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Purpose: The purpose of this study was to investigate the efficacy and indications of using dried gamma ray-sterilized amniotic membrane (AM) transplantation with bandage contact lenses for the in-office sutureless treatment of various ocular surface diseases., Methods: This study retrospectively included 56 eyes of 52 patients with various ocular surface diseases treated with sutureless dehydrated AM-assisted therapeutic contact lenses. The patients were followed up and assessed 1, 2, and 4 weeks after the treatment, and the therapeutic contact lenses were removed after 1 or 2 weeks. The size of the corneal lesion and the degree of pain experienced by each patient before and after the procedure were measured. Corneal re-epithelization rate and clinical aspects related to re-epithelialization were evaluated., Results: Complete corneal re-epithelialization of the epithelial defect was observed in 40 eyes. The complete re-epithelialization rates of persistent epithelial defect caused by infectious ulcers, neurotrophic ulcers, ulcers due to burn, toxic keratopathy, previous penetrating keratoplasty or other corneal surgeries, and severe dry eye disease were 69.2%, 80.0%, 77.8%, 100%, 75.0%, and 100%, respectively. Five patients with uncontrolled infectious ulcers, neurotrophic ulcer, bullous keratopathy, and ulcers associated with rheumatic disease did not show significant improvement. Patient pain scores significantly decreased after the procedure., Conclusions: Dehydrated AM transplantation with a bandage contact lens is minimally invasive and easily applicable through in-office procedures. This approach is expected to be more actively applied in various ocular surface disorders, not only in severe corneal diseases but also in relatively mild corneal surface diseases., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Bioactive lipids like sphingosine-1-phosphate (S1P) and lysophosphatidic acid have gained significant attention as signaling molecules with regulatory roles in stem cell proliferation and differentiation. The novel chemically synthesized sphingosine metabolite O-cyclic phytosphingosine-1-phosphate (cP1P) is derived from phytosphingosine-1-phosphate (P1P) and shares structural similarities with S1P. Previously, the role of cP1P in regulating ALK3/BMPR signaling during cardiomyocyte differentiation from human embryonic stem cells (hESCs) was demonstrated. In this study, the applicability of cP1P for endothelial cells (ECs) differentiation from hESCs was investigated an efficient method to obtain a high yield of functional ECs over several passages was standardized. The ECs derived from hESCs showed cellular and molecular characteristics similar to the native ECs. Thus, the results of this study open avenues for further research into cP1P-based stem cell differentiation for regenerative therapies.

Purpose: We aimed to design, develop, and evaluate an internet of things-enabled patch (IoT patch) for real-time remote monitoring of adherence (or patch wear time) during patch treatment in child participants in clinical trials. This study provides healthcare providers with a tool for objective, real-time, and remote assessment of adherence and for making required adjustments to treatment plans., Methods: The IoT patch had two temperature microsensors and a wireless chip. One sensor was placed closer to the skin than the other, resulting in a temperature difference depending on whether the patch was worn. When the patch was worn, it measured temperatures every 30 seconds and transmitted temperature data to a cloud server via a mobile application every 15 seconds. The patch was evaluated via 2 experiments with 30 healthy adults and 40 children with amblyopia., Results: Excellent monitoring accuracy was observed in both adults (mean delay of recorded time data, 0.4 minutes) and children (mean, 0.5 minutes). The difference between manually recorded and objectively recorded patch wear times showed good agreement in both groups. Experiment 1 showed accurate monitoring over a wide range of temperatures (from 0 to 30°C). Experiment 2 showed no significant differences in wearability (ease-of-use and comfort scores) between the IoT and conventional patches., Conclusions: The IoT patch offers an accurate, real-time, and remote system to monitor adherence to patch treatment. The patch is comfortable and easy to use. The utilization of an IoT patch may increase adherence to patch treatment based on accurate monitoring., Translational Relevance: Results show that the IoT patch can enable real-time adherence monitoring in clinical trials, improving treatment precision, and patient compliance to enhance outcomes.

Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities. Various doses of mDA progenitors were transplanted into hemi-parkinsonian rats, and a significant dose-dependent behavioral improvement was observed with a minimal effective dose range of 5,000-10,000 mDA progenitor cells. These results provided insights into determining a low cell dosage (3.15 million cells) for human clinical trials. Based on these results, approval for a phase 1/2a clinical trial for PD cell therapy was obtained from the Ministry of Food and Drug Safety in Korea, and a clinical trial for treating patients with PD has commenced., Competing Interests: Declaration of interests D.-W.K. is a chief technology officer of S. Biomedics Co., Ltd. J.H.E., M.-Y.J., H.-J.H., S.K.C., S.T.N., K.-S.J., D.-H.K., C.-Y.P., and M.S.C. are currently employed at S. Biomedics Co., Ltd. We have patents related to this work. 1. Title: method for inducing differentiation of stem cells into dopaminergic neural precursor cells, patent number: 102392133(KR), 11655450(US), 07152050(JP), and 2020202273(AU). 2. Title: efficient and universal method for neural differentiation of human pluripotent stem cells, patent number: 101168053(KR), 08551783(US), 05756019(JP), and 02502987(EP)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Anion-dependent differences in the electromechanical energy harvesting capability of perovskite halides have not been experimentally demonstrated thus far. Herein, anion-dependent piezoelectricity and bending-driven power generation in high-quality methylammonium lead halide MAPbX 3 (X = I, Br, and Cl) thin films are explored; additionally, anisotropic in situ strain is imposed to improve energy harvesting under tensile bending. After applying the maximum in situ strain of -0.73% for all the halide thin films, the MAPbI 3 thin-film harvester exhibited a peak voltage/current of ≈23.1 V/≈1703 nA as the best values, whereas MAPbBr 3 and MAPbCl 3 demonstrated ≈5.6 V/≈176 nA and ≈3.3 V/≈141 nA, respectively, under identical bending conditions. Apart from apparent ferroelectricity of tetragonal MAPbI 3 , origin of the piezoelectricity in both cubic MAPbBr 3 and MAPbCl 3 is explored as being related to organic-inorganic hydrogen bonding, lattice distortion, and ionic migration, with experimental supports of effective piezoelectric coefficient and grain boundary potential. Conclusively, piezoelectricity of the cubic halides is assumed to be due to their soft polarity modes and relatively low elastic modulus with vacancies contributing to space-charge polarization. In the case of ferroelectric MAPbI 3 , the distortion of PbI 6 octahedra and atomic displacement within each octahedron are quantitatively estimated., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Misfolded glycosylphosphatidylinositol-anchored prion protein (PrP) is primarily degraded in lysosomes but is often rapidly removed from the cell surface before endocytosis in a preemptive manner. However, this mechanism is poorly understood. In this study, we discovered a disease-causing prion mutation (Q212P) that exceptionally promoted the extracellular release of PrP. Spatiotemporal analyses combined with genome editing identified the role of sheddase ADAM10 in Q212P shedding from the cell surface. ADAM10 was observed to catalytically interacts with Q212P but non-catalytically with wild-type PrP (wtPrP). This intrinsic difference in the interaction of ADAM10 between Q212P and wtPrP allowed Q212P to selectively access the sheddase activity of ADAM10 in a redox-sensitive manner. In