical tool for the investigation of trabecular bone microstructure in human studies of osteoporosis. © 2010 American Society for Bone and Mineral Research.
- Published
- 2010
21. High-Resolution Peripheral Quantitative Computed Tomography Can Assess Microstructural and Mechanical Properties of Human Distal Tibial Bone
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John P. Bilezikian, Elizabeth Shane, X. Henry Zhang, Kiranjit K Sekhon, Mark F. Adams, X. Edward Guo, Donald J. McMahon, and X. Sherry Liu
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musculoskeletal diseases ,high-resolution peripheral quantitative computed tomography ,Male ,Materials science ,Endocrinology, Diabetes and Metabolism ,0206 medical engineering ,030209 endocrinology & metabolism ,02 engineering and technology ,computer.software_genre ,03 medical and health sciences ,Fractures, Bone ,0302 clinical medicine ,Imaging, Three-Dimensional ,Cadaver ,Voxel ,Elastic Modulus ,medicine ,Humans ,Orthopedics and Sports Medicine ,Tibia ,Quantitative computed tomography ,micro-computed tomography ,bone microstructure ,Aged ,finite element model ,Aged, 80 and over ,medicine.diagnostic_test ,Stiffness ,Anatomy ,Middle Aged ,musculoskeletal system ,020601 biomedical engineering ,Peripheral ,bone stiffness ,Radiographic Image Interpretation, Computer-Assisted ,Original Article ,Female ,Tomography ,medicine.symptom ,Cadaveric spasm ,Tomography, X-Ray Computed ,computer ,Biomedical engineering - Abstract
High-resolution peripheral quantitative computed tomography (HR-pQCT) is a newly developed in vivo clinical imaging modality. It can assess the 3D microstructure of cortical and trabecular bone at the distal radius and tibia and is suitable as an input for microstructural finite element (µFE) analysis to evaluate bone's mechanical competence. In order for microstructural and image-based µFE analyses to become standard clinical tools, validation with a current gold standard, namely, high-resolution micro-computed tomography (µCT), is required. Microstructural measurements of 19 human cadaveric distal tibiae were performed for the registered HR-pQCT and µCT images, respectively. Next, whole bone stiffness, trabecular bone stiffness, and elastic moduli of cubic subvolumes of trabecular bone in both HR-pQCT and µCT images were determined by µFE analysis. The standard HR-pQCT patient protocol measurements, derived bone volume fraction (BV/TVd), trabecular number (Tb.N*), trabecular thickness (Tb.Th), trabecular spacing (Tb.Sp), and cortical thickness (Ct.Th), as well as the voxel-based direct measurements, BV/TV, Tb.N*, Tb.Th*, Tb.Sp*, Ct.Th, bone surface-to-volume ratio (BS/BV), structure model index (SMI), and connectivity density (Conn.D), correlated well with their respective gold standards, and both contributed to µFE-predicted mechanical properties in either single or multiple linear regressions. The mechanical measurements, although overestimated by HR-pQCT, correlated highly with their gold standards. Moreover, elastic moduli of cubic subvolumes of trabecular bone predicted whole bone or trabecular bone stiffness in distal tibia. We conclude that microstructural measurements and mechanical parameters of distal tibia can be efficiently derived from HR-pQCT images and provide additional information regarding bone fragility. © 2010 American Society for Bone and Mineral Research.
- Published
- 2009
22. In Vivo Precision of Digital Topological Skeletonization Based Individual Trabecula Segmentation (ITS) Analysis of Trabecular Microstructure at the Distal Radius and Tibia by HR-pQCT
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Mishaela R. Rubin, Bin Zhou, Y. Eric Yu, X. Sherry Liu, Zhendong Zhang, Ji Wang, John P. Bilezikian, Elizabeth Shane, X. Edward Guo, and Kyle K. Nishiyama
- Subjects
0301 basic medicine ,Reproducibility ,Materials science ,medicine.diagnostic_test ,genetic structures ,Image quality ,030209 endocrinology & metabolism ,Context (language use) ,Topology ,Skeletonization ,Article ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Artificial Intelligence ,Trabecula ,Signal Processing ,medicine ,Cortical bone ,Computer Vision and Pattern Recognition ,Tibia ,sense organs ,Quantitative computed tomography ,Software - Abstract
Trabecular plate and rod microstructure plays a dominant role in the apparent mechanical properties of trabecular bone. With high-resolution computed tomography (CT) images, digital topological analysis (DTA) including skeletonization and topological classification was applied to transform the trabecular three-dimensional (3D) network into surface and curve skeletons. Using the DTA-based topological analysis and a new reconstruction/recovery scheme, individual trabecula segmentation (ITS) was developed to segment individual trabecular plates and rods and quantify the trabecular plate- and rod-related morphological parameters. High-resolution peripheral quantitative computed tomography (HR-pQCT) is an emerging in vivo imaging technique to visualize 3D bone microstructure. Based on HR-pQCT images, ITS was applied to various HR-pQCT datasets to examine trabecular plate- and rod-related microstructure and has demonstrated great potential in cross-sectional and longitudinal clinical applications. However, the reproducibility of ITS has not been fully determined. The aim of the current study is to quantify the precision errors of ITS plate-rod microstructural parameters. In addition, we utilized three different frequently used contour techniques to separate trabecular and cortical bone and to evaluate their effects on ITS measurements.Overall, good reproducibility was found for the standard HR-pQCT parameters with precision errors for volumetric BMD and bone size between 0.2% and 2.0%, and trabecular bone microstructure between 4.9% and 6.7% at the radius and tibia. High reproducibility was also achieved for ITS measurements using all three different contour techniques. For example, using automatic contour technology, low precision errors were found for plate and rod trabecular number (pTb.N, rTb.N, 0.9% and 3.6%), plate and rod trabecular thickness (pTb.Th, rTb.Th, 0.6% and 1.7%), plate trabecular surface (pTb.S, 3.4%), rod trabecular length (rTb., 0.8%), and plate-plate junction density (P-P Junc.D, 2.3%) at the tibia. The precision errors at the radius were similar to those at the tibia. In addition, precision errors were affected by the contour techniques. At the tibia, the precision error by the manual contour method was significantly different from automatic and standard contour methods for pTb.N, rTb.N and rTb.Th. Precision error using the manual contour method was also significantly different from the standard contour method for rod trabecular number (rTb.N), rod trabecular thickness (rTb.Th), rod-rod and plate-rod junction densities (R-R Junc.D and P-R Junc.D) at the tibia. At the radius, the precision error was similar between the three different contour methods. Image quality was also found to significantly affect the ITS reproducibility. We concluded that ITS parameters are highly reproducible, giving assurance that future cross-sectional and longitudinal clinical HR-pQCT studies are feasible in the context of limited sample sizes.
