Influence of greater trochanteric bone density and three-dimensional morphology on perioperative greater trochanteric fracture following total hip arthroplasty via an anterolateral approach.

BACKGROUND: Perioperative greater trochanteric fracture following total hip arthroplasty (THA) using the anterolateral approach is a recognized perioperative complication. There was no previous study to determine the relationship between bone mineral density (BMD) and three-dimensional greater trochanter morphology for perioperative greater trochanter fractures. The purpose of this study is to identify the influence of greater trochanteric bone density and three-dimensional morphology on perioperative greater trochanteric fracture following THA using the anterolateral approach. METHODS: We investigated 209 hips done primary THA using the anterolateral approach and preoperative BMD test for the proximal femoral bone with a minimum of 6 months follow-up. We picked up all patients who had perioperative greater trochanteric fractures. Multivariate analysis was done in order to investigate the influence of the greater trochanter young adult mean (YAM) and three-dimensional morphology on perioperative greater trochanteric fractures. RESULTS: There were 10 joints (10/209, 4.8%) with perioperative greater trochanteric fractures. Osteosynthesis was required only in one joint (1/209, 0.5%) because the bone fragments were significantly displaced proximally by the gluteus medius. Multivariate analysis showed the combination of Type B femoral shape (in cases where the top of the great trochanter was inside the longitudinal central axis of the planned femoral stem in computed tomography (CT)- based three-dimensional templating) and a YAM of < 80% was the only risk factor for fracture. CONCLUSIONS: The preoperative greater trochanter BMD test (YAM < 80%) and three-dimensional femoral morphology (Type B femoral shape) provide useful information to mitigate the occurrence of perioperative greater trochanter fractures associated with THA using the anterolateral approach.

Large intraosseous chronic expanding hematoma after total hip arthroplasty presenting with chronic disseminated intravascular coagulation: a case report and literature review.

BACKGROUND: A chronic expanding hematoma (CEH) is a rare complication caused by surgery or trauma; it mostly affects the soft tissues, such as those in the trunk or extremities. We present the first case of a large intraosseous CEH presenting with chronic disseminated intravascular coagulation (DIC), 22 years after total hip arthroplasty (THA); the CEH was treated with a single-stage excision and revision THA. CASE PRESENTATION: A 67-year-old man presented to our hospital with left thigh pain and an enlarging mass. He had no history of trauma, anticoagulant use, or a collagen vascular disorder. The patient initially declined surgery. Two years later, radiographs and computed tomography images revealed progressive osteolysis, marginal sclerosis, and calcification in the left femur, in addition to loosening of the femoral component. Laboratory data revealed anemia and chronic DIC of unknown causes. Magnetic resonance imaging revealed a "mosaic sign" on the mass, indicating a mix of low- and high-signal intensities on T2-weighted images. Needle biopsy prior to surgery revealed no infection or malignant findings. An intraosseous CEH was suspected due to extensive osteolysis and loosening of the femoral component. No other factors that could induce chronic DIC were identified, such as sepsis, leukemia, cancer, trauma, liver disease, aneurysms, or hemangiomas. Therefore, we speculated that the anemia and chronic DIC were caused by the large intraosseous CEH. A single-stage revision THA with surgical excision was performed to preserve the hip function and improve the chronic DIC. The postoperative histopathological findings were consistent with an intraosseous CEH. The anemia and chronic DIC improved after 7 days. There was no recurrence of intraosseous CEH or chronic DIC at the 6-month follow-up. The left thigh pain improved, and the patient could ambulate with the assistance of a walking frame. CONCLUSIONS: The loosening of the femoral component caused persistent movement, which may have caused intraosseous CEH growth, anemia, and chronic DIC. It is important to differentiate CEHs from malignant tumors with hematomas. Furthermore, the "mosaic sign" noted in this case has also been observed on magnetic resonance images in other cases of CEH.

Does Dosage or Duration of Concurrent Oral Corticosteroid Influence Elevated Risk of Postoperative Complications After Total Joint Arthroplasty?