addition, redox perturbation instigated the latent misfolding propensity of Q212P and disrupted the catalytic interaction between PrP and ADAM10, resulting in the accumulation of misfolded PrP on the cell surface. Upon recovery, active ADAM10 was able to reversibly release the surface Q212P. However, it might prove detrimental if unregulated resulting in unexpected proteotoxicity. This study provides a molecular basis of the mutant-selective shedding of PrP by demonstrating the catalytic interaction of ADAM10 with Q212P., Competing Interests: Declaration of competing interest The authors declare that no competing interests exist., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Resistance to DNA-damaging agents is one of the main reasons for the low survival of cervical cancer patients. Previous reports have suggested that the Cdc25A oncoprotein significantly affects the level of susceptibility to DNA-damaging agents, but the molecular mechanism remains unclear. In this study, we used Western blot and flow cytometry analyses to demonstrate that the deubiquitinating enzyme HAUSP stabilizes Cdc25A protein level. Furthermore, in a co-immunoprecipitation assay, we found that HAUSP interacts with and deubiquitinates Cdc25A both exogenously and endogenously. HAUSP extends the half-life of the Cdc25A protein by circumventing turnover. HAUSP knockout in HeLa cells using the CRISPR/Cas9 system caused a significant delay in Cdc25A-mediated cell cycle progression, cell migration, and colony formation and attenuated tumor progression in a mouse xenograft model. Furthermore, HAUSP-mediated stabilization of the Cdc25A protein produced enhanced resistance to DNA-damaging agents. Overall, our study suggests that targeting Cdc25A and HAUSP could be a promising combinatorial approach to halt progression and minimize antineoplastic resistance in cervical cancer., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study investigated the clinicopathologic factors associated with 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) uptake of early gastric cancer (EGC) and used them to design a clinical scoring method to predict FDG-avidity of EGC.Two hundred twenty-nine retrospectively enrolled patients underwent preoperative F-FDG positron emission tomography/computed tomography (PET/CT). Histologic information was obtained by gastrectomy (n = 195) or endoscopic mucosal dissection (n = 34). The association between clinicopathologic factors and F-FDG uptake by the primary tumor was determined. The results were used to develop a clinical scoring method.F-FDG uptake was detected in 49 (17.5%) patients. According to univariate analysis, location, gross type, World Health Organization classification, Lauren classification, size, depth of invasion, and lymphatic invasion were significant variables affecting F-FDG uptake (all P < .05). According to multivariate analysis, location (lower 3rd, P = .035), gross type (0-I, 0-IIa, P < .001), size (≥2.5 cm, P = .026), and depth of invasion (submucosa, P = .007) were significantly associated with FDG-avidity. A clinical scoring system, ranged from 0 to 4, was developed by giving one score to 4 independent variables. A cut-off value of 2.5 showed good prediction of FDG-avidity in EGCs, with a sensitivity and specificity of 65.0% and 85.2%, respectively.F-FDG uptake by EGC depends on location, gross type, size, and depth of invasion of the primary tumor. A clinical scoring system based on clinicopathologic variables can predict the FDG-avidity of primary tumors in patients with EGC.

