Novel method for endovascular fenestration using radiofrequency transseptal needle for aortic dissection with malperfusion syndrome.

Malperfusion syndrome is considered one of the most significant adverse events in aortic dissection disease and often requires invasive strategies to improve ischemia. We report the case of a patient who was presented with worsening claudication and leg rest pain due to malperfusion syndrome of type B aortic dissection. We successfully performed endovascular fenestration therapy to relieve the symptom by using a NRG radiofrequency transseptal needle (Baylis Medical, Montreal, Canada). We suggest that this novel method would be available for the patients with malperfusion syndrome of aortic dissection.

The TriAGe+ Score for Vertigo or Dizziness: A Diagnostic Model for Stroke in the Emergency Department.

BACKGROUND: Vertigo or dizziness is a common occurrence, but it remains a challenging symptom when encountered in the emergency department (ED). A diagnostic score for stroke with high accuracy is therefore required. METHODS: A single-center observational study (498 patients) was conducted. The predictor variables were derived from a multivariate logistic regression analysis with Akaike information criterion. The outcome was the occurrence of stroke. We evaluated the utility of a new diagnostic score (TriAGe+) and compared it with the ABCD2 score. RESULTS: The cohorts included 498 patients (147 with stroke [29.4%]). Eight variables were included: triggers, atrial fibrillation, male gender, blood pressure ≥140/90 mm Hg, brainstem or cerebellar dysfunction, focal weakness or speech impairment, dizziness, and no history of vertigo or dizziness or labyrinth or vestibular disease. We derived the TriAGe+ score from these variables. In the cohort, the prevalence of stroke increased significantly using the diagnostic score: 5.9% for a score of 0-4; 9.1% for 5-7; 24.7% for 8-9; and 57.3% for 10-17. At a cutoff value of 10 points, the sensitivity of the score was 77.5%, the specificity was 72.1%, and the positive likelihood ratio was 3.2. When the cutoff was defined as 5 points, the score obtained a high sensitivity (96.6%) with a good negative likelihood ratio (.15). The new score outperformed the ABCD2 score for the occurrence of stroke (C statistic, .818 versus .726; P < .001). CONCLUSIONS: The TriAGe+ score can identify the occurrence of stroke in patients with vertigo or dizziness presenting to the ED.

Antimelanoma differentiation-associated protein 5 antibody level is a novel tool for monitoring disease activity in rapidly progressive interstitial lung disease with dermatomyositis.

BACKGROUND: Antimelanoma differentiation-associated protein (anti-MDA)5 antibodies are associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). OBJECTIVES: We aimed to evaluate the relevance of monitoring anti-MDA5 antibody levels for the management of RP-ILD in patients with CADM or DM. METHODS: Twelve patients with CADM (n = 10) or DM (n = 2) accompanied by RP-ILD were included. Baseline characteristics and outcomes were recorded. Serial measurements of anti-MDA5 antibody levels were measured. All patients were treated with corticosteroids, tacrolimus and intravenous cyclophosphamide. RESULTS: All patients achieved RP-ILD remission after combined immunosuppressive therapy for a mean of 6·8 months, with significant decreases noted in the mean anti-MDA5 antibody levels at remission. Six (50%) patients became anti-MDA5 antibody negative after therapy. After a mean follow-up of 31 months, RP-ILD relapse was observed in four (33%) patients in both the anti-MDA5 antibody sustained positive group and the negative conversion group. However, relapsed patients in the sustained positive group relapsed earlier than those in the negative conversion group. Thus, a decrease in anti-MDA5 antibody levels during remission was associated with longer remission. Relapses were associated with a reincrease of anti-MDA5 antibody levels in four of four (100%) patients. In contrast, none of the patients without reincrease in anti-MDA5 antibody exhibited symptoms of relapse during follow-up. Therefore, reincrease in anti-MDA5 antibody levels was associated with relapse. CONCLUSIONS: The anti-MDA5 antibody level is a novel parameter for monitoring and a good predictor of RP-ILD relapse in patients with CADM or DM.

