Cortical and trabecular bone structure of the hominoid capitate

Morphological variation in the hominoid capitate has been linked to differences in habitual locomotor activity due to its importance in movement and load transfer at the midcarpal joint proximally and carpometacarpal joints distally. Although the shape of bones and their articulations are linked to joint mobility, the internal structure of bones has been shown experimentally to reflect, at least in part, the loading direction and magnitude experienced by the bone. To date, it is uncertain whether locomotor differences among hominoids are reflected in the bone microarchitecture of the capitate. Here, we apply a whole-bone methodology to quantify the cortical and trabecular architecture (separately and combined) of the capitate across bipedal (modern Homo sapiens), knuckle-walking (Pan paniscus, Pan troglodytes, Gorilla sp.), and suspensory (Pongo sp.) hominoids (n = 69). It is hypothesized that variation in bone microarchitecture will differentiate these locomotor groups, reflecting differences in habitual postures and presumed loading force and direction. Additionally, it is hypothesized that trabecular and cortical architecture in the proximal and distal regions, as a result of being part of mechanically divergent joints proximally and distally, will differ across these portions of the capitate. Results indicate that the capitate of knuckle-walking and suspensory hominoids is differentiated from bipedal Homo primarily by significantly thicker distal cortical bone. Knuckle-walking taxa are further differentiated from suspensory and bipedal taxa by more isotropic trabeculae in the proximal capitate. An allometric analysis indicates that size is not a significant determinate of bone variation across hominoids, although sexual dimorphism may influence some parameters within Gorilla. Results suggest that internal trabecular and cortical bone is subjected to different forces and functional adaptation responses across the capitate (and possibly other short bones). Additionally, while separating trabecular and cortical bone is normal protocol of current whole-bone methodologies, this study shows that when applied to carpals, removing or studying the cortical bone separately potentially obfuscates functionally relevant signals in bone structure.     

Baby steps towards linking calcaneal trabecular bone ontogeny and the development of bipedal human gait

Trabecular bone structure in adulthood is a product of a process of modelling during ontogeny and remodelling throughout life. Insight into ontogeny is essential to understand the functional significance of trabecular bone structural variation observed in adults. The complex shape and loading of the human calcaneus provides a natural experiment to test the relationship between trabecular morphology and locomotor development. We investigated the relationship between calcaneal trabecular bone structure and predicted changes in loading related to development of gait and body size in growing children. We sampled three main trabecular regions of the calcanei using micro-computed tomography scans of 35 individuals aged between neonate to adult from the Norris Farms #36 site (1300 AD, USA) and from Cambridge (1200–1500 AD, UK). Trabecular properties were calculated in volumes of interest placed beneath the calcaneocuboid joint, plantar ligaments, and posterior talar facet. At birth, thin trabecular struts are arranged in a dense and relatively isotropic structure. Bone volume fraction strongly decreases in the first year of life, whereas anisotropy and mean trabecular thickness increase. Dorsal compressive trabecular bands appear around the onset of bipedal walking, although plantar tensile bands develop prior to predicted propulsive toe-off. Bone volume fraction and anisotropy increase until the age of 8, when gait has largely matured. Connectivity density gradually reduces, whereas trabeculae gradually thicken from birth until adulthood. This study demonstrates that three different regions of the calcaneus develop into distinct adult morphologies through varying developmental trajectories. These results are similar to previous reports of ontogeny in human long bones and are suggestive of a relationship between the mechanical environment and trabecular bone architecture in the human calcaneus during growth. However, controlled experiments combined with more detailed biomechanical models of gait maturation are necessary to establish skeletal markers linking growth to loading. This has the potential to be a novel source of information for understanding loading levels, activity patterns, and perhaps life history in the fossil record.     