BACKGROUND: This report seeks to clarify whether the dosage and duration of preoperative concurrent corticosteroid use influence postoperative complications after primary total joint arthroplasty (TJA). METHODS: This retrospective single institutional study enrolled 1128 primary TJA cases, including 905 total hip arthroplasties and 223 total knee arthroplasties at a minimum 6 months of follow-up. Mean follow-up period was 51.9 ± 34.1 months (range 6-146). Of all joints, 120 joints (10.6%) were associated with chronic concurrent oral corticosteroid use. Multivariate analysis was performed to identify whether chronic concurrent oral corticosteroid use elevated the risk of postoperative complications including surgical site infection/periprosthetic joint infection, delayed wound healing, periprosthetic fracture, and implant loosening. For chronic concurrent oral corticosteroid user, we determined whether the dosage and duration of preoperative concurrent corticosteroid use influenced postoperative complications and have an effective threshold for postoperative complications using receiver operating characteristic curve analysis. RESULTS: The multivariate analysis revealed that American Society of Anesthesiologist Physical Status 3 was an independent risk factor for postoperative complications, while concurrent oral corticosteroid use was not an independent risk factor. When we compared joints with (n = 13) and without (n = 107) postoperative complications in chronic concurrent oral corticosteroid user, there was no statistical difference in the dosage (P = .97) and duration (P = .69) between the 2 groups. Area under the curve values for the oral corticosteroid dosages and duration were 0.482 and 0.549, respectively. CONCLUSION: This study revealed that neither dosage nor duration of concurrent oral corticosteroid use was predictive of postoperative complications after TJA. American Society of Anesthesiologist Physical Status 3 is a major factor in postoperative complications after TJA.

Cell-Level Analysis Visualizing Photodynamic Therapy with Porphylipoprotein and Talaporphyrin Sodium.

We revealed the difference in the mechanism of photodynamic therapy (PDT) between two photosensitizers: porphylipoprotein (PLP), which has recently attracted attention for its potential to be highly effective in treating cancer, and talaporphyrin sodium (NPe6). (1) NPe6 accumulates in lysosomes, whereas PLP is incorporated into phagosomes formed by PLP injection. (2) PDT causes NPe6 to generate reactive oxygen species, thereby producing actin filaments and stress fibers. In the case of PLP, however, reactive oxygen species generated by PDT remain in the phagosomes until the phagosomal membrane is destroyed, which delays the initiation of RhoA activation and RhoA*/ROCK generation. (4) After the disruption of the phagosomal membrane, however, the outflow of various reactive oxygen species accelerates the production of actin filaments and stress fibers, and blebbing occurs earlier than in the case of NPe6. (5) PLP increases the elastic modulus of cells without RhoA activity in the early stage. This is because phagosomes are involved in polymerizing actin filaments and pseudopodia formation. Considering the high selectivity and uptake of PLP into cancer cells, a larger effect with PDT can be expected by skillfully combining the newly discovered characteristics, such as the appearance of a strong effect at an early stage.

Near-Infrared Light Irradiation of Porphyrin-Modified Gold Nanoparticles Promotes Cancer-Cell-Specific Cytotoxicity.

The use of nanoparticles has been investigated as a new cancer treatment. These can induce specific cytotoxicity in cancer cells. In particular, Au nanoparticles (AuNPs) have unique characteristics. The maximum absorption spectrum of AuNPs can be adjusted to modify their size or shape to absorb near-infrared light that can penetrate into tissue without photodamage. Thus, the combination of AuNPs and near-infrared light can be used to treat cancer in deep-seated organs. To obtain effective cancer-specific accumulation of AuNPs, we focused on porphyrin and synthesized a porphyrin-attached Au compound: Au-HpD. In this study, we investigated whether Au-HpD possesses cancer-specific accumulation and cytotoxicity. Intracellular Au-HpD accumulation was higher in cancer cells than in normal cells. In order to analyze the cytotoxicity induced by Au-HpD, cancer cells and normal cells were co-cultured in the presence of Au-HpD; then, they were subjected to 870 nm laser irradiation. We observed that, after laser irradiation, cancer cells showed significant morphological changes, such as chromatin condensation and nuclear fragmentation indicative of cell apoptosis. This strong effect was not observed when normal cells were irradiated. Moreover, cancer cells underwent cell apoptosis with combination therapy.