Locomotor improvement of spinal cord-injured rats through treadmill training by forced plantar placement of hind paws.

STUDY DESIGN: Experimental training model of rats with spinal cord injury (SCI). SETTING: Osaka, JapanObjective:To investigate the effect of forced treadmill training by plantar placement (PP), as compared with dorsal placement (DP), of the dorsal paws on the locomotor behaviors of spinal cord-injured rats. METHODS: The spinal cord was contusion-injured at the thoracic level. Rats were divided into three groups: forced training involving stepping by PP and DP and non-forced training/assistance (nT). Training began 1 week after injury and was conducted for 4 weeks. Locomotor behaviors were estimated using Basso-Beattie-Bresnahan (BBB) scores, dorsiflexion of the hind paws and footprints of the hind paws. Histological and immunohistochemical examinations of the spinal cord lesions were conducted after 4 weeks of training. RESULTS: The values, respectively, of PP, DP and nT groups at 4 weeks of training were as follows: BBB scores were 15.6±0.8, 7.7±1.3 and 10.3±0.4. The paw dorsiflexion angles were 34.1±5.2, 16.4±2.4 and 23.6±3.0 degrees, respectively. The stride angles were 5.1±0.9, 13.7±4.9 and 17.8±4.0 degrees for the left paws. Cavity volumes were 10.3±2.1, 31.0±2.0 and 28.2±4.9%. In addition to cavities, there were astrocyte-devoid areas containing some loose tissues, through which many axons extended longitudinally. CONCLUSIONS: The BBB score, dorsiflexion angle and stride angle were consistently improved in the PP group. Cavity formation was more reduced, and many axons extended through coarse tissues formed in astrocyte-devoid areas at the lesion in the PP group. Forced training by PP of the hind paws promoted the behavioral and histological improvement of rats with SCI.

Plasma microRNA profiles: identification of miR-25 as a novel diagnostic and monitoring biomarker in oesophageal squamous cell carcinoma.

BACKGROUND: Recent studies have demonstrated that microRNAs are stably detectable in plasma/serum because of their binding to specific proteins or being packaged in secretory particles. This study was designed to detect novel microRNAs in plasma for cancer detection and monitoring using microRNA array-based approaches in oesophageal squamous cell carcinoma (ESCC) patients. METHODS: Through the integration of two Toray 3D-Gene microRNA array-based approaches to compare plasma microRNA levels between ESCC patients and healthy volunteers and between preoperative and postoperative ESCC patients, we identified a novel plasma biomarker in ESCC. RESULTS: (1) Eight upregulated and common microRNAs (miR-15b, 16, 17, 25, 19b, 20a, 20b, and 106a) were selected using two high-resolution microRNA array approaches. (2) Test-scale analyses by quantitative RT-PCR validated a significant higher levels of plasma miR-19b (P=0.0020) and miR-25 (P=0.0030) in ESCC patients than controls. However, a significant correlation was observed between plasma miR-19b levels and concentrations of red blood cells (P=0.0073) and haemoglobin (P=0.0072). (3) miR-25 expression was found to be significantly higher in ESCC tissues (P=0.0157) and ESCC cell lines (P=0.0093) than in normal tissues and fibroblasts. (4) In a large-scale validation analysis, plasma miR-25 levels were significantly higher in 105 preoperative (P<0.0001) ESCC patients who underwent curative oesophagectomy and 20 superficial ESCC patients who underwent endoscopic resection (P<0.0001) than in 50 healthy volunteers. (5) Plasma miR-25 levels were significantly reduced in postoperative samples than in preoperative samples (P<0.0005) and were significantly increased during ESCC recurrences (P=0.0145). CONCLUSIONS: Plasma miR-25 might be a clinically useful biomarker for cancer detection and the monitoring of tumour dynamics in ESCC patients.

Time course analysis of mechanical ventilation-induced diaphragm contractile muscle dysfunction in the rat.

