Neutrophil Extracellular Trap Formation and Deoxyribonuclease I Activity in Patients with Otitis Media with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

INTRODUCTION: No previous studies have evaluated the levels of neutrophil extracellular trap (NET) remnants or the importance of deoxyribonuclease (DNase) I activity based on the disease activity of otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV). The aim of this study was to explore the formation of NETs in the middle ear of patients with OMAAV during the onset and remission phases of the disease, with a particular focus on the relationships between the quantifiable levels of NET remnants and DNase I activity. METHODS: OMAAV patients were eligible for inclusion. Patients with otitis media with effusion (OME) were examined as controls. The levels of cell-free deoxyribonucleic acid (DNA), citrullinated-histone H3 (cit-H3)-DNA complex, and myeloperoxidase (MPO)-DNA complex were quantified using an enzyme-linked immunosorbent assay. DNase I activity was measured using a fluorometric method. RESULTS: The quantifiable levels of cell-free DNA, cit-H3-DNA complex, and MPO-DNA complex in the middle ear lavage of patients with OMAAV at onset were significantly higher than those in patients with OMAAV at remission and in patients with OME. DNase I activity in the patients with OMAAV at onset was significantly lower than those in patients with OMAAV at remission and OME and was negatively correlated with the level of MPO-DNA complex. CONCLUSIONS: This study suggests that NET remnants and DNase I activity may be potentially useful biomarkers for the diagnosis and disease activity of OMAAV.

Validity of endoscopic ossiculoplasty immediately after its introduction for ossicular chain disruption.

BACKGROUND: Transcanal endoscopic ear surgery (TEES) reportedly requires a long learning curve and may be associated with more complications and longer operative times than microscopic ear surgery (MES). In this study, we aimed to examine the usefulness and validity of TEES for ossicular chain disruption in the early stages of its introduction in our institution. METHODS: TEES was performed on 11 ears (10 with congenital ossicular chain discontinuity and 1 with traumatic ossicular chain dislocation), and MES was performed with a retroauricular incision on 18 ears (6 with congenital ossicular chain discontinuity and 12 with traumatic ossicular chain dislocation) in a tertiary referral center. Postoperative hearing results, operative times, and postoperative hospital length of stay were retrospectively reviewed. The Mann-Whitney U test and Fisher's exact test was performed to compare variables between the TEES and MES groups. Pre- and postoperative air- and bone-conduction thresholds and the air-bone gap of each group were compared using the Wilcoxon signed-rank test. The Mann-Whitney U test and Wilcoxon signed-rank was performed to compare the pre- and postoperative air-bone gaps between the diagnoses. RESULTS: No significant differences in the postoperative air-conduction thresholds, bone-conduction thresholds, air-bone gaps, or incidence of air-bone gap ≤ 20 dB were observed between the TEES and MES groups. The air-conduction thresholds and air-bone gaps of the TEES group significantly improved postoperatively. The air-conduction thresholds and air-bone gaps of the MES group also significantly improved postoperatively. No significant difference was observed in the operative times between the groups (TEES group: median, 80 min; MES group: median, 85.5 min). The TEES group had a significantly shorter postoperative hospital stay (median, 2 days) than the MES group (median, 7.5 days). CONCLUSIONS: TEES was considered appropriate for the treatment of ossicular chain disruption, even immediately after its introduction at our institution. For expert microscopic ear surgeons, ossicular chain disruption may be considered a suitable indication for the introduction of TEES.

Nanosheet coating improves stability of human pluripotent stem cell culture on glass substrates.