The prevalence and impact of sarcopenia in females undergoing total hip arthroplasty: A prospective study.

OBJECTIVES: Although both sarcopenia and hip disease decrease physical function, few studies have investigated the association. We investigated the prevalence of sarcopenia in patients awaiting total hip arthroplasty for osteoarthritis and examined the impact of sarcopenia on pre- and postoperative outcomes. METHODS: This prospective study included 96 females. Participants were classified using two criteria. Cases defined as having sarcopenia by the Asian Working Group for Sarcopenia (AWGS) criteria were categorized as the AWGS-sarcopenia (A-S) group, and others were categorized as the AWGS-non-sarcopenia (A-NS) group. Those classified by hand grip strength (HGS) constituted the lower-HGS (L-H) and normal-HGS (N-H) groups. Patient demographics, physical function, and Japanese Orthopaedic Association (JOA) score were compared between each group. RESULTS: The prevalence of the AWGS sarcopenia was 33.3%. In the pre- and postoperative analyses, the L-H group had significantly poorer physical function and JOA score than the N-H group. Postoperatively, the A-S group only demonstrated poorer HGS. CONCLUSION: Preoperative physical function and JOA score was significantly poorer in the L-H group; physical function was significantly poorer even postoperatively. A HGS test is useful for detecting a decline in the pre- and postoperative physical function in females with hip osteoarthritis.

Antibacterial Activity in Iodine-coated Implants Under Conditions of Iodine Loss: Study in a Rat Model Plus In Vitro Analysis.

BACKGROUND: We developed iodine-coated titanium implants to suppress microbial activity and prevent periprosthetic joint infection (PJI); their efficacy was demonstrated in animal and in vitro models. The iodine content in iodine-coated implants naturally decreases in vivo. However, to our knowledge, the effect of reduced iodine content on the implant's antimicrobial activity has not been evaluated to date. QUESTIONS/PURPOSES: (1) How much does the iodine content on the implant surface decrease after 4 and 8 weeks in vivo in a rat model? (2) What effect does the reduced iodine content have on the antimicrobial effect of the implant against multiple bacteria in an in vitro model? METHODS: This experiment was performed in two parts: an in vivo experiment to determine attenuation of iodine levels over time in rats, and an in vitro experiment in which we sought to assess whether the reduced iodine content observed in the in vivo experiment was still sufficient to deliver antimicrobial activity against common pathogens seen in PJI. For the in vivo experiment, three types of titanium alloy washers were implanted in rats: untreated (Ti), surface-anodized to produce an oxide film (Ti-O), and with an iodine layer on the oxidation film (Ti-I). The attenuation of iodine levels in rats was measured over time using inductively coupled plasma-mass spectrometry. Herein, only the Ti-I washer was used, with five implanted in each rat that were removed after 4 or 8 weeks. For the 4- and 8-week models, two rats and 15 washers were used. For the in vitro study, to determine the antibacterial effect, three types of washers (Ti, Ti-O, and Ti-I) (nine washers in total) were implanted in each rat. Then, the washers were removed and the antibacterial effect of each washer was examined on multiple bacterial species using the spread plate method and fluorescence microscopy. For the spread plate method, six rats were used, and five rats were used for the observation using fluorescence microscopy; further, 4- and 8-week models were made for each method. Thus, a total of 22 rats and 198 washers were used. Live and dead bacteria in the biofilm were stained, and the biofilm coverage percentage for quantitative analysis was determined using fluorescence microscopy in a nonblinded manner. Ti-I was used as the experimental group, and Ti and Ti-O were used as control groups. The total number of rats and washers used throughout this study was 24 and 213, respectively. RESULTS: Iodine content in rats implanted with Ti-I samples decreased to 72% and 65% after the in vivo period of 4 and 8 weeks, respectively (p = 0.001 and p < 0.001, respectively). In the in vitro experiment, the Ti-I implants demonstrated a stronger antimicrobial activity than Ti and Ti-O implants in the 4- and 8-week models. Both the median number of bacterial colonies and the median biofilm coverage percentage with live bacteria on Ti-I were lower than those on Ti or Ti-O implants for each bacterial species in the 4- and 8-week models. There was no difference in the median biofilm coverage percentage of dead bacteria. In the 8-week model, the antibacterial activity using the spread plate method had median (interquartile range) numbers of bacteria on the Ti, Ti-O, and Ti-I implants of 112 (104 to 165) × 105, 147 (111 to 162) × 105, and 55 (37 to 67) × 105 of methicillin-sensitive Staphylococcus aureus (Ti-I versus Ti, p = 0.026; Ti-I versus Ti-O, p = 0.009); 71 (39 to 111) × 105, 50 (44 to 62) × 105, and 26 (9 to 31)× 105 CFU of methicillin-resistant S. aureus (Ti-I versus Ti, p = 0.026; Ti-I versus Ti-O, p = 0.034); and 77 (74 to 83) × 106, 111 (95 to 117) × 106, and 30 (21 to 45) × 106 CFU of Pseudomonas aeruginosa (Ti-I versus Ti, p = 0.004; Ti-I versus Ti-O, p = 0.009). Despite the decrease in the iodine content of Ti-I after 8 weeks, it demonstrated better antibacterial activity against all tested bacteria than the Ti and Ti-O implants. CONCLUSION: Iodine-coated implants retained their iodine content and antibacterial activity against methicillin-sensitive S. aureus, methicillin-resistant S. aureus, and P. aeruginosa for 8 weeks in vivo in rats. To evaluate the longer-lasting antibacterial efficacy, further research using larger infected animal PJI models with implants in the joints of both males and females is desirable. CLINICAL RELEVANCE: Iodine-coated titanium implants displayed an antibacterial activity for 8 weeks in rats in vivo. Although the findings in a rat model do not guarantee efficacy in humans, they represent an important step toward clinical application.

