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A clear air turbulence (CAT) occurred on 30 December 2020 over Tokyo, Japan. The CAT was largely generated by breaking Kelvin‐Helmholtz (KH) instability waves in the free atmosphere. A regional numerical weather prediction model simulated the event with fine resolution (35 m). Onboard‐recorded flight data and a flight simulation were utilized to validate the meteorological simulation. The locations of the reproduced strong turbulence agree well with the regions where flights encountered turbulence on that day. In a simulation with the finest resolution, the KH waves and their breaking were resolved. When the resolution was finer, the turbulent eddies were stronger, causing meteorological effects on the airplanes. The response of a virtual airplane to the simulated turbulence was estimated using a flight simulation. By comparing onboard‐recorded data with virtual flight data, we confirm that turbulent eddies are reasonably reproduced. Plain Language Summary: Clear air turbulence (CAT) is a threat to aviation safety. CAT occurs outside clouds, making it difficult to detect by pilots and onboard radars. When an airplane encounters strong CAT, changes in aerodynamic forces and moments cause significant shaking of the airplane. Although CAT generation in the free atmosphere has been studied by high‐resolution numerical simulations, few studies simulated aircraft‐scale turbulence eddies and validated them with high‐frequency airborne observation. We investigate a past CAT event in Japan using a very high resolution (35 m) simulation based on a regional weather prediction model of daily weather forecasts. The simulated turbulence was verified by comparing the virtual flight in simulated wind fields with realistic flight data recorded by airplanes during the event. Simulated aircraft responses in finer weather simulations match flight records better. Key Points: Clear air turbulence in a real case is reproduced by the use of a numerical weather prediction modelIf the resolution is fine enough for a large eddy simulation (LES), turbulent eddies associated with Kelvin‐Helmholtz instability are reproducedTurbulence eddies are shown to be realistic because virtual flight data in the LES data agree well with real flights [ABSTRACT FROM AUTHOR]

An accident occurred when an aircraft landed at Narita International Airport, Japan, on 20 June 2012. The aircraft encountered rapid changes of winds together with strong turbulence, although the weather was fair. In the present study, a two‐domain nested regional weather prediction models are used. The results in the outer domain show that southwesterly winds associated with a synoptic extratropical cyclone were locally accelerated to the southwest of the airport resulting in strong vertical shear. The simulation in the inner domain reproduces horizontal convective rolls, which are similar to those observed by a Doppler lidar at the airport. The wind velocity component parallel to the runway had a spatial variation of about 10 m s −1. The present approach using a large eddy simulation is useful for clarifying environments and features of horizontal convective rolls and forecasting low‐level wind shear associated with them, which can be a significant risk for aircraft. Plain Language Summary: Synoptic/mesoscale fronts and downbursts (strong downdrafts from a thunderstorm and diverging winds after they hit the ground) are known to be serious threats to airplanes during takeoff and landing. However, it is less known that there is another type of danger under fair weather conditions. An aircraft landing at Narita International Airport, Japan, in the afternoon of 20 June 2012 encountered rapid changes of wind and turbulence and made a hard landing, resulting in several injuries and damage to the fuselage. A Doppler lidar, a remote sensing device for monitoring low‐level winds at the airport observed alternating regions of strong and weak winds aligned southwest–northeast, perpendicular to the runway. In order to clarify the detailed structure and mechanism of these disturbances, numerical simulations using a fine‐resolution (horizontal resolution: 100 m) nested in a coarse resolution (horizontal resolution: 1 km) are made. The simulations show that horizontal convective rolls, which occur in convective boundary layers with strong vertical shear (vertical gradient of horizontal wind speed) were prevailing. These rolls are associated with the rapid changes in wind speed and turbulence similar to those observed by the Doppler lidar and flight recorder. The present study demonstrates that the large eddy simulation is useful for clarifying the structure and mechanisms of horizontal convective rolls, which caused the aircraft accident, and also for forecasting them. Key Points: Horizontal convective rolls that caused an aircraft accident in a fair weather condition were successfully reproduced by a numerical modelCharacteristics of the rolls and turbulence as observed by a Doppler lidar and flight recorder are clarified based on the model resultsCapability of accessing and operationally predicting potentially hazardous rolls by use of a large eddy simulation is demonstrated [ABSTRACT FROM AUTHOR]