High-resolution imaging analysis using various types of cells is an essential tool for dissecting cell functions. Generally, obtaining such images requires the cells to be cultured on glass substrates; however, it often results in the unstable status of cells. In this study, we report that coating the glass substrate using nanosheet composed of hydrophobic polystyrene, with Matrigel, significantly improves the viability of human pluripotent stem cells (hPSCs). Moreover, the nanosheet coating does not affect the transcriptome status of hPSC and enables researchers to perform the high-resolution imaging assay. These results indicate that the nanosheet coating is beneficial to the cells vulnerable to glass substrate culture. Using the nanosheet coating, we revealed that the spreading status of lnc RNA XIST, essential for X-chromosome inactivation (XCI) in female cells, in the nuclei significantly differs in each hPSC line. Taken together, our study provides a novel method to investigate biological questions using high-resolution imaging techniques.

Salivary fluoride concentrations following toothbrushing with experimental toothpaste containing surface pre-reacted glass-ionomer (S-PRG) filler.

BACKGROUND: Single-blind 9 case comparative studies were conducted to evaluate salivary fluoride concentrations following toothbrushing using experimental toothpaste containing surface pre-reacted glass-ionomer (S-PRG) fillers. Preliminary tests were conducted in order to determine the volume of usage as well as the concentrations (wt %) of S-PRG filler. Based on the results given these experiments, we compared the salivary fluoride concentrations following toothbrushing with 0.5 g of 4 different types of toothpastes: 5 wt % S-PRG filler, 1400 ppm F AmF (amine fluoride), 1500 ppm F NaF (sodium fluoride), and MFP (monofluorophosphate) containing toothpaste. METHODS: Of the 12 participants, 7 participated in the preliminary study and 8 in the main study. All participants brushed their teeth using the scrubbing method for 2 min. At first, 1.0 and 0.5 g of 20 wt % S-PRG filler toothpastes were used to compare, then followed by 0.5 g of 0 (control), 1, and 5 wt % S-PRG toothpastes, respectively. The participants spat out once and rinsed with 15 mL of distilled water for 5 s. Saliva was collected for 3 min each at different time intervals of 0 (baseline), 5, 10, 15, 30, 60, 120, and 180 min after the rinsing. Fluoride concentrations were determined using a fluoride electrode, and the area under the salivary clearance - time curve (AUC: ppm‧min) of each toothpaste was calculated as the salivary fluoride retention. The main study was then conducted to evaluate the salivary fluoride concentrations as well as the AUC value using 0.5 g of 5 wt % S-PRG filler toothpaste, followed by NaF, MFP, and AmF toothpastes. RESULTS: Since there were no statistical differences between using 1.0 and 0.5 g of 20 wt % S-PRG toothpastes in salivary fluoride concentrations as well as the AUC value throughout the 180 min measurement, the volume was set as 0.5 g for the following studies. Concentrations of 5 and 20 wt % S-PRG toothpastes retained 0.09 ppm F or more in saliva even after 180 min. No statistical differences were seen in the salivary fluoride concentrations at any time intervals as well as the AUC value between 5 and 20 wt % S-PRG toothpastes. Based on these results, the concentration of 5 wt % S-PRG toothpaste was used for the main comparative study. MFP toothpaste resulted in by far the lowest salivary fluoride concentrations (0.06 ppm F at 180 min) and the AUC value (24.6 ppm‧min), whereas 5 wt % S-PRG toothpaste (0.15 ppm F at 180 min, 92.3 ppm‧min) displayed retention on par with AmF toothpaste which appeared to result in higher values (0.17 ppm F at 180 min, 103 ppm‧min), compared to NaF toothpaste (0.12 ppm F at 180 min, 49.3 ppm‧min). CONCLUSIONS: The salivary fluoride concentrations following toothbrushing with 0.5 g of 5 wt % S-PRG filler containing toothpaste showed retention similar to the best performing 1400 ppm F AmF toothpaste even 180 min after toothbrushing.

Synthesis of Carbon Nanoparticles with Cobalt-Rich Shell via Pyrolysis of Zn-ZIF@Co/Zn-ZIF: Relevance of Co(III) Precursors.

