Hypergravity stimulates mechanical behavior and micro-architecture of tibia in rats.

INTRODUCTION: The bone tissue is susceptible to hypergravity (+ G) environment. It is necessary to discuss the extent to which specific + G values are beneficial or detrimental to bone tissue. The objective of this study was to characterize the effects of high + G values on mechanical properties, microstructures, and cellular metabolism of bone. MATERIALS AND METHODS: 30 male Wistar rats aged 12 weeks were randomly divided into 5 groups, and bore different + G (namely + 1G, + 4G, + 8G, + 10G and + 12G) environments respectively for 4 weeks, 5 days each week, and 3 minutes each day. The macro-mechanical parameters, microstructure parameters, and mRNA transcription levels of the tibia were determined through the three-point bending method, micro-CT detection, and q-PCR analysis, respectively. RESULTS: As the + G value increases, hypergravity becomes increasingly detrimental to the macro-mechanical performance of rat tibia. Concerning the microstructure of cancellous bone, there appears to be a favorable trend at + 4G, followed by a progressively detrimental trend at higher G values. In addition, the mRNA transcription levels of OPG and RANKL show an initial tendency of enhanced bone absorption at +4G, followed by an increase in bone remodeling capacity as G value increases. CONCLUSION: The higher G values correspond to poorer macro-mechanical properties of the tibia, and a + 4G environment benefits the microstructure of the tibia. At the cellular level, bone resorption is enhanced in the + 4G group, but the bone remodeling capability gradually increases with further increments in G values.

Bone health in children and youth with ASD: a systematic review and meta-analysis.

Higher risk of fracture reported in individuals with autism spectrum disorder (ASD) might be linked to poor bone health and development in childhood. This study aimed to systematically review studies comparing imaged bone outcomes between children with ASD and typically developing children (TDC) or reference data, and to perform a meta-analysis comparing commonly reported bone outcomes. We searched articles published since August 2020 from PubMed, Cochrane Library, Web of Science, EMBASE, and Scopus databases. We included studies comparing areal bone mineral density (aBMD) between children with ASD and TDC in the qualitative analysis (meta-analysis), and evaluated other imaged bone outcomes qualitatively. Seven publications were identified for the systematic review, and four studies were included in the meta-analysis. The meta-analysis indicated lower aBMD at the total body (standardized mean difference = - 0.77; 95% CI, - 1.26 to - 0.28), lumbar spine (- 0.69; - 1.00 to - 0.39), total hip (- 1.00; - 1.82 to - 0.17), and femoral neck (- 1.07; - 1.54 to - 0.60) in children with ASD compared to TDC. Based on our qualitative review, limited evidence suggested 13% lower bone mineral content at the total body and 10-20% lower cortical area, cortical and trabecular thickness, and bone strength at the distal radius and tibia in children with ASD. Children with ASD have lower aBMD at the total body, lumbar spine, and hip and femoral neck compared to TDC. Limited evidence also suggests deficits in bone mineral content, micro-architecture, and strength in children with ASD.

Is the Jaw Bone Micro-Structure Altered in Response to Osteoporosis and Bisphosphonate Treatment? A Micro-CT Analysis.

The aim of the study was to quantify the micro-architectural changes of the jaw bone in response to ovariectomy, exposed or not to bisphosphonate treatment. A total of 47 Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and exposed to osteoporosis preventive treatment for eight weeks either with bisphosphonates (alendronate, ALN; group OVX-ALN) three days/week at a dose of 2 mg/kg or with saline solution (untreated control condition; group OVX). The bone morphometric parameters of the trabecular jaw bone were assessed using ex vivo micro-computed tomography. The regions of interest investigated in the maxilla were the inter-radicular septum of the second molar and the tuber. The regions quantified in the mandible included the three molar regions and the condyle. A one-way analysis of variance followed by pairwise comparison using Tukey's HSD and the Games-Howell test was conducted to explore significant differences between the groups. In the maxilla, OVX decreased the bone volume in the inter-radicular septum of the second molar. Bisphosphonate treatment was able to prevent this deterioration of the jaw bone. The other investigated maxillary regions were not affected by (un)treated ovariectomy. In the mandible, OVX had a significant negative impact on the jaw bone in the buccal region of the first molar and the inter-radicular region of the third molar. Treatment with ALN was able to prevent this jaw bone loss. At the condyle site, OVX significantly deteriorated the trabecular connectivity and shape, whereas preventive bisphosphonate treatment showed a positive effect on this trabecular bone region. No significant results between the groups were observed for the remaining regions of interest. In summary, our results showed that the effects of ovariectomy-induced osteoporosis are manifested at selected jaw bone regions and that bisphosphonate treatment is capable to prevent these oral bone changes.

