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This paper proposes a rapid X‐ray fluorescence (XRF)‐based screening method for the determination of trace uranium in solutions. In this method, uranium present in a solution was adsorbed onto graphene oxide (GO), which was collected and subjected to XRF analysis. Upon increasing the sodium ion concentration, the aggregation of GO was promoted, facilitating its collection. Since the GO‐collecting membrane filter was significantly larger than the X‐ray irradiation field of the XRF spectrometer, it was folded to 1/3 of its original length and width. The folded membrane filter was sealed to prevent uranium from contaminating the device and to ensure that the folded membrane filter was sufficiently thin. Subsequently, the amount of sodium perchlorate added to the sample solution was optimized to attain a salinity meter reading of 3%. The minimum detection limit (MDL) for uranium using this method was 0.37 ng ml−1, and the time required to simultaneously analyze six samples was approximately 2 h. Converting the MDL to the radioactivity concentration under conservative conditions generated a value of 0.037 mBq cm−3. To demonstrate the applicability of this method, a standard seawater sample was subjected to analysis, and the uranium concentration determined using our calibration curve agreed with the actual value within a margin of error. Therefore, the proposed method is suitable for screening numerous uranium‐contaminated water samples of small volumes. [ABSTRACT FROM AUTHOR]

Molecular mechanisms underlying the nephrotoxicity associated with bevacizumab are unclear. Endothelin-1 (ET-1) is involved in podocyte injury and proteinuria, and its level increases in most cases of kidney disorders. Forkhead box protein O1 (FoxO1), a transcription factor, is a major determinant of ET-1 promoter activation and is regulated by protein kinase B (Akt) phosphorylation-dependent nuclear exclusion. We evaluated the effect of bevacizumab on ET-1 production in human glomerular microvascular endothelial cells (hGECs). We analyzed the changes in the mRNA and protein levels of ET-1 in hGECs treated with bevacizumab using real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Changes in the protein levels and phosphorylation status of Akt and FoxO1 in hGECs treated with bevacizumab were analyzed by western blotting. After cell lysis, FoxO1 protein was isolated from the cytoplasmic and nuclear fractions. We also investigated the effects of AS1842856 (a FoxO1 inhibitor) on bevacizumab-induced ET-1 production. Bevacizumab significantly and dose-dependently increased the mRNA and protein levels of ET-1 in hGECs (p < 0.05). Bevacizumab treatment also led to a decrease in phosphorylated Akt protein levels. Inhibition of Akt activity by LY294002 promoted ET-1 production. Bevacizumab also induced an increase in FoxO1 protein levels in the nucleus. Inhibition of FoxO1 activity by AS1842856 resulted in decreased ET-1 levels in bevacizumab-treated hGECs. ET-1 axis activation, Akt inactivation, and FoxO1 nuclear localization are the molecular mechanisms underlying bevacizumab-induced nephrotoxicity. Therefore, inhibition of renal ET-1 production could be a promising approach to protect against or treat bevacizumab-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Purpose: Eye‐tracking approaches have been used to understand the visual search process in radiology. However, previous eye‐tracking work in computer tomography (CT) has been limited largely to single cross‐sectional images or video playback of the reconstructed volume, which do not accurately reflect radiologists' visual search activities and their interactivity with three‐dimensional image data at a computer workstation (e.g., scroll, pan, and zoom) for visual evaluation of diagnostic imaging targets. We have developed a platform that integrates eye‐tracking hardware with in‐house‐developed reader workstation software to allow monitoring of the visual search process and reader‐image interactions in clinically relevant reader tasks. The purpose of this work is to validate the spatial accuracy of eye‐tracking data using this platform for different eye‐tracking data acquisition modes. Methods: An eye‐tracker was integrated with a previously developed workstation designed for reader performance studies. The integrated system captured real‐time eye movement and workstation events at 1000 Hz sampling frequency. The eye‐tracker was operated either in head‐stabilized mode or in free‐movement mode. In head‐stabilized mode, the reader positioned their head on a manufacturer‐provided chinrest. In free‐movement mode, a biofeedback tool emitted an audio cue when the head position was outside the data collection range (general biofeedback) or outside a narrower range of positions near the calibration position (strict biofeedback). Four radiologists and one resident were invited to participate in three studies to determine eye‐tracking spatial accuracy under three constraint conditions: head‐stabilized mode (i.e., with use of a chin rest), free movement with general biofeedback, and free movement with strict biofeedback. Study 1 evaluated the impact of head stabilization versus general or strict biofeedback using a cross‐hair target prior to the integration of the eye‐tracker with the image viewing workstation. In Study 2, after integration of the eye‐tracker and reader workstation, readers were asked to fixate on targets that were randomly distributed within a volumetric digital phantom. In Study 3, readers used the integrated system to scroll through volumetric patient CT angiographic images while fixating on the centerline of designated blood vessels (from the left coronary artery to dorsalis pedis artery). Spatial accuracy was quantified as the offset between the center of the intended target and the detected fixation using units of image pixels and the degree of visual angle. Results: The three head position constraint conditions yielded comparable accuracy in the studies using digital phantoms. For Study 1 involving the digital crosshairs, the median ± the standard deviation of offset values among readers were 15.2 ± 7.0 image pixels with the chinrest, 14.2 ± 3.6 image pixels with strict biofeedback, and 19.1 ± 6.5 image pixels with general biofeedback. For Study 2 using the random dot phantom, the median ± standard deviation offset values were 16.7 ± 28.8 pixels with use of a chinrest, 16.5 ± 24.6 pixels using strict biofeedback, and 18.0 ± 22.4 pixels using general biofeedback, which translated to a visual angle of about 0.8° for all three conditions. We found no obvious association between eye‐tracking accuracy and target size or view time. In Study 3 viewing patient images, use of the chinrest and strict biofeedback demonstrated comparable accuracy, while the use of general biofeedback demonstrated a slightly worse accuracy. The median ± standard deviation of offset values were 14.8 ± 11.4 pixels with use of a chinrest, 21.0 ± 16.2 pixels using strict biofeedback, and 29.7 ± 20.9 image pixels using general biofeedback. These corresponded to visual angles ranging from 0.7° to 1.3°. Conclusions: An integrated eye‐tracker system to assess reader eye movement and interactive viewing in relation to imaging targets demonstrated reasonable spatial accuracy for assessment of visual fixation. The head‐free movement condition with audio biofeedback performed similarly to head‐stabilized mode. [ABSTRACT FROM AUTHOR]