To the best of our knowledge, this is the first report on the rapid one-pot synthesis of a unique core-shell-structured zeolitic imidazolate framework (ZIF) using Co(III) and Zn(II) precursors. The key to obtaining this unique structure is the use of a Co(III) precursor as the starting material. Transmission electron microscopy (TEM) reveals that Co was present within a 30-nm-thick shell layer of the ZIF material. Thermal decomposition of the ZIF material affords core-shell-structured carbon nanoparticles that have Co on the external surface of the carbon grain. We have previously demonstrated that this carbonaceous material obtained by thermal decomposition exhibited high performance as an adsorbent for nitric oxide, even in the presence of excess oxygen and water vapor, and therefore, it was a suitable material for NOx elimination at low temperatures. The growth mechanism of the synthesized ZIF particles and the differences between synthesized ZIF and conventional Co(II)-ZIF-67 are discussed. The reactivity of the Co(III) precursor is much lower than that of the Co(II) species, leading to slower precipitation of Co(III) than that of Zn(II), thus forming the core-shell structure.

Association of gene mutations with clinicopathologic features in patients with external auditory canal squamous cell carcinoma.

BACKGROUND: External auditory canal squamous cell carcinoma (EACSCC) is a rare form of malignant tumor. Due to the extremely limited understanding of the genomic landscape in EACSCC, the association between gene mutations and clinicopathologic features remains unclear. This study aimed to explore somatic gene mutations associated with the clinicopathological features in patients with EACSCC, and to identify the candidate gene mutations for predicting survival outcome in EACSCC. METHODS: Twenty-two tissue samples obtained from patients with EACSCC were analyzed for genetic mutations based on targeted next-generation sequencing and genetic expression based on IHC staining to investigate the driver of tumorigenesis and/or the candidates of genes for predicting clinical outcome in EACSCC. RESULTS: Gene alterations were most frequently observed in TP53 (59.1%), followed by CREBBP (9.1%). TP53 mutations showed significant correlation with T classification (P = 0.027) and p53 expression phenotype (P < 0.001). The 5-year overall survival (OS) rates for EACSCC patients with TP53 mutations and wild-type TP53 were 45.0% and 75.0%, respectively. Multivariable analysis using the Cox proportional hazards model demonstrated that TP53 mutations were independent predictors of OS rates for EACSCC patients (P = 0.007). CONCLUSION: This study has suggested that TP53 mutations have potential for use as a biomarker for identifying individuals at high risk of developing tumors and for predicting survival outcome in EACSCC. IHC staining for p53 might play a useful role as screening tool for detecting TP53 mutations in patients with EACSCC.

Reducing stray radiation with a novel detachable lead arm support in percutaneous coronary intervention.

BACKGROUND: Placing radioprotective devices near patients reduces stray radiation during percutaneous coronary intervention (PCI), a promising technique for treating coronary artery disease. Therefore, lead arm support may effectively reduce occupational radiation dose to cardiologists. PURPOSE: We aimed to estimate the reduction of stray radiation using a novel detachable lead arm support (DLAS) in PCI. MATERIALS AND METHODS: A dedicated cardiovascular angiography system was equipped with the conventional 0.5-mm lead curtain suspended from the table side rail. The DLAS was developed using an L-shaped acrylic board and detachable water-resistant covers encasing the 0.5-, 0.75-, or 1.0-mm lead. The DLAS was placed adjacent to a female anthropomorphic phantom lying on the examination tabletop at the patient entrance reference point. An ionization chamber survey meter was placed 100 cm away from the isocenter to emulate the cardiologist's position. Dose reduction using the L-shaped acrylic board, DLAS, lead curtain, and their combination each was measured at five heights (80-160 cm in 20-cm increments) when acquiring cardiac images of the patient phantom with 10 gantry angulations, typical for PCI. RESULTS: Median dose reductions of stray radiation using the L-shaped acrylic board were 9.0%, 8.8%, 12.4%, 12.3%, and 6.4% at 80-, 100-, 120-, 140-, and 160-cm heights, respectively. Dose reduction using DLAS with a 0.5-mm lead was almost identical to that using DLAS with 0.75- and 1.0-mm leads; mean dose reductions using these three DLASs increased to 16.2%, 45.1%, 66.0%, 64.2%, and 43.0%, respectively. Similarly, dose reductions using the conventional lead curtain were 95.9%, 95.5%, 83.7%, 26.0%, and 19.6%, respectively. The combination of DLAS with 0.5-mm lead and lead curtain could increase dose reductions to 96.0%, 95.8%, 93.8%, 71.1%, and 47.1%, respectively. CONCLUSIONS: DLAS reduces stray radiation at 120-, 140-, and 160-cm heights, where the conventional lead curtain provides insufficient protection.

