bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Investigation of the Mineral in Ductile and Brittle Cortical Mouse Bone
Authors: Rodriguez-Florez Naiara , Garcia-Tunon Esther , Mukadam Quresh , Saiz Eduardo , Oldknow Karla J , Farquharson Colin , Millán José Luis , Boyde Alan , Shefelbine Sandra J 
Published: November 2014

ABSTRACT

Bone is a strong and tough material composed of apatite mineral, organic matter, and water. Changes in composition and organization of these building blocks affect bone's mechanical integrity. Skeletal disorders often affect bone's mineral phase, either by variations in the collagen or directly altering mineralization. The aim of the current study was to explore the differences in the mineral of brittle and ductile cortical bone at the mineral (nm) and tissue (µm) levels using two mouse phenotypes. Osteogenesis imperfecta model, oim-/-, mice have a defect in the collagen, which leads to brittle bone; PHOSPHO1 mutants, Phospho1-/-, have ductile bone resulting from altered mineralization. Oim-/- and Phospho1-/- were compared with their respective wild-type controls. Femora were defatted and ground to powder to measure average mineral crystal size using X-ray diffraction (XRD) and to monitor the bulk mineral to matrix ratio via thermogravimetric analysis (TGA). XRD scans were run after TGA for phase identification to assess the fractions of hydroxyapatite and β-tricalcium phosphate. Tibiae were embedded to measure elastic properties with nanoindentation and the extent of mineralization with backscattered electron microscopy (BSE SEM). Results revealed that although both pathology models had extremely different whole-bone mechanics, they both had smaller apatite crystals, lower bulk mineral to matrix ratio, and showed more thermal conversion to β-tricalcium phosphate than their wild types, indicating deviations from stoichiometric hydroxyapatite in the original mineral. In contrast, the degree of mineralization of bone matrix was different for each strain: brittle oim-/- were hypermineralized, whereas ductile Phospho1-/- were hypomineralized. Despite differences in the mineralization, nanoscale alterations in the mineral were associated with reduced tissue elastic moduli in both pathologies. Results indicated that alterations from normal crystal size, composition, and structure are correlated with reduced mechanical integrity of bone. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Myelosuppressive Therapies Significantly Increase Pro-Inflammatory Cytokines and Directly Cause Bone Loss
Authors: Quach Julie M , Askmyr Maria , Jovic Tanja , Baker Emma K , Walsh Nicole C , Harrison Simon J , Neeson Paul , Ritchie David , Ebeling Peter R , Purton Louise E 
Published: November 2014

Abstract

Skeletal-related events resulting from accelerated bone loss are common complications in patients treated for a range of cancers. However, the mechanisms and rate of bone loss after myelosuppression are unclear. We, therefore, investigated this in mice and humans. We treated mice with different myelosuppressive therapies (chemotherapy or irradiation with or without transplantation) and studied their effects on bone structure. Myelosuppression of mice rapidly caused an increase in bone resorption that was not matched by bone formation. The resultant significant and persistent bone loss early after therapy was associated with increased inflammatory cytokines, in particular, monocyte chemoattractant protein 1 (MCP1). Therapy-induced bone loss was prevented with a single dose of the bisphosphonate zoledronic acid (ZA), administered before myelosuppression. Importantly, ZA treatment of mice did not impair hematopoiesis, including hematopoietic stem cell function. Furthermore, examination of serum from patients before and after autologous or allogeneic stem cell transplantion (SCT) revealed altered levels of bone turnover markers and elevated inflammatory cytokines. MCP1 levels in serum obtained between days 7 and 14 post-SCT positively correlated with bone loss observed at 100 days after allogeneic SCT. Similar to that observed in our studies in mice, the bone loss was long term, persisting at 12 months post-SCT. Furthermore, patients who received chemotherapy less than 100 days before SCT had significantly more bone loss at the hip. In these patients, serum levels of MCP1, but not routine biomarkers of bone turnover, including C-terminal cross-linking telopeptide of type-1 collagen (β-CTx), positively correlated with their bone loss. Hence, myelosuppressive therapies increase inflammation and directly contribute to bone loss. Administration of an osteoclast inhibitor before the initiation of cancer therapy is likely to have the best outcome in preventing bone loss in patients with cancer. © 2014 American Society for Bone and Mineral Research.
Investigation of the Effects of Some Drugs and Phenolic Compounds on Human Dihydrofolate Reductase Activity
Authors: Aslan Erdem , Adem Sevki 
Published: November 2014