Purpose: This study compared the pain-relieving effects of human milk, sucrose, and distilled water during examinations for retinopathy of prematurity., Methods: Forty-five preterm infants were randomly assigned to receive a pacifier dipped in one of three solutions: human milk (n=14), 24% sucrose (n=15), or distilled water (n=16), 2 minutes before an eye examination. Their pain score, pulse rate, and oxygen saturation were measured at three time points: 5 minutes before the examination, 30 seconds after speculum introduction, and 2 minutes after the examination., Results: The infants' mean gestational age and weight at birth were 33.1±2.1 weeks and 1,842±470 g, respectively. There were no between-group differences in pain relief during the eye examination. The pain score significantly increased both during ( p <.001) and after the examinations ( p =.003). Oxygen saturation decreased during the examinations ( p <.001); however, the infants in the 24% sucrose group showed higher oxygen saturation ( p =.047) during the examinations than the infants in the other groups., Conclusion: Sucking on a pacifier dipped in human milk or 24% sucrose did not reduce the pain associated with eye examinations in preterm infants. Pacifiers dipped in sucrose can be used to maintain better oxygen saturation during these examinations., Competing Interests: No existing or potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Academy of Child Health Nursing. All rights reserved.)

Objective: To evaluate the value of airway computed tomography (CT) in patients with obstructive sleep apnea (OSA) as a predictor of cerebrocardiovascular disease (CCVD) clinically, by quantitatively analyzing carotid arterial calcification (CarAC)., Materials and Methods: This study included 287 patients aged 40-80 years, who had undergone both polysomnography (PSG) and airway CT between March 2011 and October 2015. The carotid arterial calcium score (CarACS) was quantified using the modified Agatston method on each upper airway CT. The OSA severity was categorized as normal, mild, moderate, and severe using the PSG results. Clinical characteristics, comorbid diseases, and lipid profiles of all patients were analyzed, and the prevalence of CCVDs was investigated during the follow up period (52.2 ± 16.0 months)., Results: CCVD occurred in 27 patients (9.3%) at the end of follow-up, and the CCVD-present groups showed a significantly older mean age (57.5 years vs. 54.2 years), higher prevalence of hypertension (59% vs. 34%) and CarAC (51.9% vs. 20.8%), whereas sex, other comorbid diseases, and severity of OSA were not significantly different from the CCVD-absent group. A univariate analysis showed that age, hypertension, incidence of CarAC, and CarACS were risk factors for the occurrence of CCVD events. In a multivariate analysis, the incidence of CarAC was the only independent risk factor for CCVD., Conclusion: CarAC is an independent risk factor for CCVD, whereas the severity of OSA is not a contributory risk factor in patients with OSA. Therefore, additional analysis of CarACS based on airway CT scans may be useful for predicting CCVD., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2019 The Korean Society of Radiology.)

The various chaperone activities of heat shock proteins contribute to ensuring cellular proteostasis. Here, we demonstrate the non-canonical unfoldase activity as an inherent functionality of the prokaryotic molecular chaperone, Hsp33. Hsp33 was originally identified as a holding chaperone that is post-translationally activated by oxidation. However, in this study, we verified that the holding-inactive reduced form of Hsp33 ( R Hsp33) strongly bound to the translational elongation factor, EF-Tu. This interaction was critically mediated by the redox-switch domain of R Hsp33 and the guanine nucleotide-binding domain of EF-Tu. The bound R Hsp33, without undergoing any conformational change, catalyzed the EF-Tu aggregation by evoking the aberrant folding of EF-Tu to expose hydrophobic surfaces. Consequently, the oligomers/aggregates of EF-Tu, but not its functional monomeric form, were highly susceptible to proteolytic degradation by Lon protease. These findings present a unique example of an ATP-independent molecular chaperone with distinctive dual functions-as an unfoldase/aggregase and as a holding chaperone-depending on the redox status. It is also suggested that the unusual unfoldase/aggregase activity of R Hsp33 can contribute to cellular proteostasis by dysregulating EF-Tu under heat-stressed conditions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Although cyclic AMP receptor protein (CRP) has long served as a typical example of effector-mediated protein allostery, mechanistic details into its regulation have been controversial due to discrepancy between the known crystal structure and NMR structure of apo-CRP. Here, we report that the recombinant protein corresponding to its C-terminal DNA-binding domain (CDD) forms a dimer. This result, together with structural information obtained in the present NMR study, is consistent with the previous crystal structure and validates its relevance also in solution. Therefore, our findings suggest that dissociation of the CDD may be critically involved in cAMP-induced allosteric activation of CRP., (© 2017 Federation of European Biochemical Societies.)

Purpose: Cardiac images using I-123 metaiodobenzylguanidine (MIBG) are widely used to evaluate cardiac sympathetic denervation in Parkinson's disease (PD). The aim of this study was to evaluate the utility of segmental analysis on cardiac MIBG SPECT in PD patients., Materials and Methods: In total, 36 patients with PD (n = 26) or essential tremor (ET, n = 10) who underwent MIBG cardiac SPECT were enrolled. The heart-to-mediastinum (H/M) ratios of MIBG uptake were acquired on planar images. For the segmental analysis of SPECT images, we evaluated the summed defect score (SDS) using a 17-segment model. The diagnostic abilities of H/M ratios and segmental parameters on MIBG SPECT were assessed by ROC curve analysis., Results: The H/M ratios were significantly lower in PD than in ET patients (p < 0.05). On segmental analysis, SDS was significantly higher in PD patients than in the ET group (7.04 ± 4.09 vs. 2.90 ± 2.80; p = 0.006). The defect score of the anteroseptal region showed a significant difference between the groups (p = 0.002). The ROC analysis suggested only SDS (AUC = 0.785, p = 0.0003) and defect scores in the anteroseptal (AUC = 0.800, p < 0.0001) and inferior (AUC = 0.667, p = 0.013) regions showed significant diagnostic ability to differentiate PD from ET., Conclusions: Segmental parameters from cardiac MIBG SPECT images can provide additional information to differentiate PD from ET patients. Beyond H/M ratios from planar images, we recommend an MIBG SPECT study to evaluate sympathetic denervation in PD.