The cytotoxicity of cyclophosphamide is enhanced in combination with monascus pigment.

Monascus pigment is derived from red-mold rice fermented by monascus purpureus and utilized as a natural coloring agent and natural food additive in East Asia. Monascus pigment works as a radical scavenger. Some antioxidant combine cancer chemo-therapy to protect normal tissue because chemotherapy induce side effect for normal tissue. This combination therapy can attenuate the cytotoxicity of anti-cancer drugs by antioxidants effects. However, the effect of this combination therapy for cancer cells dose not investigate enough. In this study, we investigated the combination effect of anti-oxidants and anti-cancer drugs. We selected an anti-oxidant as monascus pigment and following four anti-cancer drugs: doxorubicin, tamoxifen, paclitaxicel, and cyclophosphamide. Combination treatment with monascus pigment and cyclophosphamide enhanced the cytotoxicity of cyclophosphamide. Moreover, this combination treatment accelerated apoptosis. The spot on TLC assay board of the monascus pigment and cyclophosphamide mixture is different from the spot of monascus pigment alone and cyclophosphamide alone. The interaction between monascus pigment and cyclo-phosphamide can produce some cytotoxicity compounds or accelerate intracellular cyclophosphamide accumulation. Hence, we concluded that the interaction of both cyclophosphamide and monascus pigment involved enhancement of cyclophosphamide cytotoxicity.

Intraoperative Fracture during the Insertion of Advanced Locking Screws (T2 Alpha Femur Retrograde Intramedullary Nailing System): Report of Two Cases and Identifying Causes and Prevention.

Background: Recently, the T2 alpha nailing system (Stryker, Inc.), which has advanced locking screws that can attach a screw to a rod, has been used worldwide and is expected to improve fracture fixation. We analyzed two cases of supracondylar femoral fractures in older adult patients, in which intraoperative fractures occurred during the insertion of advanced locking screws of the T2 alpha femur retrograde intramedullary nail. Case presentation: A 93-year-old and an 82-year-old woman each underwent T2 alpha femur retrograde nail fixation for supracondylar femur fractures at separate hospitals, and advanced locking screws were used as the proximal transverse locking screws. In both patients, a fracture line was observed at the proximal screw postoperatively, and the fractures were refixed with distal cable wiring and/or femoral distal plates. The patients were subsequently discharged from the same facility with no remarkable pain. Conclusions: When inserting advanced locking screws, it is necessary to enlarge the screw hole in the near-bone cortex with a counterbore drill, which might add torque to the bone cortex that could result in fractures. If the sleeve is distant from the bone, the counterbore drill will not reach the bone, the screw hole will not expand, and the insertion of advanced locking screws will apply a strong torque to the bone cortex and may result in fracture. Moreover, it is important to confirm that the counterbore drill is securely inserted under fluoroscopy and to carefully enlarge the bony foramen manually to prevent fractures during screw insertion.

