Experimental repetitive mild traumatic brain injury induces deficits in trabecular bone microarchitecture and strength in mice

To evaluate the long-term consequence of repetitive mild traumatic brain injury （mTBI） on bone, mTBI was induced in 10-week-old female C57BL/6J mice using a weight drop model, once per day for 4 consecutive days at different drop heights （0.5, 1 and 1.5 m） and the skeletal phenotype was evaluated at different time points after the impact. In vivo micro-CT （μ-CT） analysis of the tibial metaphysis at 2, 8 and 12 weeks after the impact revealed a 5%-32% reduction in trabecular bone mass. Histomorphometric analyses showed a reduced bone formation rate in the secondary spongiosa ofl.5 m impacted mice at 12 weeks post impact. Apparent modulus （bone strength）, was reduced by 30% （P 〈 0.05） at the proximal tibial metaphysis in the 1.5 m drop height group at 2 and 8 weeks post impact. Ex vivo μ-CT analysis of the fifth lumbar vertebra revealed a significant reduction in trabecular bone mass at 12 weeks of age in all three drop height groups. Serum levels of osteocalcin were decreased by 22%, 15%, and 19% in the 0.5, 1.0 and 1.5 m drop height groups, respectively, at 2 weeks post impact. Serum IGF-I levels were reduced by 18%-32% in mTBI mice compared to control mice at 2 weeks post impact. Serum osteocalcin and IGF-I levels correlated with trabecular BV/TV （r2 = 0.14 and 0.16, P 〈 0.05）. In conclusion, repetitive mTBI exerts significant negative effects on the trabecular bone microarchitecture and bone mechanical properties by influencing osteoblast function via reduced endocrine IGF-I actions.

Association Between Knee Alignment,Disease Severity and Subchondral Trabecular Bone Microarchitecture in Patients with Knee Osteoarthritis

Objective Most patients with knee osteoarthritis(OA)have alignment deformity with the change of Hip-knee-ankle(HKA)angle.The knee alignment influences load distribution at the tibial plateau.Meanwhile,change of subchondral trabecular bone microstructure is related to load bearing and OA progression.However,the relationship between knee alignment on the changes of subchondral trabecular bone microstructure and OA severity have been poorly investigated.The main goal of this work was to investigate variation in tibial plateaus subchondral trabecular bone microstructure in knee OA patients and their association with the severity of OA with the change of knee alignment.Methods Seventy-one knee OA patients planning to undergo total knee arthroplasty were enrolled in this study.The HKA angle and OA disease severity(OARSI score,compartment-specific Kellgren-Lawrence(K-L)grade and OARSI Atlas grade)based on full-leg standing posteroanterior radiographs were evaluated preoperatively in all patients.The tibial plateau collected during surgery was first used for micro-computed tomography(μCT)to analyze the subchondral trabecular bone microstructures,and then used for pathological sections to analyze cartilage degeneration(OARSI score).Pearson and spearman correlations were used to examine linear relationships between knee alignment,OA disease severity and subchondral trabecular bone microstructure.Patients were then divided into group I(HKA angle exceeds 0°in the valgus direction),group II(varus angle<10°)and group III(varus angle≥10°).The differences in subchondral trabecular bone microstructural parameters between the three groups were analyzed by the one-way ANOVA with a post hoc Tukey test.Results HKA angle was significantly correlated with all tibial plateau subchondral trabecular bone microstructure parameters.Regardless of the medial or lateral tibia,HKA angle was most strongly correlated with bone volume fraction(BV/TV),M:(r=0. 613,P<0.01);L:(r=-0.490,P<0.01).In addition,for the media-to-lateral ratios(M:L)of the subchondral trabecular bone microstructure parameters,the HKA angle is positively correlated with M:L BV/TV(r=0.658,P<0.01),M:L trabecular number(Tb.N)(r=0.525,,P<0.01),M:L trabecular thickness(Tb.Th)(r=0.636,P<0.01),and negatively correlated with M:L trabecular separation(Tb.Sp)(r=-0.636,P<0.01)and M:L Specific Bone Surface(BS/BV)(r=-0.792,P<0.01).The BV/TV,Tb.N,and Tb.Th of the medial tibia were sequentially incremented in the order of groupⅠ,Ⅱ,Ⅲof knee alignment,while the Tb.Sp and BS/BV were decreased in this order.The lateral tibia is the opposite.In addition,most of the severity indices of OA are associated with subchondral trabecular bone microstructures,of which OARSI score and BV/TV in medial tibia are the most relevant(r=0.787,P<0.01).HKA angle is significantly correlated with all OA severity grades in medial compartment,but only with OARSI score and Bone sclerosis grade in lateral compartment.Conclusions Tibial plateau subchondral trabecular bone microarchitecture is associated with the HKA angle and OA severity.With the increase of varus angle and the severity of OA,the subchondral trabecular bone in medial tibia has more obvious sclerosis changes and vice versa,suggesting that knee malalignment may promote abnormal subchondral trabecular bone remodeling by altering joint load distribution,thereby affecting the progression of OA.