Ontogenetic changes to bone microstructure in an archaeologically derived sample of human ribs

There is considerable variation in the gross morphology and tissue properties among the bones of human infants, children, adolescents, and adults. Using 18 known-age individuals (n_female = 8, n_male = 9, n_unknown = 1; birth to 21 years old), from a well-documented cemetery collection, Spitalfields Christ Church, London, UK, this study explores growth-related changes in cortical and trabecular bone microstructure. Micro-CT scans of mid-shaft middle thoracic ribs are used for quantitative analysis. Results are then compared to previously quantified conventional histomorphometry of the same sample. Total area (Tt.Ar), cortical area (Ct.Ar), cortical thickness (Ct.Th), and the major (Maj.Dm) and minor (Min.Dm) diameters of the rib demonstrate positive correlations with age. Pore density (Po.Dn) increases, but age-related changes to cortical porosity (Ct.Po) appear to be non-linear. Trabecular thickness (Tb.th) and trabecular separation (Tb.Sp) increase with age, whereas trabecular bone pattern factor (Tb.Pf), structural model index (SMI), and connectivity density (Conn.D) decrease with age. Sex-based differences were not identified for any of the variables included in this study. Some samples display clear evidence of diagenetic alteration without corresponding changes in radiopacity, which compromises the reliability of bone mineral density (BMD) data in the study of past populations. Cortical porosity data are not correlated with two-dimensional measures of osteon population density (OPD). This suggests that unfilled resorption spaces contribute more significantly to cortical porosity than do the Haversian canals of secondary osteons. Continued research using complementary imaging techniques and a wide array of histological variables will increase our understanding of age- and sex-specific ontogenetic patterns within and among human populations.     

Systemic patterns of trabecular bone across the human and chimpanzee skeleton

Aspects of trabecular bone architecture are thought to reflect regional loading of the skeleton, and thus differ between primate taxa with different locomotor and postural modes. However, there are several systemic factors that affect bone structure that could contribute to, or be the primary factor determining, interspecific differences in bone structure. These systemic factors include differences in genetic regulation, sensitivity to loading, hormone levels, diet, and activity levels. Improved understanding of inter‐/intraspecific variability, and variability across the skeleton of an individual, is required to interpret properly potential functional signals present within trabecular structure. Using a whole‐region method of analysis, we investigated trabecular structure throughout the skeleton of humans and chimpanzees. Trabecular bone volume fraction (BV/TV), degree of anisotropy (DA) and trabecular thickness (Tb.Th) were quantified from high resolution micro‐computed tomographic scans of the humeral and femoral head, third metacarpal and third metatarsal head, distal tibia, talus and first thoracic vertebra. We found that BV/TV is, in most anatomical sites, significantly higher in chimpanzees than in humans, suggesting a systemic difference in trabecular structure unrelated to local loading regime. Differences in BV/TV between the forelimb and hindlimb did not clearly reflect differences in locomotor loading in the study taxa. There were no clear systemic differences between the taxa in DA and, as such, this parameter might reflect function and relate to differences in joint loading. This systemic approach reveals both the pattern of variability across the skeleton and between taxa, and helps identify those features of trabecular structure that may relate to joint function.     

基于CT三维重建的成人第5掌骨的形态学及临床意义

目的 通过对成人第5掌骨CT三维重建数据进行测量,探讨人类第5掌骨形态学特点及临床意义,为临床手术和器械设计提供依据。方法 对医学影像工作站内留存的114例第5掌骨CT扫描进行三维重建,基于三维模型测量第5掌骨长度、掌骨头半径、掌骨弓半径和1/2掌骨弓圆心角、掌骨头偏心距和偏心比及髓腔狭部内径。结果 成人掌骨长度（51.55±3.01）mm,掌骨头半径（6.59±0.49）mm,掌骨弓半径（99.58±26.83）mm,1/2掌骨弓圆心角（15.90±3.36）°,掌骨头偏心距平均（0.49±0.26）mm,掌骨头偏心比平均（7.4±3.9）%,髓腔峡部内径平均（2.28±0.77）mm。结论 男性掌骨长度、掌骨头半径、掌骨头偏心距及髓腔峡部内径大于女性,其余指标性别间差异无显著性;左右手之间差异也无显著性。     

Using multimodal MRI to investigate alterations in brain structure and function in the BBZDR/Wor rat model of type 2 diabetes