Polphylipoprotein-induced autophagy mechanism with high performance in photodynamic therapy.

Polphylipoprotein (PLP) is a recently developed nanoparticle with high biocompatibility and tumor selectivity, and which has demonstrated unprecedentedly high performance photosensitizer in photodynamic therapy (PDT) and photodynamic diagnosis. On the basis of these discoveries, PLP is anticipated to have a very high potential for PDT. However, the mechanism by which PLP kills cancer cells effectively has not been sufficiently clarified. To comprehensively understand the PLP-induced PDT processes, we conduct multifaceted experiments using both normal cells and cancer cells originating from the same sources, namely, RGM1, a rat gastric epithelial cell line, and RGK1, a rat gastric mucosa-derived cancer-like mutant. We reveal that PLP enables highly effective cancer treatment through PDT by employing a unique mechanism that utilizes the process of autophagy. The dynamics of PLP-accumulated phagosomes immediately after light irradiation are found to be completely different between normal cells and cancer cells, and it becomes clear that this difference results in the manifestation of the characteristic effect of PDT when using PLP. Since PLP is originally developed as a drug delivery agent, this study also suggests the potential for intracellular drug delivery processes through PLP-induced autophagy.

Chondroprotective Effects of Chondrogenic Differentiated Adipose-Derived Mesenchymal Stem Cells Sheet on Degenerated Articular Cartilage in an Experimental Rabbit Model.

Adipose-derived stem cells (ADSCs) have been studied for many years as a therapeutic option for osteoarthritis (OA); however, their efficacy remains insufficient. Since platelet-rich plasma (PRP) induces chondrogenic differentiation in ADSCs and the formation of a sheet structure by ascorbic acid can increase the number of viable cells, we hypothesized that the injection of chondrogenic cell sheets combined with the effects of PRP and ascorbic acid may hinder the progression of OA. The effects of induction of differentiation by PRP and formation of sheet structure by ascorbic acid on changes in chondrocyte markers (collagen II, aggrecan, Sox9) in ADSCs were evaluated. Changes in mucopolysaccharide and VEGF-A secretion from cells injected intra-articularly in a rabbit OA model were also evaluated. ADSCs treated by PRP strongly chondrocyte markers, including type II collagen, Sox9, and aggrecan, and their gene expression was maintained even after sheet-like structure formation induced by ascorbic acid. In this rabbit OA model study, the inhibition of OA progression by intra-articular injection was improved by inducing chondrocyte differentiation with PRP and sheet structure formation with ascorbic acid in ADSCs.

Reliability and validity of OpenPose for measuring hip-knee-ankle angle in patients with knee osteoarthritis.

We aimed to assess the reliability and validity of OpenPose, a posture estimation algorithm, for measuring hip-knee-ankle (HKA) angle in patients with knee osteoarthritis, by comparing it with radiography. In this prospective study, we analysed 60 knees (30 patients) with knee osteoarthritis. We measured HKA angle using OpenPose and radiography before or after total knee arthroplasty and assessed the test-retest reliability of each method with intraclass correlation coefficient (1, 1). We evaluated the ability to estimate the radiographic measurement values from the OpenPose values using linear regression analysis and used intraclass correlation coefficients (2, 1) and Bland-Altman analyses to evaluate the agreement and error between OpenPose and radiographic measurements. OpenPose had excellent test-retest reliability (intraclass correlation coefficient (1, 1) = 1.000) and excellent agreement with radiography (intraclass correlation coefficient (2, 1) = 0.915), with regression analysis indicating a large correlation (R2 = 0.865). OpenPose also had a 1.1° fixed error and no systematic error when compared with radiography. This is the first study to validate the use of OpenPose for the estimation of HKA angle in patients with knee osteoarthritis. OpenPose is a reliable and valid tool for measuring HKA angle in patients with knee osteoarthritis. OpenPose, which enables non-invasive and simple measurements, may be a useful tool to assess changes in HKA angle and monitor the progression and post-operative course of knee osteoarthritis. Furthermore, this validated tool can be used not only in clinics and hospitals, but also at home and in training gyms; thus, its use could potentially be expanded to include self-assessment/monitoring.