What is known and Objective: Cancer drug treatment is often discontinued because of skin disorder aggravation. However, information on risk factors for skin disorders caused by anti‐epidermal growth factor receptor (EGFR) antibody drugs is limited. The aim of this study was to analyse the factors associated with skin disorders caused by anti‐EGFR antibody drugs and establish a method to minimize such aggravations. Methods: We retrospectively examined 67 colorectal cancer patients treated with anti‐EGFR antibody drugs for the first time. Results and discussion: A higher proportion of males than females experienced drug withdrawal, dose reduction or treatment discontinuation. The multiple logistic regression analysis revealed body weight as a risk factor affecting drug withdrawal, dose reduction or treatment discontinuation because of an acneiform rash. An examination of methods to avoid the aggravation of skin disorders revealed the acneiform rash grade in patients who received prophylactic minocycline was significantly lower than that in patients who did not receive prophylactic minocycline. Furthermore, among patients with grade 1 acneiform rash at the initiation of minocycline, the proportion of those who withdrew, required dose reduction or discontinued treatment was lower than that among patients with grade 2 acneiform rash. What is new and Conclusion: High body weight was identified as a novel factor for skin disorder aggravation caused by anti‐EGFR antibody drugs. The aggravation of skin disorders during cancer treatment with anti‐EGFR antibody drugs can potentially be avoided by carefully observing the onset of acneiform rash in affected patients with high body weight and using minocycline prophylactically or as an early‐stage intervention. [ABSTRACT FROM AUTHOR]