BackgroundThis is an exploratory study using multimodal magnetic resonance imaging (MRI) to interrogate the brain of rats with type 2 diabetes (T2DM) as compared to controls. It was hypothesized there would be changes in brain structure and function that reflected the human disorder, thus providing a model system by which to follow disease progression with noninvasive MRI.MethodsThe transgenic BBZDR/Wor rat, an animal model of T2MD, and age‐matched controls were studied for changes in brain structure using voxel‐based morphometry, alteration in white and gray matter microarchitecture using diffusion weighted imaging with indices of anisotropy, and functional coupling using resting‐state BOLD functional connectivity. Images from each modality were registered to, and analyzed, using a 3D MRI rat atlas providing site‐specific data on over 168 different brain areas.ResultsThere was an overall reduction in brain volume focused primarily on the somatosensory cortex, cerebellum, and white matter tracts. The putative changes in white and gray matter microarchitecture were pervasive affecting much of the brain and not localized to any region. There was a general increase in connectivity in T2DM rats as compared to controls. The cerebellum presented with strong functional coupling to pons and brainstem in T2DM rats but negative connectivity to hippocampus.ConclusionThe neuroradiological measures collected in BBBKZ/Wor rats using multimodal imaging methods did not reflect those reported for T2DB patients in the clinic. The data would suggest the BBBKZ/Wor rat is not an appropriate imaging model for T2DM.     

Development of a high‐sensitivity ELISA detecting IgG,IgA and IgM antibodies to the SARS‐CoV‐2 spike glycoprotein in serum and saliva

Detecting antibody responses during and after SARS‐CoV‐2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non‐hospitalized SARS‐CoV‐2‐infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti‐spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti‐spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT‐PCR confirmed, non‐hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti‐spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS‐CoV‐2 infection.     

ACE2 and TMPRSS2 in human saliva can adsorb to the oral mucosal epithelium

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is primarily transmitted through droplets. All human tissues with the angiotensin‐converting enzyme 2 (ACE2) and transmembrane protease serines 2 (TRMPRSS2) are potential targets of SARS‐CoV‐2. The role of saliva in SARS‐CoV‐2 transmission remains obscure. In this study, we attempted to reveal ACE2 and TRMPRSS2 protein expression in human parotid, submandibular, and sublingual glands (three major salivary glands). Then, the binding function of spike protein to ACE2 in three major salivary glands was detected. The expression of ACE2 and TMPRSS2 in human saliva from parotid glands were both examined. Exogenous recombined ACE2 and TMPRSS2 anchoring and fusing to oral mucosal epithelial cells in vitro were also unraveled. ACE2 and TMPRSS2 were found mainly to be expressed in the cytomembrane and cytoplasm of epithelial cells in the serous acinus cells in parotid and submandibular glands. Our research also discovered that the spike protein of SARS‐CoV‐2 binds to ACE2 in salivary glands in vitro. Furthermore, exogenous ACE2 and TMPRSS2 can anchor and fuse to oral mucosa in vitro. Thus, the expression of ACE2 and TMPRSS2 in human saliva might have implications for SARS‐CoV‐2 infection.     

Comparative morpho‐functional analysis of the humerus and ulna in three Western European moles species of the genus Talpa,including the newly described T. aquitania

The forelimb is involved in many behaviours including locomotion. Notably, the humero‐ulnar articulation, implicated in the elbow joint, is of particular importance for both mobility and stability. Functional constraints, induced in part by environmental plasticity, are thought to drive an important part of the bone shape as bone directly responds and remodels in response to both muscle and external forces. In this context, the study of subterranean moles is of particular interest. These moles occupy a hard and heavy medium in comparison with air or water, requiring a powerful body structure to shear and shift the soil. Their general morphology is therefore adapted to digging and to their subterranean lifestyle. The various morpho‐functional patterns, which drive diverse abilities according to the environment, are likely targets of natural selection and it is, therefore, useful to understand the relationships between the bone shape and their function. Here, we quantify, through 3D geometric morphometric methods, the interspecific variability in the morphology of the ulna and humerus of three Talpa species, including the new species Talpa aquitania, to infer their potential consequence in species digging performance. We also quantify shape covariation and morphological integration between the humerus and the ulna to test whether these bones evolve as a uniform functional unit or as more or less independent modules. Our results show that interspecific anatomical differences in the humerus and ulna exist among the three species. Shape changes are mostly located at the level of joints and muscle attachments. As the species tend to live in allopatry and the fossorial lifestyle induces strong ecological constraints, interspecific variations could be explained by the properties of the environment in which they live, such as the compactness of the soil. Our results also show that the humerus and ulna are highly integrated. The covariation between the humerus and ulna in moles is dominated by variation in the attachment areas and particularly of the attachment areas of shoulder muscles concerning the humerus, which affect the mechanical force deployed during locomotion and digging. This study also highlights that in the new species, T. aquitania, variations in anatomical structure (general shape and joints) exist and are related to the locality of collect of the individuals.     

