Blending to Make Nonhealable Polymers Healable: Nanophase Separation Observed by CP/MAS 13 C NMR Analysis.

Can commodity polymers are made to be healable just by blending with self-healable polymers? Here we report the first study on the fundamental aspect of this practically challenging issue. Poly(ether thiourea) (PTUEG3 ; Tg =27 °C) reported in 2018 is extraordinary in that it is mechanically robust but can self-heal even at 12 °C. In contrast, poly(octamethylene thiourea) (PTUC8 ; Tg =50 °C), an analogue of PTUEG3 , cannot heal below 92 °C. We found that their polymer blend self-healed in a temperature range above 32 °C even when its PTUEG3 content was only 20 mol %. Unlike PTUEG3 alone, this polymer blend, upon exposure to high humidity, barely plasticized, keeping its excellent mechanical properties due to the non-hygroscopic nature of the PTUC8 component. CP/MAS 13 C NMR analysis revealed that the polymer blend was nanophase-separated, which possibly accounts for why such a small amount of PTUEG3 provided the polymer blend with humidity-tolerant self-healable properties.

Supramolecular Polymerization in Liquid Crystalline Media: Toward Modular Synthesis of Multifunctional Core-Shell Columnar Liquid Crystals.

Recently, we discovered a modular synthetic approach for constructing core-shell columnar liquid crystals (LCs) by supramolecular polymerization in LC media. In the present work, we successfully confirmed that our modular synthetic approach has the potential to be widely extended to the development of multifunctional columnar LCs. Herein, we constructed the first core-shell columnar LC that was proved to be orientable by both electric and magnetic fields by the supramolecular polymerization of NODiskNH* in a nematic LC medium of 4-cyano-4'-pentyloxybiphenyl (5OCB). NODiskNH* is a chiral benzenetricarboxamide derivative bearing 2,2,6,6-tetramethylpiperidine 1-oxyl termini, which is known to form a helical supramolecular polymer via a triple hydrogen-bonding array. NODiskNH* alone formed a hydrogen-bonded liquid phase without any long-range structural ordering. However, a nematic LC medium of 5OCB, when mixed with NODiskNH* at a molar ratio of 1:3, underwent a "structural order-increasing" mesophase transition, affording an optically active single LC phase with a hexagonally arranged core-shell columnar geometry in a temperature range from 113 to 51 °C. Unprecedentedly, this core-shell columnar LC can orient its columns both electrically and magnetically, resulting in unidirectional columnar ordering.

Radiation dose reduction with frame rate conversion in X-ray fluoroscopic imaging systems with flat panel detector: basic study and clinical retrospective analysis.

OBJECTIVES: To (a) evaluate the interpolation frames of frame rate conversion (FRC) compared with fluoroscopic frames of conventional method, and (b) compare radiation dose and fluoroscopy time between various clinical examinations without and with FRC retrospectively. METHODS: This study consisted of a basic study and a clinical retrospective analysis. The radiation dosimetry, visual assessment and measurements of contrast to noise ratio were examined. Similarity between interpolation frames and fluoroscopic frames was evaluated using normalised cross-correlation values. In the clinical retrospective analysis approved by the institutional review board, we extracted 270 examinations performed without FRC (conventional group, 12.5 pulses/s) and with FRC (FRC group, 6.25 pulses/s) from 23 May to 31 December 2016. The fluoroscopy parameters and demographics of the two groups of the clinical examinations were compared. Statistical analyses were performed with Wilcoxon signed-rank test, Brunner-Munzel test and χ2 test. RESULTS: In the basic study, the only significant difference was that the radiation dose of FRC was approximately half that of the conventional method in the same fluoroscopy time (p = .031). The interpolation frames of FRC were similar to the fluoroscopic frames of the conventional method. In the clinical retrospective analysis, the only significant difference was that FRC reduced the fluoroscopy dose by 48% and the total dose by 31% compared with the conventional method (p < .001). There was no significant difference in the others. CONCLUSION: FRC significantly reduced the radiation dose without extending the fluoroscopy time and maintaining the image quality compared to the conventional method. KEY POINTS: • Although X-ray fluoroscopic techniques are widely used for various clinical purposes, X-ray fluoroscopic examinations have radiation risks. • Frame rate conversion is an image processing technique for radiation dose reduction. • Clinical retrospective analysis showed that FRC reduces radiation doses of patients.

Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides.

The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the ß-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the ß-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The ß-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the ß-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The ß-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood.

[Evaluation of a Post-analysis Method for Cumulative Dose Distribution in Stereotactic Body Radiotherapy].

PURPOSE: The purpose of this study was to evaluate a post-analysis method for cumulative dose distribution in stereotactic body radiotherapy (SBRT) using volumetric modulated arc therapy (VMAT) . METHOD: VMAT is capable of acquiring respiratory signals derived from projection images and machine parameters based on machine logs during VMAT delivery. Dose distributions were reconstructed from the respiratory signals and machine parameters in the condition where respiratory signals were without division, divided into 4 and 10 phases. The dose distribution of each respiratory phase was calculated on the planned four-dimensional CT (4DCT). Summation of the dose distributions was carried out using deformable image registration (DIR), and cumulative dose distributions were compared with those of the corresponding plans. RESULTS AND DISCUSSION: Without division, dose differences between cumulative distribution and plan were not significant. In the condition where respiratory signals were divided, dose differences were observed over dose in cranial region and under dose in caudal region of planning target volume (PTV). Differences between 4 and 10 phases were not significant. CONCLUSION: The present method was feasible for evaluating cumulative dose distribution in VMAT-SBRT using 4DCT and DIR.

Evaluation of In Vivo Volumetric Dosimetry for Prostate Cancer Using Electronic Portal Imaging Device.

PURPOSE: Volumetric modulated arc therapy (VMAT) is capable of acquiring projection images using electronic portal imaging device (EPID). Commercial EPID-based dosimetry software, dosimetry check (DC), allows in vivo dosimetry using projection images. The purpose of this study was to evaluate in vivo dosimetry for prostate cancer using VMAT. METHOD: VMAT plans were generated for eight patients with prostate cancer using treatment planning system (TPS), and patient quality assurances (QAs) were carried out with phantom. We analyzed five plans as phantom study and five plans as patient study. Projection images were acquired during VMAT delivery. DC converted acquired images into fluence images and used a pencil beam algorithm to calculate dose distributions delivered on the CT images of the phantom and the patients. We evaluated isocenter point doses and gamma analysis in both studies and dose indexes of planning target volume (PTV), bladder and rectum in patient study. RESULTS AND DISCUSSION: Dose differences at the isocenter were less than a criterion in both studies. Pass rates of the gamma analysis were less than a criterion by two plans in the phantom study. Dose indexes of reconstructed distribution were lower than original plans and standard deviations of PTV in reconstructed distribution were larger than original plans. The errors were caused by some issues, such as the commissioning of DC, variations in patient anatomy, and patient positioning. CONCLUSION: The method was feasible to non-invasively perform in vivo dose evaluation for prostate cancer using VMAT.

Database of normal Japanese gray matter volumes in the default mode network.

PURPOSE: To show the gray matter volumes in the default mode network (DMN) using the atlas-based method and to evaluate age-related volume change in the DMN region. Estimation of gray matter volumes is interesting research because previous reports showed an association with gray matter volume (GMV) and diseases. MATERIALS AND METHODS: We focused on five nodes of the DMN (posterior cingulate, precuneus, lateral temporal cortex [LTC], medial prefrontal cortex, and inferior parietal lobule). In all, 1122 healthy adults were included in the present study. T1-weighted magnetic resonance (MR) images were obtained using a 3T-MR scanner. To investigate GMV in the DMN, segmented gray matter images were measured by the atlas-based method, using Statistical Parametric Mapping 5. Volumes were expressed using three different methods: region of interest (ROI)-volume (mL), the volume itself; ROI-TIV (%), as a percentage of total intracranial volume (individual difference of head size is corrected); and ROI-GMV (%), as a percentage of gray matter volume (individual difference of atrophy speed for aging is corrected). RESULTS: Negative correlations between measurement values on ROI and age were observed in all five ROIs of the DMN region by two measures of volume (ROI-volume (mL) and ROI-TIV (%)), in both genders. In contrast, positive correlations between measurement values on ROI and age were observed in the posterior cingulate and LTC with ROI-GMV (%), in both genders. CONCLUSION: The present study is the first report about volume change in the DMN that includes age-related effects.