Desbuquois dysplasia (DD) type 1 is a rare skeletal dysplasia characterized by a short stature, round face, progressive scoliosis, and joint laxity. The causative gene has been identified as calcium‐activated nucleotidase 1 (CANT1), which encodes a nucleotidase that preferentially hydrolyzes UDP to UMP and phosphate. In this study, we generated Cant1 KO mice using CRISPR/Cas9‐mediated genome editing. All F0 mice possessing frameshift deletions at both Cant1 alleles exhibited a dwarf phenotype. Germline transmission of the edited allele was confirmed in an F0 heterozygous mouse, and KO mice were generated by crossing of the heterozygous breeding pairs. Cant1 KO mice exhibited skeletal defects, including short stature, thoracic kyphosis, and delta phalanx, all of which are observed in DD type 1 patients. The glycosaminoglycan (GAG) content and extracellular matrix space were reduced in the growth plate cartilage of mutants, and proliferating chondrocytes lost their typical flat shape and became round. Chondrocyte differentiation, especially terminal differentiation to hypertrophic chondrocytes, was impaired in Cant1 KO mice. These findings indicate that CANT1 is involved in the synthesis of GAG and regulation of chondrocyte differentiation in the cartilage and contribute to a better understanding of the pathogenesis of DD type 1. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic accuracy of ultrasound (US) to diagnose the directionality of testicular rotation and the degree of spermatic cord twist in pediatric patients with testicular torsion. Methods: A retrospective review of 14 pediatric patients with testicular torsion was conducted. The directionality of testicular rotation was classified as an inner or outer direction (inner, counterclockwise in the left testis [viewed from below] and clockwise in the right testis; and outer, counterclockwise in the right testis and clockwise in the left testis). The Clopper‐Pearson method and the Fisher exact, Mann‐Whitney U, and Wilcoxon signed rank sum tests were used for the statistical analyses. Results: The diagnostic accuracy of US in the directionality of testicular rotation and the degree of spermatic cord twist were 78.6% (11 of 14; 95% confidence interval, 49.2%–95.3%) and 36.4% (4 of 11; 95% confidence interval, 10.9%–69.2%), respectively. Outer rotation was seen in 50.0% of the cases. The directionality of testicular rotation and the degree of spermatic cord twist as determined by US were not significantly different between the patients with salvaged testis and those with testicular loss (inner/outer direction, 4/2 versus 4/4; P =.627; mean twist ± SD, 330.0° ± 73.5° versus 337.5° ± 115.4°; P >.999). There was no significant difference in the degree of spermatic cord twist determined by US and surgical results (343.0° ± 97.1° versus 458.2° ± 168.2°; P =.063). Conclusions: The accuracy of US in determining the directionality of testicular rotation was relatively high in our small cohort. This information may be useful for pediatric surgeons and urologists when performing early manual reduction for testicular torsion. [ABSTRACT FROM AUTHOR]

A dermal sinus/fistula is a common condition; the relevant department should be consulted for appropriate treatment. It is important for radiologists to have adequate knowledge of these conditions to provide the correct diagnosis and recommend subsequent management. This review describes the following lesions: preauricular sinus, midline sinus of the upper lip, nasal dermoid sinus cyst, cheek fistula, first branchial cleft anomaly/sublingual branchial cleft anomaly, thyroglossal duct cyst/fistula, lateral cervical sinus/fistula, congenital dermal sinus/fistula of the anterior chest region, congenital skin sinus/fistula with a sternal cleft, and congenital prepubic sinus. On the basis of the skin orifice location and ultrasound images, radiologists can provide useful information to physicians. [ABSTRACT FROM AUTHOR]

A new method based on dispersive microsolid phase extraction using graphene oxide (GO) as a solid adsorbent and total reflection X‐ray fluorescence (TXRF) spectrometry is proposed for trace determination of uranium. In the developed methodology, a suspension of GO was injected into uranium‐spiked multielement solutions including rubidium; after filtration, the membrane filter with collected GO was placed in a small volume of internal standard acid solution and the eluent containing uranium was deposited onto a fluorine resin‐coated slide glass, which is a disposable sample stage. Using GO was effective for removal of rubidium from the measurement solution to avoid interference between Rb Kα peak and U Lα peak. The high enrichment factor of 150 enables obtaining uranium detection limits of 0.042, 0.087, and 0.12 μg L−1 for ionic strength of 0.01, 0.1, and 1 mol L−1, respectively. Such low detection limits were obtained by using a benchtop TXRF spectrometer with 5‐min measurement. The proposed method is suitable for trace uranium determination in water, including high salinity samples. [ABSTRACT FROM AUTHOR]