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- 2015
23. Efficacy and Safety of Extended-Release Quetiapine Fumarate in Youth with Bipolar Depression: An 8 Week, Double-Blind, Placebo-Controlled Trial
- Author
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Willie Earley, Robert L. Findling, Melissa P. DelBello, Sherry Liu, and Sanjeev Pathak
- Subjects
Male ,medicine.medical_specialty ,Pediatrics ,Dibenzothiazepines ,Bipolar Disorder ,Adolescent ,medicine.drug_class ,Placebo-controlled study ,Atypical antipsychotic ,law.invention ,Bipolar II disorder ,Quetiapine Fumarate ,Randomized controlled trial ,Double-Blind Method ,law ,mental disorders ,Outpatients ,medicine ,Humans ,Pharmacology (medical) ,Psychiatry ,Child ,Depression (differential diagnoses) ,Psychiatric Status Rating Scales ,Original Articles ,medicine.disease ,Psychiatry and Mental health ,Treatment Outcome ,Schizophrenia ,Delayed-Action Preparations ,Pediatrics, Perinatology and Child Health ,Quetiapine ,Female ,sense organs ,Psychology ,medicine.drug ,Antipsychotic Agents - Abstract
Quetiapine is an atypical antipsychotic with demonstrated efficacy in the treatment of adolescent schizophrenia and pediatric bipolar mania. Large, placebo-controlled studies of interventions in pediatric bipolar depression are lacking. The current study investigated the efficacy and safety of quetiapine extended-release (XR) in patients 10-17 years of age, with acute bipolar depression.This multicenter, double-blind, randomized, placebo-controlled study investigated quetiapine XR (dose range, 150-300 mg/day) in pediatric outpatients with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I or bipolar II disorder (current or most recent episode depressed) treated for up to 8 weeks (ClinicalTrials.gov identifier: NCT00811473). The primary study outcome was mean change in Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary efficacy outcomes included CDRS-R-based response and remission rates.Of 193 patients randomized to treatment, 144 patients completed the study (75.3% of quetiapine XR group [n=70]; 74.0% of placebo group [n=74]). Least squares mean changes in CDRS-R total score at week 8 were: -29.6 (SE, 1.65) with quetiapine XR and -27.3 (SE, 1.60) with placebo, a between-treatment group difference of -2.29 (SE, 1.99; 95% CI, -6.22, 1.65; p=0.25; mixed-model for repeated measures analysis). Rates of response and remission did not differ significantly between treatment groups. The safety profile of quetiapine XR was broadly consistent with the profile reported previously in adult studies of quetiapine XR and pediatric studies of quetiapine immediate-release (IR). Potentially clinically significant elevations in clinical chemistry values included triglycerides (9.3%, quetiapine XR; 1.4%, placebo group) and thyroid stimulating hormone (4.7%, quetiapine XR; 0%, placebo group). An adverse event potentially related to diabetes mellitus occurred in 3.3% of the quetiapine XR versus no adverse events in the placebo group.Quetiapine XR did not demonstrate efficacy relative to placebo in this 8 week study of pediatric bipolar depression. Quetiapine XR was generally safe and well tolerated.
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- 2014
24. Accuracy of Individual Trabecula Segmentation Based Plate and Rod Finite Element Models in Idealized Trabecular Bone Microstructure
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Ji Wang, X. Sherry Liu, Keh Chih Hwang, Bin Zhou, X. Edward Guo, Baohua Ji, Yonggang Huang, and Hong Wang
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Materials science ,X-ray microtomography ,Finite Element Analysis ,Biomedical Engineering ,Shell (structure) ,Modulus ,Young's modulus ,computer.software_genre ,Bone and Bones ,symbols.namesake ,Fractures, Bone ,Trabecula ,Voxel ,Physiology (medical) ,Elastic Modulus ,medicine ,Humans ,Mechanical Phenomena ,business.industry ,Structural engineering ,X-Ray Microtomography ,Elasticity (physics) ,Finite element method ,Biomechanical Phenomena ,medicine.anatomical_structure ,symbols ,business ,computer ,Technical Briefs ,Biomedical engineering - Abstract
Currently, specimen-specific micro finite element (μFE) analysis based micro computed tomography (μCT) images have become a major computational tool for the assessment of the mechanical properties of human trabecular bone. Despite the fine characterization of the three-dimensional (3D) trabecular microstructure based on high-resolution μCT images, conventional μFE models with each voxel converted to an element are not efficient in predicting the nonlinear failure behavior of bone due to a prohibitive computational cost. Recently, a highly efficient individual trabecula segmentation (ITS)-based plate and rod (PR) modeling technique has been developed by substituting individual plates and rods with shell and beam elements, respectively. In this technical brief, the accuracy of novel PR μFE models was examined in idealized microstructure models over a broad range of trabecular thicknesses. The Young's modulus and yield strength predicted by simplified PR models strongly correlated with those of voxel models at various voxel sizes. The conversion from voxel models to PR models resulted in an ∼762-fold reduction in the largest model size and significantly accelerated the nonlinear FE analysis. The excellent predictive power of the PR μFE models, demonstrated in an idealized trabecular microstructure, provided a quantitative mechanical basis for this promising tool for an accurate and efficient assessment of trabecular bone mechanics and fracture risk.