ABSTRACTDihydrofolate reductase (DHFR) plays a fundamental role in cellular metabolism and cell growth. Inhibition of this enzyme will cause a decrease in the amount of folate that occurs in many metabolic processes, and the deficiency of which may cause various diseases. This study investigated the effects of some drugs and phenolic compounds on DHFR activity in vitro. To determine the inhibitory effect of compounds, enzyme activity was measured with a final concentration of an inhibitor ranging from 10 μM to 51 mM. DHFR was inhibited effectively by naringin, ferulic acid, and levofloxacin with IC50 values under 660 μM. Syringic acid, cefepime, ceftizoxime, cefazolin, ceftriaxone, and ceftazidime exhibited inhibitory effects on the enzyme activity with IC50 values in the range of 3.840–30.224 mM. Ki constants were calculated using the Cheng–Prusoff equation. Ki constants calculated in the range of 0.009–2.024 mM with respect to nicotinamide adenine dinucleotide phosphate oxidase (NADPH) and in the range of 0.060–5.830 mM about FH2.
Prevention of Nephrotoxicity Induced by Cyclosporine‐A: Role of Antioxidants
Authors: Damiano Sara , Ciarcia Roberto , Montagnaro Serena , Pagnini Ugo , Garofano Tiziana , Capasso Giovambattista , Florio Salvatore , Giordano Antonio 
Published: November 2014

ABSTRACTCyclosporine A (CsA) is a powerful immunosuppressive drug used to prevent allograft rejection after organ transplantation as well as in human and veterinary medicine. Unfortunately, its use is hampered by its nephrotoxic effects. The mechanisms of CsA‐induced hypertension and nephrotoxicity are not clear, but several studies suggest the possible involvement of free radicals. In this review we have summarized the effect of some antioxidants that we have used in the recent years, in combination with CsA, to better understand the exact mechanism of action of CsA and to try to open new perspectives in the treatment of CsA nephrotoxicity. J. Cell. Biochem. 116: 364–369, 2015. © 2014 Wiley Periodicals, Inc.
A Carboxy Terminal BMP/TGF‐β Binding Site in Secreted Phosphoprotein 24 kD Independently Affects BMP‐2 Activity
Authors: Tian Haijun , Li Chen‐Shuang , Zhao Ke‐Wei , Wang Jeffrey C. , Duarte M. Eugenia L. , David Cynthia L. , Phan Kevin , Atti Elisa , Brochmann Elsa J. , Murray Samuel S. 
Published: November 2014

ABSTRACTSecreted phosphoprotein 24 kD (spp24) is a bone matrix protein isolated during attempts to identify osteogenic proteins. It is not osteogenic but performs other important roles in the regulation of bone metabolism, at least in part, by binding to and affecting the activity of members of the BMP/TGF‐β family of cytokines. Spp24 exists in a number of forms that preserve the N‐terminus and are truncated at the C‐terminus. The hypothesized cytokine binding domain is present within the cystatin domain which is preserved in all of the N‐terminal products. In this report, we describe a C‐terminal fragment that is distinct from the cystatin domain and which independently binds to BMP‐2 and TGF‐β. This fragment inhibited BMP‐2 activity in an ectopic bone forming assay. A shorter C‐terminal product did not inhibit BMP‐2 activity but improved bone quality induced by BMP‐2 and produced increased calcium deposition outside of bone. Spp24 has been used to develop several potential therapeutic proteins. These results provide more information on the function of spp24 and provide other materials that can be exploited for clinical interventions. J. Cell. Biochem. 116: 667–676, 2015. © 2014 Wiley Periodicals, Inc.
Genomic Regions Targeted by DNA Topoisomerase IIβ Frequently Interact With a Nuclear Scaffold/Matrix Protein hnRNP U/SAF‐A/SP120
Authors: Miyaji Mary , Furuta Ryohei , Sano Kuniaki , Tsutsui Kimiko M. , Tsutsui Ken 
Published: November 2014

