Explicit Finite Element Models Accurately Predict Subject-Specific and Velocity-Dependent Kinetics of Sideways Fall Impact

The majority of hip fractures in the elderly are the result of a fall from standing or from a lower height. Current injury models focus mostly on femur strength while neglecting subject-specific loading. This article presents an injury modeling strategy for hip fractures related to sideways falls that takes subject-specific impact loading into account. Finite element models (FEMs) of the human body were used to predict the experienced load and the femoral strength in a single model. We validated these models for their predicted peak force, effective pelvic stiffness, and fracture status against matching ex vivo sideways fall impacts (n = 11) with a trochanter velocity of 3.1 m/s. Furthermore, they were compared to sideways impacts of volunteers with lower impact velocities that were previously conducted by other groups. Good agreement was found between the ex vivo experiments and the FEMs with respect to peak force (root mean square error [RMSE] = 10.7%, R² = 0.85) and effective pelvic stiffness (R² = 0.92, RMSE = 12.9%). The FEMs were predictive of the fracture status for 10 out of 11 specimens. Compared to the volunteer experiments from low height, the FEMs overestimated the peak force by 25% for low BMI subjects and 8% for high BMI subjects. The effective pelvic stiffness values that were derived from the FEMs were comparable to those derived from impacts with volunteers. The force attenuation from the impact surface to the femur ranged between 27% and 54% and was highly dependent on soft tissue thickness (R² = 0.86). The energy balance in the FEMS showed that at the time of peak force 79% to 93% of the total energy is either kinetic or was transformed to soft tissue deformation. The presented FEMs allow for direct discrimination between fracture and nonfracture outcome for sideways falls and bridge the gap between impact testing with volunteers and impact conditions representative of real life falls. © 2019 American Society for Bone and Mineral Research.     

Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a “one-size-fits-all” approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Combinatorial Inhibition of Myostatin and Activin A Improves Femoral Bone Properties in the G610C Mouse Model of Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a collagen-related bone disorder characterized by fragile osteopenic bone and muscle weakness. We have previously shown that the soluble activin receptor type IIB decoy (sActRIIB) molecule increases muscle mass and improves bone strength in the mild to moderate G610C mouse model of OI. The sActRIIB molecule binds multiple transforming growth factor-β (TGF-β) ligands, including myostatin and activin A. Here, we investigate the musculoskeletal effects of inhibiting activin A alone, myostatin alone, or both myostatin and activin A in wild-type (Wt) and heterozygous G610C (+/G610C) mice using specific monoclonal antibodies. Male and female Wt and +/G610C mice were treated twice weekly with intraperitoneal injections of monoclonal control antibody (Ctrl-Ab, Regn1945), anti-activin A antibody (ActA-Ab, Regn2476), anti-myostatin antibody (Mstn-Ab, Regn647), or both ActA-Ab and Mstn-Ab (Combo, Regn2476, and Regn647) from 5 to 16 weeks of age. Prior to euthanasia, whole body composition, metabolism and muscle force generation assessments were performed. Post euthanasia, hindlimb muscles were evaluated for mass, and femurs were evaluated for changes in microarchitecture and biomechanical strength using micro–computed tomography (μCT) and three-point bend analyses. ActA-Ab treatment minimally impacted the +/G610C musculoskeleton, and was detrimental to bone strength in male +/G610C mice. Mstn-Ab treatment, as previously reported, resulted in substantial increases in hindlimb muscle weights and overall body weights in Wt and male +/G610C mice, but had minimal skeletal impact in +/G610C mice. Conversely, the Combo treatment outperformed ActA-Ab alone or Mstn-Ab alone, consistently increasing hindlimb muscle and body weights regardless of sex or genotype and improving bone microarchitecture and strength in both male and female +/G610C and Wt mice. Combinatorial inhibition of activin A and myostatin more potently increased muscle mass and bone microarchitecture and strength than either antibody alone, recapturing most of the observed benefits of sActRIIB treatment in +/G610C mice. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Trabecular Bone Score Reference Values for Children and Adolescents According to Age,Sex, and Ancestry

Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z-scores, tracking of TBS Z-scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual-energy X-ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n = 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non-African Americans. We provide sex-specific TBS reference ranges and LMS values for calculation of TBS Z-scores by age and means and SD for calculation of Z-scores by pubertal stage. TBS Z-scores were positively associated with height Z-scores at some ages. TBS Z-scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z-scores. Tracking of TBS Z-scores over 6 years was lower (r = 0.47) than for aBMD or BMAD Z-scores (r = 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z-scores provide information distinct from spine aBMD and BMAD Z-scores. Our robust reference ranges for TBS in a well-characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Bone Mass,Bone Microstructure and Biomechanics in Patients with Hand Osteoarthritis