Effect of equalization filters on measurements with kerma-area product meter in a cardiovascular angiography system.

PURPOSE: This study aimed to evaluate the effect of equalization filters (EFs) on the kerma-area product ( K A P Q K M ) and incident air-kerma ( K a , i , Q K M ) using a kerma-area product (KAP) meter. In addition, potential underestimations of the K a , i , Q K M values by EFs were identified. MATERIALS AND METHODS: A portable flat-panel detector (FPD) was placed to measure the X-ray beam area (A) and EFs dimension at patient entrance reference point (PERP). Afterward, a 6-cm3 external ionization chamber was placed to measure incident air-kerma ( K a , i , Q e x t ) at PERP instead of the portable FPD. KAP reading and K a , i , Q e x t were simultaneously measured at several X-ray beam qualities with and without EFs. The X-ray beam quality correction factor by KAP meter ( k Q , Q 0 K M ) was calculated by A, K a , i , Q e x t and KAP reading to acquire the K A P Q K M and K a , i , Q K M . Upon completion of the measurements, K A P Q K M , K a , i , Q K M , and K a , i , Q e x t were plotted as functions of tube potential, spectral filter, and EFs dimension. Moreover, K a , i , Q K M / K a , i , Q e x t values were calculated to evaluate the K a , i , Q K M underestimation. RESULTS: The k Q , Q 0 K M values increased with an increase in the X-ray tube potential and spectral filter, and the maximum k Q , Q 0 K M was 1.18. K A P Q K M and K a , i , Q K M decreased as functions of EFs dimension, whereas K a , i , Q e x t was almost constant. K a , i , Q K M / K a , i , Q e x t decreased with an increase in EFs dimension but increased with an increase in tube potential and spectral filter, and the range was 0.55-1.01. CONCLUSIONS: K a , i , Q K M value was up to approximately two times lower than the K a , i , Q e x t values by EFs. When using the K a , i , Q K M value, the potential K a , i , Q K M underestimation with EFs should be considered.

Determination of geometric information and radiation field overlaps on the skin in percutaneous coronary interventions with computer-aided design-based X-ray beam modeling.

PURPOSE: This study aimed to develop a method for the determination of the source-to-surface distance (SSD), the X-ray beam area in a plane perpendicular to the beam axis at the entrance skin surface (Ap ), and the X-ray beam area on the actual skin surface (As ) during percutaneous coronary intervention (PCI). MATERIALS AND METHODS: Male and female anthropomorphic phantoms were scanned on a computed tomography scanner, and the data were transferred to a commercially available computer-aided design (CAD) software. A cardiovascular angiography system with a 200 × 200 mm flat-panel detector with a field-of-view of 175 × 175 mm was modeled with the CAD software. Both phantoms were independently placed on 40 mm thick pads, and the examination tabletop at the patient entrance reference point. Upon panning, the heart center was aligned to the central beam axis. The SSD, Ap , and As were determined with the measurement tool and Boolean intersection operations at 10 gantry angulations. RESULTS: The means and standard deviations of the SSD, Ap , and As for the male and female phantoms were 573 ± 15 and 580 ± 15 mm, 8799 ± 1009 and 9661 ± 1152 mm2 , 10495 ± 602 and 11913 ± 600 mm2 , respectively. The number of As overlaps for the male and female phantoms were 15/45 and 21/45 view combinations, respectively. CONCLUSIONS: CAD-based X-ray beam modeling is useful for the determination of the SSD, Ap , and As . Furthermore, the knowledge of the As distribution helps to reduce the As overlap in PCI.