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- 2013
25. Central QCT Reveals Lower Volumetric BMD and Stiffness in Premenopausal Women with Idiopathic Osteoporosis, Regardless of Fracture History
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Robert R. Recker, X. Sherry Liu, Emily M. Stein, Elizabeth Shane, Thomas Lang, Isra Saeed, David W. Dempster, Joan M. Lappe, Chiyuan Zhang, X. Edward Guo, Polly Young, Adi Cohen, and Donald J. McMahon
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musculoskeletal diseases ,Adult ,medicine.medical_specialty ,Bone density ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Clinical Sciences ,Clinical Biochemistry ,Osteoporosis ,Finite Element Analysis ,Urology ,Context (language use) ,Lumbar vertebrae ,Biochemistry ,Bone and Bones ,Paediatrics and Reproductive Medicine ,Endocrinology & Metabolism ,Fractures, Bone ,Endocrinology ,Bone Density ,Internal medicine ,medicine ,Endocrine Research ,Humans ,Tibia ,Quantitative computed tomography ,Bone ,Femoral neck ,Bone mineral ,medicine.diagnostic_test ,business.industry ,Biochemistry (medical) ,Middle Aged ,musculoskeletal system ,medicine.disease ,Radiography ,medicine.anatomical_structure ,Premenopause ,Female ,Radiology ,business ,Fractures - Abstract
Context: Idiopathic osteoporosis (IOP) affects otherwise healthy young individuals with intact gonadal function and no secondary cause of bone fragility. In premenopausal women with IOP, a low trauma fracture is evidence of impaired bone quality and strength. The extent to which low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) reflects low volumetric BMD, bone microstructure, and strength is uncertain in the absence of low trauma fracture. Objective:Theobjectiveofthestudywastocomparethree-dimensionalvolumetricBMDandbone stiffness in premenopausal women with IOP based on fracture history, those with idiopathic low BMD (Z score 2.0) and no low trauma fracture, and normal age-matched controls. Design: We measured volumetric BMD and bone geometry by central quantitative computed tomography (cQCT) scans of the spine and hip and estimated bone stiffness by finite element analysis of cQCT data sets in 32 premenopausal women with IOP, 12 with idiopathic low BMD, and 34 controls. Results:Subjects had comparable decreases in total and trabecular volumetric BMD, cortical thickness, and whole-bone stiffness compared with controls, regardless of fracture history. These differences remained significant after controlling for age, body mass index, and bone size. The positive predictive values of a DXA Z score of 2.0 or less for a cQCT volumetric BMD Z score of 2.0 or less were 95% at the lumbar spine, 90% at the total hip, and 86% at the femoral neck. Conclusion: Women with idiopathic low BMD alone and those with low trauma fractures had comparable deficits in bone mass, structure, and stiffness. Low areal BMD by DXA is fairly accurate for predicting low volumetric BMD by cQCT. These results are consistent with three-dimensional bone imaging at the iliac crest, radius, and tibia in premenopausal IOP and suggest that the term osteoporosis may be appropriate in women with Z scores below 2.0, whether or not there is a history of fracture. (J Clin Endocrinol Metab 97: 4244–4252, 2012)
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- 2012
26. Abnormal Microarchitecture and Stiffness in Postmenopausal Women with Ankle Fractures
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Elizabeth Shane, X. Sherry Liu, Emily M. Stein, Valerie Thomas, Felicia Cosman, Jeri W. Nieves, Thomas L. Nickolas, Donald J. McMahon, Chiyuan Zhang, Adi Cohen, X. Edward Guo, and Justin Greisberg
- Subjects
medicine.medical_specialty ,Bone density ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Osteoporosis ,Biochemistry ,Body Mass Index ,Endocrinology ,Absorptiometry, Photon ,Bone Density ,Internal medicine ,Medicine ,Humans ,Tibia ,Ankle Injuries ,Osteoporosis, Postmenopausal ,Aged ,Bone mineral ,business.industry ,Endocrine Care ,Biochemistry (medical) ,medicine.disease ,Menopause ,Postmenopause ,Trabecular bone ,medicine.anatomical_structure ,Female ,Ankle ,business ,Body mass index ,Osteoporotic Fractures - Abstract
Ankle fractures are not typically considered osteoporotic fractures. However, bone quality in patients with low trauma ankle fractures has not been explored.Women with (n = 17) and without (n = 112) a history of low trauma ankle fracture after menopause had areal bone mineral density measured by dual-energy x-ray absorptiometry, trabecular (Tb) and cortical volumetric bone mineral density, and Tb microarchitecture measured by high-resolution peripheral computed tomography of the radius and tibia. Finite element analysis was performed to estimate bone stiffness.Women with fractures were older (72 ± 2 vs. 68 ± 1 yr; P0.02) but similar with respect to race and body mass index. Mean T-scores by dual-energy x-ray absorptiometry of fracture subjects were above the osteoporotic range and did not differ from controls. By high-resolution peripheral computed tomography at the radius, fracture subjects had preferentially lower central trabecular bone density, lower Tb number, and increased separation compared with controls (P0.0001-0.04). At the tibia, fracture subjects had lower total and Tb density, lower Tb number, and increased Tb separation and network heterogeneity (P0.02). Whole-bone stiffness was 13-17% lower at the radius and tibia in fracture subjects (P0.003-0.01).Postmenopausal women with ankle fractures have disrupted microarchitecture and decreased stiffness compared with women with no fracture history, suggesting that low trauma ankle fractures should be considered similarly to other classical osteoporotic fractures.