[Dose reconstruction using respiratory signals and machine parameters during treatment in stereotactic body radiotherapy].

PURPOSE: Volumetric modulated arc therapy (VMAT) is a rotational intensity-modulated radiotherapy (IMRT) technique capable of acquiring projection images during treatment. The purpose of this study was to reconstruct the dose distribution from respiratory signals and machine parameters acquired during stereotactic body radiotherapy (SBRT). METHODS: The treatment plans created for VMAT-SBRT included the constraint of 1 mm/degree in multileaf collimator (MLC) for a moving phantom and three patients with lung tumors. The respiratory signals were derived from projection images acquired during VMAT delivery, while the machine parameters were derived from machine logs. The respiratory signals and machine parameters were then linked along with the gantry angle. With this data, the dose distribution of each respiratory phase was calculated on the planned four-dimensional CT (4D CT). The doses at the isocenter, the point of max dose and the centroid of the target were compared with those of the corresponding plans. RESULTS AND DISCUSSION: In the phantom study, the maximum dose difference between the plan and "in-treatment" results was -0.4% at the centroid of the target. In the patient study, the difference was -1.8 ± 0.4% at the centroid of the target. Dose differences of the evaluated points between 4 and 10 phases were not significant. CONCLUSION: The present method successfully reconstructed the dose distribution using the respiratory signals and machine parameters acquired during treatment. This is a feasible method for verifying the actual dose for a moving target.

[Study on cine view of relative enhancement ratio map in O2-enhanced MRI].

Magnetic resonance imaging (MRI) enables the evaluation of organ structure and function. Oxygen-enhanced MRI (O2-enhanced MRI) is a method for evaluating the pulmonary ventilation function using oxygen as a contrast agent. We created the Cine View of Relative Enhancement Ratio Map (Cine RER map) in O2-enhanced MRI to easily observe the contrast effect for clinical use. Relative enhancement ratio (RER) was determined as the pixel values of the Cine RER map. Moreover, six healthy volunteers underwent O2-enhanced MRI to determine the appropriate scale width of the Cine RER map. We calculated each RER and set 0 to 1.27 as the scale width of the Cine RER map based on the results. The Cine RER map made it possible to observe the contrast effect over time and thus is a convenient tool for evaluating the pulmonary ventilation function in O2-enhanced MRI.

[Winston-lutz test and acquisition of flexmap using rotational irradiation].

PURPOSE: IGRT (image guided radiation therapy) is a useful technique for implementing precisely targeted radiation therapy. Quality assurance and quality control (QA/QC) medical linear accelerators with a portal imaging system (electronic portal imaging device: EPID) are the key to ensuring safe IGRT. The Winston-Lutz test (WLT) provides an evaluation of the MV isocenter, which is the intersection of radiation, collimator, and couch isocenters. A flexmap can indicate a displacement of EPID from the beam center axis as a function of gantry angles which can be removed from the images. The purpose of this study was to establish a novel method for simultaneously carrying out WLT and acquiring a flexmap using rotational irradiation. We also observed long-term changes in flexmaps over a period of five months. METHOD: We employed rotational irradiation with a rectangular field (30×30 mm). First, the displacement of EPID from the beam center axis, indicated by the ball bearing (BB) center, was evaluated using an in-house program. The location of the BB center was then modified according to WLT. Second, a second irradiation was used to acquire a flexmap. We performed this examination regularly and evaluated long-term changes in the flexmap. RESULTS AND DISCUSSION: It proved feasible to perform WLT and flexmap measurements using our proposed methods. The precision of WLT using rotational irradiation was 0.1 mm. In flexmap analysis, the maximum displacement from the mean value for each angle was 0.4 mm over five months. CONCLUSION: We have successfully established a novel method of simultaneously carrying out WLT and flexmap acquisition using rotational irradiation. Maximum displacement from the mean in each angle was 0.4 mm over five months.

Association between iron content and gray matter missegmentation with voxel-based morphometry in basal ganglia.