The micro-structural analysis of lumbar vertebrae in alcoholic liver cirrhosis.

Although vertebral fracture is more common among alcoholic liver cirrhosis patients when compared to general population, current data on three-dimensional micro-architecture are scarce. Our study showed significant trabecular deterioration in lumbar vertebrae obtained from alcoholic liver cirrhosis donors, suggesting that they should be advised to undergo early-stage screening for osteoporosis. PURPOSE: Recent studies showed an increased incidence of vertebral fractures in alcoholic liver cirrhosis (ALC) patients, while data about vertebral micro-structure are still limited. The aim of this study was to compare trabecular and cortical micro-architecture of lumbar vertebrae between ALC patients and healthy age- and sex-matched controls. METHODS: Our study included lumbar vertebral samples of male cadaveric donors, divided into ALC (n = 20, age: 59 ± 6 years) and control group (n = 20, age: 59 ± 8 years). Following pathohistological verification of liver cirrhosis, trabecular and cortical bone micro-architecture was analyzed by micro-computed tomography (micro-CT). RESULTS: Micro-CT evaluation of the trabecular bone in lumbar vertebrae showed a significant decrease in bone volume fraction, trabecular thickness, trabecular number, and connectivity (p < 0.01). In contrast to trabecular deterioration, prominent alteration in cortical parameters was not observed in lumbar vertebrae of ALC patients (p > 0.05). CONCLUSIONS: Our data indicate that susceptibility to non-traumatic fractures in ALC patients could be explained by alterations in trabecular bone micro-architecture. Thus, we genuinely recommend osteological screening of the lumbar spine for all ALC patients in order to evaluate individual fracture risk. Graphical abstract.

Functional disuse initiates medullary endosteal micro-architectural impairment in cortical bone characterized by nanoindentation.

In this study, we evaluated the effect of functional disuse-induced bone remodeling on its mechanical properties, individually at periosteum and medullary endosteum regions of the cortical bone. Left middle tibiae were obtained from 5-month-old female Sprague-Dawley rats for the baseline control as well as hindlimb suspended (disuse) groups. Micro-nano-mechanical elastic moduli (at lateral region) was evaluated along axial (Z), circumferential (C) and radial (R) orientations using nanoindentation. Results indicated an anisotropic microstructure with axial orientation having the highest and radial orientation with the lowest moduli at periosteum and medullary endosteum for both baseline control as well as disuse groups. Between the groups: at periosteum, an insignificant difference was evaluated for each of the orientations (p > 0.05) and at endosteum, a significant decrease of elastic moduli in the radial (p < 0.0001), circumferential (p < 0.001) and statistically insignificant difference in axial (p > 0.05) orientation. For the moduli ratios between groups: at periosteum, only significant difference in the Z/R (p < 0.05) anisotropy ratio, whereas at endosteum, a statistically significant difference in Z/C (p < 0.001), and Z/R (p < 0.001), as well as C/R (p < 0.05) anisotropy ratios, was evaluated. The results suggested initial bone remodeling impaired bone micro-architecture predominantly at the medullary endosteum with possible alterations in the geometric orientations of collagen and mineral phases inside the bone. The findings could be significant for studying the mechanotransduction pathways involved in maintaining the bone micro-architecture and possibly have high clinical significance for drug use against impairment from functional disuse.

Usefulness of Trabecular Bone Score (TBS) to Identify Bone Fragility in Patients with Primary Hyperparathyroidism.

