Azobenzene-modified DNA aptamers evolved by capillary electrophoresis (CE)-SELEX method.

Chemically modified aptamers have recently emerged as important materials for nucleic acid based therapeutics and diagnostic tools. Here, we report in vitro evolution of azobenzene-modified DNA aptamers by capillary electrophoresis (CE)-SELEX method. Azobenzene has been considered to be a fascinating functional group due to its trans-cis photo-isomerization property. We harnessed C5-azobenzene-modified 2'-deoxyuridine (dUAz) as a azobenzene-tethered unit and subjected it to CE-SELEX with human thrombin. The obtained dUAz-modified aptamer showed strong binding affinity toward human thrombin and could be reversibly photo-isomerized by different wavelengths of light. This work demonstrates that CE-SELEX is a powerful method to obtain chemically modified aptamers and dUAz is an excellent photo-responsive nucleoside for nucleic acid photo-switches.

Usefulness of Model-Based Iterative Reconstruction in Brain CT as Compared With Hybrid Iterative Reconstruction.

OBJECTIVE: The aim of this study was to compare the contrast of gray to white matter between forward-projected model-based iterative reconstruction solution (FIRST) and hybrid iterative reconstruction (IR) by measuring computed tomography value of brain parenchyma. METHODS: Computed tomography values of the gray and white matter in 15 areas of 21 patients (7 males, 14 females; average age, 49.5 ± 10.7 years) were measured and compared between FIRST and hybrid IR with filtered back projection (FBP) using 2 different reconstruction kernels FC21 and FC26. RESULTS: The ratio of gray to white matter obtained using FIRST (1.25 ± 0.08) was significantly higher than that obtained using FBP with both kernel FC21 (1.13 ± 0.03) and kernel FC26 (1.22 ± 0.06). CONCLUSIONS: FIRST increases the contrast between the gray and white matter, and decreases noise in brain computed tomography compared with FBP with hybrid IR.

Establishing a Treatment Algorithm for Puerperal Genital Hematoma Based on the Clinical Findings.

Postpartum hemorrhage within 24 hours after delivery remains the leading cause of maternal mortality worldwide. Puerperal genital hematoma (PGHA) is a rare complication of postpartum hemorrhage, and PGHA can be life-threatening if hemostasis is not properly achieved. However, a reliable management algorithm for PGHA based on the clinical findings has not been developed. The objectives were to evaluate the management strategies for PGHA and identify the clinical findings that help select the treatment for PGHA. The medical records of women who were treated for PGHA in our department were reviewed, and data regarding the clinical findings and the treatment strategy for PGHA were analyzed. Thirty-four women who underwent treatment for PGHA were identified and divided into three groups according to the final procedure that achieved hemostasis: conservative management (CM) (n = 9), surgical management (SURG) (n = 15), and arterial embolization management (AEM) (n = 10). Regarding the clinical findings on initial evaluation, the shock index was significantly higher in the AEM group than in the CM or SURG group; and initial platelet count and fibrinogen level were significantly lower in the AEM group than in the CM group. There was no significant difference in any computed tomography (CT) finding among the three groups. In conclusion, this study clearly shows the difference in clinical findings among treatment strategies for PGHA. We suggest that the clinical findings of shock index, platelet count, and fibrinogen level together with CT findings are helpful and valuable for selecting the treatment strategy for PGHA.

Effects of barbed suture during robot-assisted radical prostatectomy on postoperative tissue damage and longitudinal changes in lower urinary tract outcome.

OBJECTIVE: To compare the postoperative tissue damage and longitudinal changes in functional and patient-reported outcomes after vesicourethral anastomosis with barbed suture and nonbarbed suture in robot-assisted laparoscopic radical prostatectomy (RARP). MATERIALS AND METHODS: This was a prospective cohort study involving 88 consecutive patients who underwent RARP. These patients were categorized into the barbed suture group (n = 50) and the nonbarbed suture group (n = 38). Urethral and periurethral damages determined by magnetic resonance imaging at nine months after RARP were compared using generalized linear models. The International Prostate Symptom Score (IPSS), quality of life (QOL) index, uroflowmetry, and the 1-h pad test were measured at baseline and at 1, 3, 6, 9, and 12 months after RARP. The findings were analyzed using mixed-effects models. Confounding was adjusted for using propensity score covariate adjustment. RESULTS: The likelihood of having Grade 2/3 urethral and periurethral damages was greater in the barbed suture group than in the nonbarbed suture group (adjusted risk ratios: 2.98 and 3.85, respectively). IPSS, QOL index, and urinary leakage transiently increased at one month after RARP in both groups. QOL index was higher in the barbed suture group than in the nonbarbed suture group at 1, 9, and 12 months (P = 0.023, P = 0.025, and P = 0.011, respectively). The barbed suture group had significantly more cases of urinary incontinence than the nonbarbed suture group at 3 months (P = 0.041). Other outcomes were comparable between the two groups at all time points. CONCLUSIONS: This cohort study showed that, after RARP, barbed sutures during VUA induced more severe tissue damage as determined by MRI and greater transient aggravation of QOL and continence function than nonbarbed sutures. The present findings suggest that using nonbarbed sutures during VUA may facilitate earlier acquisition of urinary QOL and urinary continence.