Hepatitis B virus ( HBV) reactivation has been reported during antihepatitis C treatment in patients with hepatitis C virus ( HCV) and HBV co-infection. We aimed to evaluate the frequency and risk factors of HBV reactivation during anti- HCV therapy and compared those between interferon ( IFN)-free direct-acting antiviral ( DAA) therapies and IFN-based therapies. Three hundred and twenty-two patients with HCV infection receiving anti- HCV therapy were retrospectively screened. The baseline HBV infection statuses of all eligible patients and the HBV- DNA level of all patients with current or previous HBV infection were examined at the end of treatment. In patients with baseline anti- HBs positivity, changes in anti- HBs titre were evaluated. Of 287 patients who met the inclusion criteria, 157 had current (n=4) or previous (n=153) HBV infection; 85 were treated with IFN-free DAA therapies and 72 were treated with IFN-based therapies. Six patients experienced HBV reactivation (n=2) or HBV reappearance (n=4) after IFN-free DAA therapies, while no patient developed HBV reactivation after IFN-based therapies. The risk factors of HBV reactivation or reappearance were DAA therapies and a reduction in anti- HBs titre to <12 mIU mL−1 by the end of treatment. The decline changes of anti- HBs titre were significantly higher in patients treated with DAA therapies. Although HBV reactivation hepatitis was not observed, three of four patients with HBV reactivation or reappearance after achieving HCV eradication had viremia 8 weeks after completion of therapy. A significant proportion of patients develop HBV reactivation or reappearance without hepatitis after IFN-free DAA therapies. Low levels of anti- HBs and their decrease to <12 mIU mL−1 after treatment are significant risk factors for HBV reactivation or reappearance. [ABSTRACT FROM AUTHOR]

Ito J, Oshima I, Nishio M, Sono T, Suzuki Y, Horiuchi K, Niekawa N, Ogawa M, Setoya Y, Hisanaga F, Kouda M, Tsukada K. The effect of Assertive Community Treatment in Japan. The aim of this study was to evaluate the effects of the Assertive Community Treatment (ACT) program in a Japanese mental health service setting. This study was a randomized controlled trial. ACT was the intervention condition ( n = 59), and the usual hospital-based rehabilitation program was the control condition ( n = 59). Outcome indicators include in-patient days, psychiatric symptoms, social functioning, quality of life, and client satisfaction. The follow-up period was 12 months after the intervention. We found a significant reduction of in-patient days for the ACT group demonstrated by t-test ( t = 2.33, P = 0.02). However, the results of did not show significant differences for in-patient days between the two groups ( F = 1.85, P = 0.18). The depression score for Brief Psychiatric Rating Scale for the ACT group was significantly lower than the control group at the 12-month follow-up assessment ( F = 5.57, P = 0.03). According to the t-test, the ACT group had a higher client satisfaction than the control group ( t = 2.08, P = 0.05). We concluded that ACT had a positive influence, as evidenced by a reduction of in-patient days, lower depressive symptoms, and higher client satisfaction. [ABSTRACT FROM AUTHOR]

Contents The objective of the present study was to establish a method for nuclear replacement in metaphase-II (M-II) stage porcine oocytes. Karyoplasts containing M-II chromosomes (K) and cytoplasts without chromosomes (C) were produced from in vitro-matured oocytes by a serial centrifugation method. The oocytes were then reconstructed by fusion of one karyoplast with 1, 2, 3 or 4 cytoplasts (K + 1C, K + 2C, K + 3C and K + 4C, respectively). Reconstructed oocytes, karyoplasts without fusion of any cytoplast (K) and zona-free M-II oocytes (control) were used for experiments. The rates of female pronucleus formation after parthenogenetic activation in all groups of reconstructed oocytes (58.2–77.4%) were not different from those of the K and control groups (58.2% and 66.0%, respectively). In vitro fertilization was carried out to assay the fertilization ability and subsequent embryonic development of the reconstructed oocytes. The cytoplast : karyoplast ratio did not affect the fertilization status (penetration and male pronuclear formation rates) of the oocytes. A significantly high monospermy rate was found in K oocytes (p < 0.05, 61.6%) compared with the other groups (18.2–32.8%). Blastocyst formation rates increased significantly as the number of the cytoplasts fused with karyoplasts increased (p < 0.05, 0.0–15.3%). The blastocyst rate in the K + 4C group (15.3%) was comparable with that of the control (17.8%). Total cell numbers in both the K + 3C and K + 4C groups (16.0 and 15.3 cells, respectively) were comparable with that of the control (26.2 cells). Our results demonstrate that a serial centrifugation and fusion (Centri-Fusion) is an effective method for producing M-II chromosome transferred oocytes with normal fertilization ability and in vitro development. It is suggested that the number of cytoplasts fused with a karyoplast plays a critical role in embryonic development. [ABSTRACT FROM AUTHOR]