Controlled mechanical ventilation (CMV) plays a key role in triggering the impaired diaphragm muscle function and the concomitant delayed weaning from the respirator in critically ill intensive care unit (ICU) patients. To date, experimental and clinical studies have primarily focused on early effects on the diaphragm by CMV, or at specific time points. To improve our understanding of the mechanisms underlying the impaired diaphragm muscle function in response to mechanical ventilation, we have performed time-resolved analyses between 6 h and 14 days using an experimental rat ICU model allowing detailed studies of the diaphragm in response to long-term CMV. A rapid and early decline in maximum muscle fibre force and preceding muscle fibre atrophy was observed in the diaphragm in response to CMV, resulting in an 85% reduction in residual diaphragm fibre function after 9-14 days of CMV. A modest loss of contractile proteins was observed and linked to an early activation of the ubiquitin proteasome pathway, myosin:actin ratios were not affected and the transcriptional regulation of myosin isoforms did not show any dramatic changes during the observation period. Furthermore, small angle X-ray diffraction analyses demonstrate that myosin can bind to actin in an ATP-dependent manner even after 9-14 days of exposure to CMV. Thus, quantitative changes in muscle fibre size and contractile proteins are not the dominating factors underlying the dramatic decline in diaphragm muscle function in response to CMV, in contrast to earlier observations in limb muscles. The observed early loss of subsarcolemmal neuronal nitric oxide synthase activity, onset of oxidative stress, intracellular lipid accumulation and post-translational protein modifications strongly argue for significant qualitative changes in contractile proteins causing the severely impaired residual function in diaphragm fibres after long-term mechanical ventilation. For the first time, the present study demonstrates novel changes in the diaphragm structure/function and underlying mechanisms at the gene, protein and cellular levels in response to CMV at a high temporal resolution ranging from 6 h to 14 days.

The molecular trigger for high-speed wing beats in a bee.

The high-frequency wing beat of higher-order insects is driven by self-sustained oscillations of constantly activated flight muscles. However, whether its underlying mechanism is based on flight muscle-specific features or on preexisting contractile functions is unknown. Here, we recorded X-ray diffraction movies, at a rate of 5000 frames/second, simultaneously from the two antagonistic flight muscles of bumblebees during wing beat. Signals that occurred at the right timing for triggering each wing-beat stroke were resolved in both muscles. The signals likely reflect stretch-induced myosin deformation, which would also enhance force in vertebrate muscles. The results suggest that insects use a refined preexisting force-enhancing mechanism for high-frequency wing beat, rather than developing a novel mechanism.

Recognition of endoscopic diagnosis in differentiated-type early gastric cancer by flexible spectral imaging color enhancement with indigo carmine.

BACKGROUND/AIMS: To evaluate the usefulness of flexible spectral imaging color enhancement with indigo carmine (I-FICE) in early gastric cancer (EGC) demarcation. METHODS: The study participants were 29 patients with differentiated-type EGC. The endoscope was fixed and images of the same area of EGC demarcations in each lesion were obtained using four different methods (WLE, flexible spectral imaging color enhancement (FICE), CE, and I-FICE). FICE mode at R 550 nm (Gain: 2), G 500 nm (Gain: 4), and B 470 nm (Gain: 4) was used. Four endoscopists ranked the images obtained by each method on the basis of the ease of recognition of demarcation using a 4-point system. We calculated the standard deviation of pixel values based on L*, a*, and b* color spaces in the demarcation region (Lab-SD score). RESULTS: The median ranking score for I-FICE images was significantly higher than that obtained from the other methods. Further, the average Lab-SD score was significantly higher for I-FICE images than for images obtained by the other methods. There was a good correlation between the ranking score and Lab-SD score. CONCLUSION: EGC demarcations were most easily recognized both subjectively and objectively using I-FICE image, followed by CE, FICE and WLE images.

Treatment and prognosis of angiosarcoma of the scalp and face: a retrospective analysis of 48 patients.