ABSTRACTType II DNA topoisomerases (topo II) play critical roles in some cellular events through repeated cleavage/rejoining of nuclear DNA. The β isoform (topo IIβ) is essential for the transcriptional induction of neuronal genes in terminal differentiation. Genomic sites targeted by the enzyme are nonrandom. Although previous studies have claimed that topo II cleavage sites are close to the nuclear scaffold/matrix attachment region (S/MAR), it is still unclear whether this view can be generalized. We report here that a library of cloned genomic DNA fragments targeted by topo IIβ in vivo frequently contains S/MAR and binding sites for hnRNP U/SAF‐A/SP120. Binding assays in vitro showed that a large proportion of the target DNAs bound to SP120 but their affinity to the nuclear scaffold/matrix varied significantly. Topo IIβ targets were extremely AT‐rich and often located in gene‐poor long intergenic regions (so‐called gene desert) that are juxtaposed to long genes expressed in neurons under differentiation. Sequence analysis revealed that topo IIβ targets are not just AT‐rich but are enriched with short tracts of A's and T's (termed A/T‐patches). Their affinity to the nuclear scaffold/matrix showed a moderate positive correlation with the coverage rate of A/T‐patches. The results suggest that the interaction of topo IIβ/SP120 with target regions modulates their proximity to the nuclear scaffold/matrix in a dynamic fashion and that A/T‐patch is a sequence motif assisting this process. J. Cell. Biochem. 116: 677–685, 2015. © 2014 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.
Anaerobic fluidized membrane bioreactor polishing of baffled reactor effluent during treatment of dilute wastewater
Authors: Lee Ryunkyung , McCarty Perry L. , Bae Jaeho , Kim Jeonghwan 
Published: November 2014

AbstractBACKGROUNDIn this study an anaerobic fluidized bed membrane bioreactor (AFMBR) is added as a second stage to an operating anaerobic baffled bioreactor (ABR) to form a staged anaerobic baffled‐fluidized membrane bioreactor (SAB‐FMBR) operating at ambient temperature.RESULTSThe ABR first stage was operated at 3 h hydraulic retention time (HRT) and was followed by the AFMBR operated at 0.93 to 1.16 h HRT. The SAB‐AFMBR system was fed with complex synthetic wastewater with COD averaging 250 mg L−1. GAC fluidization increased the critical flux of the AFMBR due to fouling reduction associated with the cleaning action of the GAC particles on membrane surfaces. However, sustainable flux for long‐term operation of the AFMBR was lower than the critical flux determined in short‐term tests. Overall COD removal by the SAB‐FMBR system when operating at a sustainable flux (8–9 L m−2 h−1) was 96% with effluent COD of about 11 mg L−1 and suspended solids concentration near zero. The electrical energy required for system operation in the AFMBR was 0.0087 kWh m−3, much less than that of an anaerobic MBR using biogas sparging to control membrane fouling.CONCLUSIONThe AFMBR was applied successfully as a second stage polishing system for an ABR treating complex synthetic wastewater at a temperature of 25 °C. © 2014 Society of Chemical Industry
Patient preferences regarding pharmacologic venous thromboembolism prophylaxis
Authors: Wong Adrian , Kraus Peggy S. , Lau Brandyn D. , Streiff Michael B. , Haut Elliott R. , Hobson Deborah B. , Shermock Kenneth M. 
Published: November 2014