Contents In almost all animal species, sperm acrosome reaction (AR) is a crucial step for fertilization. The step is a Ca2+-dependent secretory event that must be completed before fertilization. Many researchers have reported that several chemicals (such as ionomycin, thapsigargin and caffeine) artificially induce this step by increasing [Ca2+]i. However, little information has been known on events that occur following Ca2+ induced initiation of the sperm AR. We show here for the first time that phosphorylation of the mitogen-activated protein kinase (MAPK) pathway is required for the AR in miniature pig sperm. Following caffeine treatment artificially inducing the AR in miniature pig sperm, Raf was phosphorylated and then MAP kinase kinase (MEK) and extracellular-signal regulated kinase1 (ERK1) were also phosphorylated in a time-dependent manner. However, the total ERK1 level did not change during the culture. Pre-treatment of sperm with U0126, a MEK inhibitor, significantly suppressed both the AR and phosphorylation of MEK/ERK1 in a dose-dependent manner. Additionally, pre-incubation of the sperm with seminal vesicle (SV) fluid, which is known to contain a decapacitation factor, suppressed both the AR and MEK/ERK1 phosphorylation. These results suggest that phosphorylation of MAPK pathway plays an important role in the AR in miniature pig sperm. Moreover, the SV fluid may have an inhibitory effect on the AR via the suppression of the MAPK pathway. [ABSTRACT FROM AUTHOR]

The origin of bitumen excavated from archaeological sites in Hokkaido, the northernmost island in Japan, was sought by means of field-ionization mass spectrometry (FI–MS) and gas chromatography – mass spectrometry (GC–MS) of the hydrocarbon components. The field-ionization mass spectra were decomposed by Z-numbers into several components, where the Z-number refers to z in the formula Cn H2n+z . This is equivalent to the deficit number of H atoms, when compared to the corresponding saturated hydrocarbon, which is related to the number of saturated hydrocarbon rings in alkanes. By use of the spectral intensities of the seven alkane components in each sample, multiple discriminant analysis was employed for the data of raw bitumen samples and excavated samples from archaeological sites. Based on this method and the gas chromatogram type, the following bitumen trade in the prehistoric age of Japan was elucidated: bitumen from Niigata, one of the main sources on the main island of Japan, spread to the north in 2000bc, probably via the coastal zone, and reached a small island near the north end of Hokkaido. Bitumen from Sakhalin reached the central lowland in Hokkaido, but it went no further. Bitumen from Akita, another main source on the main island, spread over northern Honshu much earlier and reached the Oshima peninsula, the southwestern part of Hokkaido. The Akita bitumen scattered into the central lowland after the Niigata and Sakhalin bitumen. This area is believed to be the place where people from the south and the north met in those periods. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study are to investigate the efficiency of a tissue engineering approach to partial tracheal reconstruction and to improve epithelialization of the reconstructed trachea. The trachea must be resected in some cases of cancer or trauma. Various restructuring techniques are used, with no consensus on the best approach. Two problems that arise when treating tracheal defects by conventional techniques are an inability to regenerate ciliated epithelium at the reconstructed site and having to perform multiple procedures to achieve the desired repair. This study is designed to address these problems. Study Design: Preliminary, an animal experiment. Methods: Surgery was performed on five adult beagles under anesthesia. After the making of a longitudinal cervical skin incision, the trachea was exposed and a circular defect created. A polypropylene and collagen scaffold preclotted with peripheral blood was inserted to the defect site. Postoperatively, the site was evaluated fiberscopically, histologically, and radiographically. Results: All dogs did well postoperatively. Fiberscopic examination showed that the implanted scaffolds were completely covered with regenerated mucosa with capillaries in all cases. Histologic data showed ciliated epithelium regenerated at the operated site from 1 month postoperatively. Newly formed cartilage was detected in the specimens from 8 to 12 postoperative months. Computed tomography images revealed the fine luminal contour of the regenerated site. Conclusions: Good epithelial regeneration was observed after repair of a round tracheal resection using a simple tissue engineering technique, making the technique a good substitute for conventional approaches to tracheal reconstruction in patients with cancer or trauma. [ABSTRACT FROM AUTHOR]

Background It has been suggested that airway bacterial infections exacerbate allergic disorders, and bacterial components in the air affect allergic inflammation via Toll-like receptors expressed on mast cells and dendritic cells in the airway mucosa. Objective Peptidoglycan (PGN) is a major component of the bacterial cell wall. We investigated the effect of PGN on the effector phase of allergic inflammation, in comparison with the effect of CpG-oligodeoxynucleotides (CpG), which is known to be a Th1 adjuvant. Methods Ovalbumin (OVA)-sensitized mice were challenged intranasally with OVA alone or OVA together with PGN or CpG. Nasal allergic symptoms and eosinophilia were scored, and the OVA-specific cytokine response was examined in the cells of cervical lymph nodes and nasal mucosa. Bone marrow-derived mast cells (BMMCs) and dendritic cells (BMDCs) were stimulated with PGN or CpG in vitro, and the expression level of cytokines and chemokines was examined by RT-PCR. In addition, the expression level of chemokines was examined by RT-PCR in mast cells of OVA-sensitized mice challenged with OVA alone or OVA together with PGN or CpG. Results PGN exposure exacerbated the nasal allergic symptoms and eosinophilia, whereas CpG exposure suppressed them. In addition, PGN exposure increased the OVA-specific IL-4 response in the cells, whereas CpG exposure decreased it. On the other hand, there were no significant differences in the OVA-specific IFN-γ response. PGN but not CpG induced the expression of thymus and activation-regulated chemokine (TARC) and macrophage/monocyte-derived chemokine (MDC) in both BMMCs and mast cells of mice sensitized and challenged with OVA. CpG but not PGN induced the expression of IFN-β and interferon-inducible protein-10 (IP-10) in BMDCs, and histamine did not influence this effect. Conclusion These results demonstrate that PGN exposure exacerbates allergic inflammation mainly via mast cells, whereas CpG exposure suppresses allergic inflammation mainly via dendritic cells. [ABSTRACT FROM AUTHOR]