OBJECTIVE: The objective of this study was to retrospectively analyse the treatment results of clinically localised angiosarcoma of the scalp and face. METHODS: The records of 48 patients who were treated between 1987 and 2009 were reviewed. single modality or a combination of surgery, radiotherapy, chemotherapy and immunotherapy were administered. The median follow-up of all 48 patients was 13.7 months (range 2.5-105.9 months). RESULTS: At the time of analysis, 45 of 48 patients (93.8%) had disease recurrences, and the lung was the most frequent site for recurrence (37 patients). In multivariate analysis, performance status (PS) and number of tumours were significant predictors of lung-metastasis-free (LMF) rate. For patients with multifocal tumours, chemotherapy use significantly decreased the LMF rate (p=0.0072). The 2-year actuarial overall survival (OS), progression-free survival and local control rates in all 48 patients were 22.1%, 10.7% and 46.3%, respectively. In multivariate analysis, PS, number of tumours, surgery and radiotherapy were significant prognostic factors for OS. Patients treated with both surgery and radiotherapy (2-year OS: 45.8%) had a significantly more favourable OS (p<0.0001) than patients treated with either surgery or radiotherapy (2-year OS: 11.1%) and patients treated with neither surgery nor radiotherapy (2-year OS: 0%). CONCLUSIONS: Our results indicated that PS and number of tumours were significant predictors for developing lung metastases. Our results also indicated that PS, number of tumours, surgery use and radiotherapy use were independent prognostic factors for OS. Multimodal treatments including surgery and radiotherapy were effective in improving OS for patients with these tumours. Advances in knowledge Multimodal treatments including surgery and radiotherapy are effective in improving overall survival for patients with angiosarcoma of the scalp and face.

Evaluating the peak-to-valley dose ratio of synchrotron microbeams using PRESAGE fluorescence.

Synchrotron-generated microbeam radiotherapy holds great promise for future treatment, but the high dose gradients present conventional dosimetry with a challenge. Measuring the important peak-to-valley dose ratio (PVDR) of a microbeam-collimated synchrotron source requires both a dosimeter and an analysis method capable of exceptional spatial resolution. The PVDR is of great interest since it is the limiting factor for potential application of the microbeam radiation therapy technique clinically for its tissue-sparing properties (i.e. the valley dose should be below the tolerance of normal tissue). In this work a new method of measuring the dose response of PRESAGE dosimeters is introduced using the fluorescence from a 638 nm laser on a confocal laser-scanning microscope. This fluorescent microscopy method produces dosimetry data at a pixel size as low as 78 nm, giving a much better spatial resolution than optical computed tomography, which is normally used for scanning PRESAGE dosimeters. Using this technique the PVDR of the BL28B2 microbeam at the SPring-8 synchrotron in Japan is estimated to be approximately 52:1 at a depth of 2.5 mm. The PVDR was also estimated with EBT2 GAFchromic films as 30.5:1 at the surface in order to compare the PRESAGE fluorescent results with a more established dosimetry system. This estimation is in good agreement with previously measured ratios using other dosimeters and Monte Carlo simulations. This means that it is possible to use PRESAGE dosimeters with confocal microscopy for the determination of PVDR.

Comparison of lens- and fiber-coupled CCD detectors for X-ray computed tomography.

X-ray imaging detectors with an identical phosphor and a CCD chip but employing lens- and fiber-coupling between them have been compared. These are designed for X-ray imaging experiments, especially computed tomography, at the medium-length beamline at the SPring-8 synchrotron radiation facility. It was found that the transmittance of light to the CCD is about four times higher in the fiber-coupled detector. The uniformity of response in the lens-coupled detector has a global shading of up to 40%, while pixel-to-pixel variation owing to a chicken-wire pattern was dominant in the fiber-coupled detector. Apart from the higher transmittance, the fiber-coupled detector has a few characteristics that require attention when it is used for computed tomography, which are browning of the fiber, discontinuity in the image, image distortion, and dark spots in the chicken-wire pattern. Thus, it is most suitable for high-speed tomography of samples that tend to deform, for example biological and soft materials.

Mechanism of latency relaxation in frog skeletal muscle.

The latency relaxation is a small drop of tension before skeletal muscle begins to develop active tension. This phenomenon was found nearly one century ago but its origin has not been clarified. In this review, the hypotheses for its mechanism are discussed in terms of the recent experimental results using X-ray diffraction. The latency relaxation takes place almost simultaneously as the structural change of the regulatory protein troponin, an unspecified structural change of the thick filament, and increase in stiffness. It seems difficult to associate all of these with the latency relaxation by assuming a simple mechanism.

