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In vitro and animal studies have indicated that extracts from the peel of the Japanese Citrus sudachi, including sudachitin, ameliorate hyperlipidemia and reduce obesity. Sudachitin, a polymethoxylated flavone, has been reported as having favorable effects on lipid and glucose metabolism but results from clinical trials have been inconsistent. The aim of this study was to determine the effect of consuming capsules of sudachi peel extract powder on visceral fat in Japanese men and women in a randomized controlled trial. This was a 12‐week randomized, double‐blind, placebo‐controlled trial involving 41 participants aged 30–65 years with BMI 23–30 kg/m2, randomly allocated to receive either sudachi peel extract powder (sudachitin 4.9 mg/day, n = 21) or placebo (n = 20) of identical appearance. The primary outcome measure was visceral fat mass, assessed during intervention. Thirty‐eight of the 41 subjects completed the protocol. Compared with placebo, sudachi peel extract powder significantly reduced the ratio of visceral fat to subcutaneous fat, and moderately reduced waist circumference, a metabolic syndrome marker. Glycemic control and lipid profile were not changed significantly in these subjects. Consumption of capsules of sudachi peel extract powder favorably improves the ratio of visceral fat to subcutaneous fat in individuals at risk for developing diabetes, especially in individuals with large visceral fat area, while not adversely affecting glycemic control., Extracts of Citrus sudachi (sudachi) peel, containing the polymethoxylated flavone sudachitin, have shown promise in vitro and in animal models. Compared with placebo, sudachi peel extract significantly reduced the ratio of visceral fat to subcutaneous fat (−0.0265%, p = .0485), and moderately reduced visceral fat and waist circumference.

Background/purpose With the advancement of an over aging society, the average number of remaining teeth has increased. However, these remaining teeth do not always have sufficient alveolar bone support, and sometimes fabricated connected crowns are applied. This study evaluated the influence of crown material, crown thickness, and alveolar bone resorption on the stress distribution within the abutment teeth of connected crowns. Materials and methods Using structural analysis software, a premolar crown model was fabricated. Three kinds of crown materials, two types of crown thickness, two types of post and core systems, and two levels of alveolar bone were assumed and evaluated for the stress distribution within the abutment teeth. Results The higher material properties crown was, the more stress was concentrated at the marginal area. The composite resin core showed larger stress values around the marginal area, and the metal core showed larger stress values at the tip of the post. Alveolar bone resorption progressed, the marginal area stress value increased. Conclusion The low elastic modulus crown material polyetheretherketone (PEEK) prevented stress concentrations at the marginal area of the crown and dentine, even with alveolar bone resorption. However, the amount of bone resorption has a great influence on the stress distribution around the tip of the post compared to the type of crown material.

Purpose To investigate the risk of debonding of resin-bonded fixed dental prosthesis frameworks and the effects on the periodontal tissue in patients with reduced alveolar bone levels. Materials & methods The abutment teeth were the upper central incisor and the canine. Resin-bonded fixed dental prosthesis framework fabricated using zirconia was set to models with five different alveolar bone levels. A 200-N load (the maximum clenching force of the anterior teeth) was applied to the center of the pontic to analyze the internal stress on the framework, adhesive cement, and periodontal tissue using finite element analysis. Results The mean maximum principal stress generated in the framework was 25.33 and 29.35 MPa in the models with the normal and the lowest alveolar bone level, respectively. Regarding shear stress on the adhesive cement, stress concentration was observed on the connector side in all models, and it increased on the cervical side of the central incisor as the alveolar bone level decreased. In addition, the mean maximum and minimum principal strains generated on the periodontal ligament of the central incisor and canine tended to increase as alveolar bone loss progressed. Furthermore, the mean maximum principal stress on the cortical bone was the greatest in the model with the most significant bone loss at 5.10 MPa. Conclusions This study suggested that the risk of debonding and periodontal tissue damage might be higher when resin-bonded fixed dental prosthesis frameworks were used in patients with reduced alveolar bone levels compared to those in a healthy state. This article is protected by copyright. All rights reserved.