[Measurement Accuracy of CT Beam Width with a Portable Flat-panel Detector].

PURPOSE: X-ray film or computed radiography (CR) system has been employed in clinical setting, and these devices are gradually replaced by portable flat-panel detector (FPD) systems. They may be employed to measure the beam width instead of the traditional CR system. In this study, we estimated the accuracy of beam width measured by the portable FPD system. METHOD: A CR cassette and FPD were placed at the isocenter, and the pixel values were measured in a single axial CT scanning at a tube potential of 80 kVp, tube currents of 10-40 mA (5 mA steps), and tube rotation time of 0.5 s. Then, the FPD was sandwiched between 0.5 mm copper plate and 2 mm lead plate to avoid the pixel saturation and artifact from the FPD electronic substrates. The beam widths were measured at selected nominal beam widths (40, 80, 120 and 160 mm) using a double exposure technique (tube currents of 10 and 20 mA). RESULT: Log-linear relationships for two systems were obtained between the pixel value and radiation exposure for parameters less than or equal to 12.5 mAs. A test for the equivalence with confidence intervals showed that the measurement accuracy of the CR and FPD systems was equivalent. CONCLUSION: The portable FPD system could be utilized for the measurement of the CT beam width as well as CR system.

Fabrication of a nanofiber Bragg cavity with high quality factor using a focused helium ion beam.

Nanofiber Bragg cavities (NFBCs) are solid-state microcavities fabricated in an optical tapered fiber. NFBCs are promising candidates as a platform for photonic quantum information devices due to their small mode volume, ultra-high coupling efficiencies, and ultra-wide tunability. However, the quality (Q) factor has been limited to be approximately 250, which may be due to limitations in the fabrication process. Here we report high Q NFBCs fabricated using a focused helium ion beam. Whenan NFBC with grooves of 640 periods is fabricated, the Q factor is over 4170, which is more than 16 times larger than that previously fabricated using a focused gallium ion beam.

Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice.

In female mammals, activation of Xist (X-inactive specific transcript) is essential for establishment of X chromosome inactivation. During early embryonic development in mice, paternal Xist is preferentially expressed whereas maternal Xist (Xm-Xist) is silenced. Unlike autosomal imprinted genes, Xist imprinting for Xm-Xist silencing was erased in cloned or parthenogenetic but not fertilized embryos. However, the molecular mechanism underlying the variable nature of Xm-Xist imprinting is poorly understood. Here, we revealed that Xm-Xist silencing depends on chromatin condensation states at the Xist/Tsix genomic region and on Rnf12 expression levels. In early preimplantation, chromatin decondensation via H3K9me3 loss and histone acetylation gain caused Xm-Xist derepression irrespective of embryo type. Although the presence of the paternal genome during pronuclear formation impeded Xm-Xist derepression, Xm-Xist was robustly derepressed when the maternal genome was decondensed before fertilization. Once Xm-Xist was derepressed by chromatin alterations, the derepression was stably maintained and rescued XmXpΔ lethality, indicating that loss of Xm-Xist imprinting was irreversible. In late preimplantation, Oct4 served as a chromatin opener to create transcriptional permissive states at Xm-Xist/Tsix genomic loci. In parthenogenetic embryos, Rnf12 overdose caused Xm-Xist derepression via Xm-Tsix repression; physiological Rnf12 levels were essential for Xm-Xist silencing maintenance in fertilized embryos. Thus, chromatin condensation and fine-tuning of Rnf12 dosage were crucial for Xist imprint maintenance by silencing Xm-Xist.

Estimation of primary radiation output for wide-beam computed tomography scanner.