Development of immersion vaccine for bacterial cold-water disease in ayu Plecoglossus altivelis.

Flavobacterium psychrophilum (F. psychrophilum) is the causative agent of bacterial cold-water disease (BCWD) that occurs in ayu Plecoglossus altivelis. Formalin-killed cell of F. psychrophilum has long been studied as an immersion vaccine for BCWD. In this study, we explored the possibility of F. psychrophilum collagenase (fpcol) for use as the immersion vaccine. BCWD convalescent ayu sera contained specific IgM antibodies against somatic F. psychrophilum and fpcol, meaning that fpcol is a promising antigen for the vaccine development. The recombinant fpcol was successfully expressed in Escherichia coli and Brevibacillus chosinensis (B. chosinensis). The culture supernatant of the B. chosinensis was used as an immersion vaccine solution. The vaccinated ayu were then challenged by soaking into F. psychrophilum culture. In two experimental groups, the relative percentages of survivals were 63 and 38%, respectively, suggesting that fpcol is promising as the immersion vaccine for ayu-BCWD.

Mechanisms of global diversification in the marine species Madeiran Storm-petrel Oceanodroma castro and Monteiro's Storm-petrel O. monteiroi: Insights from a multi-locus approach.

The evolutionary mechanisms underlying the geographic distribution of gene lineages in the marine environment are not as well understood as those affecting terrestrial groups. The continuous nature of the pelagic marine environment may limit opportunities for divergence to occur and lineages to spatially segregate, particularly in highly mobile species. Here, we studied the phylogeography and historical demography of two tropically distributed, pelagic seabirds, the Madeiran Storm-petrel Oceanodroma castro, sampled in the Azores, Madeira, Galapagos and Japan, and its sister species Monteiro's Storm-petrel O. monteiroi (endemic to the Azores), using a multi-locus dataset consisting of 12 anonymous nuclear loci and the mitochondrial locus control region. Both marker types support the existence of four significantly differentiated genetic clusters, including the sampled O. monteiroi population and three populations within O. castro, although only the mitochondrial locus suggests complete lineage sorting. Multi-locus coalescent analyses suggest that most divergence events occurred within the last 200,000years. The proximity in divergence times precluded robust inferences of the species tree, in particular of the evolutionary relationships of the Pacific populations. Despite the great potential for dispersal, divergence among populations apparently proceeded in the absence of gene flow, emphasizing the effect of non-physical barriers, such as those driven by the paleo-oceanographical environments, philopatry and local adaptation, as important mechanisms of population divergence and speciation in highly mobile marine species. In view of the predicted climate change impacts, future changes in the demography and evolutionary dynamics of marine populations might be expected.

Missed causative tumors in diagnosing tumor-induced osteomalacia with (18)F-FDG PET/CT: a potential pitfall of standard-field imaging.

OBJECTIVE: We describe herein two tumor-induced osteomalacia (TIO) cases for whom the causative lesions, located in their popliteal fossa, that were not identified in the standard field of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT), which usually images only the head, trunk, and proximal parts of the extremities. CLINICAL PRESENTATION AND INTERVENTION: A 47 years old Japanese man with multiple pathological fractures due to osteomalacia, accompanied by muscle weakness, hypophosphatemia, and an elevation of alkaline phosphatase (ALP) was referred to our hospital. A (18)F-FDG PET/CT scan was performed, but no (18)F-FDG uptake was detected in the standard field of imaging. Magnetic resonance imaging revealed a small subcutaneous tumor (1.9×1.2×0.6cm) of the left posteriomedial knee, displaying uniform enhancement on gadolinium-enhanced T1-weighted fat-suppression imaging. The tumor was resected widely and diagnosed as phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). The other patient was a 31 years old Japanese woman with multiple pathological fractures, hypophosphatemia and elevated of ALP and was referred to our hospital on suspicion of TIO. Although the causative lesion was not identified in the standard field of (18)F-FDG PET/CT, (18)F-FDG uptake (SUVmax 2.9) was detected on the right knee in the additional whole-body (18)F-FDG PET/CT. Magnetic resonance imaging revealed a soft-tissue tumor (6.4×4.1×2.9cm) in the right posterior knee. Following biopsy, the tumor was marginally resected, and was pathologically diagnosed as PMTMCT. CONCLUSION: Once patients are suspected to have TIO, a whole-body nuclear imaging study such as (18)F-FDG PET/CT should be performed, in order not to miss the hidden causative tumor, especially occurring in the distal extremities.