Aims To evaluate the prognostic impact of fragmented QRS (fQRS) on idiopathic dilated cardiomyopathy (DCM). Methods and results We conducted a prospective observational study of 290 consecutive patients with DCM (left ventricular ejection fraction ≤ 40%) and narrow QRS who underwent cardiac magnetic resonance. We defined fQRS as the presence of various RSR′ patterns in ≥2 contiguous leads representing the anterior (V1–V5), inferior (II, III, and aVF), or lateral (I, aVL, and V6) myocardial segments. Multiple fQRS was defined as the presence of fQRS in ≥2 myocardial segments. Patients were divided into three groups: no fQRS, single fQRS, or multiple fQRS. The primary endpoint was a composite of hard cardiac events consisting of heart failure death, sudden cardiac death (SCD), or aborted SCD. The secondary endpoints were all-cause death and arrhythmic event. During a median follow-up of 3.8 years (interquartile range, 1.8–6.2), 31 (11%) patients experienced hard cardiac events. Kaplan–Meier analysis showed that the rates of hard cardiac events and all-cause death were similar in the single-fQRS and no-fQRS groups and higher in the multiple-fQRS group (P = 0.004 and P = 0.017, respectively). Multivariable Cox regression identified that multiple fQRS is a significant predictor of hard cardiac events (hazard ratio, 2.23; 95% confidence interval, 1.07–4.62; P = 0.032). The multiple-fQRS group had the highest prevalence of a diffuse late gadolinium enhancement pattern (no fQRS, 21%; single fQRS, 22%; multiple fQRS, 39%; P Conclusion Multiple fQRS, but not single fQRS, is associated with future hard cardiac events in patients with DCM.

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein highly expressed by prostate cancer cells. PSMA-based radioligand therapy (RLT) emerged as a promising therapeutic option for prostate cancer in the early 2000s, and has been clinically validated with great enthusiasm during these past two decades. Last year, the European Association of Nuclear Medicine (EANM) published the procedure guidelines for the safe clinical practice of Lutetium-177 (177Lu)-labelled PSMA RLT. In addition, PSMA RLT with alpha-ray-emitting radioisotopes has been also developed recently. Following the clinical use of 177Lu-PSMA RLT, PSMA-targeted positron-emission tomography (PET) with Gallium-68 (68Ga) has been performed inevitably for “theranostics” for the last decade; prostate cancer is going to be treated with PSMA-RLT based on the diagnosis by PSMA-PET. Furthermore, the diagnostic usefulness of 68Ga-PSMA PET has been documented in various diseases beyond prostate cancer more recently. Regrettably, Japan is behind European countries and the United States in this field, and has just made a belated start of their clinical trials. In this review article, we briefly overviewed the current status of PSMA RLT and PSMA PET. We hope that this topic will be a particular focus of attention for most ANM readers in Japan, and that our efforts will help to facilitate the early approval of PSMA RLT and PSMA PET by the Japanese government even if only slightly.

BACKGROUND The clinical characteristics and prognostic outcomes of dilated cardiomyopathy (DCM) with a familial history (FHx) via pedigree analysis are unclear.Methods and Results:We conducted a prospective observational study of 514 consecutive Japanese patients with DCM. FHx was defined as the presence of DCM in ≥1 family member within 2-degrees relative based on pedigree analysis. The primary endpoint was a composite of major cardiac events (sudden cardiac death and pump failure death). The prevalence of FHx was 7.4% (n=38). During a median follow-up of 3.6 years, 77 (15%) patients experienced a major cardiac event. Multivariable Cox regression analysis identified FHx as independently associated with major cardiac events (hazard ratio [HR] 4.32; 95% confidence interval [CI], 2.04-9.19; P

Our report presents the smallest bronchial carcinoid thus far associated with peripheral squamous cell carcinoma. A 79‐year‐old Japanese man presented with an abnormal shadow on chest radiography. Chest computed tomography revealed an ill‐defined nodule at the left S9a area without lymph node involvement. At the time of bronchoscopy, a nodule of ~1 mm in diameter with a smooth surface was observed at the orifice of the left B8. Left lower lobectomy was performed. Pathologically, the S9a tumour was keratinizing squamous cell carcinoma with surgical stage IA3, and the left B8 tumour was a typical bronchial carcinoid. The patient was alive without recurrence 2 years after the surgery. Cases of combined carcinoid and lung cancer are rare. It may be possible to identify bronchial carcinoids early by careful observation of the bronchi during bronchoscopy for peripheral neoplastic lesions., Our report presents the smallest bronchial carcinoid thus far associated with peripheral squamous cell carcinoma. Cases of combined carcinoid and lung cancer are rare. It may be possible to identify bronchial carcinoids early by careful observation of the bronchi during bronchoscopy for peripheral neoplastic lesions.