BACKGROUND: Patients with primary hyperparathyroidism usually show decreased bone strength that are often not well diagnosed by conventional Dual-energy X-ray absorptiometry (DXA). Trabecular Bone Score (TBS) is a new technique for assessing bone microarchitecture indirectly. This cross-sectional study evaluates the usefulness of TBS in patients with primary hyperparathyroidism in clinical practice. METHODOLOGY: Bone mineral density (BMD) by DXA and TBS values by TBS InSight® software were determined in 72 patients with primary hyperparathyroidism to analyze its relationship with fragility fractures. A receiver operating curve was performed to evaluate the usefulness of TBS as predictor of fragility fractures. FRAX index with and without adjustment by TBS was calculated. Additionally, longitudinal data of a subgroup of patients according to the therapeutic management were also evaluated. RESULTS: A total of 51.4% of the patients showed degraded microarchitecture while only 37.5% of them were diagnosed of osteoporosis by DXA. No significant correlation was found between TBS values and BMD parameters. However, TBS values were lower in osteoporotic patients compared to those classified as normal by BMD (1.16 ± 0.12vs 1.26 ± 0.17; p = 0.043) and in patients with fragility fractures compared to nonfractured patients (1.19 ± 0.03vs 1.24 ± 0.02, p < 0.001). The area under the curve for TBS performed better than the combination of femoral, hip and spine-BMD for prevalent fractures (0.714vs 0.679). TBS-adjusted FRAX was higher than nonadjusted model for both major osteoporotic and hip fracture (4.5% vs 3%; 0.9% vs 0.7%; p < 0.001). At follow-up, an improvement in TBS values was observed in treated patients (medical or surgical) vs nontreated close to significance (1.27 ± 0.10vs 1.24 ± 0.11, p = 0.074). CONCLUSIONS: TBS could be a useful tool to identify increased fracture risk in patients with primary hyperparathyroidism underdiagnosed by BMD. Moreover, FRAX adjusted by TBS could be a more robust tool for predicting the risk of osteoporotic fracture to help in therapeutic decisions in this population.

An automated algorithm for the detection of cortical interruptions and its underlying loss of trabecular bone; a reproducibility study.

BACKGROUND: We developed a semi-automated algorithm that detects cortical interruptions in finger joints using high-resolution peripheral quantitative computed tomography (HR-pQCT), and extended it with trabecular void volume measurement. In this study we tested the reproducibility of the algorithm using scan/re-scan data. METHODS: Second and third metacarpophalangeal joints of 21 subjects (mean age 49 (SD 11) years, 17 early rheumatoid arthritis and 4 undifferentiated arthritis, all diagnosed < 1 year ago) were imaged twice by HR-pQCT on the same day with repositioning between scans. The images were analyzed twice by one operator (OP1) and once by an additional operator (OP2), who independently corrected the bone contours when necessary. The number, surface and volume of interruptions per joint were obtained. Intra- and inter-operator reliability and intra-operator reproducibility were determined by intra-class correlation coefficients (ICC). Intra-operator reproducibility errors were determined as the least significant change (LSCSD). RESULTS: Per joint, the mean number of interruptions was 3.1 (SD 3.6), mean interruption surface 4.2 (SD 7.2) mm2, and mean interruption volume 3.5 (SD 10.6) mm3 for OP1. Intra- and inter-operator reliability was excellent for the cortical interruption parameters (ICC ≥0.91), except good for the inter-operator reliability of the interruption surface (ICC = 0.70). The LSCSD per joint was 4.2 for the number of interruptions, 5.8 mm2 for interruption surface, and 3.2 mm3 for interruption volume. CONCLUSIONS: The algorithm was highly reproducible in the detection of cortical interruptions and their volume. Based on the LSC findings, the potential value of this algorithm for monitoring structural damage in the joints in early arthritis patients needs to be tested in clinical studies.

Association between regional heterogeneity in the mid-facial bone micro-architecture and increased fragility along Le Fort lines.

BACKGROUND/AIM: Le Fort lines have traditionally been considered as zones of weakness in the mid-facial skeleton although the structural basis of increased bone fragility at these sites has not yet been investigated. Considering recent findings of occlusal loading-related regional heterogeneity in the mid-facial bone micro-architecture, the aim of this study was to explore whether such heterogeneity in cortical and cancellous bone micro-architecture may contribute to increased fragility at Le Fort fracture sites. MATERIALS AND METHODS: Twenty-five cortical and thirteen cancellous bone specimens were harvested from a dry skull and analyzed by micro-CT. Specimens were classified into Le Fort or Non-Le Fort groups based on their location in the mid-facial skeleton. RESULTS: Cortical bone along Le Fort lines showed tendencies toward lower thickness (1.5±0.63 vs 1.75±0.79; P=.39) and greater porosity (11.48±5.67 vs 10.28±5.28; P=.59). A significant difference was detected in the trabecular degree of anisotropy which was higher in cancellous bone from Le Fort fracture sites (2.14±0.69 vs 1.58±0.34; P=.02). CONCLUSIONS: Regional heterogeneity in cortical bone micro-architecture could not fully explain increased fragility of the mid-facial skeleton at the Le Fort lines. However, regional differences in trabecular bone anisotropy may contribute to increased bone fragility.