A mass that developed in the lung of a 10-year-old mixed-breed dog was pathologically examined. Histopathological examination showed papillary and tubular growth of glandular epithelium-like cells in some areas and growth of squamous cells arranged in nests in other areas, showing coexistence of adenocarcinoma and squamous cell carcinoma in a lung tumour. Immunohistochemical staining with anti-keratin–cytokeratin antibody was strongly positive for cytoplasms in both components. Electron microscopically, the neoplastic cells of the adenocarcinoma component had features of glandular cells, with microvilli, numerous free ribosomes, large round secretory granules and intercellular desmosomes. Non-keratinized squamous cells had tonofilaments and intercellular desmosomes. These findings led to the diagnosis of primary adenosquamous carcinoma, which demonstrates phenotypic profiles characteristic of both epidermal keratinocytes and glandular epithelium. [ABSTRACT FROM AUTHOR]

However, there was no report that endoscopic myotomy for rectal tumor with severe fibrosis after surgical hemorrhoids treatment. This case suggested that endoscopic myotomy is useful for treating large tumors with severe fibrosis after surgical hemorrhoids treatment, while avoiding stoma formation. [Extracted from the article]

A 79-year-old man with chronic kidney disease was referred to our hospital for the workup of anemia that progressed in 1 month (hemoglobin level, from 10.1 to 4.9 g/dL).Unenhanced computed tomography (CT) revealed dilation of the main pancreatic duct (MPD) and atrophic pancreatic parenchyma lesion was identified. (c) Contrast-enhanced computed tomography showing a relatively hypervascular mass (arrow) including a noncontrast lesion in the pancreatic tail 1 day after endoscopic retrograde pancreatography. gl Microscopically, the MPD was filled with tumour cells with high-grade dysplasia, showing complex intraductal papillo-tubular growth with hemorrhage around the tumour (b,c). [Extracted from the article]

Background: SPLIT was founded in 1995 in order to collect comprehensive prospective data on pediatric liver transplantation, including waiting list data, transplant, and early and late outcomes. Since 2011, data collection of the current registry has been refined to focus on prospective data and outcomes only after transplant to serve as a foundation for the future development of targeted clinical studies. Objective: To report the outcomes of the SPLIT registry from 2011 to 2018. Methods: This is a multicenter, cross‐sectional analysis characterizing patients transplanted and enrolled in the SPLIT registry between 2011 and 2018. All patients, <18 years of age, received a first liver‐only, a combined liver‐kidney, or a combined liver‐pancreas transplant during this study period. Results: A total of 1911 recipients from 39 participating centers in North America were registered. Indications included biliary atresia (38.5%), metabolic disease (19.1%), tumors (11.7%), and fulminant liver failure (11.5%). Greater than 50% of recipients were transplanted as either Status 1A/1B or with a MELD/PELD exception score. Incompatible transplants were performed in 4.1%. Kaplan‐Meier estimates of 1‐year patient and graft survival were 97.3% and 96.6%. First 30 days of surgical complications included reoperation (31.7%), hepatic artery thrombosis (6.3%), and portal vein thrombosis (3.2%). In the first 90 days, biliary tract complications were reported in 13.6%. Acute cellular rejection during first year was 34.7%. At 1 and 2 years of follow‐up, 39.2% and 50.6% had normal liver tests on monotherapy (tacrolimus or sirolimus). Further surgical, survival, allograft function, and complications are detailed. [ABSTRACT FROM AUTHOR]