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- 2011
27. Extended-release quetiapine fumarate (quetiapine XR): a once-daily monotherapy effective in generalized anxiety disorder. Data from a randomized, double-blind, placebo- and active-controlled study
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Guy Chouinard, Hans Eriksson, Sherry Liu, Julio Bobes, Antti Ahokas, I. Eggens, and Borwin Bandelow
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Adult ,Male ,medicine.medical_specialty ,Dibenzothiazepines ,Generalized anxiety disorder ,Adolescent ,Placebo ,Gastroenterology ,Drug Administration Schedule ,law.invention ,03 medical and health sciences ,Quetiapine Fumarate ,Young Adult ,0302 clinical medicine ,Drug Delivery Systems ,Randomized controlled trial ,Extrapyramidal symptoms ,Double-Blind Method ,law ,Internal medicine ,Medicine ,Humans ,Pharmacology (medical) ,Psychiatry ,Aged ,Pharmacology ,Psychiatric Status Rating Scales ,Dose-Response Relationship, Drug ,business.industry ,Middle Aged ,medicine.disease ,Paroxetine ,Anxiety Disorders ,030227 psychiatry ,3. Good health ,Psychiatry and Mental health ,Treatment Outcome ,Tolerability ,Quetiapine ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug ,Antipsychotic Agents - Abstract
The efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) once-daily monotherapy in generalized anxiety disorder (GAD) was assessed. This multicentre, double-blind, randomized, placebo- and active-controlled, phase III trial consisted of a 1- to 4-wk enrolment/wash-out period and a 10-wk (8-wk active treatment, 2-wk post-treatment drug-discontinuation) study period; 873 patients were randomized to 50 mg or 150 mg quetiapine XR, 20 mg paroxetine, or placebo. Primary endpoint was change from randomization at week 8 in Hamilton Rating Scale for Anxiety (HAMA) total score. At week 8, all active agents produced significant improvements in HAMA total and psychic subscale scores vs. placebo; HAMA somatic subscale scores were significantly reduced only by 150 mg quetiapine XR. Significant separation from placebo (-2.90) in HAMA total score was observed at day 4 for 50 mg quetiapine XR (-4.43, p
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- 2010
28. Bone Microarchitecture and Stiffness in Premenopausal Women with Idiopathic Osteoporosis
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Robert R. Recker, Joan M. Lappe, Halley Rogers, Elizabeth Shane, Donald J. McMahon, X. Edward Guo, Adi Cohen, J. LeMaster, Emily M. Stein, and X. Sherry Liu
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musculoskeletal diseases ,Adult ,medicine.medical_specialty ,Bone density ,genetic structures ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Osteoporosis ,Context (language use) ,Biochemistry ,Bone and Bones ,Cohort Studies ,Young Adult ,Endocrinology ,Bone Density ,Reference Values ,Internal medicine ,medicine ,Humans ,Tibia ,Prospective Studies ,Quantitative computed tomography ,Prospective cohort study ,Bone mineral ,medicine.diagnostic_test ,business.industry ,Biochemistry (medical) ,Middle Aged ,musculoskeletal system ,medicine.disease ,Radius ,Premenopause ,Original Article ,Female ,business ,Tomography, X-Ray Computed ,Body mass index ,Algorithms - Abstract
Context: Idiopathic osteoporosis (IOP) is an uncommon disorder in which low areal bone mineral density (aBMD) and/or fractures occur in otherwise healthy premenopausal women. Objectives: Our objectives were to characterize bone mass, microarchitecture, and trabecular bone stiffness in premenopausal IOP and to determine whether women with low aBMD who have never fractured have abnormal microarchitecture and stiffness. Design, Setting, and Patients: We conducted a prospective cohort study of 27 normal controls and 31 women with IOP defined by low trauma fracture (n = 21) or low BMD (Z score ≤−2.0; n = 10). Main Outcome Measures: We assessed aBMD by dual-energy x-ray absorptiometry; volumetric BMD and cortical and trabecular microarchitecture of the radius and tibia by high-resolution (82 μm) peripheral quantitative computed tomography; and trabecular bone stiffness (elastic moduli), estimated by micro-finite element analysis. Results: Fracture subjects did not differ from controls by age or body mass index, which was lower in low-BMD subjects than controls. Fracture subjects also had lower aBMD than controls at all sites (P < 0.05–0.0001). Bone size was similar in controls and fracture subjects but 10.6% smaller in low-BMD subjects (P < 0.05). Every trabecular parameter in both fracture and low-BMD groups was markedly worse than controls (P < 0.01–0.0001). Cortical thickness was significantly lower in both fracture and low-BMD groups at the tibia but not radius. Bone stiffness estimated by micro-finite element analysis was comparably reduced in low-BMD and fracture groups. Conclusion: Premenopausal women with IOP had marked trabecular microarchitectural deterioration at the radius and tibia. Cortical parameters were affected only at the tibia. Although they had not fractured, microarchitectural deterioration was similar in IOP women with low BMD and those with fractures.
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- 2009
29. Implications of Noise and Resolution on Mechanical Properties of Trabecular Bone Estimated by Image-based Finite-Element Analysis
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Suzanne Wehrli, Chamith S. Rajapakse, X. Henry Zhang, X. Edward Guo, Felix W. Wehrli, Jeremy F. Magland, and X. Sherry Liu
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Adult ,Male ,Materials science ,Finite Element Analysis ,Noise (electronics) ,Article ,Humans ,Orthopedics and Sports Medicine ,Femur ,Elastic modulus ,Aged ,Lumbar Vertebrae ,Tibia ,Resolution (electron density) ,Isotropy ,Reproducibility of Results ,Anatomy ,Middle Aged ,Magnetic Resonance Imaging ,Finite element method ,Elasticity ,Biomechanical Phenomena ,Trabecular bone ,Linear Models ,Female ,Preclinical imaging ,Image based ,Biomedical engineering - Abstract
Recent advances in micro-magnetic resonance imaging (microMRI) now allow noninvasive assessment of mechanical properties of trabecular bone (TB) in vivo by micro finite-element analysis. The first aim of this work was to address the implications of limited resolution and signal-to-noise ratio on elastic properties of TB derived under conditions of in vivo imaging via simulation at various resolutions and noise levels on the basis of models derived from microCT images at 21 microm isotropic voxel size from cores of cadaveric human TB (n = 13) from three anatomic sites. The second aim was to compare how elastic constants derived from actual MR images at 9.4 Tesla at 50 microm isotropic voxel size compare with those from high-resolution microCT. Elastic moduli computed from simulated in vivo microMR images were highly correlated with those obtained from microCT (R(2) = 0.99) and the data were relatively immune to noise. Correlations of similar strength were obtained between estimated moduli from microCT and acquired high-field MR images. Systematic errors manifesting in significant deviations of the slopes from unity are caused by higher apparent bone-volume fraction of the MR images but can potentially be corrected with appropriate histogram-standardization techniques.