Chlorpromazine-induced changes in membrane micro-architecture inhibit thrombopoiesis in rat megakaryocytes.

Chlorpromazine often causes severe and persistent thrombocytopenia. Several clinical studies have suggested the presence of an as-yet-unknown mechanism in this drug-induced thrombocytopenia, by which the platelet production from megakaryocytes may directly be affected. As we previously demonstrated in rat peritoneal mast cells or adipocytes, chlorpromazine is amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membrane. Therefore, it can induce some structural changes in the megakaryocyte membrane surface and thus affect the process of thrombopoiesis. In the present study, employing the standard patch-clamp whole-cell recording technique, we examined the effects of chlorpromazine on the membrane capacitance and Kv1.3-channel currents in rat megakaryocytes. By electron microscopic imaging of the cellular surface, we also examined the effects of chlorpromazine on the membrane micro-architecture of megakaryocytes. Chlorpromazine markedly decreased the membrane capacitance of megakaryocytes, indicating the decreased number of invaginated plasma membranes, which was not detected by the fluorescent imaging techniques. As shown by electron microscopy, chlorpromazine actually changed the membrane micro-architecture of megakaryocytes, and was likely to halt the process of pro-platelet formation in the cells. This drug persistently decreased the membrane capacitance and almost totally and irreversibly inhibited the Kv1.3-channel currents in megakaryocytes. This study demonstrated for the first time that chlorpromazine is likely to inhibit the process of thrombopoiesis persistently in megakaryocytes, as detected by the long-lasting decrease in the membrane capacitance and the irreversible suppression of the Kv1.3-channel currents. Chlorpromazine-induced changes in the membrane micro-architecture are thought to be responsible for its persistent effects.

Disrupted trabecular bone micro-architecture in middle-aged male HIV-infected treated patients.

OBJECTIVES: HIV-infected individuals are at increased risk of incident fractures. Evaluation of trabecular bone micro-architecture is an important tool to assess bone strength, but its use has not yet been reported in middle-aged HIV-infected male individuals. The aim of the study was to compare bone micro-architecture between HIV-infected and HIV-uninfected men. METHODS: In this cross-sectional study, 53 HIV-infected male individuals with a mean (± standard deviation) age of 49 ± 9 years who had been receiving antiretroviral therapy including tenofovir disoproxil fumarate (DF) for at least 60 months were compared with 50 HIV-uninfected male controls, matched for age and ethnic origin. We studied the volumetric bone density and micro-architecture of the radius and tibia using high-resolution peripheral quantitative computed tomography (HR-p QCT). RESULTS: Volumetric trabecular bone density was 17% lower in the tibia (P < 10(-4) ) and 16% lower in the radius (P < 10(-3) ) in HIV-infected patients compared with controls. By contrast, the cortical bone density was normal at both sites. The tibial trabecular micro-architecture differed markedly between patients and controls: bone volume/total volume (BV/TV) and trabecular number were each 13% lower (P < 10(-4) for both). Trabecular separation and inhomogeneity of the network were 18% and 24% higher in HIV-infected patients than in controls, respectively. The radial BV/TV and trabecular thickness were each 13% lower (P < 10(-3) and 10(-2) , respectively). Cortical thickness was not different between the two groups. CONCLUSIONS: The findings of lower volumetric trabecular bone density and disrupted trabecular micro-architectural parameters in middle-aged male HIV-infected treated patients help to explain bone frailty in these patients.

3D-Microarchitectural patterns of Hyperostosis frontalis interna: a micro-computed tomography study in aged women.

