Near-infrared-II fluorescence/magnetic resonance double modal imaging of transplanted stem cells using lanthanide co-doped gadolinium oxide nanoparticles.

To ensure maximum therapeutic safety and efficacy of stem cell transplantation, it is essential to observe the kinetics of behavior, accumulation, and engraftment of transplanted stem cells in vivo. However, it is difficult to detect transplanted stem cells with high sensitivity by conventional in vivo imaging technologies. To diagnose the kinetics of transplanted stem cells, we prepared multifunctional nanoparticles, Gd2O3 co-doped with Er3+ and Yb3+ (Gd2O3: Er, Yb-NPs), and developed an in vivo double modal imaging technique with near-infrared-II (NIR-II) fluorescence imaging and magnetic resonance imaging (MRI) of stem cells using Gd2O3: Er, Yb-NPs. Gd2O3: Er, Yb-NPs were transduced into adipose tissue-derived stem cells (ASCs) through a simple incubation process without cytotoxicity under certain concentrations of Gd2O3: Er, Yb-NPs and were found not to affect the morphology of ASCs. ASCs labeled with Gd2O3: Er, Yb-NPs were transplanted subcutaneously onto the backs of mice, and successfully imaged with good contrast using an in vivo NIR-II fluorescence imaging and MRI system. These data suggest that Gd2O3: Er, Yb-NPs may be useful for in vivo double modal imaging with NIR-II fluorescence imaging and MRI of transplanted stem cells.

Thrombotic microangiopathy in a patient with anti-signal recognition particle antibody-positive immune-mediated necrotizing myopathy.

We describe the case of a 61-year-old woman with anti-signal recognition particle (SRP) antibody-positive immune-mediated necrotizing myopathy (IMNM) who exhibited biopsy-confirmed thrombotic microangiopathy (TMA). The patient developed proximal-dominant muscle weakness and was diagnosed with anti-SRP antibody-positive IMNM based on muscle biopsy results and serological examination. A high-dose corticosteroid prescription was initiated, followed by intravenous methylprednisolone and intravenous immunoglobulin therapy (IVIg). The patient showed IVIg-induced hemolytic anemia with preserved ADAMTS13 activity. Transient oral tacrolimus administration was initiated. Approximately 8 weeks after admission, the serum creatinine levels gradually increased. Renal histological examination revealed TMA, including ischemic changes in the renal tubules, stenosis, and occlusion of the interlobular arteries with fibrinoid necrosis of the afferent arteriolar walls. The arteriolar walls demonstrated an accumulation of C1q and C3c. Myofiber damage in patients with IMNM accounts for the activation of the classical pathway of the complement cascade in the sarcolemma due to antibody deposition. Additionally, a membrane attack complex is observed on capillaries in the muscle tissues of patients with anti-SRP antibody-positive IMNM. Although drug-induced pathomechanisms, such as IVIg and tacrolimus, can trigger the development of TMA, we suggest that the presence of serum anti-SRP antibodies would be implicated in complement-associated kidney vascular damage.

Partial penectomy for severe penile ulceration caused by cholesterol crystal embolization.

Introduction: Cholesterol crystal embolism is a rare microembolic disease caused by cholesterol crystals that can present with various symptoms after vascular surgery, catheterization, or anticoagulation therapy. We report a case of penile ulceration caused by cholesterol crystal embolism. Case presentation: A 72-year-old man undergoing maintenance dialysis for end-stage renal failure presented with penile pain and a black glans ulcer. Despite low-density lipoprotein apheresis, he was referred to our hospital because of lack of improvement. Based on his medical history and clinical presentation, including artificial vascular replacement and right toe amputation, cholesterol crystal embolism was suspected and partial penectomy was performed, thus confirming the diagnosis. Penile pain resolved after surgery, and he was discharged on Day 10. Unfortunately, he died after small bowel perforation developed 2 months after surgery. Conclusion: Penile ulcers caused by cholesterol crystal embolism may indicate the severity and progression of disease and typically require surgical intervention.

In Vivo Real-Time Quantum Dots Imaging to Track Transplanted Adipose Stem Cells in Different Inflammatory States of Acute Liver Failure Mice.