Bone density, microarchitecture and stiffness in Caucasian and Caribbean Hispanic postmenopausal American women

Hispanic Americans of Caribbean origin are a fast-growing subset of the US population, but there are no studies on bone density, microstructure and biomechanical integrity in this minority group. In this study, we aimed to compare Caucasian and Caribbean Hispanic postmenopausal American women with respect to these characteristics. Thirty-three Caribbean Hispanics were age-matched to thirty-three Caucasian postmenopausal women. At the lumbar spine, the Hispanic women had significantly lower areal bone mineral density （aBMD）. At the radius by high-resolution peripheral quantitative computed tomography （HR-pQCT）, there were minimal differences between Hispanic and Caucasian women. At the tibia, Hispanic women had lower trabecular volumetric bone density and trabecular number, and higher trabecular separation. Individual trabecula segmentation （ITS） analyses indicated that at the tibia, Hispanic women not only had significantly lower bone volume fraction, but also had significantly lower rod bone volume fraction, plate trabecular number, rod trabecular number and lower plate-plate, plate-rod and rod-rod junction densities compared to Caucasian women. The differences in bone quantity and quality contributed to lower whole bone stiffness at the radius, and both whole bone and trabecular bone stiffness at the tibia in Hispanic women. In conclusion, Hispanic women had poorer bone mechanical and microarchitectural properties than Caucasian women, especially at the load-bearing distal tibia.

Oral administration of egg white ovotransferrin prevents osteoporosis in ovariectomized rats

Ovotransferrin,an iron-binding glycoprotein,accounting for approximately 12%of egg white protein,is a member of transferrin fam ily.Our previous studies showed that ovotransferrin stimulates the proliferation and differentiation of osteoblasts,while inhibits osteoclastogenesis and resorption activity.The work aims to study the efficacy of orally administered ovotransferrin on the prevention of osteoporosis using ovariectomized(OVX)Sprague-Dawley rats.Oral administration of ovotransferrin showed no negative effect on body weight,food intake and organ weight.After 12-week treatment,feeding ovotransferrin at a dose of 1%(1 g ovotransferrin/100 g diet)prevented OVX-induced bone loss and maintained relatively high bone mineral density and integrated bone microarchitecture.The serum concentration of biomarkers indicating bone formation was increased in ovotransferrin administration groups,while the bone resorption biomarkers were decreased.Ovotransferrin feeding also decreased the production of serum cytokine TNF-αand IL-6,which are two stimulators for osteoclast differentiation.In addition to its direct regulatory role on bone turnover,ovotransferrin supplementation might benefit osteoporosis prevention by inhibiting adipogenesis,and regulating immune response.Our results suggested the potential application of ovotransferrin as a functional food ingredient on the prevention of osteoporosis.

Efficient cache replacement framework based on access hotness for spacecraft processors

A notable portion of cachelines in real-world workloads exhibits inner non-uniform access behaviors.However,modern cache management rarely considers this fine-grained feature,which impacts the effective cache capacity of contemporary high-performance spacecraft processors.To harness these non-uniform access behaviors,an efficient cache replacement framework featuring an auxiliary cache specifically designed to retain evicted hot data was proposed.This framework reconstructs the cache replacement policy,facilitating data migration between the main cache and the auxiliary cache.Unlike traditional cacheline-granularity policies,the approach excels at identifying and evicting infrequently used data,thereby optimizing cache utilization.The evaluation shows impressive performance improvement,especially on workloads with irregular access patterns.Benefiting from fine granularity,the proposal achieves superior storage efficiency compared with commonly used cache management schemes,providing a potential optimization opportunity for modern resource-constrained processors,such as spacecraft processors.Furthermore,the framework complements existing modern cache replacement policies and can be seamlessly integrated with minimal modifications,enhancing their overall efficacy.