Purpose Oligodontia significantly affects oral function and esthetics. Recognition of skeletal and dental patterns may aid in proper diagnosis and development of appropriate interventions. The aim of this study was to analyze skeletal and dental patterns for pre-adolescent patients with a diagnosis of oligodontia. Patients and methods This study included 19 oligodontia patients (age: 9.5±1.3, Hellman's developmental stage IIIA~IIIB) along with a control group that comprised of 19 participants (age: 9.9±1.6) without any skeletal disharmony or congenitally missing teeth, with an Angle class I relationship and general crowding. Average cephalometric measurements among the oligodontia group were compared to the control group. The correlation between number of congenitally missing teeth (CMT) and each measurement was investigated. Skeletal measurements for both male and female patients in the oligodontia group and the control group were also compared. Results No significant difference between the experimental and the control group was observed with respect to skeletal angular and linear measurements, except the gonial angle. Differences in dental pattern measurements were observed. The oligodontia group had significantly smaller Mo-Ms and Is-Mo than the control group (p

BACKGROUND In patients with chronic heart failure with reduced ejection fraction (HFrEF), cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) and exercise-based cardiac rehabilitation (ECR) enhances exercise capacity. This study examined the relationship between the 2 responses.Methods and Results:Sixty-four consecutive HFrEF patients who participated in a 3-month ECR program after CRT were investigated. Patients were categorized according to a median improvement in peak oxygen uptake (PVO2) after ECR of 7% as either good (n=32; mean percentage change in PVO2[%∆PVO2]=23.2%) or poor (n=32; mean %∆PVO2=2.5%) responders. There was no significant difference in baseline characteristics between the good and poor responders, except for PVO2(51% vs. 59%, respectively; P=0.01). The proportion of good CRT responders was similar between the good and poor responders (%∆LVEF ≥10%; 53% vs. 47%, respectively; P=NS). Overall, there was no significant correlation between %∆LVEF after CRT and %∆PVO2after ECR. Notably, among poor CRT responders (n=32), the prevalence of atrial fibrillation (0% vs. 29%; P

Background Coronary computed tomography angiography (CCTA) non-invasively visualizes lipid-rich plaque. However, this ability is not fully validated in vivo. The current study aimed to elucidate the association of CCTA features with near-infrared spectroscopy-derived lipidic plaque measure in patients with coronary artery disease. Methods 95 coronary lesions (culprit/non-culprit = 51/44) in 35 CAD subjects were evaluated by CCTA and NIRS imaging. CT density, positive remodeling, spotty calcification, napkin-ring sign and NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI4mm) were analyzed by two independent physicians. The association of CCTA-derived plaque features with maxLCBI4mm ≥ 400 was evaluated. Results The median CT density and maxLCBI4mm were 57.7 Hounsfield units (HU) and 304, respectively. CT density (r = -0.75, p Conclusions CT density

Solitary fibrous tumour of the pleura (SFTP) arising in a cavity is extremely rare. A 66‐year‐old Japanese male presented with an abnormal shadow on his chest X‐ray. Chest computed tomography showed a cavity of approximately 18 mm in diameter between the upper and lower lobes that contained a solid nodule within. Under the thoracoscope, the peduncle cystic tumour was removed with sufficient surgical margin. Macroscopically, a tumour of about 15 mm in diameter arose in the cystic cavity. Immunohistochemical stains were positive for CD34, bcl‐2, and signal transduction and activator of transcription 6 (STAT6) but negative for smooth muscle actin (SMA), desmin, and epithelial membrane antigen (EMA), and a diagnosis of SFTP was made. The patient remains well without recurrence or any complications at two and a half years after the operation. SFTP should be considered when a tumour arises in a cavity existing in an interlobar space. It is important to determine whether the tumour is pedunculated or sessile during surgery and to perform the appropriate surgical procedure., Solitary fibrous tumour of the pleura (SFTP) is a rare neoplasm. Moreover, cavity formation associated with SFTP is extremely rare. To our knowledge, only one such case has been previously reported.

This study aims to elucidate the relationships between the flexural strength and surface topography of composite resin blocks, utilized for the CAD/CAM system, after milling in various step-over amounts. The rectangular specimens were milled from CAD/CAM blocks with step-over amount 0.01, 0.02, 0.05, 0.1, and 0.2 mm; further, a three-point bending test was conducted to reveal the flexural strength. The surface morphology after milling was assessed by a 3D laser microscope. The surface roughness significantly decreased by reducing the step-over amount. Although there was significant association between the surface roughness and flexural strength by the Pearson correlation, the 95% confidence intervals of the flexural strength were between the mirror-polished and sand-blasted groups. These results suggest that a precise step-over amount enables us to obtain a smooth surface. Furthermore, the flexural strength of the rough surface milled by a large step-over amount caused no damage to the composite resin for CAD/CAM crown.

