Iterative Reconstruction of Micro Computed Tomography Scans Using Multiple Heterogeneous GPUs.

Graphics processing units (GPUs) facilitate massive parallelism and high-capacity storage, and thus are suitable for the iterative reconstruction of ultrahigh-resolution micro computed tomography (CT) scans by on-the-fly system matrix (OTFSM) calculation using ordered subsets expectation maximization (OSEM). We propose a finite state automaton (FSA) method that facilitates iterative reconstruction using a heterogeneous multi-GPU platform through parallelizing the matrix calculations derived from a ray tracing system of ordered subsets. The FSAs perform flow control for parallel threading of the heterogeneous GPUs, which minimizes the latency of launching ordered-subsets tasks, reduces the data transfer between the main system memory and local GPU memory, and solves the memory-bound of a single GPU. In the experiments, we compared the operation efficiency of OS-MLTR for three reconstruction environments. The heterogeneous multiple GPUs with job queues for high throughput calculation speed is up to five times faster than the single GPU environment, and that speed up is nine times faster than the heterogeneous multiple GPUs with the FIFO queues of the device scheduling control. Eventually, we proposed an event-triggered FSA method for iterative reconstruction using multiple heterogeneous GPUs that solves the memory-bound issue of a single GPU at ultrahigh resolutions, and the routines of the proposed method were successfully executed on each GPU simultaneously.

Development of Limited-Angle Iterative Reconstruction Algorithms with Context Encoder-Based Sinogram Completion for Micro-CT Applications.

Limited-angle iterative reconstruction (LAIR) reduces the radiation dose required for computed tomography (CT) imaging by decreasing the range of the projection angle. We developed an image-quality-based stopping-criteria method with a flexible and innovative instrument design that, when combined with LAIR, provides the image quality of a conventional CT system. This study describes the construction of different scan acquisition protocols for micro-CT system applications. Fully-sampled Feldkamp (FDK)-reconstructed images were used as references for comparison to assess the image quality produced by these tested protocols. The insufficient portions of a sinogram were inpainted by applying a context encoder (CE), a type of generative adversarial network, to the LAIR process. The context image was passed through an encoder to identify features that were connected to the decoder using a channel-wise fully-connected layer. Our results evidence the excellent performance of this novel approach. Even when we reduce the radiation dose by 1/4, the iterative-based LAIR improved the full-width half-maximum, contrast-to-noise and signal-to-noise ratios by 20% to 40% compared to a fully-sampled FDK-based reconstruction. Our data support that this CE-based sinogram completion method enhances the efficacy and efficiency of LAIR and that would allow feasibility of limited angle reconstruction.

Cardiovascular Safety of Romosozumab Compared to Commonly Used Anti-osteoporosis Medications in Postmenopausal Osteoporosis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The aim of this study was to investigate the cardiovascular safety of romosozumab in postmenopausal women with osteoporosis. Romosozumab, a monoclonal antibody targeting sclerostin, has been shown to increase bone mineral density and reduce the risk of osteoporotic fractures. However, in previous studies, romosozumab therapy was identified as a potential risk factor for cardiovascular events, particularly in patients with predisposing cardiovascular disease. METHODS: A systematic literature search was performed in the Cochrane Library, Embase, PubMed, and Web of Science databases to identify randomized controlled trials (RCTs) comparing the safety and efficacy of romosozumab versus alendronate, teriparatide, denosumab, or placebo in postmenopausal women with osteoporosis. Contrast-based network meta-analysis was performed using a random-effects model. The pooled estimates are presented as risk ratios with 95% confidence intervals. RESULTS: Of the 5282 articles retrieved, 25 RCTs were included in this review (n = 24,942), and 18 randomized controlled trials (n = 16,777) were included in the network meta-analysis. The results indicated no significant differences in cardiovascular mortality rate between romosozumab and placebo. Regarding the risk of major cardiovascular events, no significant differences were found in the direct evidence or the network meta-analysis with placebo as the reference. CONCLUSION: Romosozumab might be a safe option for treating postmenopausal women with osteoporosis. The cardiovascular concerns associated with this treatment seem less significant than previously suggested, although additional real-world data are required to confirm this conclusion.

Assessment of Cement Leakage in Decompressed Percutaneous Kyphoplasty.