A new approach for structure analysis of two-dimensional membrane protein crystals using X-ray powder diffraction data.

The application of powder diffraction methods to problems in structural biology is generally regarded as intractable because of the large number of unresolved, overlapping X-ray reflections. Here, we use information about unit cell lattice parameters, space group transformations, and chemical composition as a priori information in a bootstrap process that resolves the ambiguities associated with overlapping reflections. The measured ratios of reflections that can be resolved experimentally are used to refine the position, the shape, and the orientation of low-resolution molecular structures within the unit cell, in leading to the resolution of the overlapping reflections. The molecular model is then made progressively more sophisticated as additional diffraction information is included in the analysis. We apply our method to the recovery of the structure of the bacteriorhodopsin molecule (bR) to a resolution of 7 Å using experimental data obtained from two-dimensional purple membrane crystals. The approach can be used to determine the structure factors directly or to provide reliable low-resolution phase information that can be refined further by the conventional methods of protein crystallography.

Evaluation of the distribution and orientation of remineralized enamel crystallites in subsurface lesions by X-ray diffraction.

Remineralization is the process by which hydroxyapatite (HAp) is restored in enamel subsurface lesions, and transversal microradiography (TMR) has been used to analyze remineralization in terms of the recovery of mineral content. In this study, we directly detected the distribution and orientation of longitudinal HAp crystallite at the remineralized zone in enamel subsurface lesions by using an X-ray microbeam (6-mum diameter) diffraction method. This method was demonstrated and involves the simultaneous detection of wide-angle X-ray diffraction (WAXRD) and small-angle X-ray scattering (SAXS). WAXRD reflects the amount of HAp crystallites, and SAXS reflects that of voids in crystallites. The polished surface of a bovine enamel block was divided into three zones of sound, demineralized, and remineralized zones. Thin sections of approximately 150 mum thickness were then cut perpendicular to the surface, and subjected to WAXRD and SAXS following TMR. The increase in the amount of HAp crystallites and the decrease in voids in the crystallites at the remineralized zone were detected by WAXRD and SAXS, respectively, which was consistent with the result of TMR. This study indicates that both the spatial distribution and orientation of the restored HAp crystals in the remineralization process at the subsurface lesion can be simultaneously analyzed by the X-ray diffraction methods.

Websites offer helpful information concerning consultation with headache specialists.

Patients with severe primary headache may benefit from consultation with headache specialists, but doctor attendance rates in Japan are very low. More headache patients might consult headache specialists if these specialists were more widely recognized by the public. To determine what information prompted patients to seek consultation with a headache specialist, we questioned 256 primary headache patients about the source of the helpful information concerning consultation with headache specialists. From 191 patients, a total of 235 responses to the questionnaire were obtained. The most common response was 'websites' (33.2%), followed by 'professionals' (23.8%), 'acquaintances' (20.9%), 'print media' (6.8%) and 'TV/radio' (3.4%). Patients who indicated websites showed the most severe pain and highest impact of headache, and accounted for 52.4% of those with cluster headaches. Development of websites concerning headache specialists would seem likely to increase doctor attendance rates for patients with primary headache.

Endoscopic submucosal dissection for colorectal tumors: technical difficulties and rate of perforation.

BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) for colorectal tumors is not generally recommended because of the technical difficulties and complications, including perforation. These aspects of ESD are thoroughly analyzed in our retrospective study. PATIENTS AND METHODS: We studied 105 colorectal tumors, from 100 patients, that were treated by ESD at the Kyoto Prefectural University of Medicine or Nara City Hospital between 2005 and 2008. We analyzed tumor size, operation time, rate of en bloc resection, and complications. In addition, we thoroughly investigated the cases of perforation. RESULTS: The average tumor size was 30.4 mm; average operation time, 102 min; and rate of en bloc resection, 88.5 %. Perforation occurred in 10.4 % of the ESD procedures. Of the 11 perforations, 8 were detected during ESD and treated by clip closure during endoscopy, while 3 were evident only on subsequent routine computed tomography (CT); these were also managed conservatively. A case of postoperative hemorrhage was also observed. CONCLUSIONS: ESD effectively achieved a high rate of en bloc resection. However, the perforation rate was substantial; hence, improvement in the ESD method is required. The outcomes of ESD, especially for early colorectal malignancies, need to be assessed further.