BACKGROUNDThe 2012 American College of Chest Physicians venous thromboembolism prevention guidelines emphasized the importance of considering patient preferences when ordering venous thromboembolism prophylaxis.OBJECTIVEDetermine patient preferences regarding pharmacologic venous thromboembolism prophylaxis.DESIGNSingle‐center, mixed‐methods survey.SETTINGAcademic medical center.PATIENTSConsecutive hospitalized patients on surgical and medical units.MEASUREMENTSPatients were asked about their preferences regarding the route of administration for pharmacologic venous thromboembolism prophylaxis and the rationale for their preference. Qualitative analyses of themes were determined from patient rationale.RESULTSOf the 227 patients, a majority (60.4%) preferred an oral medication, if equally effective to subcutaneous options. Dislike of needles (30.0%) and pain from injection (27.7%) were identified as rationales for their preference. Patients favoring subcutaneous administration (27.5%) identified a presumed faster onset of action (40.3%) as the primary reason for their preference. Patients with a preference for subcutaneous injections were less likely to refuse prophylaxis than patients who preferred an oral route of administration (37.5% vs 51.3%, P < 0.0001).LIMITATIONOnly medical and surgical patients participated.CONCLUSIONIn a sample of consecutive medical and surgical patients, a majority preferred an oral route of administration for prophylaxis. Patients preferring subcutaneous injections were less likely to refuse doses of ordered pharmacologic prophylaxis. These results indicate use of an oral agent for venous thromboembolism prophylaxis may improve adherence and that integrating patient preferences into care may increase delivery of effective prophylaxis and reduce the incidence of venous thromboembolism. Journal of Hospital Medicine 2015;10:108–111. © 2014 Society of Hospital Medicine
On the covariability of seasonal temperature and precipitation in Spain, 1956–2005
Authors: Rodrigo F. S. 
Published: November 2014

ABSTRACTIn this work, the covariability between the standardized anomalies of seasonal mean temperature and total rainfall in four Spanish sites during the periods 1956–1980 and 1981–2005 is analysed. Original data are standardized using the reference period 1971–2000. Using the hypothesis of bivariate normal distribution, the climate states corresponding to each period may be characterized by the confidence ellipses at the 95% confidence level. Movements of the ellipses indicate changes in the vector mean (translations), changes in the sign of the correlation coefficient (rotations) and in the variance–covariance matrix (deformations). Significance of these changes is assessed by Hotelling's, difference between correlation coefficients, and Barlett's tests, respectively. Results indicate a general translation towards higher (lower) mean temperature (precipitation) in the second period. Significant changes in the variance–covariance matrix did not show a clear pattern. Future developments of this methodology are outlined.
Functionally deficient mesenchymal stem cells reside in the bone marrow niche with M2‐macrophages and amyloid‐β protein adjacent to loose total joint implants
Authors: Margulies Bryan S. , DeBoyace Sean D. , Parsons Adrienne M. , Policastro Connor G. , Ee Jessica﻿ S.S. , Damron Timothy﻿ S. 
Published: November 2014

ABSTRACTWe sought to demonstrate whether there is a difference in the local mesenchymal stem cells (MSC) niche obtained from patients undergoing their first total joint replacement surgery versus those patients undergoing a revision surgery for an failing total joint implant. Bone marrow aspirates collected from patients undergoing revision total joint arthroplasty were observed to be less clonal and the expression of PDGFRα, CD51, ALCAM, endoglin, CXCL12, nestin, and nucleostemin were decreased. Revision MSC were also less able to commit to an osteoblast‐lineage or an adipocyte‐lineage. Further, in revision MSC, OPG, and IL6 expression were increased. Monocytes, derived from revision whole marrow aspirates, were less capable of differentiating into osteoclasts, the cells implicated in the pathologic degradation of bone. Osteoclasts were also not observed in tissue samples collected adjacent to the implants of revision patients; however, the alternatatively activated M2‐macrophage phenotype was observed in parallel with pathologic accumulations of amyloid‐β, τ‐protien and 3‐nitrotyrosine. Despite the limited numbers of patients examined, our data suggest that nucleostemin may be a useful functional marker for MSC while the observation of M2‐macrophage infiltration around the implant lays the foundation for future investigation into a novel mechanism that we propose is associated with loose total joint implants. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:615–624, 2014.
Autologous implantation of BMP2‐expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones
Authors: Ishihara Akikazu , Weisbrode Steve E. , Bertone Alicia L. 
Published: November 2014