Stem cell therapy plays an important role in regenerative therapy; however, there is little information on the in vivo dynamics of transplanted stem cells and the influence of the inflammation of affected tissues or organs on these dynamics. In this study, we revealed real-time dynamics of transplanted adipose tissue-derived stem cells (ASCs) and the influence of the inflammatory states on these dynamics in acute liver failure mice. Quantum dots (QDs) labeling did not affect the cytokine profile of ASCs, and intravenously transplanted ASCs labeled with QDs could be detected in real time with high efficiency without laparotomy. Until 30 min after ASC transplantation, no marked differences in the behavior or accumulation of transplanted ASCs in the liver were observed among the three groups with different degrees of liver damage (normal, weak, and strong). However, significant differences in the engraftment rate of transplanted ASCs in the liver were observed among the three groups from 4 h after transplantation. The engraftment rate was inversely correlated with the extent of the liver damage. These data suggested that QDs are useful for in vivo real-time imaging of transplanted cells, and the inflammatory state of tissues or organs may affect the engraftment rate of transplanted cells.

In Vivo Multimodal Imaging of Stem Cells Using Nanohybrid Particles Incorporating Quantum Dots and Magnetic Nanoparticles.

The diagnosis of the dynamics, accumulation, and engraftment of transplanted stem cells in vivo is essential for ensuring the safety and the maximum therapeutic effect of regenerative medicine. However, in vivo imaging technologies for detecting transplanted stem cells are not sufficient at present. We developed nanohybrid particles composed of dendron-baring lipids having two unsaturated bonds (DLU2) molecules, quantum dots (QDs), and magnetic nanoparticles in order to diagnose the dynamics, accumulation, and engraftment of transplanted stem cells, and then addressed the labeling and in vivo fluorescence and magnetic resonance (MR) imaging of stem cells using the nanohybrid particles (DLU2-NPs). Five kinds of DLU2-NPs (DLU2-NPs-1-5) composed of different concentrations of DLU2 molecules, QDs525, QDs605, QDs705, and ATDM were prepared. Adipose tissue-derived stem cells (ASCs) were labeled with DLU2-NPs for 4 h incubation, no cytotoxicity or marked effect on the proliferation ability was observed in ASCs labeled with DLU2-NPs (640- or 320-fold diluted). ASCs labeled with DLU2-NPs (640-fold diluted) were transplanted subcutaneously onto the backs of mice, and the labeled ASCs could be imaged with good contrast using in vivo fluorescence and an MR imaging system. DLU2-NPs may be useful for in vivo multimodal imaging of transplanted stem cells.

Surface modification of hydroxyapatite nanoparticles for bone regeneration by controlling their surface hydration and protein adsorption states.

Autogenous bone and metallic implant grafting has been used to repair and regenerate bone defects. However, there are still many unresolved problems. It is suggested that bioceramic nanoparticles should be developed and designed to promote effective bone regeneration. In addition, it is necessary to synthesize bioceramic nanoparticles that can support proteins related to bone repair and regeneration such as collagen and albumin. As the protein-interactive bioceramic, hydroxyapatite (HA) deserves to be mentioned and has several attractive properties that are useful in biomedical fields (e.g., biocompatibility, protein adsorption capacity and stability in the physiological environment). In order to prepare novel HA nanoparticles with high biocompatibility, it can be considered that human bones are mainly composed of HA and contain a small amount of silicate, and therefore, the design of coexistence of HA with silicate can be focused. Moreover, it is proposed that the state of the hydration layer on the nanoparticle surfaces can be controlled by introducing heteroelements and polymer chains, which have a great influence on the subsequent protein adsorption and cell adhesion. In this perspective, in order to develop novel bioceramic nanoparticles for the treatment of bone defect, the design of highly biocompatible HA nanoparticles and the control of the hydration layer and protein adsorption states on the surfaces were systematically discussed based on their surface modification techniques, which are very important for the proper understanding of the interface between cells and bioceramics, leading to the further application in biomedical fields.

Investigation of Inclusion States of Silicate and Carbonate Ions in Hydroxyapatite Particles Prepared under the Presence of Sodium Silicate.