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- 2009
30. Dissociation of the neuronal regulation of bone mass and energy metabolism by leptin in vivo
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Vijay K. Yadav, X. Sherry Liu, Gerard Karsenty, Martin G. Myers, Yu Shi, Nina Suda, and X. Edward Guo
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Leptin ,medicine.medical_specialty ,Sympathetic Nervous System ,media_common.quotation_subject ,Mutation, Missense ,Biology ,Bone resorption ,Bone and Bones ,Bone remodeling ,Mice ,Internal medicine ,medicine ,Animals ,Receptor ,media_common ,Neurons ,Multidisciplinary ,Leptin receptor ,Leptin Deficiency ,Osteoblasts ,digestive, oral, and skin physiology ,Appetite ,Biological Sciences ,Endocrinology ,Receptors, Leptin ,Bone Remodeling ,Energy Metabolism ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
The leptin regulation of bone remodeling, which has been documented through studies of loss-of-function mutations of this hormone or of its receptor in mice and humans, still raised several unanswered questions. For instance, it has been assumed but not formally demonstrated that this regulation occurs through neuronal means. Likewise, it has not been possible until now to dissociate the influence leptin exerts on appetite and energy expenditure from this function. We show here through mouse genetic studies that a deletion of the leptin receptor in neurons results in an increase in bone formation and bone resorption, resulting in a high bone mass as seen in leptin-deficient mice. In contrast, the same deletion in osteoblasts only does not influence bone remodeling. Furthermore, through the use of l / l mice, a model of gain of function in leptin signaling harboring a Y985L substitution in the leptin receptor, we show that leptin signaling inhibits bone mass accrual by up-regulating sympathetic activity independently of any change in appetite or energy expenditure. This work establishes that in vivo leptin regulates bone mass accrual by acting through neuronal means and provides a direct demonstration that this function of leptin can occur independently of its regulation of energy metabolism.
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- 2008
31. In Vivo μMRI-Based Finite Element and Morphological Analyses of Tibial Trabecular Bone in Eugonadal and Hypogonadal Men Before and After Testosterone Treatment
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Felix W. Wehrli, Chamith S. Rajapakse, X. Henry Zhang, Branimir Vasilic, X. Sherry Liu, Maria Benito, X. Edward Guo, and Peter J. Snyder
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Male ,medicine.medical_specialty ,Time Factors ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Finite Element Analysis ,In vivo ,Testosterone treatment ,Internal medicine ,Medicine ,Humans ,Orthopedics and Sports Medicine ,Testosterone ,Tibia ,business.industry ,Hypogonadism ,Original Articles ,Distal tibia ,Androgen ,medicine.disease ,Magnetic Resonance Imaging ,Elasticity ,Testosterone Gel ,Trabecular bone ,Endocrinology ,Anisotropy ,business - Abstract
Osteoporosis is a major public health problem in men. Hypogonadal men have decreased BMD and deteriorated trabecular bone architecture compared with eugonadal men. Testosterone treatment improves their BMD and trabecular structure. We tested the hypothesis that testosterone replacement in hypogonadal men would also improve their bone's mechanical properties. Ten untreated severely hypogonadal and 10 eugonadal men were selected. The hypogonadal men were treated with a testosterone gel for 24 mo to maintain their serum testosterone concentrations within the normal range. Each subject was assessed before and after 6, 12, and 24 mo of testosterone treatment by microMRI of the distal tibia. A subvolume of each microMR image was converted to a microfinite element (microFE) model, and six analyses were performed, representing three compression and three shear tests. The anisotropic stiffness tensor was calculated, from which the orthotropic elastic material constants were derived. Changes in microarchitecture were also quantified using newly developed individual trabeculae segmentation (ITS)-based and standard morphological analyses. The accuracy of these techniques was examined with simulated microMR images. Significant differences in four estimated anisotropic elastic material constants and most morphological parameters were detected between the eugonadal and hypogonadal men. No significant change in estimated elastic moduli and morphological parameters was detected in the eugonadal group over 24 mo. After 24 mo of treatment, significant increases in estimated elastic moduli E(22) (9.0%), E(33) (5.1%), G(23) (7.2%), and G(12) (9.4%) of hypogonadal men were detected. These increases were accompanied by significant increases in trabecular plate thickness. These results suggest that 24 mo of testosterone treatment of hypogonadal men improves estimated elastic moduli of tibial trabecular bone by increased trabecular plate thickness.
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- 2008
32. A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats
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Ji Zhu, Yejia Zhang, X. Sherry Liu, Tiao Lin, Wei Ju Tseng, Abhishek Chandra, Shao Yun Hsu, Dongming Sun, Wise Young, Michael A. Levine, Ling Qin, Shi Gui Yan, Haoruo Jia, and Wei Tong
- Subjects
Chronic stage ,Pathology ,medicine.medical_specialty ,Histology ,Physiology ,business.industry ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Osteoblast ,Metaphysis ,medicine.disease ,Bone resorption ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Osteoclast ,medicine ,Animal studies ,business ,Spinal cord injury ,030217 neurology & neurosurgery - Abstract
Spinal cord injury (SCI)-induced bone loss represents the most severe osteoporosis with no effective treatment. Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae, and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography (µCT), micro-finite element, histology, and serum biochemical analyses. At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI.
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- 2015
33. Orthotopic forelimb allotransplantation in the rat model.
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Zhu, Hainan, Xie, Feng, Luo, Xusong, Qin, Ling, Sherry Liu, X., Scott Levin, Lawrence, and Li, Qingfeng
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- 2016
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34. A 13-year-old boy with fatigue and dizziness.
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Al-Gazi, Mohanad Shalan and Siying Sherry Liu
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- *
DIZZINESS , *FATIGUE (Physiology) , *ADOLESCENCE - Abstract
A case study is presented of a 13-year-old boy with the history of fatigue, nausea and lightheadedness. Electrocardiogram and echocardiogram investigations were negative; along with further investigations which included complete blood count, ferritin, and liver function tests. He was diagnosed for postural orthostatic tachycardia syndrome.
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- 2017
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35. Dependence of mechanical properties of trabecular bone on plate-rod microstructure determined by individual trabecula segmentation (ITS).