The homo- or hetero-dimerization of proteins plays critical roles in the mitotic progression. The TRAF-interacting protein (TRAIP) is crucial in early mitotic progression and chromosome alignment defects in the metaphase. The TRAIP is a 469 amino acid protein, including the Really Interesting New Gene (RING), coiled-coil (CC), and leucine zipper (LZ) domain. In general, the CC or LZ domain containing proteins forms homo- or hetero-dimerization to achieve its activity. In this study, a number of TRAIP mutants were used to define the TRAIP molecular domains responsible for its homo-dimerization. A co-immunoprecipitation assay indicated that the TRAIP forms homo-dimerization through the CC domain. The cells, expressing the CC domain-deleted mutant that could not form a homo-dimer, increased the mitotic index and promoted mitotic progression., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Backgrounds: We evaluated the prognostic value of the intratumoral heterogeneity of (18) F-FDG uptake in oral cavity cancer., Materials and Methods: We enrolled 45 patients who underwent pretreatment (18) F-FDG PET/CT. The intratumoral heterogeneity of (18) F-FDG uptake was represented as the heterogeneity factor (HF), defined as the derivative (dV/dT) of a volume-threshold function for a primary tumor. We measured the maximum standardized uptake value (SUVmax ) and volumetric PET parameters. The relationship between HF and clinical parameters, as well as other PET parameters, was evaluated., Results: The HF was significantly correlated with SUVmax (r = -0.353, P = 0.017), metabolic tumor volume (r = -0.708, P < 0.0001), and total lesion glycolysis (r = -0.709, P < 0.0001). A multivariate analysis revealed not only cervical lymph node metastasis (hazard ratio = 5.983; P = 0.022) but also HF (hazard ratio = 2.49 × 10(-4) ; P = 0.002) to be independent predictors of overall survival. Those patients with HF < -0.13 showed a worse prognosis than those with HF ≥ -0.13 (P = 0.005)., Conclusions: The intratumoral heterogeneity of (18) F-FDG uptake may be a significant prognostic factor for overall survival in addition to cervical lymph node metastasis in oral cavity cancer. J. Surg. Oncol. 2014 110:702-706. © 2014 Wiley Periodicals, Inc., (© 2014 Wiley Periodicals, Inc.)

Purpose: We investigated the relation between carotid artery FDG uptake and cardiovascular risk based on the Framingham risk score (FRS) and evaluated the possible role of FDG uptake in terms of risk stratification of asymptomatic adults., Methods: We evaluated 290 adults who underwent FDG PET/CT as part of general health screens. We calculated target-to-background ratios, corrected for pre-scan blood glucose levels, and obtained "TBRglu" values for both common carotid arteries. The FRS and the presence/absence of metabolic syndrome were recorded for each subject. Relationships among TBRglu values, metabolic syndrome status, and clinical parameters were assessed., Results: Carotid artery FDG uptake was significantly associated with clinical risk factors. Stepwise multiple regression analysis revealed that triglyceride levels, diabetes, and metabolic syndrome were independent determinants of high TBRglu. Of subjects with metabolic syndrome, those exhibiting high carotid artery FDG uptake had significantly higher levels of high sensitivity C-reactive protein (hsCRP). In subjects who did not have metabolic syndrome, FRSs were significantly elevated in those exhibiting high carotid artery FDG uptake compared to those with low uptake (13.1 ± 7.0 vs. 8.2 ± 7.4), as was also true of subjects with the syndrome (21.8 ± 16.0 vs. 13.5 ± 11.9)., Conclusion: High carotid FDG uptake is significantly associated with clinical risk factors and a greater FRS. Of subjects with metabolic syndrome, those with high carotid uptake had significantly higher hsCRP concentrations and FRSs. Therefore, carotid artery FDG activity may serve as a possible biomarker allowing cardiovascular risk stratification of asymptomatic populations.