Objectives: To compare defect sizes in congenital diaphragmatic hernia (CDH) measured by postnatal ultrasound (US) between neonates who underwent thoracoscopic surgery and neonates who underwent open surgery and between neonates who underwent primary repair and those who underwent patch repair; additionally, to compare the accuracy of US diagnosis with that of surgical diagnosis for the location of the diaphragmatic hernia and the hernial contents. Methods: We included 8 neonates who underwent preoperative US evaluations of CDH. We compared anterior‐to‐posterior diaphragm defect sizes between thoracoscopic and open surgery approaches and between primary and patch repair by using the Mann‐Whitney U test. The diaphragm was divided into 3 segments: anterior, lateral, and posterior. We evaluated the location of the diaphragmatic hernia and the hernial contents. Results: Four neonates who underwent open surgery had larger diaphragmatic hernias than those who underwent thoracoscopic surgery (mean ± SD, 30.5 ± 5.6 versus 16.3 ± 3.3 mm; P = .030). They were also larger in neonates who underwent patch repair than in those who underwent primary repair (33.0 ± 3.0 versus 17.6 ± 4.2 mm; P = .037). Detection of anterior and lateral diaphragm segments was consistent between US and surgical findings. Three of 4 neonates who underwent open surgery and all 3 neonates who underwent patch repair did not show the lateral segment. The hernial contents were also consistent between US and surgical findings. Conclusions: Postnatal US examinations of neonates with CDH could provide surgeons with useful information to determine the surgical approach and repair method. However, since our study cohort was small, further studies are needed with a larger number of neonates with CDH. [ABSTRACT FROM AUTHOR]

Introduction: Single‐incision laparoscopic cholecystectomy (SILC) is more challenging than conventional (multiport) laparoscopic cholecystectomy (CLC) because of the increased likelihood of instrument collision and the limited surgical workspace. In SILC, procedural difficulties may increase when the port‐to‐target distance is long. We aimed to assess the correlation between port‐to‐target distance and procedural difficulty. Methods: Thirty‐six consecutive patients who underwent SILC at our hospital were included in this study. The umbilicus‐to‐Calot's triangle distance (UCD) was measured intraoperatively. The correlations between the UCD and operative time were analyzed, and for comparison, CLC cases during the same period (n = 28) were similarly analyzed. Moreover, UCD was estimated from preoperative CT (UCD‐CT), and the usefulness of UCD‐CT was assessed during SILC and CLC. Results: Thirty‐four patients successfully underwent SILC. There were positive correlations between the UCD and pneumoperitoneum time. Multivariate linear regression analysis, including BMI and height, which were previously reported to have a correlation with longer operative time in SILC, showed that UCD is an independent predictive factor for prolonged operative duration. However, BMI and height were not independent predictive factors. UCD and UCD‐CT had a very strong positive correlation; therefore, UCD was estimated from CT. UCD‐CT had a strong positive correlation with operative time in SILC, but not in CLC. Conclusions: A longer UCD is an important predictive factor for difficult cases of SILC, but this finding is not applicable in CLC. The usefulness of UCD is specific to SILC. [ABSTRACT FROM AUTHOR]

This report describes the evaluations of 2 patients with congenital diaphragmatic hernias using ultrasound (US). Identifying the size of the diaphragmatic defect is important when determining the type of surgical repair required. In case 1, the US evaluation of a Bochdalek hernia showed the rim of the anterolateral diaphragm; therefore, thoracoscopic primary repair was performed. In case 2, (Morgagni‐Larrey hernia), US revealed the left side of a retrosternal diaphragmatic hernia sac; therefore, thoracoscopic repair from the left thorax was performed. Ultrasound was useful for detecting the location and defect size of the diaphragmatic hernia and determining optimal surgical management. [ABSTRACT FROM AUTHOR]