A halitosis test for objective evaluation is required. Halitosis is due to Volatile Sulfur Compounds (VSCs) produced by bacterial metabolism. In this study, we proposed a method for discriminating among sulfur compounds using a Quartz Crystal Microbalance (QCM) sensor array combined with a preconcentrator. The adjustment of the temperature profile, the optimization of the flow path sequence and the use of a dehumidification filter enabled VSC measurement under a high-humidity condition. Moreover, the result of principal component analysis indicated that three types of VSCs were separated using the sensor-array output pattern.Multiple QCMs with different coating films were used as a sensor array and the pattern recognition of eight different sensor responses enabled the odor identification. The preconcentrator was used not only for improving limit of detection but for eliminating the influence of humidity by adjusting the desorption temperature. The headspace over the liquid (water or ODO) where VSC was dissolved with the concentration of 0.1% (w/w) was used as the samples.An experiment on the discrimination among VSCs was performed. The headspace vapor of each sample was supplied to the preconcentrator for 30 s, followed by an exposure of the vapor thermally desorbed at 170°C to the QCM sensor array. The sensing films suitable for VSCs were selected among the various candidates and the peaks of the sensor responses to VSCs were analyzed using principal component analysis. Each sample was measured 10 times at the intervals of 30 min. As a result, it was found that three kinds of VSCs were successfully discriminated. Furthermore, it was found that the sensor responses increased in case of longer accumulation time. Thus, it is possible to detect the sample with lower concentration. This measurement method will be effective to diagnose halitosis objectively. [ABSTRACT FROM AUTHOR]

The use of sampling bags to collect breath odor has not been well established. The aim of this study was to compare and judge the quality and performance of three commercially available sampling bags. An aluminized polyethylene bag (Aluminum Bag, Tokyo Deodorant Inc., Japan), the Tedlar® bag (Tedlar® Bag, Tokyo Deodorant Inc.), and a polyester bag (Flek-Sampler® Nioibukuro; Omi Odorair Service Co. Ltd., Japan) were assessed. A GC instrument (GC14-B, Shimadzu, Japan) equipped with a flame photometric detection system were used to measure the concentrations of volatile sulfur compounds (VSC: hydrogen sulfide, methyl mercaptan, and dimethyl sulfide) released from the sampling bags over time. An electronic nose (e-nose) (Odor Discrimination Analyzer FF-1, Shimadzu, Japan) was used to assess the characteristics of the gas eluted from the inner surfaces of the bags. The GC results showed that the Tedlar® bag had the highest performance, with 73% of the VSC concentration lasting for up to 4 days. The disadvantage of this bag, however, is that the Tedlar® bag itself has an odor that disturbs the e-nose's response and organoleptic evaluation. The polyester bags were only able to hold hydrogen sulfide for 2 h. The e-nose's responses were strongly associated with changes in humidity within the polyester bag. The humidity was more stable within the aluminized polyethylene bag, which was able to sustain 94% of the VSC concentration for up to 24 h. In conclusion, Tedlar® bags are beneficial for GC usage. Aluminum coated polyester bags are beneficial for GC measurements, e-nose measurements, and organoleptic judgements. Polyester bags have poor hold of VSC, but the low cost suits required disposability for the measurements of individual patients. Thus, breath odor sampling bags should be selected based on the specificity of the measuring instrument. [ABSTRACT FROM AUTHOR]

In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population., (© 2024 The Author(s). Microbiology and Immunology published by The Societies and John Wiley & Sons Australia, Ltd.)

Aim: To investigate the relationships between various clinical variables and the metformin-induced accumulation of fluorodeoxyglucose (FDG) in the intestine, with distinction between the intestinal wall and lumen, in individuals with type 2 diabetes who were receiving metformin treatment and underwent 18 F-labelled FDG ([ 18 F]FDG) positron emission tomography (PET)-MRI., Materials and Methods: We evaluated intestinal accumulation of [ 18 F]FDG with both subjective (a five-point visual scale determined by two experienced radiologists) and objective analyses (measurement of the maximum standardized uptake value [SUV max ]) in 26 individuals with type 2 diabetes who were receiving metformin and underwent [ 18 F]FDG PET-MRI. [ 18 F]FDG accumulation within the intestinal wall was discriminated from that in the lumen on the basis of SUV max ., Results: SUV max for the large intestine was correlated with blood glucose level (BG) and metformin dose, but not with age, body mass index, HbA1c level or estimated glomerular filtration rate (eGFR). SUV max for the small intestine was not correlated with any of these variables. Visual scale analysis yielded essentially similar results. Metformin dose and eGFR were correlated with SUV max for the wall and lumen of the large intestine, whereas BG was correlated with that for the wall. Multivariable analysis identified metformin dose as an explanatory factor for SUV max in the wall and lumen of the large intestine after adjustment for potential confounders including BG and eGFR., Conclusions: Metformin dose is an independent determinant of [ 18 F]FDG accumulation in the wall and lumen of the large intestine in individuals treated with this drug., (© 2020 John Wiley & Sons Ltd.)