Biological hydroxyapatite (HA) contains the different minor ions which favour its bio-reactivity in vivo. In this study, the preparation of HA particles containing both silicate and carbonate ions under the presence of sodium silicate was investigated, and the physicochemical properties were evaluated according to the contents and states of silicate and carbonate ions. The increment in the silicate ion reduced the crystallinity and expanded the crystalline size along with a-axis. Solid-state 29Si-NMR spectra indicated the increase in the adsorption of oligomeric silicate species on the HA particle surfaces in addition to the substitution state of silicate ions, suggesting the occurrence of the surface coating of silicates on the surfaces. The possible states of carbonate and silicate ions at the HA surfaces will provide the bioactivity.

A Randomized Controlled Trial for the Intervention Effect of Early Exercise Therapy on Axial Pain after Cervical Laminoplasty.

Introduction: Cervical isometric muscle strengthening and cervical range of motion (ROM) training are recommended after laminoplasty (LP). However, their preventive effects on axial pain are unclear. We examined whether neck extension muscle strengthening and cervical ROM training from the early postoperative period effectively suppress postoperative axial pain. Methods: Sixty-one patients undergoing a muscle-preserving LP attached to C2 and C7 for cervical spondylotic myelopathy or ossification of the posterior longitudinal ligament were randomly allocated to the cervical exercise (33 patients) or nonexercize (28 patients) groups. Postoperative cervical collars were not worn in any cases. The cervical exercise group underwent neck extension isometric muscle strengthening and cervical ROM exercises for 3 months starting on postoperative day 2. Changes in axial pain (visual analog scale [VAS]) from baseline at 2 weeks and 3 months after surgery were evaluated as the primary outcome. Cervical muscle strength, cervical ROM, and Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) scores were evaluated as secondary outcomes. Results: Axial pain was significantly exacerbated at 2 weeks after LP compared with before surgery, and then, a significant improvement was observed at 3 months after surgery. No significant interaction was observed between the intervention and nonintervention groups. There was no difference in secondary outcomes between groups. The change in the VAS of axial pain from before surgery to 3 months after surgery showed a greater decreased neck extension muscle strength resulting in severer axial pain. Conclusions: Cervical muscle strengthening and cervical ROM exercise from the early postoperative period did not relieve axial pain at 2 weeks and 3 months after a muscle-preserving LP attached to C2 and C7. No significant difference in neck extension muscle and cervical movement was observed between the intervention and nonintervention groups. Therefore, a muscle-preserving LP attached to C2 and C7 is a good strategy to prevent axial pain in the early postoperative period.Clinical Trials Registration Number: UMIN000040692.

PEG functionalization effect of silicate-containing hydroxyapatite particles on effective collagen fibrillation with hydration layer state change.

Silicate-containing hydroxyapatite (SiHA) particles were synthesized and functionalized with polyethylene glycol-silane (PEG-silane) for clarifying the effect of the bioceramic surface hydration layer states on the collagen (Col) fibrillation degree. Plate-like SiHA particles were obtained containing the SiO44- ion inside and/or outside the particles. PEG-silane was successfully functionalized on SiHA particles, and the hydration layer and Col adlayer states on the particles were precisely investigated for exemplifying the importance of the water molecular states at the interface. The ratio of free to intermediate water in the hydration layers of the particles decreased when containing silicate components, and it significantly increased with increasing PEG-silane molecular occupancy, where the asymmetric stretching vibration component ratio in the free water clearly increased. In a quartz crystal microbalance with dissipation (QCM-D) measurement, the frequency change (Δf) and the energy dissipation change (ΔD) values increased with Col adsorption on the particles for 32-34 min and then Δf slightly increased (or stopped increasing) and ΔD dramatically increased, indicating the effective water mobility and state changes with the Col fibrillation at the interface. The Col fibrillation degree evaluated by tan δ and the protein secondary structure of the adlayers clearly increased due to the PEG-silane functionalization, and the tendency was supported by the increase in the fibril density under SEM observation. Surprisingly, it was found that the fibrillation degree based on the protein secondary structure was significantly correlated with the asymmetric stretching vibration component ratio in the free water molecules of the hydration layer on the particles, suggesting the importance of the hydration layer states on bioceramics for controlling Col fibrillation.

Can Hip-Knee Line Angle Distinguish the Size of Pelvic Incidence?-Development of Quick Noninvasive Assessment Tool for Pelvic Incidence Classification.