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Bin Zhou, X. Sherry Liu, Ji Wang, X. Lucas Lu, Fields, Aaron J., and X. Edward Guo
- Subjects
- *
CANCELLOUS bone , *MICROMECHANICS , *COMPOSITE materials research , *ORTHOPEDIC implants , *OSTEOPOROSIS treatment - Abstract
Individual trabecula segmentation (ITS) technique can decompose the trabecular bone network into individual trabecular plates and rods and is capable of quantifying the plate/rod-related microstructural characteristics of trabecular bone. This novel technique has been shown to be able to provide in-depth insights into micromechanics and failure mechanisms of human trabecular bone, as well as to distinguish the fracture status independent of area bone mineral density in clinical applications. However, the plate/rod microstructural parameters from ITS have never been correlated to experimentally determined mechanical properties of human trabecular bone. In this study, on-axis cylindrical trabecular bone samples from human proximal tibia (n = 22), vertebral body (n = 10), and proximal femur (n = 21) were harvested, prepared, scanned using micro computed-tomography (µCT), analyzed with ITS and mechanically tested. Regression analyses showed that the plate bone volume fraction (pBV/TV) and axial bone volume fraction (aBV/TV) calculated by ITS analysis correlated the best with elastic modulus (R²=0.96-0.97) and yield strength (R² = 0.95-0.96). Trabecular plate-related microstructural parameters correlated highly with elastic modulus and yield strength, while most rod-related parameters were found inversely and only moderately correlated with the mechanical properties. In addition, ITS analysis also identified that trabecular bone at human femoral neck had the highest trabecular plate-related parameters while the other sites were similar with each other in terms of plate-rod microstructure. [ABSTRACT FROM AUTHOR]
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- 2014
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36. A quantitative atlas of histone modification signatures from human cancer cells.
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LeRoy, Gary, DiMaggio, Peter A., Chan, Eric Y., Zee, Barry M., Blanco, M Andres, Bryant, Barbara, Flaniken, Ian Z., Sherry Liu, Yibin Kang, Trojer, Patrick, and Garcia, Benjamin A.
- Subjects
HISTONES ,EPIGENETICS ,GENE expression ,CELL lines ,CHROMATIN ,METHYLATION - Abstract
Background: An integral component of cancer biology is the understanding of molecular properties uniquely distinguishing one cancer type from another. One class of such properties is histone post-translational modifications (PTMs). Many histone PTMs are linked to the same diverse nuclear functions implicated in cancer development, including transcriptional activation and epigenetic regulation, which are often indirectly assayed with standard genomic technologies. Thus, there is a need for a comprehensive and quantitative profiling of cancer lines focused on their chromatin modification states. Results: To complement genomic expression profiles of cancer lines, we report the proteomic classification of 24 different lines, the majority of which are cancer cells, by quantifying the abundances of a large panel of single and combinatorial histone H3 and H4 PTMs, and histone variants. Concurrent to the proteomic analysis, we performed transcriptomic analysis on histone modifying enzyme abundances as a proxy for quantifying their activity levels. While the transcriptomic and proteomic results were generally consistent in terms of predicting histone PTM abundance from enzyme abundances, several PTMs were regulated independently of the modifying enzyme expression. In addition, combinatorial PTMs containing H3K27 methylation were especially enriched in breast cell lines. Knockdown of the predominant H3K27 methyltransferase, enhancer of zeste 2 (EZH2), in a mouse mammary xenograft model significantly reduced tumor burden in these animals and demonstrated the predictive utility of proteomic techniques. Conclusions: Our proteomic and genomic characterizations of the histone modification states provide a resource for future investigations of the epigenetic and non-epigenetic determinants for classifying and analyzing cancer cells. [ABSTRACT FROM AUTHOR]
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- 2013
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37. Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis.
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Yadav, Vijay K., Balaji, Santhanam, Suresh, Padmanaban S., X. Sherry Liu, Xin Lu, Zhishan Li, Guo, X. Edward, Mann, J. John, Balapure, Anil K., Gershon, Michael D., Medhamurthy, Rudraiah, Vidal, Marc, Karsenty, Gerard, and Ducy, Patricia
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OSTEOPOROSIS ,BONE diseases ,BONE resorption ,SEROTONIN ,BIOSYNTHESIS ,CHEMICAL synthesis ,ENZYMES - Abstract
Osteoporosis is a disease of low bone mass most often caused by an increase in bone resorption that is not sufficiently compensated for by a corresponding increase in bone formation. As gut-derived serotonin (GDS) inhibits bone formation, we asked whether hampering its biosynthesis could treat osteoporosis through an anabolic mechanism (that is, by increasing bone formation). We synthesized and used LP533401, a small molecule inhibitor of tryptophan hydroxylase-1 (Tph-1), the initial enzyme in GDS biosynthesis. Oral administration of this small molecule once daily for up to six weeks acts prophylactically or therapeutically, in a dose–dependent manner, to treat osteoporosis in ovariectomized rodents because of an isolated increase in bone formation. These results provide a proof of principle that inhibiting GDS biosynthesis could become a new anabolic treatment for osteoporosis. [ABSTRACT FROM AUTHOR]
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- 2010
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38. Maintenance Treatment for Patients With Bipolar I Disorder: Results From a North American Study of Quetiapine in Combination With Lithium or Divalproex (Trial 127).