Objectives/hypothesis: Vocal fold scar remains a therapeutic challenge. Mesenchymal stromal cells (MSCs) are promising tools for regenerative medicine. Nevertheless, few in vivo studies have directly compared various sources of MSCs. The aim of this study was to investigate the therapeutic potential of adipose-derived stromal cells (ASCs) in comparison with bone marrow-derived stromal cells (BMSCs) for vocal fold regeneration., Study Design: Prospective animal experiments with controls., Methods: Two months after stripping of the lamina propria, 18 beagles were divided into four implantation groups: atelocollagen alone (collagen group), atelocollagen with BMSCs (BMSC-collagen), atelocollagen with ASCs (ASC-collagen), or a sham-treated group. One or 6 months after implantation, vibratory and histological examinations were performed., Results: Mucosal vibration was significantly improved in both of the MSC-implanted groups compared with the sham-treated group, whereas only the ASC-collagen group showed a significantly smaller glottal gap than the collagen group. Moreover, in the ASC-collagen group, a significant reduction of collagen density was observed compared to the sham-treated group, and there was a trend for better restoration of hyaluronic acid (HA). Implanted MSCs were detected 1 month postimplantation; however, none survived 6 months postimplantation., Conclusions: Although implantation of an atelocollagen sponge and ASCs into vocal fold scars induced vibratory recovery comparable to that of BMSCs, ASCs might have more potential in terms of restoration of HA and suppression of excessive collagen deposition., Level of Evidence: NA Laryngoscope, 126:1143-1150, 2016., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To examine if macroscopic classification with a magnifying gastrointestinal endoscope with narrow band imaging (ME-NBI) is useful in predicting pathological depth of tumor invasion in laryngo-pharyngeal cancer., Study Design: Retrospective study., Methods: Preoperative endoscopy reports and postoperative pathological reports on 139 laryngo-pharyngeal cancer lesions were retrospectively reviewed, and the association between macroscopic findings in the lesions and the depth of tumor invasion was analyzed statistically., Results: The ratios of lesions macroscopically classified as 0-I (superficial and protruding), 0-IIa (slightly elevated), 0-IIb (true flat), 0-IIc (slightly depressed), and 0-III (superficial and excavated) in the preoperative endoscopy reports were 3%, 25%, 71%, 1%, and 0%, respectively. Regarding the depth of tumor invasion in the postoperative pathological reports, the ratios of lesions classified as EP (carcinoma in situ), SEP (tumor invades subepithelial layer), and MP (tumor invades muscularis propria) were 73%, 26%, and 1%, respectively. The ratios of subepithelial invasion or muscular invasion in 0-I, 0-IIa, and 0-IIb were 100%, 54%, and 14%, respectively, and showed significant difference (P < 0.0001). Only one of 139 lesions invaded the muscular propria., Conclusions: This study is the first one to show that macroscopic findings by ME-NBI predict the depth of tumor invasion in superficial laryngo-pharyngeal cancer. It was indicated that there is a little chance of muscular invasion if the lesion is endoscopically diagnosed as 0-I or 0-II. A new T stage classification based on the depth of tumor invasion may be needed in order to adapt the classification to include transoral surgery., Level of Evidence: 4., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Vocal fold scarring presents therapeutic challenges. Recently, cell therapy with mesenchymal stromal cells has become a promising approach. The aim of this study was to compare the therapeutic potential of adipose-derived stem cells (ASC) with bone marrow-derived stem cells (BMSC) for vocal fold regeneration., Study Design: Prospective animal experiments with controls., Methods: The vocal folds of Sprague-Dawley rats were unilaterally injured. Two months after injury, rats were treated with a local injection of ASC (ASC group), BMSC (BMSC group), or saline (sham-treated group). The GFP-labeled ASC and BMSC were extracted from CAG-EGFP rats. Larynges were harvested for histological and immunohistochemical examinations 1 and 3 months posttransplantation and for quantitative real-time polymerase chain reaction (PCR) 1 month posttransplantation., Results: After 1 month, no surviving cells from the transplant were detected. Histological examination showed significantly increased hyaluronic acid (HA) and decreased dense collagen deposition in both ASC and BMSC groups compared to shams 1 and 3 months after treatment. Real-time PCR revealed that hyaluronan synthase 1 (Has1) and Has2 were upregulated in only the ASC group compared with the sham-treated group. Fibroblast growth factor 2 (basic) (Fgf2), hepatocyte growth factor (Hgf) and Has3 were upregulated in both cell transplantation groups. ASC seemed to upregulate Hgf more than did BMSC., Conclusions: The regenerative effects of ASC and BMSC transplantation were found to be similar for the restoration. It is suggested that ASC might have more potential because of better recovery of HA, a superior antifibrotic effect, and the upregulation of Hgf., Level of Evidence: N/A., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Reactive oxygen species (ROS) are associated with aging. Astaxanthin (AST) is a strong antioxidant and has been reported to prevent various ROS-induced diseases. In the current study, we investigated the effect of AST on age-associated histological and mRNA changes of vocal folds., Study Design: Prospective animal experiment with control., Methods: Six-month-old Sprague-Dawley rats were fed on a normal powder diet with 0.01% (w/w) AST (aged AST-treated group) or without AST (aged sham-treated group). After 12 months of feeding, the larynges were harvested for histology, immunohistochemical detection of 4-hydroxy-2-nonenal (4-HNE), and quantitative real-time polymerase chain reaction for basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). Thirteen-week-old rats were used as a young control group (young group)., Results: The expression of 4-HNE, an oxidative stress marker, significantly increased in the two aged groups compared with the young group. Histological examination showed that the deposition of hyaluronic acid in the lamina propria (LP) was significantly reduced in the aged sham-treated group compared with the young group, but no significant difference was observed between the aged AST-treated group and the young group. There were no significant differences in the mRNA expression of bFGF and HGF between the aged AST-treated group and the young group, although the expression of these genes was significantly reduced in the aged sham-treated group as compared with the young group., Conclusions: These results suggest that AST has the potential to attenuate age-associated changes of vocal folds., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To describe the clinical presentation of peripheral facial palsy caused by neoplastic meningitis., Study Design: Retrospective case series., Methods: Retrospective review, including accompanying symptoms and magnetic resonance imaging (MRI) findings., Results: Between January and December 2011, six patients were diagnosed with peripheral facial palsy caused by neoplastic meningitis. The patient age at presentation ranged from 56 to 77 years. The tumor origins were as follows: malignant lymphoma (n = 3), lung cancer (n = 2), and kidney cancer (n = 1). In three patients, sudden sensorineural hearing loss accompanied the facial palsy. Three patients were judged to be