This study aimed to explore effective measurement angles for pelvic incidence (PI) classification and to develop a quick, noninvasive assessment tool for PI classification. We defined five variation types of hip-knee line (HKL) angles and tested the discrimination ability of the receiver operating characteristic (ROC) analysis using 125 photographs of upright standing posture from the right lateral side. ROC analysis revealed an applicable HKL angle defined by the line connecting the most raised part of the buttock and the central point of the knee and the midthigh line. The acceptable cut-off points for discriminating small or large PIs in terms of HKL angle were 18.5° for small PI (sensitivity, 0.91; specificity, 0.79) and 21.5° for large PI discrimination (sensitivity, 0.74; specificity, 0.72). In addition, we devised a quick noninvasive assessment tool for PI classification using the cut-offs of the HKL angle with a view to practical application. The results of intra- and inter-rater reliability ensured a substantial/moderate level of the tool (Cohen's kappa coefficient, 0.79; Fleiss's kappa coefficient, 0.50-0.54). These results revealed that the HKL angle can distinguish the size of the PI with a high/moderate discrimination ability. Furthermore, the tool indicated acceptable inter-/intra-rater reliability for practical applications.

Expression and cell transformation activity of dynactin-associated protein isoforms.

Overexpression of human dynactin-associated protein isoform a (dynAPa) transforms NIH3T3 cells. DynAPa is a single-pass transmembrane protein with a carboxy-terminal region exposed to the outside of cells. According to the NCBI RefSeq database, there may be two other splicing variants of the encoding gene (dynAPb and c). DynAPa and c differ in some amino-terminal residues (NH2 -MVA in dynAPa and NH2 -MEYQLL in dynAPc). DynAPb has the same amino-terminal residues as dynAPc, but lacks 55 residues in the intracellular region. All three isoforms have the same carboxy-terminal region, including the transmembrane domain. Expression of mRNAs of three splicing variants was found in human cancer cell lines ACHN and Caki-1. The subcellular localization and in vitro cell transformation ability of the three isoforms were examined using NIH3T3 cells overexpressing each respective isoform. All isoforms were found to be localized to the Golgi apparatus and plasma membrane, where the carboxy-terminal region was exposed to the outside of cells. Cell transformation was tested using focus formation due to loss of contact inhibition of cell proliferation, and colony formation was examined on soft agar and spheroid formation in ultralow U-bottomed wells. DynAPa robustly formed foci and colonies on soft agar and spheroid, whereas these abilities were considerably decreased for dynAPb and completely lost in dynAPc. These findings warrant dissection studies to identify the dynAP domain that is required for cell transformation.

Control of the hydration layer states on phosphorus-containing mesoporous silica films and their reactivity evaluation with biological fluids.

Transparent phosphorus-containing MPS (PMPS) films were synthesized by the introduction and reaction of phosphoric acid into the silica framework during the sol-gel reaction. We then investigated the hydration layer structures formed on the PMPS films and achieved the selective adsorption of fibronectin (Fn). In particular, the surface analyses indicated that the P atom was distributed at the outermost surfaces of the PMPS films. The PMPS films exhibited a high transparency (e.g., averaged transmittance value in the visible light region: 79%), and the haze value (0.14%) decreased with the increasing P/Si molar concentration. Solid-state 29Si-NMR and Fourier transform infrared spectroscopy (FT-IR) spectra indicated the formation of Si-O-P bonds, suggesting that the condensation reaction between the Si-O- and P-O- groups effectively occurs in the silica framework. The larger amount of P-O- and P[double bond, length as m-dash]O groups at the Si-O-P bonding site on the films affects the water molecular adsorption states (i.e., formation of the hydration layer), which was supported by the Brunauer-Emmett-Teller (BET) surface areas of N2 and water vapor, leading to enhancement of the hydrogen bondability of the PMPS films with the increased formation of Si-O-P bonds. The deconvolution results of the FT-IR spectra demonstrated that the ratio of free water to bonding water increased significantly with an increase in the formation of Si-O-P bonding, and the resulting O-H stretching vibration in the hydration layer became more asymmetric. It is suggested that the water molecules are irregularly hydrogen-bonded with the different functional groups of Si-O-, P-O- and P[double bond, length as m-dash]O. In the immersion experiment of the PMPS films in phosphate buffer, the resultant P/Si molar concentration of the PMPS film decreased upon increasing the immersion time and the mesostructures were preserved. The amount of Fn adsorption significantly increased as the O-H stretching vibration of the water molecules became more asymmetric, whereas the adsorption of fibrinogen was completely suppressed by the films. Therefore, we found that the addition of phosphoric acid in the MPS film synthesis significantly affects the hydration layer structures on the film surfaces to provide the possibility of selective protein adsorption.