PURPOSE: To show an association between T2-weighted signal intensity (T2-SI) variation and missegmentation in the putamen of healthy adults, using 3.0-tesla magnetic resonance scanner and voxel-based morphomery (VBM). MATERIALS AND METHODS: Contiguous sagittal T1-weighted images and axial T2-weighted images of the brain were obtained from 1380 healthy participants using a 3.0 Tesla (T) MR scanner. After image preprocessing with Statistical Parametric Mapping 5, the association between T2-SI ratio (= A/B, where A is the mean of the T2-SI in the putamen, and B is that in the thalamus) variation and gray matter missegmentation was assessed using VBM. RESULTS: A significant positive correlation was revealed between T2-SI ratio and bilateral putamen volume on the gray matter images. In addition, we found a significant negative correlation between T2-SI ratio and bilateral putamen volume on the white matter images. We consider that these results show the influence of missegmentation. CONCLUSION: To the best of our knowledge, this is the first VBM study to demonstrate an association between T2-SI variation and gray matter missegmentation. These results indicate the possibility that VBM may be more affected by individual differences in iron content levels than by individual differences in tissue volumes if detected-regions with VBM contained substantial iron deposition.

Bilateral pre- and postcentral gyrus volume positively correlates with T2-SNR of putamen in healthy adults.

INTRODUCTION: The aim of the present study was to investigate the correlation between local gray matter volume and signal-to-noise ratio on T2-weighted imaging (T2-SNR) of putamen in healthy adults using two tools: voxel-based morphometry (VBM) treating age as a confounding covariate to control for age-related gray matter volume changes and high spatial resolution T1-weighted imaging acquired with a 3.0-T magnetic resonance (3T-MR) scanner. METHODS: Contiguous sagittal T1-weighted images and axial T2-weighted images of the brain were obtained from 1,380 healthy participants. T2-SNR of putamen was defined as A/B, where A is the mean T2-weighted signal intensity (T2-SI) in the right and left sides of putamen, and B is the background noise. The software Statistical Parametric Mapping 5 was used for image segmentation. The association between T2-SNR of putamen and gray matter volume was assessed with VBM, treating age as a confounding covariate. RESULTS: A significant positive correlation was obtained between T2-SNR of putamen and bilateral pre- and postcentral gyrus volume. CONCLUSION: To the best of our knowledge, this is the first VBM study to show an age-independent relationship between T2-SNR of putamen and bilateral pre- and postcentral gyrus volumes in healthy adults.

Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra provides reduced effect of scanner for cortex volumetry with atlas-based method in healthy subjects.

INTRODUCTION: This study aimed to investigate whether the effect of scanner for cortex volumetry with atlas-based method is reduced using Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) normalization compared with standard normalization. METHODS: Three-dimensional T1-weighted magnetic resonance images (3D-T1WIs) of 21 healthy subjects were obtained and evaluated for effect of scanner in cortex volumetry. 3D-T1WIs of the 21 subjects were obtained with five MRI systems. Imaging of each subject was performed on each of five different MRI scanners. We used the Voxel-Based Morphometry 8 tool implemented in Statistical Parametric Mapping 8 and WFU PickAtlas software (Talairach brain atlas theory). The following software default settings were used as bilateral region-of-interest labels: "Frontal Lobe," "Hippocampus," "Occipital Lobe," "Orbital Gyrus," "Parietal Lobe," "Putamen," and "Temporal Lobe." RESULTS: Effect of scanner for cortex volumetry using the atlas-based method was reduced with DARTEL normalization compared with standard normalization in Frontal Lobe, Occipital Lobe, Orbital Gyrus, Putamen, and Temporal Lobe; was the same in Hippocampus and Parietal Lobe; and showed no increase with DARTEL normalization for any region of interest (ROI). CONCLUSION: DARTEL normalization reduces the effect of scanner, which is a major problem in multicenter studies.

Volatile organic compounds and ionic substances contamination in cell processing facilities during rest period; a preliminary assessment of exposure to cell processing operators.