Although seen frequently during dissections and autopsies, Hyperostosis frontalis interna (HFI) - a morphological pattern of the frontal bone thickening - is often ignored and its nature and development are not yet understood sufficiently. Current macroscopic classification defines four grades/stages of HFI based on the morphological appearance and size of the affected area; however, it is unclear if these stages also depict the successive phases in the HFI development. Here we assessed 3D-microarchitecture of the frontal bone in women with various degrees of HFI expression and in an age- and sex-matched control group, hypothesizing that the bone microarchitecture bears imprints of the pathogenesis of HFI and may clarify the phases of its development. Frontal bone samples were collected during routine autopsies from 20 women with HFI (age: 69.9 ± 11.1 years) and 14 women without HFI (age: 74.1 ± 9.7 years). We classified the HFI samples into four groups, each group demonstrating different macroscopic type or stage of HFI. All samples were scanned by micro-computed tomography to evaluate 3D bone microarchitecture in the following regions of interest: total sample, outer table, diploe and inner table. Our results revealed that, compared to the control group, the women with HFI showed a significantly increased bone volume fraction in the region of diploe, along with significantly thicker and more plate-like shaped trabeculae and reduced trabecular separation and connectivity density. Moreover, the inner table of the frontal bone in women with HFI displayed significantly increased total porosity and mean pore diameter compared to controls. Microstructural reorganization of the frontal bone in women with HFI was also reflected in significantly higher porosity and lower bone volume fraction in the inner vs. outer table due to an increased number of pores larger than 100 µm. The individual comparisons between the control group and different macroscopic stages of HFI revealed significant differences only between the control group and the morphologically most pronounced type of HFI. Our microarchitectural findings demonstrated clear differences between the HFI and the control group in the region of diploe and the inner table. Macroscopic grades of HFI could not be distinguished at the level of bone microarchitecture and their consecutive nature cannot be supported. Rather, our study suggests that only two different types of HFI (moderate and severe HFI) have microstructural justification and should be considered further. It is essential to record HFI systematically in human postmortem subjects to provide more data on the mechanisms of its development.

Role of endocortical contouring methods on precision of HR-pQCT-derived cortical micro-architecture in postmenopausal women and young adults.

UNLABELLED: Precision errors of cortical bone micro-architecture from high-resolution peripheral quantitative computed tomography (pQCT) ranged from 1 to 16 % and did not differ between automatic or manually modified endocortical contour methods in postmenopausal women or young adults. In postmenopausal women, manually modified contours led to generally higher cortical bone properties when compared to the automated method. INTRODUCTION: First, the objective of the study was to define in vivo precision errors (coefficient of variation root mean square (CV%RMS)) and least significant change (LSC) for cortical bone micro-architecture using two endocortical contouring methods: automatic (AUTO) and manually modified (MOD) in two groups (postmenopausal women and young adults) from high-resolution pQCT (HR-pQCT) scans. Second, it was to compare precision errors and bone outcomes obtained with both methods within and between groups. METHODS: Using HR-pQCT, we scanned twice the distal radius and tibia of 34 postmenopausal women (mean age ± SD 74 ± 7 years) and 30 young adults (27 ± 9 years). Cortical micro-architecture was determined using AUTO and MOD contour methods. CV%RMS and LSC were calculated. Repeated measures and multivariate ANOVA were used to compare mean CV% and bone outcomes between the methods within and between the groups. Significance was accepted at P < 0.05. RESULTS: CV%RMS ranged from 0.9 to 16.3 %. Within-group precision did not differ between evaluation methods. Compared to young adults, postmenopausal women had better precision for radial cortical porosity (precision difference 9.3 %) and pore volume (7.5 %) with MOD. Young adults had better precision for cortical thickness (0.8 %, MOD) and tibial cortical density (0.2 %, AUTO). In postmenopausal women, MOD resulted in 0.2-54 % higher values for most cortical outcomes, as well as 6-8 % lower radial and tibial cortical BMD and 2 % lower tibial cortical thickness. CONCLUSIONS: Results suggest that AUTO and MOD endocortical contour methods provide comparable repeatability. In postmenopausal women, manual modification of endocortical contours led to generally higher cortical bone properties when compared to the automated method, while no between-method differences were observed in young adults.

Could the median-palate accommodate wide-bodied implants in order to support maxillary over-dentures? A radiomorphometric study of human cadavers.