Symptomatic osteoporotic compression fractures are commonly addressed through vertebroplasty and kyphoplasty. However, cement leakage poses a significant risk of neurological damage. We introduced "aspiration percutaneous kyphoplasty", also known as "decompressed kyphoplasty", as a method to mitigate cement leakage and conducted a comparative analysis with high viscosity cement vertebroplasty. We conducted a retrospective study that included 136 patients with single-level osteoporotic compression fractures. Among them, 70 patients underwent high viscosity cement vertebroplasty, while 66 patients received decompressed percutaneous kyphoplasty with low-viscosity cement. Comparison parameters included cement leakage rates, kyphotic angle alterations, and the occurrence of adjacent segment fractures. The overall cement leakage rate favored the decompressed kyphoplasty group (9.1% vs. 18.6%), although statistical significance was not achieved (p = 0.111). Nonetheless, the risk of intradiscal leakage significantly reduced in the decompressed kyphoplasty cohort (p = 0.011), which was particularly evident in cases lacking the preoperative cleft sign on X-rays. Kyphotic angle changes and the risk of adjacent segment collapse exhibited similar outcomes (p = 0.739 and 0.522, respectively). We concluded that decompressed kyphoplasty demonstrates efficacy in reducing intradiscal cement leakage, particularly benefiting patients without the preoperative cleft sign on X-rays by preventing intradiscal leakage.

Effects of early aquatic exercise intervention on trunk strength and functional recovery of patients with lumbar fusion: a randomized controlled trial.

This study investigated the effectiveness of an early aquatic exercise program on trunk muscle function and functional recovery of patients with lumbar fusion. Twenty-eight subjects were divided into two equal groups. Patients in the aquatic group performed two 60-min aquatic exercise sessions and three 60-min home exercise sessions per week for 6 weeks, whereas those in the control group performed five sessions of 60-min home exercises per week for 6 weeks. The primary outcomes were the Numerical Pain Rating Scale (NPRS) and Oswestry Disability Index (ODI), and the secondary outcomes were Timed Up and Go Test (TUGT), trunk flexor and extensor muscle strength, lumbopelvic stability, and lumbar multifidus muscle thickness measured pre- and post-intervention. Compared with participants in the control group, those in the experimental group showed significant improvement in NPRS, ODI, trunk extensor strength, lumbopelvic control, lumbar multifidus muscle thickness, and relative change in multifidus muscle thickness (significant time by group interactions, P < 0.05). Participants in both groups showed significant time effects (P < 0.001) for TUGT and trunk flexor strength outcome. Aquatic exercise combined with home exercise was superior to home exercise alone in reducing pain, disability and improving muscle strength, lumbopelvic stability, and lumbar multifidus muscle thickness.

Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and -independent apoptosis via Smad or Akt signaling pathways in HOS cells.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and has also been associated with a high degree of malignancy and enhanced metastatic capacity. Curcumin (CUR) is well known for its anti-osteosarcoma activity. However, both demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are natural curcumin analogues/congeners from turmeric whose role in osteosarcoma development remains unknown. METHODS: To evaluate the growth inhibitory effects of CUR, DMC and BDMC on osteosarcoma (HOS and U2OS), breast (MDA-MB-231), and melanoma (A2058) cancer cells, we employed the MTT assay, annexin V-FITC /7-AAD staining, and clonogenic assay. RESULTS: CUR,DMC, and BDMC all decreased the viability of HOS, U2OS, MDA-MB-231, and A2058 cancer cells. Additionally, CUR,DMC, and BDMC induced the apoptosis of HOS cells through activation of Smad 2/3 or repression of Akt signaling pathway. Furthermore, the combination of CUR,DMC, and BDMC synergistically reduced cell viability, colony formation and increased apoptosis than either two or a single agent in HOS cells. CONCLUSIONS: The combination of these three compounds could be used as a novel target for the treatment of osteosarcoma.

Ouabain Induces Apoptotic Cell Death Through Caspase- and Mitochondria-dependent Pathways in Human Osteosarcoma U-2 OS Cells.

BACKGROUND/AIM: Ouabain, a plant-derived product/substance with Na+/K+-ATPase inhibiting properties, has been shown to exert anti-cancer activity on human cancer cells. This is the first study to investigate the effect of ouabain on apoptotic cell death of human osteosarcoma-derived U-2 OS cells. MATERIALS AND METHODS: Flow cytometry was used to examine cell viability, cell cycle, and reactive oxygen species (ROS), Ca2+, mitochondrial membrane potential (MMP) and caspase activity. Morphological changes were examined by contrast-phase microscopy, while apoptosis-associated protein levels were analyzed by western blot. RESULTS: Ouabain, at concentrations of 5-60 µM, significantly decreased the total viable cells and induced cell morphological changes in a time-dependent manner. It also time-dependently decreased G0/G1 phase and increased S and G2/M phase in U-2 OS cells. The production of ROS and the levels of MMPs (ΔΨm) were inhibited, while Ca2+ production in U-2 OS cells was increased. Regarding cell apoptosis, flow cytometry assay revealed increased caspase-3, -8, and -9 activities in U-2 OS cells. Moreover, western blot results showed that ouabain increased the expression of pro-apoptotic protein Bax and decreased the expression of anti-apoptotic protein Bcl-2 in U-2 OS cells. Furthermore, results also showed that ouabain increased cytochrome c release, apoptosis-inducing factor (AIF) and endonuclease (Endo) G that is associated with apoptosis through caspase-dependent and -independent pathway in U-2 OS cells. CONCLUSION: Our findings provide important insight into the cytotoxic effects of ouabain on U-2 OS cells, in vitro, which are mediated at least partly via cell apoptosis induction.