ABSTRACTCell‐mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein‐2 (BMP2) gene transduction. Autologous DFb or BMP2‐expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra‐medullar infusion into tibiae and delayed intra‐osseous injection into femoral drill defects. Both delivery methods of DFb‐BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non‐transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra‐osseous injection of DFb‐BMP2. Our results suggested that BMP2‐expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb‐BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1455–1465, 2015.
The effect of disc degeneration on anterior shear translation in the lumbar spine
Authors: Melnyk Angela D. , Kelly Adrienne , Chak Jason D. , Wen Tian Lin , Cripton Peter A. , Dvorak Marcel F. , Oxland Thomas R. 
Published: November 2014

ABSTRACTMany pathologies involving disc degeneration are treated with surgery and spinal implants. It is important to understand how the spine behaves mechanically as a function of disc degeneration. Shear loading is especially relevant in the natural and surgically stabilized lumbar spine. The objective of our study was to determine the effect of disc degeneration on anterior translation of the lumbar spine under shear loading. We tested 30 human cadaveric functional spinal units (L3–4 and L4–5) in anterior shear loading. First, the specimens were imaged in a 1.5 T magnetic resonance scanner. The discs were graded according to the Pfirrmann classification. The specimens were then loaded up to 250 N in anterior shear with an axial compression force of 300 N. Motion of the vertebrae was captured with an optoelectronic camera system. Inter‐ and intra‐observer reliability for disc grading was determined (Cohen's and Fleiss' Kappa), and a non‐parametric test was performed on the translation data to characterize the effect of disc degeneration on this parameter. We found fair to moderate agreement between and within observers for the disc grading. We found no significant effect of disc degeneration on anterior shear translation (Kruskal‐Wallis ANOVA). Our results indicate that disc degeneration, as classified with the Pfirrmann scale, does not predict lumbar spinal motion in shear. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:450–457, 2015.
Effect of medial opening wedge high tibial osteotomy on intraarticular knee and ankle contact pressures
Authors: Suero Eduardo M. , Sabbagh Yaman , Westphal Ralf , Hawi Nael , Citak Musa , Wahl Friedrich M. , Krettek Christian , Liodakis Emmanouil 
Published: November 2014

ABSTRACTHigh tibial osteotomy (HTO) is a commonly used surgical technique for treating moderate osteoarthritis (OA) of the medial compartment of the knee by shifting the center of force towards the lateral compartment. Previous studies have documented the effects of HTO on the biomechanics of the knee. However, the effects of the procedure on the contact pressures within the ankle joint have not been as well described. Seven cadavers underwent an HTO procedure with sequential 5° valgus realignment of the leg up to 15° of correction. An axial force of up to 550 N was applied and the intraarticular pressure was recorded. Minor valgus realignment of the proximal tibia does not significantly alter the biomechanics of the ankle. However, moderate‐to‐large changes in proximal tibial alignment result in significantly decreased tibiotalar contact surface area and in changes in intraarticular ankle pressures. These findings are clinically relevant, as they provide a biomechanical rationale for the diagnosis and treatment of ankle symptoms in the setting of lower limb malalignment or after alignment correction procedures. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:598–604, 2015.
Nanoemulsions as an effective medium for encapsulation and stabilization of cholesterol/β‐cyclodextrin inclusion complex
Authors: Kaur Khushwinder 
Published: November 2014

AbstractBACKGROUNDInclusion complex formation between β‐cyclodextrin (β‐CD) and suitable guest molecules such as cholesterol (Ch) has regularly been exploited to design self‐assembled structures. In the present study an effective nanoemulsion medium (lecithin/Tween 80/ethyl oleate/water) was selected for solubilizing and stabilizing Ch and Ch/β‐CD inclusion complex. Phase solubility, spectroscopic, thermodynamic, Z‐average diameter and morphological analyses were conducted.RESULTSPhase solubility data analysis demonstrated an increase in Ch solubility at low β‐CD concentrations (0.01–0.35 mmol L−1). Transmission electron microscopy and Z‐average diameter data indicated the spherical nature of the droplets and confirmed the formation of nanoemulsions with an average size of less than 50 nm. The negative value of ΔG obtained during analysis further indicated that the binding was spontaneous in nature.CONCLUSIONPrimarily, this research demonstrates the use of nanoemulsions as a medium in food matrices, instead of water, for hosting Ch in β‐CD. © 2014 Society of Chemical Industry