INTRODUCTION: Atrophy of the alveolar bone is an irreversible multifactorial phenomenon, the rate of which varies between individuals and between the jaws. This atrophy of the alveolar ridges presents severe limitations for the oral rehabilitation of the edentulous patients and poses a clinical challenge to the prosthodontists and implant surgeons. The present research aimed to investigate whether the median-palate of elderly edentulous subjects is anatomically suitable for implant placement. MATERIALS AND METHODS: A total of 32 samples were harvested from the maxillae of 16 human cadavers. One dentate male subject was included for contrast. Bone quality and quantity were analysed at two regions: the median-palate and the edentulous maxillary alveolar ridge. Samples were scanned through micro-CT, and the region of analysis (ROA) identified and dissected. Bone volume to tissue volume ratio (%BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp) and trabecular bone pattern factor (Tb.Pf) were evaluated for the two regions using Skyscan CTAn(®). RESULTS: The results of bone volume fraction obtained from CTAn(®) of the median-palatal region show higher values than the respective premolar sites in 12 of 15 (80%) edentulous samples. However, this difference was statistically non-significant (P = 0.06). Similarly, the trabecular number for 10 of 15 samples (66.6%) from the median-palate shows greater values than the respective premolar site (P = 0.07). Trabecular thickness of 10 of 15 (66.6%) premolar samples is larger than in the median-palatal region. However, these differences were also statistically non-significant (P = 0.25). Statistically significant difference (P = 0.04) was found between the Tb.Sp values of the two regions. CONCLUSION: The results indicate that the anterior median-palate is structurally better than their respective maxillary premolar region in elderly edentulous persons, and an implant can be placed to anchor an overdenture. The best site for a wide-body implant was established to be 6-8 mm posterior to the incisive foramen in elderly edentulous patients.

Assessing sleep architecture and cognition in older adults with depressive symptoms attending a memory clinic.

BACKGROUND: While depression is intrinsically and bidirectionally linked with both sleep disturbance and cognition, the inter-relationships between sleep, cognition, and brain integrity in older people with depression, especially those with late-onset depression are undefined. METHODS: One hundred and seventy-two older adults (mean age 64.3 ± 6.9 years, Depression: n = 66, Control: n = 106) attending a memory clinic underwent a neuropsychological battery of declarative memory, executive function tasks, cerebral magnetic resonance imaging and overnight polysomnography with quantitative electroencephalography. RESULTS: The time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep, slow-wave activity, sleep spindles, hippocampal volume and prefrontal cortex thickness did not differ between depression and control and depression onset groups. However, sleep onset latency (p = 0.005) and REM onset latency (p = 0.02) were later in the Depression group compared to controls. Less SWS was associated with poorer memory (r = 0.31, p = 0.023) in the depression group, and less SWS was related to better memory in the control group (r = -0.20, p = 0.043; Fishers r-to-z = -3.19). LIMITATIONS: Longitudinal studies are needed to determine if changes in sleep in those with depressive symptoms predict cognitive decline and illness trajectory. CONCLUSION: Older participants with depressive symptoms had delayed sleep initiation, suggestive of delayed sleep phase. The association between SWS and memory suggests SWS may be a useful target for cognitive intervention in older adults with depression symptoms. Reduced hippocampal volumes did not mediate this relationship, indicating a broader distributed neural network may underpin these associations.

Predicting the Fracture Toughness of Human Cancellous Bone in Fractured Neck of Femur Patients Using Bone Volume and Micro-Architecture.

The current protocol used to determine if an individual is osteoporotic relies on assessment of the individual's bone mineral density (BMD), which allows clinicians to judge the condition of a patient with respect to their peers. This, in essence, evaluates a person's fracture risk, because BMD is a good surrogate measure for strength and stiffness. In recent studies, the authors were the first to produce fracture toughness (FT) data from osteoporotic (OP) and osteoarthritic (OA) patients, by using a testing technique which basically analyzes the prerequisite stress conditions for the onset of growth of a major crack through cancellous bone tissue. FT depends mainly on bone quantity (BV/TV, bone volume/tissue volume), but also on bone micro-architecture (mArch), the inner trabecular design of the bone. The working research hypothesis of the present study is that mArch offers added prediction power to BV/TV in determining FT parameters. Consequently, our aim was to investigate the use of predictive models for fracture toughness and also to investigate if there are any significant differences between the models produced from samples loaded across (AC, transverse to) the main trabecular orientation and along (AL, in parallel) the trabeculae. In multilinear regression analysis, we found that the strength of the relationships varied for a crack growing in these two orthogonal directions. Adding mArch variables in the Ac direction helped to increase the R2 to 0.798. However, in the AL direction, adding the mArch parameters did not add any predictive power to using BV/TV alone; BV/TV on its own could produce R2 = 0.730. The present results also imply that the anisotropic layout of the trabeculae makes it more difficult for a major crack to grow transversely across them. Cancellous bone models and remodels itself in a certain way to resist fracture in a specific direction, and thus, we should be mindful that architectural quality as well as bone quantity are needed to understand the resistance to fracture.