Portal venous gas is occasionally encountered in children with intestinal pneumatosis, identified on real‐time ultrasound imaging as hyperechoic foci with quick movement. The origin of the portal venous gas can be identified by following the hyperechoic foci along the branches of the portal vein, providing an estimate of the location of intestinal pneumatosis. This approach may be useful for predicting the patient's prognosis. Our report describes 2 cases of portal venous gas while estimating the area of intestinal pneumatosis, which were evaluated with real‐time ultrasound. [ABSTRACT FROM AUTHOR]

Objective: An anorectal malformation (ARM) in neonates requires urgent surgery, with the type of surgery being dependent on the type of malformation (low, intermediate, or high). Distal rectal pouch and perineum (pouch‐perineum) distance is reported to be useful for differentiating the type of ARM; however, the impact of an opened fistula on pouch‐perineum distance is not well known. The purpose of this study was to evaluate the difference in pouch‐perineum distance between neonates with a low‐type ARM with and without an opened fistula. Methods: We included 24 neonates with low‐type ARM who underwent sonography before surgery. Eight neonates already had an opened fistula before sonography, and 16 did not. The pouch‐perineum distance was measured using the perineal approach. Mann‐Whitney U and Spearman's correlation coefficient tests were used for statistical analysis. Results: The mean pouch‐perineum distance in all neonates with a low‐type ARM was 8.3 ± 2.9 mm. The pouch‐perineum distance was substantially longer for an ARM with than without an opened fistula (10.6 ± 3.4 mm vs. 7.1 ± 1.7 mm; P = .02). No appreciable correlation was identified between the pouch‐perineum distance and the postnatal day of examination (ρ = −.23, P = .26) or birth weight (ρ = .15, P = .47). Conclusion: The pouch‐perineum distance is substantially longer in neonates with an ARM with an opened fistula than in those without an opened fistula. Caution should be exercised by the sonographic examiner in evaluating pouch‐perineum distance in neonates with an opened fistula to prevent an incorrect surgical procedure based on misdiagnosis of the type of ARM. [ABSTRACT FROM AUTHOR]

We estimate the velocity structures of P (Vp) and S waves (Vs) in southern Hokkaido, Japan, where a large number of crustal low‐frequency earthquakes (LFEs) have occurred. To investigate the relationship between structure and crustal seismicity, we compare the obtained velocity heterogeneity between the crustal LFE regions, which are characterized by active volcanoes, Quaternary volcanoes, and seismic swarms. The tomographic results show that low‐velocity zones (LVZs) with high Vp/Vs are located around the Moho discontinuity beneath active volcanoes, and the LVZs extend horizontally from beneath the active volcanoes to other LFE regions. In southern Hokkaido, crustal LFEs also appear inside and below the upper crust as well as around the Moho discontinuity. These intermediate‐depth and deep LFEs are located around the LVZs with a high Vp/Vs ratio, indicating the contribution of partial melt to the LFEs genesis, even at a distance from the active volcanoes. At intermediate depths of the crust, LFEs are distributed even in the high‐velocity zones, adjacent to the LVZs. This indicates that the partial melt migrations within the crust affect the activity of LFE at the intermediate depths. Below the seismic swarms in the upper crust, LVZs with crustal LFEs are distributed, probably owing to upward migrations of fluid originating from the solidification of the partial melt; this indicates a link between the shallow and deep crustal seismicity in southern Hokkaido. Key Points: Constructing detailed P and S wave velocity structures in southern Hokkaido, JapanPartial melt and their movement are related to the genesis of crustal low‐frequency earthquakesShallow and deep crustal seismicity are linked through fluid and melt migrations [ABSTRACT FROM AUTHOR]

We investigate seismic wave velocity structure and spatial distribution of the seismicity in the source region of the 2016 Kumamoto earthquake sequence. A one-dimensional mean velocity shows that the seismogenic zone has a high-velocity and low-Vp/Vs ratio relative to the average velocity structure of Kyushu Island. This indicates that the crust is relatively strong, capable of sustaining sufficiently high strain energy to facilitate two large ( M j > 6.5) earthquakes in close proximity to one another in rapid succession. Three-dimensional tomography of the seismogenic zone around the source of the 2016 Kumamoto earthquake sequence yields Vp = 6 km/s and Vs = 3.5 km/s. Most large-displacement areas (asperities) of the M j 7.3 event overlap with the seismogenic zone and the overlying surface layer. Aftershock seismicity is distributed deeper than the conventional seismogenic zone, which suggests decreased strength due to fluids or increased stress, both caused by coseismic slip. [ABSTRACT FROM AUTHOR]