Evaluation of enamel crystallites in subsurface lesion by microbeam X-ray diffraction.

Early caries lesion is a demineralization process that takes place in the top 0.1 mm layer of tooth enamel. In this study, X-ray microbeam diffraction was used to evaluate the hydroxyapatite crystallites in the subsurface lesion of a bovine enamel section and the results are compared with those obtained by transversal microradiography, a method commonly used for evaluation of tooth mineral. Synchrotron radiation from SPring-8 was used to obtain a microbeam with a diameter of 6 microm. Wide-angle X-ray diffraction reports the amount of hydroxyapatite crystals, and small-angle X-ray scattering reports that of voids in crystallites. All three methods showed a marked decrease in the enamel density in the subsurface region after demineralization. As these diffraction methods provide structural information in the nanometre range, they are useful for investigating the mechanism of the mineral loss in early caries lesion at a nanometre level.

Deterministic retrieval of complex Green's functions using hard X rays.

A massively parallel deterministic method is described for reconstructing shift-invariant complex Green's functions. As a first experimental implementation, we use a single phase contrast x-ray image to reconstruct the complex Green's function associated with Bragg reflection from a thick perfect crystal. The reconstruction is in excellent agreement with a classic prediction of dynamical diffraction theory.

A method of dosimetry for synchrotron microbeam radiation therapy using radiochromic films of different sensitivity.

This paper describes a method of film dosimetry used to measure the peak-to-valley dose ratios for synchrotron microbeam radiation therapy (MRT). Two types of radiochromic film (manufactured by International Specialty Products, NJ, USA) were irradiated in a phantom and also flush against a microbeam collimator (beam width 25 microm, centre-to-centre spacing 200 microm) on beamline BL28 B2 at the SPring-8 synchrotron. Four experiments are reported: (1) the HD-810 and EBT varieties of radiochromic film were used to record 'peak' dose and 'valley' (regions in between peaks) dose, respectively; (2) a stack of HD-810 film sheets was microbeam-irradiated and analysed to investigate a possible dose build-up effect; (3) a very high MRT dose was delivered to HD-810 film to elicit a measurable valley dose to compare with the result obtained using broad beam radiation; (4) the half value layer of the beam with and without the microbeam collimator was measured to investigate the effect of the collimator on the beam quality. The valley dose obtained for films placed flush against the collimator was approximately 0.2% of the peak dose. Within the water phantom, the valley dose had increased to between 0.7 and 1.8% of the peak dose, depending on the depth in the phantom. We also demonstrated, experimentally and by Monte Carlo simulation, that the dose is not maximal on the surface and that there is a dose build-up effect. The microbeam collimator did not make an appreciable difference to the beam quality. The values of the peak-to-valley ratio reported in this paper are higher than those predicted by previously published Monte Carlo simulation papers.

Dynamic measures of regional lung air volume using phase contrast x-ray imaging.

Phase contrast x-ray imaging can provide detailed images of lung morphology with sufficient spatial resolution to observe the terminal airways (alveoli). We demonstrate that quantitative functional and anatomical imaging of lung ventilation can be achieved in vivo using two-dimensional phase contrast x-ray images with high contrast and spatial resolution (<100 microm) in near real time. Changes in lung air volume as small as 25 microL were calculated from the images of term and preterm rabbit pup lungs (n = 28) using a single-image phase retrieval algorithm. Comparisons with plethysmography and computed tomography showed that the technique provided an accurate and robust method of measuring total lung air volumes. Furthermore, regional ventilation was measured by partitioning the phase contrast images, which revealed differences in aeration for different ventilation strategies.