Embryonic craniofacial bone volume and bone mineral density in Fgfr2+/P253R and nonmutant mice

Background : Quantifying multiple phenotypic aspects of individual craniofacial bones across early osteogenesis illustrates differences in typical bone growth and maturation and provides a basis for understanding the localized and overall influence of mutations associated with disease. We quantify the typical pattern of bone growth and maturation during early craniofacial osteogenesis and determine how this pattern is modified in Fgfr2^+/P253R Apert syndrome mice. Results: Early differences in typical relative bone density increase are noted between intramembranous and endochondral bones, with endochondral bones normally maturing more quickly during the prenatal period. Several craniofacial bones, including the facial bones of Fgfr2^+/P253R mice, display lower volumes during the earliest days of osteogenesis and lower relative densities until the perinatal period relative to unaffected littermates. Conclusions: Estimates of bone volume and linear measures describing morphology do not necessarily covary, highlighting the value of quantifying multiple facets of gross osteological phenotypes when exploring the influence of a disease causing mutation. Differences in mechanisms of osteogenesis likely underlie differences in intramembranous and endochondral relative density increase. The influence of the FGFR2 P253R mutation on bone volume changes across the prenatal period and again after birth, while its influence on relative bone density is more stable. Developmental Dynamics 243:541–551, 2014. © 2013 Wiley Periodicals, Inc.     

Trabecular architecture of the great ape and human femoral head

Studies of femoral trabecular structure have shown that the orientation and volume of bone are associated with variation in loading and could be informative about individual joint positioning during locomotion. In this study, we analyse for the first time trabecular bone patterns throughout the femoral head using a whole‐epiphysis approach to investigate how potential trabecular variation in humans and great apes relates to differences in locomotor modes. Trabecular architecture was analysed using microCT scans of Pan troglodytes (n = 20), Gorilla gorilla (n = 14), Pongo sp. (n = 5) and Homo sapiens (n = 12) in medtool 4.1. Our results revealed differences in bone volume fraction (BV/TV) distribution patterns, as well as overall trabecular parameters of the femoral head between great apes and humans. Pan and Gorilla showed two regions of high BV/TV in the femoral head, consistent with hip posture and loading during two discrete locomotor modes: knuckle‐walking and climbing. Most Pongo specimens also displayed two regions of high BV/TV, but these regions were less discrete and there was more variability across the sample. In contrast, Homo showed only one main region of high BV/TV in the femoral head and had the lowest BV/TV, as well as the most anisotropic trabeculae. The Homo trabecular structure is consistent with stereotypical loading with a more extended hip compared with great apes, which is characteristic of modern human bipedalism. Our results suggest that holistic evaluations of femoral head trabecular architecture can reveal previously undetected patterns linked to locomotor behaviour in extant apes and can provide further insight into hip joint loading in fossil hominins and other primates.     

Early movement restriction leads to enduring disorders in muscle and locomotion

Motor control and body representation in the central nervous system (CNS) as well as musculoskeletal architecture and physiology are shaped during development by sensorimotor experience and feedback, but the emergence of locomotor disorders during maturation and their persistence over time remain a matter of debate in the absence of brain damage. By using transient immobilization of the hind limbs, we investigated the enduring impact of postnatal sensorimotor restriction (SMR) on gait and posture on treadmill, age‐related changes in locomotion, musculoskeletal histopathology and Hoffmann reflex in adult rats without brain damage. SMR degrades most gait parameters and induces overextended knees and ankles, leading to digitigrade locomotion that resembles equinus. Based on variations in gait parameters, SMR appears to alter age‐dependent plasticity of treadmill locomotion. SMR also leads to small but significantly decreased tibial bone length, chondromalacia, degenerative changes in the knee joint, gastrocnemius myofiber atrophy and muscle hyperreflexia, suggestive of spasticity. We showed that reduced and atypical patterns of motor outputs, and somatosensory inputs and feedback to the immature CNS, even in the absence of perinatal brain damage, play a pivotal role in the emergence of movement disorders and musculoskeletal pathologies, and in their persistence over time. Understanding how atypical sensorimotor development likely contributes to these degradations may guide effective rehabilitation treatments in children with either acquired (ie, with brain damage) or developmental (ie, without brain injury) motor disabilities.     