Combined adipose-derived mesenchymal stem cell and antibiotic therapy can effectively treat periprosthetic joint infection in rats.

Periprosthetic joint infection (PJI) is characterized by biofilm infection, which is difficult to alleviate while preserving implant integrity. Furthermore, long-term antibiotic therapy may increase the prevalence of drug-resistant bacterial strains, necessitating a non-antibacterial approach. Adipose-derived stem cells (ADSCs) exert antibacterial effects; however, their efficacy in PJI remains unclear. This study investigates the efficacy of combined intravenous ADSCs and antibiotic therapy in comparison to antibiotic monotherapy in a methicillin-sensitive Staphylococcus aureus (MSSA)-infected PJI rat model. The rats were randomly assigned and equally divided into 3 groups: no-treatment group, antibiotic group, ADSCs with antibiotic group. The ADSCs with antibiotic group exhibited the fastest recovery from weight loss, with lower bacterial counts (p = 0.013 vs. no-treatment group; p = 0.024 vs. antibiotic group) and less bone density loss around the implants (p = 0.015 vs. no-treatment group; p = 0.025 vs. antibiotic group). The modified Rissing score was used to evaluate localized infection on postoperative day 14 and was the lowest in the ADSCs with antibiotic group; however, no significant difference was observed between the antibiotic group and ADSCs with antibiotic group (p < 0.001 vs. no-treatment group; p = 0.359 vs. antibiotic group). Histological analysis revealed a clear, thin, and continuous bony envelope, a homogeneous bone marrow, and a defined, normal interface in the ADSCs with antibiotic group. Moreover, the expression of cathelicidin expression was significantly higher (p = 0.002 vs. no-treatment group; p = 0.049 vs. antibiotic group), whereas that of tumor necrosis factor (TNF)-α and interleukin(IL)-6 was lower in the ADSCs with antibiotic group than in the no-treatment group (TNF-α, p = 0.010 vs. no-treatment group; IL-6, p = 0.010 vs. no-treatment group). Thus, the combined intravenous ADSCs and antibiotic therapy induced a stronger antibacterial effect than antibiotic monotherapy in a MSSA-infected PJI rat model. This strong antibacterial effect may be related to the increased cathelicidin expression and decreased inflammatory cytokine expression at the site of infection.

Force measurement enabling precise analysis by dynamic force spectroscopy.

Dynamic force spectroscopy (DFS) makes it possible to investigate specific interactions between two molecules such as ligand-receptor pairs at the single-molecule level. In the DFS method based on the Bell-Evans model, the unbinding force applied to a molecular bond is increased at a constant rate, and the force required to rupture the molecular bond is measured. By analyzing the relationship between the modal rupture force and the logarithm of the loading rate, microscopic potential barrier landscapes and the lifetimes of bonds can be obtained. However, the results obtained, for example, in the case of streptavidin/biotin complexes, have differed among previous studies and some results have been inconsistent with theoretical predictions. In this study, using an atomic force microscopy technique that enables the precise analysis of molecular interactions on the basis of DFS, we investigated the effect of the sampling rate on DFS analysis. The shape of rupture force histograms, for example, was significantly deformed at a sampling rate of 1 kHz in comparison with that of histograms obtained at 100 kHz, indicating the fundamental importance of ensuring suitable experimental conditions for further advances in the DFS method.

Direct analysis of the actin-filament formation effect in photodynamic therapy.