Introduction: Cell processing operators (CPOs) use a variety of disinfectants that vaporize in the workspace environment. These disinfectants can induce allergic reactions in CPOs, due to their long working hours at cell processing facilities (CPFs). Ionic substances such as CH3COO- generated from peracetic acid, nitrogen oxides (NOx) and sulfur oxides (SOx) from outdoor environment are also known to pollute air. Therefore, our objective was to assess the air quality in CPFs and detect volatile organic compounds (VOCs) from disinfectants and building materials, and airborne ionic substances from outdoor air. Methods: Sampling was conducted at three CPFs: two located in medical institutions and one located at a different institution. Air samples were collected using a flow pump. Ion chromatographic analysis of the anionic and cationic compounds was performed. For VOC analysis, a thermal desorption analyzer coupled with capillary gas chromatograph and flame ionization detector was used. Results: Analysis of the ionic substances showed that Cl-, NOx, and SOx, which were detected in large amounts in the outdoor air, were relatively less in the CPFs. Ethanol was detected as the main component in the VOC analysis. Toluene was detected at all sampling points. As compared to the other environments, air in the incubator contained larger amounts of VOCs, that included siloxane, tetradecane, and aromatics. Conclusions: No VOCs or ionic substances of immediate concern to the health of the CPOs were detected during the non-operating period. However, new clinical trials of cell products are currently underway in Japan, and a variety of new cell products are expected to be approved. With an increase in cell processing, health risks to CPOs that have not been considered previously, may become apparent. We should continue to prepare for the future expansion of the industry using a scientific approach to collect various pieces of information and make it publicly available to build a database.

Repeatability of measured brain volume by atlas-based method using T1-weighted image.

The aims of this study were to (1) investigate the repeatability of measured volumes using the atlas-based method in each area of the brain, and (2) validate our hypothesis that the repeatability of the measured volumes with the atlas-based method was improved by using smoothed images. T1-weighted magnetic resonance images were obtained in five healthy subjects using the 1.5-T scanner. We used Statistical Parametric Mapping 5 and WFU PickAtlas software (theory of the Talairach brain atlas). Volumes inside region-of-interest (ROI) were measured in ten sets (five subjects × right and left) on six ROIs, respectively. One set comprises five images (one subject × five 3D-T1WIs). The percentage change was defined as [100 × (measured volume-mean volume in each set)/mean volume in each set)]. As a result, the average percentage changes using non-smoothed image on each ROI were as follows: gray matter, 0.482%; white matter, 0.375%; cerebrospinal fluid images, 0.731%; hippocampus, 0.864%; orbital gyrus, 1.692%; cerebellum posterior lobe, 0.854%. Using smoothed images with large FWHM resulted in improved repeatability on orbital gyrus. This is the first report of repeatability in each brain structure and improved repeatability with smoothed images using the atlas-based method.

Anomalous Chiral Transfer: Supramolecular Polymerization in a Chiral Medium of a Mesogenic Molecule.

Here, we report a medium-to-polymer anomalous chiral transfer in the supramolecular polymerization of a tetraphenylporphyrin-based achiral hydrogen-bonding monomer (TPP) in a chiral medium of 5-cyanobiphenyl CB*. A mixture of TPP in (R)-CB* ([TPP]=7.7 mol %) at 40 °C gave a columnar oblique LC mesophase, where the individual columns were composed of an optically active helical supramolecular polymer of TPP as a consequence of a successful medium-to-polymer chiral transfer. Meanwhile, upon dilution of CB* with achiral 5-cyanobiphenyl CB, the optical activity of the system showed an anomalous bell-shaped dependency on the composition of CB*/CB, where the gabs value of 0.049 at CB*/CB=50/50 was 6.0 times larger than the gabs value of CB* alone. Such anomalous chiroptical amplification in CD is most likely due to a change in the stacking geometry of TPP in the oblique columnar LC upon lateral compression.

Degradation of soluble VEGF receptor-1 by MMP-7 allows VEGF access to endothelial cells.

Vascular endothelial growth factor (VEGF) signaling in endothelial cells serves a critical role in physiologic and pathologic angiogenesis. Endothelial cells secrete soluble VEGF receptor-1 (sVEGFR-1/sFlt-1), an endogenous VEGF inhibitor that sequesters VEGF and blocks its access to VEGF receptors. This raises the question of how VEGF passes through this endogenous VEGF trap to reach its membrane receptors on endothelial cells, a step required for VEGF-driven angiogenesis. Here, we show that matrix metalloproteinase-7 (MMP-7) degrades human sVEGFR-1, which increases VEGF bioavailability around the endothelial cells. Using a tube formation assay, migration assay, and coimmunoprecipitation assay with human umbilical vein endothelial cells (HUVECs), we show that the degradation of sVEGFR-1 by MMP-7 liberates the VEGF(165) isoform from sVEGFR-1. The presence of MMP-7 abrogates the inhibitory effect of sVEGFR-1 on VEGF-induced phosphorylation of VEGF receptor-2 on HUVECs. These data suggest that VEGF escapes the sequestration by endothelial sVEGFR-1 and promotes angiogenesis in the presence of MMP-7.