Decompressed percutaneous vertebroplasty: a secured bone cement delivery procedure for vertebral augmentation in osteoporotic compression fractures.

UNLABELLED: The purpose of this study was to assess the efficacy of a new assistive procedure for injecting cement in percutaneous vertebroplasty (PV). Percutaneous vertebroplasty is frequently used for treating patients with osteoporotic vertebral compression fractures. However, the leakage of bone cement during PV may lead to serious complications, such as spinal cord compression or pulmonary embolism. Herein we present a secure procedure designed to safely and effectively deliver the bone cement into the vertebral column. MATERIALS AND METHODS: Thirty-five patients with a total of 50 levels of osteoporotic compression fracture were consecutively recruited for the study. During a routine PV operation, acrylic cement was injected with a simultaneous application of a continuous negative pressure to the contralateral side of the vertebral body. This negative pressure exerts a pulling force that attracts the bone cement to flow within the vertebral body. RESULTS: With the proposed decompressed PV procedure, cross-filling of the vertebrographies was achieved for all 50 fracture levels, with no paravertebral venous plexus leakage. Three of the 50 levels (6%) exhibited contrast-medium leakage into the intradisc or cortical defect regions. After decompressed cement injection, excellent cross-filling of bone cement deposition was achieved in 38 of the 50 levels (76%; cement cross-filling region >75%), good cross-filling deposition was achieved in 7 levels (14%; cement cross-filling region >50%), deposition was poor in 3 levels (6%; cement cross-filling region <50%), and deposition failed in 2 levels (4%; fixed cement with no sign of cross-filling). Routine postoperative reviews revealed that six fracture levels (12%) had minimal cement leakage, with two leaking into the disc and four into paravertebral cortical defect regions. CONCLUSIONS: Compared to the reported 20-88% cement leakage rate for the conventional PV procedure, the proposed decompressed PV procedure offers a more secure and effective way to perform cement injection, and reduces the likelihood of cement leakage.

Simvastatin inhibits pro-inflammatory mediators through induction of heme oxygenase-1 expression in lipopolysaccharide-stimulated RAW264.7 macrophages.

It has been reported that the anti-inflammatory activity of 3-hydroxy-3-methyl-glutary coenzyme A (HMG-CoA) reductase inhibitors (statins) is independent of their hypocholesterolemic effect. Previous studies indicated that induction of heme oxygenase-1 (HO-1) exerts a cytoprotective activity in several inflammatory diseases. Here, the possibility that HO-1 is involved in the anti-inflammatory action of simvastatin, using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages as a model system has been specifically addressed. Our results demonstrated that in the presence of LPS, simvastatin significantly increased HO-1 expression and activity in a dose-dependent manner compared to that of LPS-stimulated alone macrophages. Moreover, simvastatin significantly inhibited LPS-induced inducible nitric oxide synthase (NOS) expression, and formation of pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), nitrite and free radicals, but enhanced interleukin-10 (IL-10) production. Similarly, the IκB-α degradation and nuclear transcription factor-κB translocation and activation caused by LPS were significantly suppressed by simvastatin. However, these anti-inflammatory activities of simvastatin were markedly reversed by addition of a HO-1 inhibitor zinc protoporphyrin (ZnPP). Accordingly, the present results indicate that the anti-inflammatory activity of simvastatin could, at least in part, be regulated by induction of HO-1-mediated processes.

Clinical and immunological responses to undiluted and diluted smallpox vaccine with vaccinia virus of Lister strain.

The potential to increase the supply of vaccine by diluting the vaccinia virus of Lister strain to face possible bioterrorism with smallpox was evaluated. Vaccinia-naïve subjects (n=97) were randomized to receive either undiluted or diluted (1:5, 1:10) vaccine, and previously vaccinated subjects (n=122) were randomized to receive either undiluted or diluted (1:10, 1:30) vaccine. Except two subjects who received 1:30 diluted vaccine, the vaccination of all subjects was successful clinically. All subjects had significant vaccinia-specific T cell and antibody responses. The diluted vaccine was not associated with decreased local or systemic reactions, lower T cell responses, or higher antibody titers when compared with undiluted vaccine. Here we show the diluted vaccine of Lister strain can be used in vaccinia-naïve subjects and previously vaccinated subjects if viral titer > or =10(8) and 10(7.5) pfu/mL after dilution, respectively. The reactogenicity of vaccinia virus may not be a dose-dependent response.