Purpose: We investigated whether (131)I whole-body scintigraphy could predict functional changes in salivary glands after radioiodine therapy., Methods: We evaluated 90 patients who received initial high-dose (≥3.7 GBq) radioiodine therapy after total thyroidectomy. All patients underwent diagnostic (DWS) and post-ablation (TWS) (131)I whole-body scintigraphy. Visual assessment of salivary radioiodine retention on DWS and TWS was used to divide the patients into two types of groups: a DWS+ or DWS- group and a TWS+ or TWS- group. Salivary gland scintigraphy was also performed before DWS and at the first follow-up visit. Peak uptake and %washout were calculated in ROIs of each gland. Functional changes (Δuptake or Δwashout) of salivary glands after radioiodine therapy were compared between the two groups., Results: Both peak uptake and the %washout of the parotid glands were significantly lower after radioiodine therapy (all p values <0.001), whereas only the %washout were significantly reduced in the submandibular glands (all p values <0.05). For the parotid glands, the TWS+ group showed larger Δuptake and Δwashout after radioiodine therapy than did the TWS- group (all p values <0.01). In contrast, the Δuptake and Δwashout of the submandibular glands did not significantly differ between the TWS+ and TWS- groups (all p values >0.05). Likewise, no differences in Δuptake or Δwashout were apparent between the DWS+ and DWS- groups in either the parotid or submandibular glands (all p values >0.05)., Conclusion: Salivary gland radioiodine retention on post-ablation (131)I scintigraphy is a good predictor of functional impairment of the parotid glands after high-dose radioiodine therapy.

Unlabelled: The aim of this study was to compare the diagnostic utility of visual versus semi-quantitative analysis of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome (SS)., Patients, Methods: 99mTc-pertechnetate salivary gland scintigraphy was performed in 145 patients (133 women, 12 men) with clinically suspicious SS. The images were interpreted with visual and semiquantitative methods and the diagnostic performances for SS were compared using uptake and excretory functional parameters., Results: In total, 76 patients (52.4%) were finally diagnosed with SS. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of visual analysis for the diagnosis of SS were 88.2%, 48.6%, 65.1%, 79.1%, and 69.2%, respectively. Semiquantitative values, the area under the ROC curve for uptake ratio and percentage excretion in the right salivary glands were significantly greater than 0.5 (p < 0.05). However, the percentage excretion in the left salivary glands did not show a statistically significant diagnostic ability for SS. The diagnostic ability of visual assessment was greater than that of the semiquantitative method in terms of evaluating uptake and excretory function in the submandibular glands., Conclusion: Visual analysis of salivary gland scintigraphy showed greater diagnostic utility than semiquantitative assessment in the diagnosis of SS, especially in the submandibular glands.

We report a case of isolated splenic metastasis from ovarian cancer detected with 18F-FDG PET/CT. A 66-year-old woman with ovarian cancer was referred for 18F-FDG PET/CT to determine the cause of elevated serum CA-125 levels about 48 months after surgery. 18F-FDG PET/CT showed focal, intense uptake in the spleen, with no other abnormal findings. A splenectomy was performed, and the lesion was confirmed as metastasis from ovarian cancer pathologically.

After total thyroidectomy for papillary thyroid carcinoma, a 37-year-old woman underwent a 2-mCi (131)I whole-body scan which demonstrated focal uptake in the anterior neck and in the oropharynx. Preoperative contrast-enhanced neck computed tomography demonstrated a small enhancing nodule typical for ectopic thyroid at the tongue base. She was then treated with 150 mCi (131)I. Small asymptomatic lingual thyroid remnants typically do not affect high-dose (131)I therapy.

Mediastinal inflammatory pseudotumor is a rare benign disease with its capability for local invasion and rapid growth. We present a case of middle-mediastinal inflammatory pseudotumor and report its contrast-enhanced chest computed tomography, (18)F-fluorodeoxyglucose positron emission tomography/computed tomography and pathologic findings.