Dynamic Alterations in Microarchitecture, Mineralization and Mechanical Property of Subchondral Bone in Rat Medial Meniscal Tear Model of Osteoarthritis

Background： The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis （OA）. However, the characteristics ofsubchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA. Methods： A medial meniscal tear （MMT） operation was pertbrmed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density （TMD）, mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates （BPs） and trabecular bones （Tbs） were measured using micro-computed tomography scanning, conibcal Raman microspectroscopy and nanoindentation testing, respectively. Results： Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early （reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing （Tb.Sp） at 2 and 4 weeks） to bone accretion late （increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks）. The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks. Conclusion： The microarchitecture, mineralization and mechanical properties of subchondral bone changed in a time-dependent manner as OA progressed.

Comparative Study between Bone Tissue Engineering Scaffolds with Bull and Rat Cancellous Microarchitectures on Tissue Differentiations of Bone Marrow Stromal Cells： A Numerical Investigation

Tissue-engineered bone scaffolds provide temporary mechanical support for bone tissue growth. Mechanical stimuli are transferred to seeded cells through the scaffold structure to promote cell proliferation and differentiation. This paper presents a numerical investigation specifically on bone and cartilage tissue differentiation with the aim to provide a theoretical basis for scaffold design and bone defect repair in clinics. In this study, the scaffold structures were established on the basis of cancellous bone microarchitectures. For finite element simulations, inlet velocity and compressive strain were applied under in vitro culture conditions. The influences of this scaffold mor- phology and macro-level culture conditions on micro-mechanical stimuli at scaffold surfaces were investigated. Correlations between the microarchitectural parameters and the mechanical parameters, as well as the cell differentiation parameters were analyzed. Highly het- erogeneous stress distributions were observed on the scaffolds with irregular morphology. Cell differentiation on the scaffold was more sensitive to the inlet velocity than the axial strain. In addition, cartilage differentiation on the scaffolds with structures comprising more plate-like trabeculae was more pronounced than on those with more rod-like trabeculae. This paper is helpful to gain more insight into the mechanical environments under in vitro culture conditions that approximate the in vivo mechanical environments of Bone Marrow Stromal Ceils （BMSCs）.

A decellularized nerve matrix scaffold inhibits neuroma formation in the stumps of transected peripheral nerve after peripheral nerve injury

Traumatic painful neuroma is an intractable clinical disease characterized by improper extracellular matrix(ECM)deposition around the injury site.Studies have shown that the microstructure of natural nerves provides a suitable microenvironment for the nerve end to avoid abnormal hyperplasia and neuroma formation.In this study,we used a decellularized nerve matrix scaffold(DNM-S)to prevent against the formation of painful neuroma after sciatic nerve transection in rats.Our results showed that the DNM-S effectively reduced abnormal deposition of ECM,guided the regeneration and orderly arrangement of axon,and decreased the density of regenerated axons.The epineurium-perilemma barrier prevented the invasion of vascular muscular scar tissue,greatly reduced the invasion ofα-smooth muscle actin-positive myofibroblasts into nerve stumps,effectively inhibited scar formation,which guided nerve stumps to gradually transform into a benign tissue and reduced pain and autotomy behaviors in animals.These findings suggest that DNM-S-optimized neuroma microenvironment by ECM remodeling may be a promising strategy to prevent painful traumatic neuromas.

Critical review of bone health,fracture risk and management of bone fragility in diabetes mellitus

The risk of fracture is increased in both type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,in contrast to the former,patients with T2DM usually possess higher bone mineral density.Thus,there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes.Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk.Moreover,some antidiabetic medications further enhance the fragility of the bone.On the other hand,antiosteoporosis medications can affect the glucose homeostasis in these patients.It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk.Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature.With the advancement in imaging technology,newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes.The purpose of this review is to explore the patho-physiology behind poor bone health in diabetic patients.Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.

Fractal lacunarity of trabecular bone and magnetic resonance imaging:New perspectives for osteoporotic fracture risk assessment