Breast cancer patients have a generally increased risk of developing second cancers. The object of this study was to clarify the increased as well as decreased incidence of cancers in breast cancer patients using autopsy cases. 164 211 autopsy cases in the Annual of Pathological Autopsy Cases in Japan from 2002 to 2010 were analyzed for multiple primary cancer (MPC). Female MPC cases (4222 cases) were selected. We investigated the cancer incidence observed in breast cancer associated MPC. The Chi-squared test was used for analysis. All P-values were two-sided, and differences at P < 0.05 were considered significant. Breast cancer associated MPC showed a significantly increased incidence of ovarian, pancreatic, and skin cancer (Odds Ratio [95 % confidence interval (CI)]) = 1.464 [1.03, 2.08], 1.414 [1.08, 1.85] and 2.092 [1.28, 3.41]), and a decreased incidence of colorectal and cervical cancer (OR [95 % CI]) = 0.732 [0.60, 0.90], 0.605 [0.38, 0.96]). Our findings of an increased incidence of malignancies in breast cancer associated MPC cases were consistent with the results of previous population-based studies. This study is the first study to analyze massive autopsy data on MPC which provide new evidence clinically and pathologically. [ABSTRACT FROM AUTHOR]

Mono- (Cu or Au) and bi-metallic AuCu nanoparticles were prepared by a modified polyol reduction method and deposited onto Al2O3 followed by calcination at 500°C in air. The synthesised catalysts were tested for their activity for NO reduction with CO in excess H2O between 50 and 500°C at a contact time relevant for automotive convertors. The bi-metallic catalysts showed a significantly higher activity than Cu/Al2O3 and Au/Al2O3, and the latter was inert for the target reaction. In addition, the activity depended greatly on the Au/Cu ratio, which thus demonstrates a synergy effect between these two metals. Operando UV/Vis spectroscopy provided direct evidence for the transformation of initially oxidised CuOx species into metallic Cu0, which is the only active species for NO reduction. Promotion with Au was found to accelerate the reduction of Cu2+/Cu+ to Cu0. [ABSTRACT FROM AUTHOR]

Human gut microbiota is being increasingly recognized as a player in colorectal cancers (CRCs). Evidence suggests that Fusobacterium nucleatum ( F. nucleatum) may contribute to disease progression and is associated with CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in CRCs; however, to date, there are no reports about the relationship between F. nucleatum and molecular features in the early stage of colorectal tumorigenesis. Therefore, we investigated the presence of F. nucleatum in premalignant colorectal lesions. In total, 465 premalignant lesions (343 serrated lesions and 122 non-serrated adenomas) and 511 CRCs were studied. We determined the presence of F. nucleatum and analyzed its association with molecular features including CIMP, MSI and microRNA-31 status. F. nucleatum was detected in 24% of hyperplastic polyps, 35% of sessile serrated adenomas (SSAs), 30% of traditional serrated adenomas (TSAs) and 33% of non-serrated adenomas. F. nucleatum was more frequently detected in CIMP-high premalignant lesions than in CIMP-low/zero lesions ( p = 0.0023). In SSAs, F. nucleatum positivity increased gradually from sigmoid colon to cecum ( p = 0.042). F. nucleatum positivity was significantly higher in CRCs (56%) than in premalignant lesions of any histological type ( p < 0.0001). In conclusion, F. nucleatum was identified in premalignant colorectal lesions regardless of histopathology but was more frequently associated with CIMP-high lesions. Moreover, F. nucleatum positivity increased according to histological grade, suggesting that it may contribute to the progression of colorectal neoplasia. Our data also indicate that F. nucleatum positivity in SSAs may support the 'colorectal continuum' concept. [ABSTRACT FROM AUTHOR]