Can self-monitoring mobile health apps reduce sedentary behavior? A randomized controlled trial.

OBJECTIVE: To examine whether the self-monitoring interventions of a mobile health app reduce sedentary behavior in the short and long terms. METHOD: We designed a double-blind randomized control trial. Participants were selected from among the staff of a medical institution and registrants of an online research firm. Forty-nine participants were randomly assigned to either a control group (n = 25) or an intervention group (n = 24). The control group was given only the latest information about sedentary behavior, and the intervention was provided real-time feedback for self-monitoring in addition to the information. These interventions provided for 5 weeks (to measure the short-term effect) and 13 weeks (to measure the long-term effect) via the smartphone app. Measurements were as follows: subjective total sedentary time (SST), objective total sedentary time (OST), mean sedentary bout duration (MSB), and the number of sedentary breaks (SB). Only SST was measured by self-report based on the standardized International Physical Activity Questionnaire and others were measured with the smartphone. RESULTS: No significant results were observed in the short term. In the long term, while no significant results were also observed in objective sedentary behavior (OST, MSB, SB), the significant differences were observed in subjective sedentary behavior (SST, ßint  - ßctrl between baseline and 9/13 weeks; 1.73 and 1.50 h/d, respectively). CONCLUSIONS: Real-time feedback for self-monitoring with smartphone did not significantly affect objective sedentary behavior. However, providing only information about sedentary behavior to users with smartphones may make misperception on the amount of their subjective sedentary behavior.

Effects of physical therapy on blood pressure in daily clinical practice-a pilot study.

[Purpose] Most exercise therapy procedures induce hemodynamic changes and could be a cardiovascular risk. This pilot study investigated factors that induce an exaggerated increase in blood pressure during exercise therapy. [Participants and Methods] We measured the blood pressure and pulse rate before and after exercise therapy for ambulation on days 1, 2, and 7 of the exercise therapy in patients (n=23; age, 69 ± 11 years) who were hospitalized for a stroke or an orthopedic surgery. [Results] Each participant's blood pressure and pulse rate were significantly increased after the exercise therapy. Regression analysis demonstrated that the increase in systolic blood pressure was independently predicted by body weight and pulse rate before the exercise therapy. In the logistic regression analysis, age and body weight were independent predictors of the exaggerated increase in systolic blood pressure (fourth quartile). [Conclusion] A significant increase in blood pressure was induced by exercise therapy. There was a correlation between systolic blood pressure increase and pulse rate before the exercise therapy. Old age or increased body weight predicts exaggerated increase in blood pressure during exercise therapy.

[Good's syndrome developing hemophagocytic lymphohistiocytosis following thymectomy].

This report presents the case of a 68-year-old female patient previously diagnosed with thymoma by her local doctor. She was referred to our hospital for surgery, and the thymoma was removed and diagnosed as a World Health Organization (WHO) classification type AB thymoma. After surgery, she experienced general malaise, a loss of appetite, and weight loss, so she visited our hospital in May 2019. A blood test showed hypogammaglobulinemia and low B lymphocytes. A bone marrow examination revealed no morphological abnormalities. Flow cytometric analysis indicated a marked decrease in both the B cell-related surface markers CD19 and CD20 and the T cell-related surface marker CD4, and the CD4/CD8 ratio was also low. She was diagnosed with Good's syndrome, and immunoglobulin replacement therapy was administered. She subsequently developed hemophagocytic lymphohistiocytosis (HLH) due to infection and was treated according to the HLH2004 protocol, but she finally succumbed to multiple organ damage as a result of sepsis. Given that Good's syndrome is associated with both humoral and cellular immune dysfunctions, affected patients tend to develop severe infections and have a poor prognosis. In such cases, early detection, regular immunoglobulin replacement therapy, and infection prevention therapies are important.