Electroencephalographic slowing during REM sleep in older adults with subjective cognitive impairment and mild cognitive impairment.

STUDY OBJECTIVES: In older adults with Alzheimer's disease, slowing of electroencephalographic (EEG) activity during REM sleep has been observed. Few studies have examined EEG slowing during REM in those with mild cognitive impairment (MCI) and none have examined its relationship with cognition in this at-risk population. METHODS: Two hundred and ten older adults (mean age = 67.0, SD = 8.2 years) underwent comprehensive neuropsychological, medical, and psychiatric assessment and overnight polysomnography. Participants were classified as subjective cognitive impairment (SCI; n = 75), non-amnestic MCI (naMCI, n = 85), and amnestic MCI (aMCI, n = 50). REM EEG slowing was defined as (δ + θ)/(α + σ + ß) power and calculated for frontal, central, parietal, and occipital regions. Analysis of variance compared REM EEG slowing between groups. Correlations between REM EEG slowing and cognition, including learning and memory, visuospatial and executive functions, were examined within each subgroup. RESULTS: The aMCI group had significantly greater REM EEG slowing in the parietal and occipital regions compared to the naMCI and SCI groups (partial η2 = 0.06, p < 0.05 and 0.06, p < 0.05, respectively), and greater EEG slowing in the central region compared to SCI group (partial η2 = 0.03, p < 0.05). Greater REM EEG slowing in parietal (r = -0.49) and occipital regions (r = -0.38 [O1/M2] and -0.33 [O2/M1]) were associated with poorer visuospatial performance in naMCI. CONCLUSIONS: REM EEG slowing may differentiate older adults with memory impairment from those without. Longitudinal studies are now warranted to examine the prognostic utility of REM EEG slowing for cognitive and dementia trajectories.

Investigating the three-dimensional myocardial micro-architecture in the laminar structure using X-ray phase-contrast microtomography.

A comprehensive grasp of the myocardial micro-architecture is essential for understanding diverse heart functions. This study aimed to investigate three-dimensional (3D) cardiomyocyte arrangement in the laminar structure using X-ray phase-contrast microtomography. Using the ID-19 beamline at the European Synchrotron Radiation Facility, we imaged human left ventricular (LV) wall transparietal samples and reconstructed them with an isotropic voxel edge length of 3.5 µm. From the reconstructed volumes, we extracted different regions to analyze the orientation distribution of local cardiomyocyte aggregates, presenting findings in terms of helix and intrusion angles. In regions containing one sheetlet population, we observed cardiomyocyte aggregates running along the local LV wall's radial direction at the border of sheetlets, branching and merging into a complex network around connecting points of different sheetlets, and bending to accommodate vessel passages. In regions with two sheetlet populations, the helix angle of local cardiomyocyte aggregates experiences a nonmonotonic change, and some cardiomyocyte aggregates run along the local radial direction. X-ray phase-contrast microtomography is a valuable technique for investigating the 3D local myocardial architecture at microscopic level. The arrangement of local cardiomyocyte aggregates in the LV wall proves to be both regional and complex, intricately linked to the local laminar structure.

High-resolution three-dimensional micro-computed tomography assessment of micro-architectural patterns in non-adults with cribra orbitalia: Correlation between macro- and micro-scale bone features.