Objective: It is known that the poor image quality of (18)F-fluorodeoxyglucose ((18)F-FDG) PET scans leads to interpretation difficulty in patients with uncontrolled diabetes mellitus (DM). We usually delay (18)F-FDG PET examination when patients show high glucose levels. This study was performed to evaluate the usefulness and effects of ultrashort-acting insulin on (18)F-FDG PET/computed tomography (CT) imaging in DM patients., Materials and Methods: A total of 105 DM patients (68 men and 37 women) were included. Ultrashort-acting insulin was intravenously injected when patients showed high glucose levels (>190 mg/dl). (18)F-FDG was injected 60 min after ultrashort-acting insulin injection, and PET/CT images were acquired. Image quality was graded by consensus using the following scale: 1, good; 2, moderate; and 3, poor. The mean standardized uptake value (SUV(mean)) of the liver, gluteal muscle, and brain was assessed to evaluate the effects of ultrashort-acting insulin., Results: The group administered ultrashort-acting insulin (n=52, blood glucose level: 243.7 ± 46.2 mg/dl) showed a significantly higher glucose level compared with the group not administered ultrashort-acting insulin (n=53, 177.1 ± 5.2 mg/dl). Nevertheless, the image quality of the group with ultrashort-acting insulin was not significantly different from that of the group without ultrashort-acting insulin (χ(2) -test, P=0.47). No significant differences were seen in SUV(mean) in the liver (P=0.13), gluteal muscle (P=0.71), and brain (P=0.16) between groups., Conclusion: Ultrashort-acting insulin can be used to improve the image quality of F-FDG PET/CT in uncontrolled DM patients without significant differences in SUV.

Objective: The aim of this study was to document the subjective and objective findings of symptomatic late-onset sialadenitis after radioiodine therapy in patients with differentiated thyroid cancer., Methods: Subjective symptoms related to sialadenitis and Tc-99m pertechnetate salivary gland scintigram findings were assessed in 118 patients (26 males, 92 females) both before and during the late phase (mean 338 days) after the administration of radioiodine., Results: Twelve of the 118 patients (10.2 %) complained of symptomatic sialadenitis in the late phase without symptoms during the early phase (within 7 days of radioiodine administration). Significant associations were found between subjective symptoms and visual scintigram findings during the late phase (p = 0.023). Furthermore, uptake and excretion by both parotid glands were significantly affected by radioiodine therapy., Conclusions: Symptomatic late-onset sialadenitis occurred at an incidence of 10.2 %, and salivary gland function was affected in both parotids in most patients.

Several studies have demonstrated that the Chinese herb Gastrodia elata Blume can protect against amyloid beta-peptide (Aβ)-induced cell death. To investigate the possible therapeutic effects of Gastrodia elata Blume on Alzheimer's disease, we established a rat model of Alzheimer's disease by injecting Aβ25-35 into bilateral hippocampi. These rats were intragastrically administered 500 or 1 000 mg/kg Gastrodia elata Blume per day for 52 consecutive days. Morris water maze tests showed that Gastrodia elata Blume treatment significantly improved the spatial memory of Alzheimer's disease rats. Congo red staining revealed that Gastrodia elata Blume significantly reduced the number of amyloid deposits in the hippocampus of these rats. Western blot analysis showed that choline acetyltransferase expression in the medial septum and hippocampus was significantly increased by the treatment of Gastrodia elata Blume, while Ellman method showed significant decrease in the activity of acetylcholinesterase in all three regions (prefrontal cortex, medial septum and hippocampus). These findings suggest that long-term administration of Gastrodia elata Blume has therapeutic potential for Alzheimer's disease.