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Suppes, Trisha, Vieta, Eduard, Sherry Liu, Brecher, Martin, and Paulsson, Björn
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BIPOLAR disorder ,CLINICAL drug trials ,DRUG efficacy ,MENTAL health services ,AFFECTIVE disorders ,PEOPLE with bipolar disorder ,BLOOD sugar - Abstract
Objective: The authors evaluated the efficacy and safety of quetiapine plus lithium or divalproex in the prevention of recurrent mood events in patients with stabilized bipolar I disorder. Method: A total of 1,953 patients received open-label quetiapine (400-800 mg/day in flexible, divided doses) with either lithium or divaiproex (target serum concentrations 0.5-i .2 meq/liter and 50125 μg/ml, respectively) for up to 36 weeks. After at least 12 weeks-of clinical stability, 628 patients were randomly assigned to double-blind treatment with quetiapine or placebo, in combination with lithium or divalproex, for up to 104 weeks. The primary efficacymeasure was time to recurrence of any mood event (mania, depression, or a mixed episode). Results: Fewer patients in the quetiapine group experienced a mood event compared with the placebo group (20.3% versus 52.1%). The hazard ratio for time to recurrence of a mood event was 0.32. Hazard ratios were similar for mania and depression events (0.30 and 0.33, respectively). Sedation, weight increase, and hypothyroidism occurred more frequently in the quetiapine group, as did discontinuations due to adverse events. The incidence and incidence density of a single emergent blood glucose value ⩾126 mg/dl were higher in the quetiapine group (12.6% versus 5.4%; 18.44 versus 9.56 patients per 100 patient-years). Adverse events were generally consistent with the known tolerability profile of quetiapine. Conclusions: In patients stabilized on quetiapine plus lithium or divalproex, continued treatment was associated with a significant risk reduction in the time to recurrence of any mood event compa red with placebo and lithium ordivalproex. [ABSTRACT FROM AUTHOR]
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- 2009
39. Signaling through the M3 Muscarinic Receptor Favors Bone Mass Accrual by Decreasing Sympathetic Activity
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Monzur Murshed, X. Edward Guo, X. Sherry Liu, Gerard Karsenty, Yu Shi, Jürgen Wess, Vijay K. Yadav, and Franck Oury
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medicine.medical_specialty ,Sympathetic nervous system ,Sympathetic Nervous System ,Physiology ,Regulator ,HUMDISEASE ,Biology ,Article ,Bone and Bones ,Bone resorption ,Bone remodeling ,Mice ,Parasympathetic nervous system ,Osteogenesis ,Parasympathetic Nervous System ,Internal medicine ,Muscarinic acetylcholine receptor ,medicine ,Animals ,Bone Resorption ,Receptor ,Molecular Biology ,Mice, Knockout ,Neurons ,Receptor, Muscarinic M3 ,Cell Biology ,Autonomic nervous system ,Endocrinology ,medicine.anatomical_structure - Abstract
SummaryBone remodeling is regulated by various neuronal inputs, including sympathetic tone, which is known to inhibit bone mass accrual. This aspect of sympathetic nervous system function raises the prospect that the other arm of the autonomic nervous system, the parasympathetic nervous system, may also affect bone remodeling. Here, we use various mutant mouse strains, each lacking one of the muscarinic receptors that mediate parasympathetic activity, to show that the parasympathetic nervous system acting through the M3 muscarinic receptor is a positive regulator of bone mass accrual, increasing bone formation and decreasing bone resorption. Gene expression studies, cell-specific gene deletion experiments, and analysis of compound mutant mice showed that the parasympathetic nervous system favors bone mass accrual by acting centrally and by decreasing the sympathetic tone. By showing that both arms of the autonomic nervous system affect bone remodeling, this study further underscores the importance of neuronal regulation of bone.
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40. Type III collagen is a key regulator of the collagen fibrillar structure and biomechanics of articular cartilage and meniscus.
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Wang, Chao, Brisson, Becky K., Terajima, Masahiko, Li, Qing, Hoxha, Kevt'her, Han, Biao, Goldberg, Abby M., Sherry Liu, X., Marcolongo, Michele S., Enomoto-Iwamoto, Motomi, Yamauchi, Mitsuo, Volk, Susan W., and Han, Lin
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- *
CARTILAGE , *ARTICULAR cartilage , *COLLAGEN , *BIOMECHANICS , *KNEE , *NUCLEAR forces (Physics) - Abstract
Despite the fact that type III collagen is the second most abundant collagen type in the body, its contribution to the physiologic maintenance and repair of skeletal tissues remains poorly understood. This study queried the role of type III collagen in the structure and biomechanical functions of two structurally distinctive tissues in the knee joint, type II collagen-rich articular cartilage and type I collagen-dominated meniscus. Integrating outcomes from atomic force microscopy-based nanomechanical tests, collagen fibril nanostructural analysis, collagen cross-link analysis and histology, we elucidated the impact of type III collagen haplodeficiency on the morphology, nanostructure and biomechanical properties of articular cartilage and meniscus in Col3a1 +/− mice. Reduction of type III collagen leads to increased heterogeneity and mean thickness of collagen fibril diameter, as well as reduced modulus in both tissues, and these effects became more pronounced with skeletal maturation. These data suggest a crucial role of type III collagen in mediating fibril assembly and biomechanical functions of both articular cartilage and meniscus during post-natal growth. In articular cartilage, type III collagen has a marked contribution to the micromechanics of the pericellular matrix, indicating a potential role in mediating the early stage of type II collagen fibrillogenesis and chondrocyte mechanotransduction. In both tissues, reduction of type III collagen leads to decrease in tissue modulus despite the increase in collagen cross-linking. This suggests that the disruption of matrix structure due to type III collagen deficiency outweighs the stiffening of collagen fibrils by increased cross-linking, leading to a net negative impact on tissue modulus. Collectively, this study is the first to highlight the crucial structural role of type III collagen in both articular cartilage and meniscus extracellular matrices. We expect these results to expand our understanding of type III collagen across various tissue types, and to uncover critical molecular components of the microniche for regenerative strategies targeting articular cartilage and meniscus repair. • Collagen III regulates fibril structure and mechanics in both collagen II-rich cartilage and collagen I-dominated meniscus. • Collagen III affects the aggrecan network compression possibly by mediating the aggrecan and collagen network integration. • Collagen III regulates cartilage pericellular matrix micromechanics, potentially mediating chondrocyte mechanotransduction. • Disruption of structure due to reduced collagen III outweighs increase in collagen cross-linking, causing reduced modulus. [ABSTRACT FROM AUTHOR]
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- 2020
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41. Trabecular Bone Deficit and Enhanced Anabolic Response to Re-Ambulation after Disuse in Perlecan-Deficient Skeleton
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Ashutosh Parajuli, Shaopeng Pei, Hongbo Zhao, Jerahme R. Martinez, X. Lucas Lu, X. Sherry Liu, Mary C. Farach-Carson, Catherine B. Kirn-Safran, and Liyun Wang
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perlecan ,schwartz-jampel syndrome ,trabecular bone ,osteoporosis ,osteoclastogenesis ,hindlimb suspension ,re-ambulation ,micro-computed tomography ,Microbiology ,QR1-502 - Abstract
Perlecan/Hspg2, a large monomeric heparan sulfate proteoglycan, is found in the basement membrane and extracellular matrix, where it acts as a matrix scaffold, growth factor depot, and tissue barrier. Perlecan deficiency leads to skeletal dysplasia in Schwartz-Jampel Syndrome (SJS) and is a risk factor for osteoporosis. In the SJS-mimicking murine model (Hypo), inferior cortical bone quality and impaired mechanotransduction in osteocytes were reported. This study focused on trabecular bone, where perlecan deficiency was hypothesized to result in structural deficit and altered response to disuse and re-loading. We compared the Hypo versus WT trabecular bone in both axial and appendicular skeletons of 8-38-week-old male mice, and observed severe trabecular deficit in Hypo mice, approximately 50% reduction of Tb.BV/TV regardless of skeletal site and animal age. Defects in endochondral ossification (e.g., accelerated mineralization), increases in osteoclast activity, and altered differentiation of bone progenitor cells in marrow contributed to the Hypo phenotype. The Hypo trabecular bone deteriorated further under three-week hindlimb suspension as did the WT. Re-ambulation partially recovered the lost trabecular bone in Hypo, but not in WT mice. The novel finding that low-impact loading could counter detrimental disuse effects in the perlecan-deficient skeleton suggests a strategy to maintain skeletal health in SJS patients.