PURPOSE: To estimate in-air primary radiation output in a wide-beam multidetector computed tomography (CT) scanner. MATERIALS AND METHODS: A 6-cc ionization chamber was placed free-in-air at the isocenter, and two sheets of lead (1-mm thickness) were placed on the bottom of the gantry cover, forming apertures of 40-80 mm in increments of 8 mm. The air-kerma rate profiles were measured with and without the apertures ( K ˙ w - A , K ˙ w / o - A ) for 4.8 s at tube potentials of 80, 100, 120, and 135 kVp, tube current of 50 mA, and rotation time of 0.4 s. The nominal beam width was varied from 40 to 160 mm in increments of 40 mm. Upon completion of data acquisition, the K ˙ w / o - A were plotted as a function of the measured beam width, and the extrapolated dose rates ( K ˙ 0 - w / o - A ) at zero beam width were calculated by second-order least-squares estimation. Similarly, the K ˙ w - A were plotted as a function of the radiation field (measured beam width × aperture size at the isocenter), and the extrapolated dose rates ( K ˙ 0 - w - A ) were compared with the K ˙ 0 - w / o - A . RESULTS: The means and standard errors of the K ˙ w / o - A with 40-, 80-, 120-, and 160-mm nominal beam widths at 120 kVp were 10.94 ± 0.01, 11.13 ± 0.01, 11.22 ± 0.01, and 11.31 ± 0.01 mGy/s, respectively, and the K ˙ 0 - w / o - A was reduced to 10.67 ± 0.02 mGy/s. The K ˙ 0 - w - A of 40-, 80-, 120-, and 160-mm beam widths were reduced to 10.6 ± 0.1, 10.6 ± 0.2, 10.5 ± 0.1, and 10.6 ± 0.1 mGy/s and were not significantly different from the K ˙ 0 - w / o - A . CONCLUSIONS: A method for describing the in-air primary radiation output in a wide-beam CT scanner was proposed that provides a means to characterize the scatter-to-primary ratio of the CT scanner.

[Visualization of Four Intracranial Stents and In-stent Stenosis with Stenotic Models by 3D-TOF-MRA].

In recent years, various types of stents are deployed for the treatment of intracranial artery stenosis and aneurysms. Digital subtraction angiography has been considered to be the gold standard for the follow-up study. However, magnetic resonance angiography (MRA) is less invasive and the recent advances may contribute to the imaging of patients with intracranial stents. Then, a phantom study was carried out to evaluate the MR lumen visibility with these stents. Four stents [low-profile visualized intraluminal support (LVIS), Neuroform Atlas, Neuroform EZ, and Enterprise 2] were placed into plastic tubes with 3 mm inner diameter, and fixed in a container filled with agar. Time-of-flight MRA (TOF-MRA) was performed for these stents, and the signal intensities inside and outside the stents were measured on ImageJ software. Furthermore, 25%, 50%, and 75% stenosis models were created and passed through these stents to evaluate the diagnostic accuracy of in-stent stenosis. The signal intensity inside the LVIS stent was the highest among the four stents (P<0.001), and no significant difference was found between the signal intensities inside and outside the LVIS stent. The diagnostic accuracy with LVIS was also higher than that of Enterprise 2 (P<0.001). In conclusion, the visibility with LVIS indicates that TOF-MRA could be reliably utilized as a diagnostic tool for the detection of in-stent stenosis.

[Evaluation of Radiation Dose and Image Quality for Angiographic System with Spectral Shaping Filter].