Polymerase incorporation of a 2'-deoxynucleoside-5'-triphosphate bearing a 4-hydroxy-2-mercaptobenzimidazole nucleobase analogue.

Here, we describe the enzymatic construction of a new larger base pair formed between adenine (A) and a 4-hydroxy-2-mercaptobenzimidazole (SB) nucleobase analogue. We investigated the enzymatic incorporation of 2'-deoxynucleoside-5'-triphosphate bearing a SB nucleobase analogue (dSBTP) into oligonucleotides (ONs) by DNA polymerases. dSBTP could be effectively incorporated at the site opposite a dA in a DNA template by several B family DNA polymerases. These findings provide new insights into various aspects of biotechnology, including the design of non-natural base pairs.

Radiological and pathological characteristics of synovial hemangioma of the knee.

Synovial hemangioma, a rare benign tumor that occurs most frequently in the knee in children and young adults, has four histological subtypes: Venous, arteriovenous, cavernous and capillary hemangiomas. Since the clinical presentation and radiological findings of synovial hemangioma are non-specific, there is frequently a long period between the onset and the diagnosis. The cases of nine patients, pathologically diagnosed with synovial hemangioma and surgically treated, were retrospectively analyzed. All nine patients had persistent knee pain. In addition, three patients also had a swollen knee with intra-articular hemorrhage. Plain radiography revealed intra-articular phleboliths in two patients. In seven patients, T1-weighted magnetic resonance imaging showed low signal intensity with small signal voids. On T2-weighted imaging, all patients showed high signal intensity containing small signal voids. All patients underwent surgical excision; there was no postoperative recurrence after the final operation, and the knee pain had disappeared at the final follow-up. From the pathological findings, the diagnoses were venous hemangioma, cavernous hemangioma and capillary hemangioma (three patients each).

Subclinical involvement of the trunk muscles in idiopathic inflammatory myopathies.

BACKGROUND: Whole-body magnetic resonance imaging (WB-MRI) is a useful tool for revealing the disease-specific distribution of affected muscles and clinically asymptomatic muscle involvements in idiopathic inflammatory myopathies (IIMs). PURPOSE: To examine inflammatory changes in the systemic skeletal muscles, including the thoracoabdominal trunk, in IIMs using WB-MRI. MATERIAL AND METHODS: We prospectively obtained WB-MRI axial images from 10 patients with IIMs, including antisynthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), sporadic inclusion body myositis, and myopathy associated with antimitochondrial antibody. We evaluated 108 systemic skeletal muscles in short-tau inversion recovery (STIR) images and rated changes in signal intensity using a semiquantitative scale. Correlations between STIR sum score, peak creatine kinase (CK) and muscle strength were examined. We also investigated the correlation between STIR sum score within the thoracoabdominal trunk and forced vital capacity. RESULTS: High STIR signal changes were frequently identified in asymptomatic and routinely unexamined muscles. Thoracoabdominal trunk muscles were frequently involved in ASS and IMNM. Peak CK was positively correlated with the STIR sum score (R 2 = 0.62, p < .01). There was no significant correlation between the STIR sum score within the thoracoabdominal trunk and forced vital capacity. CONCLUSION: WB-MRI can detect subclinical muscle inflammation in the systemic muscles including the trunk muscles. STIR sum score is positively correlated with serum peak CK level; therefore, it could be a biomarker of overall muscle inflammation.

Cauda equina movement during the Valsalva maneuver in two patients with Lumbar spinal canal stenosis.

Lumbar spinal canal stenosis (LSS) is a common spinal disorder among older people. Some LSS patients say that their pain worsens when they lift heavy objects. The Valsalva maneuver is the optimal breathing pattern for producing maximal force. Herein, we present two cases of LSS where the movement of the cauda equina was observed during the Valsalva maneuver.Case Summary:Case 1: A 74-year-old female with a history of LSS presented to our Department of Urology with frequent urination. The patient was diagnosed as having uterine and bladder prolapse. Pelvic cine MRI scan was conducted for detailed evaluation. While the Valsalva maneuver was performed to diagnose pelvic organ prolapses, we observed movement of the cauda equina. Spine MRI and CT, performed one year before presentation, showed severe LSS due to degenerative spondylolisthesis.Case 2: A 73-year-old male underwent radical prostatectomy for prostate cancer. A follow-up cine MRI to confirm urethrorrhea showed the cauda equina moving during the Valsalva maneuver. Moderate LSS due to degenerative spondylolisthesis was retrospectively found on abdominal CT performed before prostatectomy.Conclusion: The findings of our report suggest that movement of the cauda equina during the Valsalva maneuver may be implicated in LSS.