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- 2020
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42. Is Gamma Knife surgery, omitting adjunct whole brain radiation treatment, feasible for patients with 20 or more brain metastases?
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Jiani SL, Karlsson B, Vellayappan B, Ang Y, Wu P, Yeo TT, and Nga V
- Abstract
Background: The importance of the number of brain metastases (BM) when deciding between whole brain radiation treatment (WBRT) and radiosurgery is controversial. We hypothesized that the number of BM is of limited importance when deciding radiation strategy, and offered Gamma Knife surgery (GKS) also for selected patients with 20 or more BM., Methods: The outcome following single session GKS for 75 consecutive patients harboring 20 or more (20+) BM was analyzed. Data was collected both retro- and prospectively., Results: The median survival time was 9 months. Two grade 3 complications occurred, 1 resolved and 1 did not. Sex and clinical condition at the time of GKS (ECOG value) were the only parameters significantly related to survival time. Eighteen patients developed leptomeningeal dissemination with or without distant recurrences (DR), and another 32 patients developed DR a total of 73 times. DR was managed with GKS 24 times, with WBRT 3 times and with systemic treatment or best supportive care 46 times. The median time to developing DR was unrelated to the number of BM, but significantly longer for patients older than 65 years, as well as for patients with NSCLC., Conclusions: GKS is a reasonable treatment option for selected patients with 20 or more BM. It is better to decide the optimal management of post-GKS intracranial disease progression once it occurs rather than trying to prevent it by using adjunct WBRT., Competing Interests: None of the authors have declared any conflict of interest., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
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- 2024
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43. Pregnancy and Lactation Impair Subchondral Bone Leading to Reduced Rat Supraspinatus Tendon-to-Bone Insertion Site Failure Properties.
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Fung AK, Shetye SS, Li Y, Zhou Y, Sherry Liu X, and Soslowsky LJ
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- Animals, Female, Pregnancy, Rats, Biomechanical Phenomena, Mechanical Phenomena, Tendons pathology, Tendons physiopathology, Tendons physiology, Bone and Bones pathology, Lactation, Rats, Sprague-Dawley, Rotator Cuff pathology, Rotator Cuff physiopathology
- Abstract
Pregnant women experience weight gain, gait changes, and biochemical fluctuations that impair joint function and alter the maternal skeleton. Hormonal changes increase pelvic ligament laxity in preparation for childbirth and affect peripheral joint laxity. Calcium demands also rise during pregnancy and lactation, resulting in reduced bone mineral density (BMD) and maternal bone loss. Altered tendon properties and bone loss during pregnancy and lactation may impact tendon insertion sites, such as rotator cuff tendons where insertion site ruptures are common. However, the effects of pregnancy and lactation at the tendon-to-bone interface have not been investigated. Therefore, the objective of this study was to evaluate supraspinatus tendon mechanical properties and insertion site microstructure during pregnancy, lactation, and postweaning recovery in female rats. We hypothesized that pregnancy and lactation would compromise supraspinatus tendon mechanical properties and subchondral bone microstructure. Female rats were divided into virgin, pregnancy, lactation, and recovery groups, and supraspinatus tendons were mechanically evaluated. Surprisingly, tendon mechanics was unaffected by pregnancy and lactation. However, tendon modulus decreased two-weeks postweaning. Additionally, tendons failed by bony avulsion at the insertion site, and the lactation group exhibited reduced failure properties corresponding to decreased subchondral bone mineralization. Lactation also resulted in dramatic bone loss at the epiphysis, but trabecular bone microarchitecture recovered postweaning. In conclusion, lactation following pregnancy impaired trabecular bone microstructure and subchondral bone mineralization, leading to reduced supraspinatus tendon-to-bone insertion site failure properties. These findings will contribute toward understanding the pathogenesis of tendon-to-bone disorders., (Copyright © 2020 by ASME.)
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- 2020
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44. Reproduction Differentially Affects Trabecular Bone Depending on Its Mechanical Versus Metabolic Role.
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de Bakker CMJ, Tseng WJ, Li Y, Zhao H, Altman-Singles AR, Jeong Y, Robberts J, Han L, Kim DG, and Sherry Liu X
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- Animals, Biomechanical Phenomena, Bone Density, Bone Remodeling, Cancellous Bone physiology, Female, Finite Element Analysis, Rats, Spine metabolism, Spine physiology, Cancellous Bone metabolism, Mechanical Phenomena, Reproduction
- Abstract
During pregnancy and lactation, the maternal skeleton provides calcium for fetal/infant growth, resulting in substantial bone loss, which partially recovers after weaning. However, the amount of bone that is lost and the extent of post-weaning recovery are highly variable among different skeletal sites, and, despite persistent alterations in bone structure at some locations, reproductive history does not increase postmenopausal fracture risk. To explain this phenomenon, we hypothesized that the degree of reproductive bone loss/recovery at trabecular sites may vary depending on the extent to which the trabecular compartment is involved in the bone's load-bearing function. Using a rat model, we quantified the proportion of the load carried by the trabeculae, as well as the extent of reproductive bone loss and recovery, at two distinct skeletal sites: the tibia and lumbar vertebra. Both sites underwent significant bone loss during pregnancy and lactation, which was partially recovered post-weaning. However, the extent of the deterioration and the resumption of trabecular load-bearing capacity after weaning varied substantially. Tibial trabecular bone, which bore a low proportion of the total applied load, underwent dramatic and irreversible microstructural deterioration during reproduction. Meanwhile, vertebral trabecular bone bore a greater fraction of the load, underwent minimal deterioration in microarchitecture, and resumed its full load-bearing capacity after weaning. Because pregnancy and lactation are physiological processes, the distinctive responses to these natural events among different skeletal sites may help to elucidate the extent of the trabecular bone's structural versus metabolic functions.
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- 2017
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