Osteoporosis represents one major health condition for our growing elderly population. It accounts for severe morbidity and increased mortality in postmenopausal women and it is becoming an emerging health concern even in aging men. Screening of the population at risk for bone degeneration and treatment assessment of osteoporotic patients to prevent bone fragility fractures represent useful tools to improve quality of life in the elderly and to lighten the related socio-economic impact. Bone mineral density(BMD) estimate by means of dual-energy X-ray absorptiometry is normally used in clinical practice for osteoporosis diagnosis. Nevertheless, BMD alone does not represent a good predictor of fracture risk. From a clinical point of view, bone microarchitecture seems to be an intriguing aspect to characterize bone alteration patterns in aging and pathology. The widening into clinical practice of medical imaging techniques and the impressive advances in information technologies together with enhanced capacity of power calculation have promoted proliferation of new methods to assess changes of trabecular bone architecture(TBA) during aging and osteoporosis. Magnetic resonance imaging(MRI) has recently arisen as a useful tool to measure bone structure in vivo. In particular, high-resolution MRI techniques have introduced new perspectives for TBA characterization by non-invasive non-ionizing methods. However, texture analysis methods have not found favor with clinicians as they produce quite a few parameters whose interpretation is difficult. The introduction in biomedical field of paradigms, such as theory of complexity, chaos, and fractals, suggests new approaches and provides innovative tools to develop computerized methods that, by producing a limited number of parameters sensitive to pathology onset and progression, would speed up their application into clinical practice. Complexity of living beings and fractality of several physio-anatomic structures suggest fractal analysis as a promising approach to quantify morphofunctional changes in both aging and pathology. In this particular context, fractal lacunarity seems to be the proper tool to characterize TBA texture as it is able to describe both discontinuity of bone network and sizes of bone marrow spaces, whose changes are an index of bone fracture risk. In this paper, an original method of MRI texture analysis, based on TBA fractal lacunarity is described and discussed in the light of new perspectives for early diagnosis of osteoporotic fractures.

New Generation Processor Architecture Research

With the rapid development of microelectronics and hardware,the use of ever faster micro processors and new architecture must be continued to meet tomorrow′s computing needs. New processor microarchitectures are needed to push performance further and to use higher transistor counts effectively.At the same time,aiming at different usages,the processor has been optimized in different aspects,such as high performace,low power consumption,small chip area and high security. SOC (System on chip)and SCMP (Single Chip Multi Processor) constitute the main processor system architecture.

A robust methodology for the quantitative assessmentof the rat jawbone microstructure

Micro-computed tomography can be applied for the assessment of the micro-architectural characteristics of the cortical and trabecular bones in either physiological or disease conditions. However, reports often lack a detailed description of the methodological steps used to analyse these images, such as the volumes of interest, the algorithms used for image filtration, the approach used for image segmentation, and the bone parameters quantified, thereby making it difficult to compare or reproduce the studies. This study addresses this critical need and aims to provide standardized assessment and consistent parameter reporting related to quantitative jawbone image analysis. Various regions of the rat jawbones were screened for their potential for standardized micro-computed tomography analysis. Furthermore, the volumes of interest that were anticipated to be most susceptible to bone structural changes in response to experimental interventions were defined. In the mandible, two volumes of interest were selected, namely, the condyle and the trabecular bone surrounding the three molars. In the maxilla, the maxillary tuberosity region and the inter-radicular septum of the second molar were considered as volumes of interest. The presented protocol provides a standardized and reproducible methodology for the analysis of relevant jawbone volumes of interest and is intended to ensure global, accurate, and consistent reporting of its morphometry. Furthermore, the proposed methodology has potential, as a variety of rodent animal models would benefit from its implementation.

HISTOMORPHOMETRIC STUDY OF SUBCHONDRAL BONE OF NECROTIC FEMORAL HEAD IN RABBITS INDUCED BY METHYLPREDNISOLONE COMBINED WITH LOW-DOSE LIPOPOLYSACCHARIDE

Objective To investigate the histomorphometric features of the necrotic femoral head of rabbits induced by methylprednisolone combined with lipopolysaccharide. Methods Thirty-two mole adult New Zealand white rabbits were used. Among them, 16 were injected with lipopolysaccharide and methylprednisolone （ osteonecrosis group） , and another 16 were sham-injected with saline （ control group）. Magnetic resonance （MR） imaging was taken for femoral heads of the rabbits in both groups at the end of 2, 4 and 6 weeks after the injection. All the rabbits were then killed 6 weeks later. The femoral heads of the rabbits were collected and processed for histological and histomorphometric analysis. Results Femoral head necrosis occurred in 14 rabbits of the osteonecrosis group which were confirmed by histological evaluation and MR imaging. Osteonecrotic femoral heads, compared to controls, were characterized by lower values of bone volume/tissue volume （ P 〈 0. 01 ）, tabecular thichness （ P 〈 0. 01 ） , osteoid surface/bone surface （ P 〈 0. 05 ）, mineralizing apposition rate （ P 〈 0 05 ）, and bone formation rate/bone surface （ P 〈0. 05 ）. However, tabecular separation and eroded surface/bone surface were higher in osteonecrotic femoral heads than in controls （ P 〈 0. 01 ）. Trabecular number and osteoclast surface/ bone surface did not differ significantly. Conclusion The results demonstrated that osteoporosis was apparent in osteonecrotic femoral heads induced by methylprednisolone and lipopolysaccharide, due mainly to trabecular thinning rather than reduction of trabecular number. This might be due to reduced bone formation combined with increased bone resorption.