The impact of primary hand osteoarthritis (HOA) on bone mass, microstructure, and biomechanics in the affected skeletal regions is largely unknown. HOA patients and healthy controls (HCs) underwent high-resolution peripheral quantitative computed tomography (HR-pQCT). We measured total, trabecular, and cortical volumetric bone mineral densities (vBMDs), microstructural attributes, and performed micro–finite element analysis for bone strength. Failure load and scaled multivariate outcome matrices from distal radius and second metacarpal (MCP2) head measurements were analyzed using multiple linear regression adjusting for age, sex, and functional status and reported as adjusted Z-score differences for total and direct effects. A total of 105 subjects were included (76 HC: 46 women, 30 men; 29 HOA: 23 women, six men). After adjustment, HOA was associated with significant changes in the multivariate outcome matrix from the MCP2 head (p < .001) (explained by an increase in cortical vBMD (Δz = 1.07, p = .02) and reduction in the trabecular vBMD (Δz = −0.07, p = .09). Distal radius analysis did not show an overall effect of HOA; however, there was a gender-study group interaction (p = .044) explained by reduced trabecular vBMD in males (Δz = −1.23, p = .02). HOA was associated with lower failure load (−514 N; 95%CI, −1018 to −9; p = 0.05) apparent in males after adjustment for functional status. HOA is associated with reduced trabecular and increased cortical vBMD in the MCP2 head and a reduction in radial trabecular vBMD and bone strength in males. Further investigations of gender-specific changes of bone architecture in HOA are warranted. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Unpleasant Bodily Odour in a Psychoanalytic Treatment: Bridge or Drawbridge to a Troubled Past?

In this paper, I explore the topic of primitive bodily communications and countertransference enactments, with a particular focus on the part played by bodily odour. To explore this topic, I discuss a two-year treatment with a patient who presented with a mix of borderline and narcissistic diagnostic features. I describe meaningful aspects of the difficulties faced in countertransference work when receiving and making sense of the patient's use of primitive defences and I highlight their expression through a very uncomfortable symptom: an extremely unpleasant bodily smell. My thesis is that the smell communicated preverbal and unsymbolized experiences of early physical and emotional neglect, as well as evacuating the toxicity of those experiences. In this way the smell acted both as a bridge, which could help me reconstruct my patient's early traumatic past, and as a drawbridge, to keep me at distance and maintain his past dissociated. The invasive and aversive nature of the smell can also be seen as representing the approach-avoidance dilemma typical of a disorganized attachment state of mind, acting both as a bridge and as a drawbridge to attachment and relating.     

黄连与吴茱萸不同比例组成的方剂的不同药理作用研究

目的：探讨黄连与吴茱萸不同比例组成的方剂的不同药理作用。方法：用党参与黄芪给大鼠灌胃造成类热证模型，观察不同比例配伍的黄连与吴茱萸对它们的影响。结果：黄连与吴茱萸比例为6：1的左金丸和2：1的甘露散有显著的消除类热证的作用，1：1的茱萸丸对肝细胞超微结构的影响中表现出有减轻类热证的作用，而体温（t）、血清皮质醇（Cor）、17－羟皮质类固醇（17－OHCS）的改变则未见减轻类热证或增强类热证的作用。结论：认为不同比例配伍的黄连与吴茱萸对类热证的病理改变有不同的影响。     

新生鼠胰岛干细胞分离、培养和分化的实验研究

目的　探索新生鼠胰岛干细胞体外分离鉴定、培养以及体外分化的方法。方法　用胶原酶消化新生大鼠胰腺 ,将消化的组织碎片在pH7.4～ 7.6条件下经含血清RPMI 164 0及无血清RPMI164 0 (添加bFGF ,EGF ,N 2 )培养液中培养 ,观察形成类胰岛样细胞团的全过程。用胰岛素释放实验检测胰岛功能 ,免疫荧光法检测nestin的表达。结果　胰腺消化碎片培养 3 6h内 ,可见nestin阳性细胞贴壁 ,添加bFGF ,EGF ,N2后nestin阳性细胞快速增长 ,18～ 2 4d形成类胰岛样细胞团 ,并可表达胰岛素。结论　胰腺细胞中nestin阳性细胞具有胰岛干细胞特点 ,经体外培养可获得类胰岛样细胞团     

全层缝合在预防阑尾炎术后切口感染中的应用

目的：探讨全层缝合在预防阑尾炎术后切口感染的治疗效果。方法：将皮肤、皮下组织、腹外斜肌腱膜全层褥式缝合(腹膜不予缝合)。结果：56例患者无一例感染，也未发现近期并发症。结论：此方法对预防切口感染有较好疗效，且能缩短手术时间，操作简单，建议值得临床应用。