Synthesis of nanostructured silica/hydroxyapatite hybrid particles containing amphiphilic triblock copolymer for effectively controlling hydration layer structures with cytocompatibility.

We synthesized nanostructured mesoporous silica (MS)/hydroxyapatite (HA) hybrid particles in the presence of amphiphilic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO20PPO70PEO20) triblock copolymer (P123). The particles exhibited slit-shaped mesostructures and underwent hybridization reaction between the MS and HA phases containing P123. Furthermore, the aggregated form of the particles exhibited dispersion stability in water in the monodispersed state (average particle size: 145 nm and coefficient of variation: 4.3% in the case of the maximum added amount of P123). Then, the structures of the hydration layer and the adsorbed protein on the particles were investigated to understand the effect of the hydration layer structures on the protein secondary structures. The ratio of the bonding water (intermediate and nonfreezing water) to free water increased upon hybridization, and it decreased with increasing P123 concentration. Upon hybridization, the component ratio of the asymmetric O-H stretching vibration between free water molecules decreased, and that of the symmetric O-H stretching vibration of intermediate water molecules increased. With increasing P123 concentration, the asymmetric O-H stretching vibration between free water molecules increased and the symmetric O-H stretching vibration of intermediate water molecules decreased. It was found that the protein native state component ratios of α-helix and ß-sheet increased with increasing symmetric O-H stretching vibration between intermediate water molecules, and they decreased with decreasing asymmetric O-H stretching vibration between free water molecules. Moreover, the cytotoxicity against osteoblasts (MC3T3-E1) was evaluated and the hybrid particles exhibited a high cell density, indicating their bioactivity. On the hybrid particles interacting with P123, the cells were three-dimensionally assembled and uniaxially grown with the culture. Therefore, this is the first successful report of the synthesis of nanostructured MS/HA hybrid particles interacting with P123, and the controlled hydration layer structures on the particle surfaces were found to contribute to the protein secondary structures, promoting cytocompatibility.

Identifying characteristics of indicators of sedentary behavior using objective measurements.

OBJECTIVE: Recent attention has been focused on sedentary behavior (SB) affecting health outcomes, but the characteristics of indicators reflecting SB remain to be identified. This cross-sectional study aims to identify the characteristics of indicators of SB, focusing on the examination of correlations, reliability, and validity of sedentary variables assessed by the smartphone app. METHOD: Objectively measured data of SB of eligible 46 Japanese workers obtained from smartphones were used. We assessed the characteristics of current indicators being used with a 10-minute or 30-minute thresholds, in addition to the conventional indicators of total sedentary time, mean sedentary bout duration, and total number of sedentary bouts. They were evaluated from three perspectives: (a) association among the indicators, (b) reliability of the indicators, and (c) criterion validity. RESULTS: Total sedentary time under 10 minutes (U10) and U30 had negative associations with Total sedentary time (r = -.47 and -.21 respectively). The correlation between Mean sedentary bout duration and Total number of sedentary bouts was -.84, whereas between Mean sedentary bout duration 10, 30 and Total number of sedentary bouts were -.54 and -.21, respectively. The intraclass correlation coefficients of almost all indicators were around .80. Mean sedentary bout duration, Mean sedentary bout duration 10, Total number of sedentary bouts, Total sedentary time 30, U30 and U10 have significant differences between three BMI groups. CONCLUSION: This study comprehensively revealed the rationale of advantage in the current indicator being used with a 10-minute or 30-minute threshold, rather than the conventional total amount of SB.

Full-color computer-generated hologram using wavelet transform and color space conversion.

In this study, we presented the acceleration of full-color computer-generated holograms (CGHs) bi using WAvelet ShrinkAge-Based superpositIon (WASABI). The WASABI method uses a wavelet transform. Furthermore, the light wave superposition is calculated by using 3%, 5%, and 10% of the light wave components in wavelet space. The WASABI method is implemented for generating full-color CGHs and is used to further combine the color space conversion from the RGB color space to the YCbCr color space. We report that the WASABI method is 10-33 times faster than the conventional look-up table method and 2-7 times faster than the depth layer method based on fast Fourier transform. Further, the WASABI method in the YCbCr color space is approximately 1.5 times faster than that in the RGB color space.