tumor-free at the onset of the facial palsy. In two patients, the malignancy was not diagnosed at the onset of facial palsy and hearing loss. Only one patient was diagnosed as having a tumor at the onset of the facial palsy. On the MRI, a mass lesion was detected in the internal auditory canals (IAC) of four patients; one had a solitary IAC tumor. In this patient, the diagnosis required a histopathological study using a translabyrinthine approach. In the other two patients, the facial nerve was enhanced with gadolinium, but it was difficult to differentiate the observed condition from Bell's palsy. In these patients, repeated cytological studies led to the correct diagnoses., Conclusions: The clinical symptoms and MRI findings of peripheral facial palsy caused by neoplastic meningitis sometimes mimic those of benign facial palsy., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Previous animal studies demonstrated that hepatocyte growth factor (HGF) has the potential to regenerate scarred vocal folds. In addition, HGF is now produced under a good manufacturing practice (GMP) procedure. Therefore, human clinical trials of HGF are warranted in patients with vocal fold scarring. In the current study, we investigated the pharmacokinetics and the local tissue responses of HGF administered to rat vocal folds., Study Design: Prospective animal experiment., Methods: Five μg of recombinant human HGF was administered to the vocal folds of Sprague-Dawley rats (n = 60) using a microsyringe. The concentration of HGF in larynges and blood was investigated by enzyme-linked immunosorbent assay. To evaluate the local tissue responses caused by HGF administration, endoscopic and histological examinations were performed., Results: HGF concentration in the larynges was 50.1 μg/g tissue 5 minutes after administration. The concentration decreased rapidly to 1.71 μg/g tissue at 12 hours after administration and to 0.29 ng/g tissue at 24 hours after administration. Seven days after administration, HGF concentration was minimal in one-half of the cases and was not detected in the other cases. Transmission of HGF to blood was detected in two of six cases at 5 minutes after administration, but was no longer detected 12 hours later. Endoscopic and histological examinations revealed no edema or erythema of the vocal folds in any of the cases., Conclusions: The current results contribute to the safety and pharmacokinetic management of future clinical trials using HGF administered to vocal folds., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Our previous studies demonstrated a regenerative effect of recombinant human hepatocyte growth factor (HGF) on vocal fold scarring using full-length HGF. However, clinical application has not yet been achieved because of the lack of a good manufacturing practice (GMP) for full-length HGF. Another natural form of human HGF, 5 amino acid-deleted type HGF (dHGF), has been newly produced under a GMP procedure. In the current study, we investigated the effect of dHGF in comparison with full-length HGF for the treatment of vocal fold scars using a canine model., Study Design: Prospective animal experiment., Methods: The vocal folds of nine beagles were unilaterally injured. Four weeks after injury, the vocal folds were treated with an intracordal injection of full-length HGF (full HGF group), dHGF (dHGF group), or phosphate-buffered saline (sham group). Vibratory and histological examinations were performed for each group 6 months after injury., Results: Vibratory examinations demonstrated significantly lower phonation threshold pressure and a higher ratio of normalized mucosal wave amplitude in both the full HGF and dHGF groups as compared to the sham group. Histological examination showed restoration of hyaluronic acid in both the full HGF and dHGF groups as compared to the sham group. No significant differences were observed for each parameter between the full HGF group and the dHGF group., Conclusions: dHGF showed the same potential for regenerative effects on vocal fold scars as full-length HGF. dHGF should be applicable for human clinical trials in patients with vocal fold scars., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Our previous study demonstrated that a large amount of reactive oxygen species (ROS) is produced during the early phase of vocal fold wound healing. In the current study, we investigated the effect of astaxanthin, which is a strong antioxidant, on the regulation of oxidative stress and scarring during vocal fold wound healing., Study Design: Prospective animal experiment with control., Methods: Sprague-Dawley rats were dosed with astaxanthin (Ast-treated group, 100 mg/kg/day) or olive oil (sham-treated group) by oral gavage daily from preinjury day 1 to postinjury day 4. After vocal folds were injured under the endoscope, larynges were harvested for histological and immunohistochemical examinations on postinjury days 1, 3, 5, and 56, and quantitative real time polymerase chain reaction (PCR) on postinjury days 1 and 3., Results: The expression of 4-hydroxy-2-nonenal, which is an oxidative stress marker, was reduced significantly in the lamina propria of the Ast-treated group as compared to the sham-treated group. Histological examination showed significantly less tissue contraction with favorable deposition of hyaluronic acid in the lamina propria of the Ast-treated group compared to the sham-treated group. Real time PCR revealed significantly upregulated mRNA expression of basic fibroblast growth factor on postinjury day 1 and procollagen type I in the Ast-treated group compared to the sham-treated group., Conclusions: These findings suggest that astaxanthin has the potential to prevent vocal fold scarring by regulating oxidative stress during the early phase of vocal fold wound healing., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: A subset of CD4+ T cells in the synovium of patients with rheumatoid arthritis (RA) produce CXCL13, a chemokine that is crucial for the formation of germinal centers. This study was undertaken to determine the relevance of this population to known subsets of T helper cells and to proinflammatory cytokines, and how these cells are generated., Methods: The expression of Th markers and CXCL13 by CD4+ T cells in RA synovium and the involvement of proinflammatory cytokines in CXCL13 production were assessed. We also investigated whether CXCL13+CD4+ T cells could be newly induced., Results: CXCL13+CD4+ T cells in RA synovium were negative for interferon-γ (IFNγ), interleukin-4 (IL-4), IL-17, FoxP3, and CXCR5 and expressed low levels of inducible T cell costimulator, indicating that this population is a distinct human CD4 subset. T cell receptor (TCR) stimulation of CD4+ T cells, obtained from RA synovium with low expression of CXCL13, promptly induced CXCL13 production and addition of proinflammatory cytokines supported the long-term production of CXCL13. These findings indicate that CXCL13-producing CD4+ T cells can be in a memory state ready to be reactivated upon TCR stimulation and that proinflammatory cytokines are involved in persistent CXCL13 production. TCR stimulation of CD4+ T cells from the blood of healthy volunteers, together with proinflammatory cytokine supplementation, induced a population that produced CXCL13, but not IFNγ. Synovial T cells recruited CXCR5+ cells in a CXCL13-dependent manner., Conclusion: CXCL13-producing CD4+ T cells induced in RA synovium may play a role in the recruitment of CXCR5+ cells, such as B cells and circulating follicular helper T cells, and in ectopic lymphoid neogenesis at sites of inflammation., (Copyright © 2013 by the American College of Rheumatology.)