Complex procedures for interventional radiology can result in high radiation doses to patients and physicians. A spectral shaping filter (SSF) has recently been developed and equipped with angiographic systems to modulate the X-ray beam spectrum. In our feasibility study, the radiation doses to patients and physicians, air kerma rate at image receptor, and image quality were evaluated when SSF was applied in fluoroscopy. Polymethyl methacrylate (PMMA) phantom, a catheter attached on the bottom was placed on the examination table. The entrance air kerma rate at patient entrance reference point, H* (10) rate at a distance of 100 cm from the center of PMMA, air kerma rate at image receptor and the fluoroscopic catheter images were recorded as a function of PMMA thickness. Contrast-to-noise ratio (CNR) was used for the objective image quality. As a subjective image quality evaluation, three physicians (cardiologist, neurologist, and radiologist) rated the catheter images by a Likert scale. With SSF, the entrance air kerma rate and H* (10) rate reduced by about 34 and 21%, respectively. The air kerma rate at image receptor in conventional filter mode increased when the PMMA was up to 10 cm and then CNR was also improved. However, no significant differences were found in the subjective image qualities. In conclusion, SSF was contributed to the reduction of the radiation doses to patients and physicians while the subjective image quality was not affected.

Chromatin condensation of Xist genomic loci during oogenesis in mice.

Repression of maternal Xist (Xm-Xist) during preimplantation in mouse embryos is essential for establishing imprinted X chromosome inactivation. Nuclear transplantation (NT) studies using nuclei derived from non-growing (ng) and full-grown (fg) oocytes have indicated that maternal-specific repressive modifications are imposed on Xm-Xist during oogenesis, as well as on autosomal imprinted genes. Recent studies have revealed that histone H3 lysine 9 trimethylation (H3K9me3) enrichments on Xm-Xist promoter regions are involved in silencing at the preimplantation stages. However, whether H3K9me3 is imposed on Xm-Xist during oogenesis is not known. Here, we dissected the chromatin states in ng and fg oocytes and early preimplantation stage embryos. Chromatin immunoprecipitation experiments against H3K9me3 revealed that there was no significant enrichment within the Xm-Xist region during oogenesis. However, NT embryos with ng nuclei (ngNT) showed extensive Xm-Xist derepression and H3K9me3 hypomethylation of the promoter region at the 4-cell stage, which corresponds to the onset of paternal Xist expression. We also found that the chromatin state at the Xist genomic locus became markedly condensed as oocyte growth proceeded. Although the condensed Xm-Xist genomic locus relaxed during early preimplantation phases, the extent of the relaxation across Xm-Xist loci derived from normally developed oocytes was significantly smaller than those of paternal-Xist and ngNT-Xist genomic loci. Furthermore, Xm-Xist from 2-cell metaphase nuclei became derepressed following NT. We propose that chromatin condensation is associated with imprinted Xist repression and that skipping of the condensation step by NT leads to Xist activation during the early preimplantation phase.

Clinical Significance of Squamous Differentiation in Urothelial Carcinoma of the Bladder.

The prognostic value of squamous differentiation (SD) in urothelial carcinoma (UC) of the bladder is unclear. The aim of this study was to identify the clinical significance of SD in UC in terms of oncological outcomes in patients undergoing radical cystectomy (RC). We evaluated consecutive patients with muscle-invasive bladder cancer (MIBC; clinical T2-4aN0M0) treated with RC at our institution from March 2003 to March 2017. We enrolled 20 and 81 patients with UC with SD (UCSD) and pure UC, respectively. Postoperative survival outcomes were compared between the patients with UCSD and pure UC using the Kaplan-Meier method. Pre- and postcystectomy factors that influenced the overall survival (OS) and recurrence-free survival (RFS) were investigated in these patients. Multivariate Cox regression models were used to identify the predictors of OS and RFS. With a median follow-up time of 31 months, the 5-year OS rate of the UCSD and pure UC groups was 41.1% and 69.7% ( P = .002) and the 5-year RFS rate was 51.8% and 59.5% ( P = .027), respectively. The shape of the Kaplan-Meier curves for UCSD suggested a more rapid course of the disease within the first 2 years than observed in pure UC. Multivariate analyses suggested that SD in UC was significantly associated with OS (hazard ratio [HR]: 4.22; 95% confidence interval [CI]: 1.20-14.8; P = .024) and close to significance for a lower RFS (HR: 2.13, 95% CI: 0.74-6.15, P = .064). Our results indicate that SD may be an independent predictor of OS and RFS in UC of MIBC in patients undergoing RC.