A liquid-phase split-type synthesis of all the stereoisomers of dendroamide A, which exhibits multidrug-resistance reversing activity, has been carried out. The key to the concise synthesis was the fluorous-Fmoc protection strategy of each of the starting materials ( D- and L-alanine and D- and L-valine). By using the fluorous-Fmoc encoding method, the target stereoisomers were effectively synthesized individually in fewer steps than by the corresponding linear synthetic routes. [ABSTRACT FROM AUTHOR]

The CpG island methylator phenotype (CIMP) is a distinct form of epigenomic instability. Many CIMP-high colorectal cancers (CRCs) with BRAF mutation are considered to arise from serrated pathway. We recently reported that microRNA-31 (miR-31) is associated with BRAF mutation in colorectal tumors. Emerging new approaches have revealed gradual changes in BRAF mutation and CIMP-high throughout the colorectum in CRCs. Here, we attempted to identify a possible association between miR-31 and epigenetic features in serrated pathway, and hypothesized that miR-31 supports the 'colorectal continuum' concept. We evaluated miR-31 expression, BRAF mutation and epigenetic features including CIMP status in 381 serrated lesions and 222 non-serrated adenomas and examined associations between them and tumor location (rectum; sigmoid, descending, transverse and ascending colon and cecum). A significant association was observed between high miR-31 expression and CIMP-high status in serrated lesions with BRAF mutation ( p = 0.0001). In contrast, miR-31 was slightly but insignificantly associated with CIMP status in the cases with wild-type BRAF. miR-31 expression in sessile serrated adenomas (SSAs) with cytological dysplasia was higher than that in SSAs, whereas, no significant difference was observed between traditional serrated adenomas (TSAs) and TSAs with high-grade dysplasia. The frequency of miR-31, BRAF mutation CIMP-high and MLH1 methylation increased gradually from the rectum to cecum in serrated lesions. In conclusion, miR-31 expression was associated with CIMP-high status in serrated lesions with BRAF mutation. Our data also suggested that miR-31 plays an important role in SSA evolution and may be a molecule supporting the colorectal continuum. [ABSTRACT FROM AUTHOR]

Background: Congenital diaphragmatic hernia (CDH) mortality still remains high, due to lung hypoplasia and persistent pulmonary hypertension of the neonate (PPHN). Effective management of PPHN and time of operation are quite important to the improvement of CDH treatment. In order to determine the optimal time for operation, we monitored PPHN with cardiac ultrasound. Methods: PPHN was assessed with three parameters: patent ductus arteriosus flow patterns (PDAFP), %left ventricular diameter at diastole, and left ventricular fraction of shortening (LVFS). Four patients with an antenatal diagnosis were treated under this protocol. Diaphragm repair was performed when PDAFP became left to right shunt dominant and the pre- and postoperative course was analyzed with regular chart reviews. Results: The alveolar-arterial oxygen difference levels of four patients were 590, 335, 613 and 530 mmHg, and operations were carried out when the patients were 2, 2, 3 and 2 days old, respectively. In three of the four patients (all except case 3) the PDAFP changed from right to left shunt dominant or bidirectional (BD), to left to right shunt dominant within 48 h. The %left ventricular diameter at diastole was relatively stable around the time of operation. The LVFS of all patients decreased after the operation. Only the LVFS of case 3 decreased temporarily to less than 30% (which indicates poor left ventricular function) but recovered. No patients needed extracorporeal membrane oxygenation support. All patients survived the procedure and were extubated. Case 3, who took 10 days to become left to right shunt dominant after the operation, needed home oxygenation therapy for 10 months. Conclusions: PDAFP was a reliable marker of PPHN on a high-frequency oscillatory ventilator to determine the optimal time for the operation for CDH. The optimal time for operation is supposed to be the time when PDAFP become left to right shunt dominant. [ABSTRACT FROM AUTHOR]

We examined 73 children with respiratory infections for Chlamydophila (Chlamydia) pneumoniae and Mycoplasma pneumoniae using real-time PCR assay and serological tests. C. pneumoniae and M. pneumoniae infections were found in 11 (15.1%) and 6 (8.2%) cases, respectively. The sensitivities and specificities of real-time PCR versus definite diagnosis of acute infection were 63.6% and 100% for C. pneumoniae, and 100% and 100% for M. pneumoniae, respectively. C. pneumoniae PCR-negative results appeared to be due to poor growth of the organism. The sensitivity and specificity of ImmunoCard tests were 33.3% and 82.1%, respectively, indicating that the efficacy of rapid diagnosis was disputable. The present results suggest that real-time PCR is suitable for rapid diagnosis as a first screening test to determine first-line antibacterial agents to be used against these infectious diseases. [ABSTRACT FROM AUTHOR]