3 Tesla MRI detects accelerated hippocampal volume reduction in postmenopausal women.

PURPOSE: To clarify age-related structural changes specific to hippocampal volume by hierarchizing according to age, gender, and menopausal status. Many studies report the neuroprotective effects of estrogen and age-related brain volume changes; however, there are no studies regarding age-related change specific to hippocampal volume in terms of age, gender, and menopausal status. MATERIALS AND METHODS: T1-weighted MR images were obtained in 412 healthy adults divided into eight groups according to age and gender, to analyze brain volume change focusing on hippocampal volume. RESULTS: Voxel-based morphometry (VBM) revealed significantly smaller gray matter volume in the hippocampus bilaterally in females aged in their fifties (51 of 59 females were at menopause) compared with females in their forties (3 of 46 females were at menopause). No significant difference was found, however, between female groups in their fifties versus sixties, or sixties versus seventies; or between male groups in their forties versus fifties, fifties versus sixties, or sixties versus seventies. In addition, VBM revealed significant hippocampal volume reduction bilaterally in all postmenopausal women compared with all premenopausal women. CONCLUSION: The results of the current study suggest that the menopause may be associated with hippocampal volume reduction.

Entorhinal cortex volume measured with 3T MRI is positively correlated with the Wechsler Memory Scale-Revised logical/verbal memory score for healthy subjects.

INTRODUCTION: Previous studies revealed a correlation between local brain volume and cognitive function. The aim of the present study was to investigate the correlation between local gray matter volume and the Wechsler Memory Scale-Revised (WMS-R) logical/verbal memory (WMS-R-verbal) score in healthy adults using a 3 Tesla magnetic resonance scanner and voxel-based morphometry (VBM). METHODS: T1-weighted magnetic resonance images were obtained in 1,169 healthy adults. The T1-weighted images in native space were bias-corrected, spatially normalized, and segmented into gray matter, white matter, and cerebrospinal fluid images with Statistical Parametric Mapping 5. To investigate regionally the specific effects of the WMS-R-verbal score on the gray matter images, simple regression analysis was performed by VBM treating age, total intracranial volume, and gender as confounding covariates. A P value of less than 0.05 corrected with false discovery rate in voxel difference was considered to be statistically significant. RESULTS: Our study showed a significant positive correlation between the WMS-R-verbal score and the bilateral entorhinal cortex volume. In the right entorhinal, T value is 4.75, and the size of the clusters is 155 voxels. In the left entorhinal, T value is 4.08, and the size of the clusters is 23 voxels. A significant negative correlation was not found. CONCLUSION: To our knowledge, this is the first VBM study showing that entorhinal cortex volume is positively correlated with the WMS-R-verbal score for healthy subjects. Therefore, in our structural neuroimaging study, we add evidence to the hypothesis that the entorhinal cortex is involved in verbal memory processing.

Prostate-specific antigen enhances bioavailability of insulin-like growth factor by degrading insulin-like growth factor binding protein 5.

In the bone matrix, insulin-like growth factors (IGFs) are the most abundant growth factors and IGF binding protein 5 (IGFBP-5) is the major IGFBP. Our previous study suggested that IGFs stored in the bone matrix and prostate-specific antigen (PSA) play an important role in prostate cancer (PC) bone metastasis. However, it is not clear how IGF signaling is activated in the bone microenvironment of PC metastasis. Therefore, we investigated whether PSA degrades IGFBP-5 and enhances biological activity of IGF. Enzymatically active PSA degraded the recombinant IGFBP-5 protein in a dose- and time-dependent manner and a serine protease inhibitor suppressed this degradation. Furthermore, PSA induced IGF-mediated type I IGF receptor phosphorylation that was inhibited by coincubation with IGFBP-5. The present study indicates PSA derived from PC cells can enhance IGF bioavailability in the bone microenvironment of PC metastasis, thereby permitting PC survival and malignant progression in the bone microenvironment.