A second generation genetic linkage map of Japanese flounder (Paralichthys olivaceus).

BACKGROUND: Japanese flounder (Paralichthys olivaceus) is one of the most economically important marine species in Northeast Asia. Information on genetic markers associated with quantitative trait loci (QTL) can be used in breeding programs to identify and select individuals carrying desired traits. Commercial production of Japanese flounder could be increased by developing disease-resistant fish and improving commercially important traits. Previous maps have been constructed with AFLP markers and a limited number of microsatellite markers. In this study, improved genetic linkage maps are presented. In contrast with previous studies, these maps were built mainly with a large number of codominant markers so they can potentially be used to analyze different families and populations. RESULTS: Sex-specific genetic linkage maps were constructed for the Japanese flounder including a total of 1,375 markers [1,268 microsatellites, 105 single nucleotide polymorphisms (SNPs) and two genes]; 1,167 markers are linked to the male map and 1,067 markers are linked to the female map. The lengths of the male and female maps are 1,147.7 cM and 833.8 cM, respectively. Based on estimations of map lengths, the female and male maps covered 79 and 82% of the genome, respectively. Recombination ratio in the new maps revealed F:M of 1:0.7. All linkage groups in the maps presented large differences in the location of sex-specific recombination hot-spots. CONCLUSIONS: The improved genetic linkage maps are very useful for QTL analyses and marker-assisted selection (MAS) breeding programs for economically important traits in Japanese flounder. In addition, SNP flanking sequences were blasted against Tetraodon nigroviridis (puffer fish) and Danio rerio (zebrafish), and synteny analysis has been carried out. The ability to detect synteny among species or genera based on homology analysis of SNP flanking sequences may provide opportunities to complement initial QTL experiments with candidate gene approaches from homologous chromosomal locations identified in related model organisms.

Sonographic assessment of fatty liver infiltration using the measurement of para- and perirenal fat thickness.

PURPOSE: Usefulness of abdominal ultrasonography for quantitative estimation of fatty liver by measurement of para- and perirenal sonographic fat thickness (UFT) was investigated. METHODS: Study subjects were 286 patients hospitalized for the treatment of diabetes. These subjects underwent blood chemistry studies, abdominal ultrasonography, and CT. On sonography, the thickness of combined para- and perirenal fat was measured between the kidney and the inner aspect of the abdominal musculature. Measurements on both sides were averaged as the UFT. Fatty liver infiltration was graded on a scale of grade 0 to 3: 0, none; 1, mild; 2, moderate; and 3, severe. With abdominal CT, the ratio of CT attenuation value of the liver to that of the spleen (L/S ratio) was measured. RESULTS: A positive correlation was found between UFT and FL grade or between UFT and L/S ratio (p < 0.0001). Positive correlations were also found between UFT and glutamic pyruvic transaminase (p < 0.05), or cholinesterase (p < 0.0001). CONCLUSION: Measurement of UFT is a useful method for the quantification of fatty liver as well as for the quantification of visceral fat.

Very late relapse of high-grade osteosarcoma: A case report and review of the literature.

RATIONALE: Osteosarcoma is the most common primary malignant bone tumor in children. The prognosis of osteosarcoma has improved with the use of aggressive systemic chemotherapy in addition to surgery. The relapse of osteosarcomas is usually as lung metastasis observed within 2 to 3 years after the initial treatment. A relapse is rarely observed at >10 years. PATIENT CONCERNS: We report the case of a 51-year-old Japanese man who was treated for high-grade osteosarcoma of the femur at 13 years old. He was referred to our hospital with a suspicion of primary lung cancer based on back pain, respiratory distress, and an abnormal mass on chest radiograph. DIAGNOSES: Computed tomography-guided biopsy confirmed the lung lesion as a metastatic recurrence of high-grade osteosarcoma without local recurrence. INTERVENTIONS: Chemotherapy was planned, but the patient's general condition rapidly deteriorated and thus palliative therapy was provided. OUTCOMES: The patient died 2 months after the initial consultation. LESSONS: The survival durations of osteosarcoma patients have been prolonged by recent progress in multimodality therapy, and thus clinicians as well as osteosarcoma patients should always keep in mind the possibility of very late relapse.