Background: Patients with a defect in methylmalonyl-coenzyme A mutase (MCM) are classified as having methylmalonic acidemia, which is divided into two subclasses: mut0 and mut−. Fifty-five disease-causing mutations have been identified. Although most are private mutations, only three (E117X, G717V, and N219Y) are reportedly common in Japanese, Black, and Caucasian populations, respectively. Here we identified mutations in 11 Japanese patients with MCM deficiency. Methods: Mutational analysis was performed in 11 unrelated Japanese patients with MCM deficiency using polymerase chain reaction and direct sequencing. Results: Three novel (L494X, R727X, and 449_461del) and six previously reported (R93H, E117X, N219Y, R369H, G648D and IVS2 + 5G>A) mutations were identified. The L494X mutation was found in three unrelated patients, and the R93H, E117X, R369H, G648D, and IVS2 + 5G>A mutations occurred more than once. Two of the patients were classified as mut− phenotype because of residual [14C]-propionate incorporation in the presence of a high concentration of hydroxocobalamin. The two mut− patients were heterozygous for the G648D mutation and presented with lethargy and metabolic acidosis after 2 years of life. Their psychomotor development has been documented as normal. The patients with the R727X or 449_461del mutations clinically exhibited mut0 phenotype. Two patients with mut0 phenotype died in infancy. One presented early in the neonatal period; the other was symptomatic in the late infantile period. Conclusions: The L494X, R93H, E117X, R369H, G648D, and IVS2 + 5G>A mutations are found in more than two unrelated families in the Japanese population. The short-term outcome was generally poor in patients with mut0, and therefore alternative treatments should be considered. [ABSTRACT FROM AUTHOR]

Examines the cytofluorometric DNA analysis by stathmokinetic method of experimental thyroid neoplasms in rats. Administration of carcinogenic substance; Use of vincristine in the process of tumorigenesis and progression; Discussion on the histological differences between aneuploid and diploid in the mitotic index.

This case report describes two siblings with a dyskinetic form of cerebral palsy who had repeated episodes of fever-induced bilateral ballistic movements. The boy and his sister experienced the first episodes during early childhood. The movements developed over several hours and required rapid intervention. Electroencephalograms during the attacks showed no paroxysms, and brain magnetic resonance imaging scans revealed no lesions. The brother died of acute renal failure at age 5 due to rhabdomyolysis after his fifth episode of prolonged bilateral ballistic movements. This is the first report of an inherited disorder characterized by repeated episodes of violent movements. © 2007 Movement Disorder Society [ABSTRACT FROM AUTHOR]

The article presents a case study of a five-year-old boy with cerebral palsy due to neonatal asphyxia who was inflicted with valproate hepatotoxicity. Information on Alpers' syndrome is presented and the initiation of carbamazepin therapy for the boy is reported. Results of the study also indicated that neonatal asphyxia was the cause of initial brain damage.

Review: [43 refs. [ABSTRACT FROM AUTHOR]

Autism has been associated with chromosomal aberrations, including duplications at chromosome 4, and the identification of genetic factors contributing to the etiology of this disease is the focus of much research. Here we report a Japanese girl with mosaic of chromosome 4p duplication, mos 46,XX,dup(4)(p12p16)[54]/46,XX[6], who was diagnosed with autism at 3 years of age. Fluorescence in situ hybridization (FISH) with probes covering the region spanning a cluster of the gamma aminobutyric acid A (GABA-A) receptor subunit genes in the proximal short arm of chromosome 4 demonstrated total three signals for the GABRG1, GABRA4, and GABRA2 genes, but only two signals for GABRB1. This suggests that aberrant copy number of the GABA-A receptor subunit genes may contribute to the etiology of autism in this patient., (2007 Wiley-Liss, Inc.)