Skeletal porous lesions such as cribra orbitalia (CO) have long been of interest to bioanthropologists worldwide, mainly due to their high prevalence in osteological material. Previous studies considered CO as an external morphological manifestation, and therefore, research has mainly focused on visible (macroscopic) CO patterns. However, the understanding of CO-induced micro-scale bone changes is still scarce. Therefore, we performed high-resolution micro-computed tomography imaging to investigate three-dimensional CO-induced micro-architectural patterns in non-adults, with a particular focus on the correlation between macroscopic and micro-architectural orbital features. Cortical and trabecular micro-architectural changes in the orbital roof were analyzed in non-adults younger than 15 years, using orbital roof samples with and without macroscopic traces of CO (n = 28). A widely accepted five-grade macroscopic CO scoring system was applied to analyze CO severity. Areas affected with CO (area 1) and areas without macroscopic CO traces (area 2) were analyzed separately. The conducted high-resolution analysis showed that cortical and trabecular micro-architecture varied with CO presence, lesion severity (CO grade), and the analyzed area. Inter-grade comparisons suggested that most of the analyzed micro-architectural parameters were not significantly different between adjacent CO grades. Based on the micro-architectural evaluation of areas 1 and 2, the porous lesions were much more extensive than revealed by gross examination. In addition, micro-architectural differences were particularly pronounced in younger non-adults. In summary, our pilot study suggests that the macroscopic examination of CO reflects only the tip of the iceberg, as the micro-architectural changes seem to be much larger than macroscopically identified. RESEARCH HIGHLIGHTS: Cribra orbitalia (CO) represents orbital porous lesions. A high-resolution microscopic assessment of CO-induced changes in non-adults was done by micro-computed tomography. The microarchitecture was affected by CO presence, CO grade, area, and age.

Digital microfabrication of user-defined 3D microstructures in cell-laden hydrogels.

Complex 3D interfacial arrangements of cells are found in several in vivo biosystems such as blood vasculature, renal glomeruli, and intestinal villi. Current tissue engineering techniques fail to develop suitable 3D microenvironments to evaluate the concurrent effects of complex topography and cell encapsulation. There is a need to develop new fabrication approaches that control cell density and distribution within complex 3D features. In this work, we present a dynamic projection printing process that allows rapid construction of complex 3D structures using custom-defined computer-aided-design (CAD) files. Gelatin-methacrylate (GelMA) constructs featuring user-defined spiral, pyramid, flower, and dome micro-geometries were fabricated with and without encapsulated cells. Encapsulated cells demonstrate good cell viability across all geometries both on the scaffold surface and internal to the structures. Cells respond to geometric cues individually as well as collectively throughout the larger-scale patterns. Time-lapse observations also reveal the dynamic nature of mechanical interactions between cells and micro-geometry. When compared to conventional cell-seeding, cell encapsulation within complex 3D patterned scaffolds provides long-term control over proliferation, cell morphology, and geometric guidance. Overall, this biofabrication technique offers a flexible platform to evaluate cell interactions with complex 3D micro-features, with the ability to scale-up towards high-throughput screening platforms.

Longitudinal trajectories of spectral power during sleep in middle-aged and older adults.

Age-related changes in sleep appear to contribute to cognitive aging and dementia. However, most of the current understanding of sleep across the lifespan is based on cross-sectional evidence. Using data from the Sleep Heart Health Study, we investigated longitudinal changes in sleep micro-architecture, focusing on whether such age-related changes are experienced uniformly across individuals. Participants were 2,202 adults (ageBaseline = 62.40 ± 10.38, 55.36 % female, 87.92 % White) who completed home polysomnography assessment at two study visits, which were 5.23 years apart (range: 4-7 years). We analyzed NREM and REM spectral power density for each 0.5 Hz frequency bin, including slow oscillation (0.5-1 Hz), delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), and beta-1 (15-20 Hz) bands. Longitudinal comparisons showed a 5-year decline in NREM delta (p <.001) and NREM sigma power density (p <.001) as well as a 5-year increase in theta power density during NREM (p =.001) and power density for all frequency bands during REM sleep (ps < 0.05). In contrast to the notion that sleep declines linearly with advancing age, longitudinal trajectories varied considerably across individuals. Within individuals, the 5-year changes in NREM and REM power density were strongly correlated (slow oscillation: r = 0.46; delta: r = 0.67; theta r = 0.78; alpha r = 0.66; sigma: r = 0.71; beta-1: r = 0.73; ps < 0.001). The convergence in the longitudinal trajectories of NREM and REM activity may reflect age-related neural de-differentiation and/or compensation processes. Future research should investigate the neurocognitive implications of longitudinal changes in sleep micro-architecture and test whether interventions for improving key sleep micro-architecture features (such as NREM delta and sigma activity) also benefit cognition over time.