Photodynamic therapy (PDT) is a method in which a photosensitizer is administered in vivo and irradiated with light to generate reactive oxygen species (ROS), thereby causing the selective death of cancer cells. Since PDT is a noninvasive cancer treatment method with few adverse effects, it has attracted considerable attention and is increasingly used. In PDT, there are two dominant processes based on the actin filament (A-filament) formation effect: the destruction of cells by necrosis and vascular shutdown. Despite the importance of its fine control, the mechanism of the reaction process from the generation of reactive oxygen by photoinduction inducing the formation of A-filament and its polymerization to form stress fibers (S-fibers) has not yet been clarified because, for example, it has been difficult to directly observe and quantify such processes in living cells by conventional methods. Here, we have combined atomic force microscopy (AFM) with other techniques to reveal the mechanism of the A-filament and S-fiber formation processes that underlie the cell death process due to PDT. First, it was confirmed that activation of the small G protein RhoA, which is a signal that induces an increase in A-filament production, begins immediately after PDT treatment. The production of A-filament did not increase with increasing light intensity when the amount of light was large. Namely, the activation of RhoA reached an equilibrium state in about 1 min: however, the production of A-filament and its polymerization continued. The observed process corresponds well with the change in the amount of phosphorylated myosin-light chains, which induce A-filament polymerization. The increase in the elastic modulus of cells following the formation of S-fiber was confirmed by AFM for the first time. The distribution of generated A-filament and S-fiber was consistent with the photosensitizer distribution. PDT increases A-filament production, and when the ROS concentration is high, blebbing occurs and cells die, but when it is low, cell death does not occur and S-fiber is formed. That is, it is expected that vascular shutdown can be controlled efficiently by adjusting the amount of photosensitizer and the light intensity.

Potential of Gold Nanoparticles for Noninvasive Imaging and Therapy for Vascular Inflammation.

PURPOSE: Macrophages contribute to the progression of vascular inflammation, making them useful targets for imaging and treatment of vascular diseases. Gold nanoparticles (GNPs) are useful as computed tomography (CT) contrast agents and light absorbers in photothermal therapy. In this study, we aimed to assess the viability of macrophages incubated with GNPs after near-infrared (NIR) laser light exposure and to evaluate the utility of intravenously injected GNPs for in vivo imaging of vascular inflammation in mice using micro-CT. PROCEDURES: Mouse macrophage cells (RAW 264.7) were incubated with GNPs and assessed for GNP cellular uptake and cell viability before and after exposure to NIR laser light. For in vivo imaging, macrophage-rich atherosclerotic lesions were induced by carotid ligation in hyperlipidemic and diabetic FVB mice (n = 9). Abdominal aortic aneurysms (AAAs) were created by angiotensin II infusion in ApoE-deficient mice (n = 9). These mice were scanned with a micro-CT imaging system before and after the intravenous injection of GNPs. RESULTS: The CT attenuation values of macrophages incubated with GNPs were significantly higher than those of cells incubated without GNPs (p < 0.04). Macrophages incubated with and without GNPs showed similar viability. The viability of macrophages incubated with GNPs (100 µg/ml or 200 µg/ml) was decreased by high-intensity NIR laser exposure but not by low-intensity NIR laser exposure. In vivo CT images showed higher CT attenuation values in diseased carotid arteries than in non-diseased contralateral arteries, although the difference was not statistically significant. The CT attenuation values of the perivascular area in AAAs of mice injected with GNPs were significantly higher than those of mice without injection (p = 0.0001). CONCLUSIONS: Macrophages with GNPs had reduced viability upon NIR laser exposure. GNPs intravenously injected into mice accumulated in sites of vascular inflammation, allowing detection of carotid atherosclerosis and AAAs in CT imaging. Thus, GNPs have potential as multifunctional biologically compatible particles for the detection and therapy of vascular inflammation.

Dabigatran Etexilate Induces Cytotoxicity in Rat Gastric Epithelial Cell Line via Mitochondrial Reactive Oxygen Species Production.