Response of trabecular bone,thyroid C and follicular cells to synthetic salmon calcitonin in middle‐aged orchidectomized male rats

In contrast to studies in women, male osteoporosis is poorly understood and strictly related to advancing age. Among the first antiresorptive substances used in the prevention and treatment of osteoporosis is calcitonin (CT), a hypocalcemic hormone that potently inhibits osteoclastic bone resorption. Natural CT is produced and secreted by thyroid C‐cells. The other endocrine population of thyroid cells produces thyroid hormones (TH), which also affect bone turnover. The aim of this study was to evaluate the influence of salmon CT on trabecular bone microarchitecture with special reference to effects on the structure and function of both CT‐ and TH‐producing thyroid cells in orchidectomized (Orx) middle‐aged rats. Twenty‐four male Wistar rats aged 15 months were randomly divided into Orx and sham‐operated (SO) groups. One group of Orx animals received (s.c.) synthetic salmon CT (Orx + CT; 100 IU kg⁻¹ b.w.) subcutaneously every second day for 6 weeks. The second Orx group and SO rats were given the same volume of vehicle alone by the same schedule. Trabecular bone histomorphometrical parameters were: cancellous bone area (B.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) were obtained with an ImageJ public‐domain image‐processing program. The peroxidase–antiperoxidase method was applied for localization of CT in C‐cells. Anti‐human CT antisera served as the primary antibodies. For immunohistochemical characterization of vascular endothelial growth factor (VEGF) in thyroid tissue, rabbit antisera against human VEGF, served as primary antibodies. CT‐immunopositive thyroid C‐cells, thyroid follicular epithelium, interstitium and colloid were evaluated morphometrically. Blood serum samples were analyzed for CT, osteocalcin (OC), and thyroxine (T₄), and calcium (Ca²⁺) concentration was determined in urine samples. Salmon CT application significantly increased B.Ar, TbTh and TbN, but markedly decreased Tb.Sp. Administration of exogenous CT significantly decreased mean volume (Vc) and relative volume density (Vv) of thyroid C‐cells in relation to both SO and Orx groups. The Vv of the colloid was higher, whereas the V_V of the follicular epithelium was lower after CT treatment compared with Orx alone. CT treatment markedly elevated serum CT, whereas serum OC, T₄ and urinary Ca²⁺ concentrations were lower than in the Orx group. These results indicate that salmon CT stimulates trabecular bone microarchitecture, strongly inhibits thyroid C‐cells and changes the structure of the thyroid gland, indicating hypoactivity.     

Prognostic relevance of adding MRI data to WHO 2016 and cIMPACT‐NOW updates for diffuse astrocytic tumors in adults. Working toward the extended use of MRI data in integrated glioma diagnosis

Assess the contribution of preoperative MRI data in improving grading of adult astrocytomas reclassified according to the WHO 2016 and cIMPACT‐NOW update 3. Retrospective unicentric cohort study of 679 adult patients treated for newly diagnosed diffuse astrocytic and oligodendroglial tumors (January 2006–December 2016). We first systematically compared radiological (contrast enhancement present [CE+] vs. absent [CE−]) and histopathological findings (microvascular proliferation present [MPV+] vs. absent [MPV−]) to validate whether this comparing step of neoangiogenesis represents an efficient method to appreciate the representativity of the tumoral sampling. We focused on 629 cases of astrocytomas for radio‐histological integrated analyses. In 598 cases (95.1%), neoangiogenesis evaluated by MRI or histology (CE+/MPV+ or CE−/MPV−) was identical. For the CE+/MPV− and CE−/MPV+ groups (23 cases), the radio‐histological face‐to‐face evaluation allowed us to assess that for 13 cases (56.5%) the reason for this discrepancy was an undersampled tumor. We analyzed the group of CE+/MPV− (n = 8) and CE−/MPV+ (n = 2) in verified image‐guided tumoral samples. Finally, we identified three new prognostic subgroups for molecular glioblastomas: (1) “non‐representative sampling” (n = 9), (2) “Non neoangiogenic glioblastoma at the time of diagnosis, without contrast enhancement and microvascular proliferation” (n = 8), and (3) “contrast enhancing glioblastoma but without microvascular proliferation in a representative sample” (n = 4). Neoangiogenesis processes should be assessed to improve the prognosis accuracy of the current integrated diagnosis. We suggest adding imaging analyses during the neuropathological analysis of astrocytomas in adults.