Comparison of the University of Pittsburgh staging system and the eighth edition of the American Joint Committee on Cancer TNM classification for the prognostic evaluation of external auditory canal cancer.

BACKGROUND: The purpose was to compare survival differences between patients with external auditory canal (EAC) cancer treated according to the University of Pittsburgh modified TNM staging system and those treated in accordance with the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual on the TNM staging system for cutaneous cancers of the head and neck. METHODS: We performed a retrospective, single-institution review of 60 patients with EAC cancer treated with curative intent between September 2002 and March 2018. Survival outcomes were measured on the basis of the two staging systems. RESULTS: The C-index values for the overall survival (OS) rate revealed that the University of Pittsburgh staging system had higher prognostic accuracy than the 8th edition of the AJCC staging system. Univariable and multivariable analysis showed that T classification according to the University of Pittsburgh staging system was an independent predictor of the OS rate (hazard ratio 5.25; 95% confidence interval 1.38-24.9; P = 0.015). Meanwhile, the AJCC staging system could not differentiate T2 from T3-4 cancers. CONCLUSION: The University of Pittsburgh staging system for patients with EAC cancer is a valuable tool for use in clinical decision-making and predicting survival outcome.

[Introduction and Applications of 3D Printing in Radiological Technology].

A 3D printing emerges as a common procedure in clinical radiology practice after installation of a module that converts the digital imaging and communications in medicine (DICOM) dataset into stereolithography (STL) data on medical workstations. However, they did not conventionally provide the appropriate filtering, sculpting, hollowing out, and Boolean (subtraction) operations on STL data. These functions are indispensable to handle the STL data to fabricate the smooth, low-cost, and sophisticated models. Here are some tips for handling the 3D data with three software packages through making a sample lumbar spine model. Because they are all free- and open-source software with the exception of Boolean operations, they could make it easy for anyone to fabricate their 3D model imaged by CT or MRI. We tested the loop subdivision surface algorithms for the smoothing, the sculpting function for removing a sharp prick, and the hollowing function to save the cost. Computer-aided design (CAD) is also used to fabricate the devices in medical research. We designed and developed a cap attached to a glass dosimeter to show the effectiveness of CAD in radiological research. Lastly, we discuss the important matters for 3D printing and examples of the clinical applications.

Efficient production of trophoblast lineage cells from human induced pluripotent stem cells.

Human induced pluripotent stem cells (hiPSCs) are potentially useful in both clinical applications and basic biological research. hiPSCs can differentiate into extra-embryonic cells in the presence of BMP4. However, the differentiation potential of hiPSCs can be affected by culture conditions or genetic variation. In this study, we investigated the effect of various BMP4 concentrations on the expression states of trophoblast markers and the optimal conditions for trophoblast induction. A high-fidelity gene expression assay using hiPSC lines showed that the expression levels of various trophoblast marker genes, such as KRT7, GCM1, CGB, and HLA-G, were upregulated by BMP4 in a dose-dependent manner in all types of hiPSCs used in this study. Treatment with high doses of BMP4 for prolonged periods increased the ratio of cells with trophoblast markers irrespective of the presence of bFGF. We found that the expression states of major pluripotency- and differentiation-related protein-coding genes in BMP4-treated cells depended on culture conditions rather than donor cell types. However, miRNA expression states were affected by donor cell types rather than BMP4 dose. Furthermore, the effect of the presence of bFGF on differentiation potential of KRT7-positive cells differed among iPSC types. Mechanistically, chromatin states around KRT7 promoter regions were comparable among the iPSC types used in this study, indicating that hiPSC chromatin state at these regions is not a parameter for cytotrophoblast differentiation potential. In conclusion, the optimal conditions for trophoblast differentiation from hiPSCs differ according to parental cell line.