Dabigatran is a novel oral anticoagulant that directly inhibits free and fibrin-bound thrombins and exerts rapid and predictable anticoagulant effects. While the use of this reagent has been associated with an increased risk of gastrointestinal bleeding, the reason why dabigatran use increases gastrointestinal bleeding risk remains unknown. We investigated the cytotoxicity of dabigatran etexilate and tartaric acid, the two primary components of dabigatran. The cytotoxicity of dabigatran etexilate and tartaric acid was measured in a cell viability assay. Intracellular mitochondrial reactive oxygen species (mitROS) production and lipid peroxidation were measured using fluorescence dyes. Cell membrane viscosity was measured using atomic force microscopy. The potential of ascorbic acid as an inhibitor of dabigatran cytotoxicity was also evaluated. The cytotoxicity of dabigatran etexilate was higher than that of tartaric acid. Dabigatran etexilate induced mitROS production and lipid peroxidation and altered the cell membrane viscosity. Ascorbic acid inhibited the cytotoxicity and mitROS production induced by dabigatran etexilate. Therefore, we attributed the cytotoxicity of dabigatran to dabigatran etexilate, and proposed that the cytotoxic effects of dabigatran etexilate are mediated via mitROS production. Additionally, we demonstrated that dabigatran cytotoxicity can be prevented via antioxidant treatment.

Correlation between lag screw route and the ideal insertion point of the intramedullary nail.

Understanding the morphology of the superior aspect of the proximal femur is critical for treating femoral fracture. We assessed the correlation among the ideal insertion point of the femoral nail, femur head-neck axis, and native anteversion. One hundred patients with normal femurs were included in this study. Computed tomography (CT) images of the proximal femur superior aspect and amount of native anteversion were acquired. Generalised Procrustes analysis showed the morphological characteristics of the superior proximal femur according to native anteversion amount. Morphological characteristics were represented by 4 parameters; the correlation between parameters and native anteversion was investigated using CT data. The passing point of the line from the proximal femoral canal parallel to the native anteversion at the greater trochanter was located more posteriorly (mean 35.6%); the passing point of native anteversion was posterior in the femoral neck and head, although the line of the head-neck centre passed more anteriorly at the greater trochanter (mean 67.5%). This posterior translation was significantly associated with native anteversion amount. Morphometric geometric analysis showed that the lag screw could not pass head-neck centre from the nail inserted into proximal femoral canal. Anterior insertion of the nail was needed for positioning the lag screw centre.

Change in leg length after open-wedge high tibial osteotomy can be predicted from the opening width: A three-dimensional analysis.

BACKGROUND: The purpose of this study was to evaluate true change in leg length after open-wedge high tibial osteotomy (OWHTO) using three-dimensional (3D) assessments, examine the factors that influence leg lengthening and verify their validity in clinical practice. METHODS: Study 1: a retrospective case series simulation study, included 46 patients (55 knees) that underwent knee arthroplasty or HTO. OWHTO was simulated from preoperative computed tomography using 3D preoperative planning software. Uni- and multivariate regression analyses were conducted to identify predictors related to change in leg length. Study 2: a retrospective case series study, included 53 patients (55 knees) that underwent OWHTO in another institution. Change in leg length was measured preoperatively and 1 year postoperatively and was compared with the predicted change in leg length calculated using the formula obtained from Study 1. RESULTS: Study 1: the true change in leg length significantly increased and showed a strong correlation with the opening width. The change in leg length was predicted using the formula "change in leg length = opening width × 0.75-1.5." Study 2: the predicted change in leg length showed no significant difference from the change in leg length 1 year postoperatively and a strong correlation with the measured change. CONCLUSIONS: The true change in leg length after OWHTO was predicted using the formula obtained from the 3D model. Predicting the change in leg length preoperatively can be a basis to consider other HTOs.

Hidden variety of biotin-streptavidin/avidin local interactions revealed by site-selective dynamic force spectroscopy.

By site-selective dynamic force spectroscopy realized with the combination of cross-linkers and anatomic force microscope with a force feedback system, we have revealed, for the first time, that the slight difference between the local structures of amino acid residues at the middle sites, SER45 and THR35 for streptavidin and avidin, respectively, strongly affects the microscopic reaction processes, i.e., the variation governs the type of bond as well as the fine structure of the potential landscape. For streptavidin, a bridged or direct hydrogen bond is induced depending on the molecular structure in the buffer solution. For avidin, in contrast, only a direct hydrogen bond is observed for all the buffer solutions used in the experiment. Since final functions in a system are realized through the assembly of local effects, the obtained results indicate the importance of analyzing the reaction processes with respect to the local structures of molecules, for further development of nanoscale functional devices.