Purpose: Bone metastasis is an important factor for the treatment and prognosis of breast cancer patients. Whole-body bone scintigraphy (WBBS) can evaluate skeletal metastases, and (18)F-FDG PET/CT seems to exhibit high specificity and accuracy in detecting bone metastases. However, there is a limitation of (18)F-FDG PET in assessing sclerotic bone metastases because some lesions may be undetectable. Recent studies showed that (18)F-fluoride PET/CT is more sensitive than WBBS in detecting bone metastases. This study aims to evaluate the usefulness of (18)F-fluoride PET/CT by comparing it with WBBS and (18)F-FDG PET/CT in breast cancer patients with osteosclerotic skeletal metastases., Materials and Methods: Nine breast cancer patients with suspected bone metastases (9 females; mean age ± SD, 55.6 ± 10.0 years) underwent (99m)Tc-MDP WBBS, (18)F-FDG PET/CT and (18)F-fluoride PET/CT. Lesion-based analysis of five regions of the skeletons (skull, vertebral column, thoracic cage, pelvic bones and long bones of extremities) and patient-based analysis were performed., Results: (18)F-fluoride PET/CT, (18)F-FDG PET/CT and WBBS detected 49, 20 and 25 true metastases, respectively. Sensitivity, specificity, positive predictive value and negative predictive value of (18)F-fluoride PET/CT were 94.2 %, 46.3 %, 57.7 % and 91.2 %, respectively. Most true metastatic lesions on (18)F-fluoride PET/CT had osteosclerotic change (45/49, 91.8 %), and only four lesions showed osteolytic change. Most lesions on (18)F-FDG PET/CT also demonstrated osteosclerotic change (17/20, 85.0 %) with three osteolytic lesions. All true metastatic lesions detected on WBBS and (18)F-FDG PET/CT were identified on (18)F-fluoride PET/CT., Conclusion: (18)F-fluoride PET/CT is superior to WBBS or (18)F-FDG PET/CT in detecting osteosclerotic metastatic lesions. (18)F-fluoride PET/CT might be useful in evaluating osteosclerotic metastases in breast cancer patients.

Malignant fibrous histiocytoma (MFH) is the most common soft tissue tumor which often occurs in the extremities and the retroperitoneum. Primary mediastinal MFH is rare; thus, findings on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) of mediastinal MFH have not been reported yet. We report herein the case of a 64-year-old man who was presented with a superior mediastinal mass. The mass showed intense (18)F-FDG uptake with central metabolic defect on PET/CT. The maximum standardized uptake value was 17.4. After tumor removal via median sternotomy, an MFH of the storiform-pleomorphic type was diagnosed on histopathologic examination. We present the first report of (18)F-FDG PET/CT imaging of MFH in the superior mediastinum.

Objectives: Gastrodia elata (GE) Blume (Orchidaceae) has been previously known for its therapeutic benefits against neurodegenerative diseases. Microglial activation and death have been implicated in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer's disease. In this study, GE and its pure components, gastrodin and 4-hydroxybenzyl alcohol (4HBA), were applied to β-amyloid-induced BV2 mouse microglial cells., Materials and Methods: Cell viability was assessed by the MTT assay and Western blotting was also performed., Results: β-amyloid-induced cell death was shown to be induced time- and dose-dependently. To examine the cell death mechanism, we confirmed the involvement of ER stress signaling. C/EBP homologous protein (CHOP), a pro-apoptotic ER stress protein, was expressed at high levels but glucose-regulated protein 78 (GRP78), an anti-apoptotic ER stress protein with chaperone activity, was only slightly affected by treatment with β-amyloid. However, pretreatment with GE and its components inhibited the expression of CHOP but increased that of GRP78 in β-amyloid-treated cells. This study also showed that a single treatment with GE extracts, gastrodin, or 4HBA induced the expression of GRP78, a marker for enhanced protein folding machinery, suggesting a protective mechanism for GE against β-amyloid., Conclusions: This study reveals the protective effects of GE against β-amyloid-induced cell death, possibly through the enhancement of protein folding machinery of a representative protein, GRP78, and the regulation of CHOP in BV2 mouse microglial cells.

A novel combined method for locating box H/ACA small nucleolar RNAs (snoRNAs) is described, together with a software tool. The method adopts both a probabilistic hidden Markov model (HMM) and a minimum free energy (MFE) rule, and filters possible candidate box H/ACA snoRNAs obtained from genomic DNA sequences. With our novel method 12 known box H/ACA snoRNAs, and one strong candidate were identified in 30 nucleolar protein genomic sequences.