A fast nearest neighbor classifier based on self-organizing incremental neural network.

A fast prototype-based nearest neighbor classifier is introduced. The proposed Adjusted SOINN Classifier (ASC) is based on SOINN (self-organizing incremental neural network), it automatically learns the number of prototypes needed to determine the decision boundary, and learns new information without destroying old learned information. It is robust to noisy training data, and it realizes very fast classification. In the experiment, we use some artificial datasets and real-world datasets to illustrate ASC. We also compare ASC with other prototype-based classifiers with regard to its classification error, compression ratio, and speed up ratio. The results show that ASC has the best performance and it is a very efficient classifier.

Random field model for integration of local information and global information.

This paper presents a proposal of a general framework that explicitly models local information and global information in a conditional random field. The proposed method extracts global image features as well as local ones and uses them to predict the scene of the input image. Scene-based top-down information is generated based on the predicted scene. It represents a global spatial configuration of labels and category compatibility over an image. Incorporation of the global information helps to resolve local ambiguities and achieves locally and globally consistent image recognition. In spite of the model's simplicity, the proposed method demonstrates good performance in image labeling of two datasets.

An enhanced self-organizing incremental neural network for online unsupervised learning.

An enhanced self-organizing incremental neural network (ESOINN) is proposed to accomplish online unsupervised learning tasks. It improves the self-organizing incremental neural network (SOINN) [Shen, F., Hasegawa, O. (2006a). An incremental network for on-line unsupervised classification and topology learning. Neural Networks, 19, 90-106] in the following respects: (1) it adopts a single-layer network to take the place of the two-layer network structure of SOINN; (2) it separates clusters with high-density overlap; (3) it uses fewer parameters than SOINN; and (4) it is more stable than SOINN. The experiments for both the artificial dataset and the real-world dataset also show that ESOINN works better than SOINN.

Developmental word grounding through a growing neural network with a humanoid robot.

This paper presents an unsupervised approach of integrating speech and visual information without using any prepared data. The approach enables a humanoid robot, Incremental Knowledge Robot 1 (IKR1), to learn word meanings. The approach is different from most existing approaches in that the robot learns online from audio-visual input, rather than from stationary data provided in advance. In addition, the robot is capable of learning incrementally, which is considered to be indispensable to lifelong learning. A noise-robust self-organized growing neural network is developed to represent the topological structure of unsupervised online data. We are also developing an active-learning mechanism, called "desire for knowledge," to let the robot select the object for which it possesses the least information for subsequent learning. Experimental results show that the approach raises the efficiency of the learning process. Based on audio and visual data, they construct a mental model for the robot, which forms a basis for constructing IKRI's inner world and builds a bridge connecting the learned concepts with current and past scenes.

Developmental word acquisition and grammar learning by humanoid robots through a self-organizing incremental neural network.

We present a new approach for online incremental word acquisition and grammar learning by humanoid robots. Using no data set provided in advance, the proposed system grounds language in a physical context, as mediated by its perceptual capacities. It is carried out using show-and-tell procedures, interacting with its human partner. Moreover, this procedure is open-ended for new words and multiword utterances. These facilities are supported by a self-organizing incremental neural network, which can execute online unsupervised classification and topology learning. Embodied with a mental imagery, the system also learns by both top-down and bottom-up processes, which are the syntactic structures that are contained in utterances. Thereby, it performs simple grammar learning. Under such a multimodal scheme, the robot is able to describe online a given physical context (both static and dynamic) through natural language expressions. It can also perform actions through verbal interactions with its human partner.

Nonparametric Density Estimation Based on Self-Organizing Incremental Neural Network for Large Noisy Data.

With the ongoing development and expansion of communication networks and sensors, massive amounts of data are continuously generated in real time from real environments. Beforehand, prediction of a distribution underlying such data is difficult; furthermore, the data include substantial amounts of noise. These factors make it difficult to estimate probability densities. To handle these issues and massive amounts of data, we propose a nonparametric density estimator that rapidly learns data online and has high robustness. Our approach is an extension of both kernel density estimation (KDE) and a self-organizing incremental neural network (SOINN); therefore, we call our approach KDESOINN. An SOINN provides a clustering method that learns about the given data as networks of prototype of data; more specifically, an SOINN can learn the distribution underlying the given data. Using this information, KDESOINN estimates the probability density function. The results of our experiments show that KDESOINN outperforms or achieves performance comparable to the current state-of-the-art approaches in terms of robustness, learning time, and accuracy.