Security Vulnerabilities in Microprocessors

Microprocessors such as those found in PCs and smartphones are complex in their design and nature.In recent years,an increasing number of security vulnerabilities have been found within these microprocessors that can leak sensitive user data and information.This report will investigate microarchi­tecture vulnerabilities focusing on the Spectre and Meltdown exploits and will look at what they do,how they do it and,the real-world impact these vulnerabilities can cause.Additionally,there will be an introduction to the basic concepts of how several PC components operate to support this.

Local treatment of osteoporosis with alendronate-loaded calcium phosphate cement

Background A new treatment strategy is to target specific areas of the skeletal system that are prone to clinically significant osteoporotic fractures.We term this strategy as the ＂local treatment of osteoporosis＂.The study was performed to investigate the effect of alendronate-loaded calcium phosphate cement （CPC） as a novel drug delivery system for local treatment of osteoorosis.Methods An in vitro study was performed using CPC fabricated with different concentrations of alendronate （ALE,0,2,5,10 weight percent （wt％））.The microstructure,setting time,infrared spectrum,biomechanics,drug release,and biocompatibility of the composite were measured in order to detect changes when mixing CPC with ALE.An in vivo study was also performed using 30 Sprague-Dawley rats randomly divided into six groups：normal,Sham （ovariectomized （OVX） ＋ Sham）,CPC with 2％ ALE,5％ALE,and 10％ ALE groups.At 4 months after the implantation of the composite,animals were sacrificed and the caudal vertebrae （levels 4-7） were harvested for micro-CT examination and biomechanical testing.Results The setting time and strength of CPC was significantly faster and greater than the other groups.The ALE release was sustained over 21 days,and the composite showed good biocompatibility.In micro-CT analysis,compared with the Sham group,there was a significant increase with regard to volumetric bone mineral density （BMD） and trabecular number （Tb.N） in the treated groups （P ＜0.05）.Trabecular spacing （Tb.Sp） showed a significant increase in the Sham group compared to other groups （P ＜0.01）.However,trabecular thickness （Tb.Th） showed no significant difference among the groups.In biomechanical testing,the maximum compression strength and stiffness of trabecular bone in the Sham group were lower than those in the experimental groups.Conclusions The ALE-loaded CPC displayed satisfactory properties in vitro,which can reverse the OVX rat vertebral trabecular bone microarchitecture and biomechanical properties in vivo.

Whole body vibration with rest days could improve bone quality of distal femoral metaphysis by regulating trabecular arrangement

Low-magnitude, high-frequency vibration(LMHFV) with rest days(particularly seven rest days) was considerably effective in improving the morphological and mechanical properties of rat proximal femur. However, current knowledge is limited regarding the possible benefit of this mechanical regimen to other bone sites and whether the optimal rest days are the same. This study followed our previous experiment on LMHFV loading with rest days for three-month-old male Wistar rats. The experiment involved seven groups, namely, vibrational loading for X day followed with X day rest(X=1, 3, 5, 7), daily vibrational loading,tail suspension and baseline control. Micro-computed tomography(micro-CT) scanning was used to evaluate the microarchitecture of the distal femoral trabecular bone. Micro-CT image-based microfinite element analysis was performed for each distal femoral metaphysis. LMHFV with rest days substantially changed the trabecular arrangement from remarkably plate-like to rod-like. Vibrational loading with 1 day rest was substantially effective in improving the architecture and apparent-and tissuelevel mechanical properties of the rat distal femoral metaphysis. This study may provide an improved understanding of the sitespecific responses of bone tissue to LMHFV with rest days for a substantially effective therapy of a targeted bone site.

THE EFFECTS OF COD BONE GELATIN ON TRABECULAR MICROSTRUCTURE AND MECHANICAL PROPERTIES OF CANCELLOUS BONE

Osteoporosis is a common clinical complication of post-menopausal women and the elderly and can significantly complicate the severity of bone fragility. The purpose of this study is to investigate how cod bone gelatin administration influences trabecular biomechanical properties after ovariectomy. Both biomechanical properties and trabecular microarchitectures were evaluated for cancellous bone samples from female ovariectomized rats, which were either shamoperated or treated with marine peptide （0.75, 1.5, 3.0, 6.0 g/kg body weight） for 90 days. The results have confirmed that cod bone gelatin treatment is effective in the prevention of mechanical property loss by preserving bone mass and trabecular architecture.