Objectives/hypothesis: Vocal fold scar and sulcus are still challenges. Basic fibroblast growth factor (bFGF) has proven to be effective to resolve scar tissue in animal models. This study reports the efficacy of regenerative treatments using bFGF on vocal fold scar and sulcus in human cases., Study Design: Retrospective chart review., Methods: Fifteen cases (7 scar; 8 sulcus) were treated by either local injection of bFGF (n = 6) or regenerative surgery using bFGF (n = 9). Injection regimen was to locally apply 10 micrograms of bFGF in 0.5 mL saline into each vocal fold under topical anesthesia repeatedly (4 times with intervals of 1 week between each injection). The regenerative surgical procedure consisted of the dissection of scar tissue and the implant of gelatin sponge with bFGF. Follow-up periods ranged from 6 months to 24 months., Results: Maximum Phonation Time (MPT); Voice Handicap Index (VHI)-10; and Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale were assessed in both groups. The injection group showed significant improvement on VHI-10 and GRBAS. The regenerative surgery group showed significant improvement in all parameters. Jitter and shimmer were evaluated in the surgery group, and the results indicated improvement in six and five cases of nine cases, respectively. No major adverse effects were observed in both treatment groups., Conclusions: Regenerative treatments using bFGF has shown to be effective for improvement of vocal function in scar and sulcus., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)