To evaluate the anatomical classification and location of breast sentinel lymph nodes, preoperative computed tomography-lymphography examinations were retrospectively reviewed for sentinel lymph nodes in 464 cases clinically diagnosed with node-negative breast cancer between July 2007 and June 2016. Anatomical classification was performed based on the numbers of lymphatic routes and sentinel lymph nodes, the flow direction of lymphatic routes, and the location of sentinel lymph nodes. Of the 464 cases reviewed, anatomical classification could be performed in 434 (93.5 %). The largest number of cases showed single route/single sentinel lymph node (n = 296, 68.2 %), followed by multiple routes/multiple sentinel lymph nodes (n = 59, 13.6 %), single route/multiple sentinel lymph nodes (n = 53, 12.2 %), and multiple routes/single sentinel lymph node (n = 26, 6.0 %). Classification based on the flow direction of lymphatic routes showed that 429 cases (98.8 %) had outward flow on the superficial fascia toward axillary lymph nodes, whereas classification based on the height of sentinel lymph nodes showed that 323 cases (74.4 %) belonged to the upper pectoral group of axillary lymph nodes. There was wide variation in the number of lymphatic routes and their branching patterns and in the number, location, and direction of flow of sentinel lymph nodes. It is clinically very important to preoperatively understand the anatomical morphology of lymphatic routes and sentinel lymph nodes for optimal treatment of breast cancer, and computed tomography-lymphography is suitable for this purpose.

Early identification of high-risk or vulnerable atherosclerotic plaques prone to rupture and performing preemptive therapy prior to catastrophic cardiovascular events are optimal goals of plaque imaging. Despite the advances in imaging modalities to identify vulnerable characteristics, the predictive value of the imaging techniques in the clinical setting is still developing. In this regard, reliable and high-sensitive imaging modalities identifying vulnerable plaque characters that may lead to future cardiovascular events will be useful. In this review article, we describe a current non-invasive plaque imaging technique to identify high-risk coronary plaque features.

Micro-/nanostructured implant surfaces mimicking natural bone architecture are expected to have positive effects on osteoblast proliferation. In this study, to clarify the optimal microstructure scale on micro-/nano-titanium surfaces, highly controlled microstructure surfaces were fabricated with a titania nanotube oxide layer by sandblast treatment and electrochemical anodization. Average surface roughness (Ra ) and mean width of the profile elements (RSm ) increased in proportion to the size of the blasting media. The crystalline structure and wettability were similar for all samples after anodizing and annealing. MG63 osteoblast-like osteosarcoma cells showed reduced spreading area on smaller microstructure surfaces after incubation for 24 h. Cell proliferation assays, including cell counting and cell cycle analyses, showed that micro-/nanosurfaces with smaller microstructures (Ra = 0.6 µm, RSm = 11.1 µm) had the most positive effect. This result indicated that smaller microstructures of hierarchical surfaces enhanced cell proliferation, despite similar chemical compositions and wettabilities. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2589-2596, 2017.

We report a rare case where the inferior vena cava connected to the azygos vein, a diagnosis triggered by observation of an enlarged azygos vein traversing an azygos fissure. A 16‐year‐old male patient presented with an abnormal shadow on chest X‐ray. Chest computed tomography showed an enlarged azygos vein connecting to the inferior vena cava, with no other connection to the atrium. There were no associated malformations. The patient remains alive and has been asymptomatic for the past two years. If the flow through the connection was to be interrupted during the course of thoracic or abdominal surgery, this would invariably prove to be fatal. In addition, this abnormality prevents direct access to the atrium on attempting interventional radiology via the inferior vena cava, for example, during ablation. When an azygos lobe is identified on a chest X‐ray, a prominent solid structure traversing it may represent an engorged azygos vein with an anomalous course., We report a rare case of the inferior vena cava connecting to the azygos, in a 16‐year‐old male patient who presented with an abnormal shadow on chest X‐ray. The azygos vein was enlarged and ran through an azygos fissure, inviting the diagnosis.

Purpose This study introduces a newly developed zirconia complete denture (ZrD) that incorporates a ceria-stabilized zirconia/alumina nano-composite framework fabricated with computer-aided design/computer-aided manufacture (CAD/CAM). Materials and methods Twenty-nine edentulous patients received either a maxillary ZrD (n = 10) or a maxillary conventional complete denture (CD) (n = 19). Patient satisfaction was evaluated before and 12 months after prosthesis placement using the McGill Denture Satisfaction Instrument. Results During follow-up periods of up to 2 years, no denture fractures were found in the ZrD or CD group. All aspects of patient satisfaction improved, and no significant group differences were found. Conclusion Within the limitations of this study, it can be concluded that maxillary complete dentures with nano-zirconia frameworks might be an alternative prosthetic treatment option.

BACKGROUND Although peak oxygen uptake (pVO2) is a well-established powerful prognostic predictor in heart failure (HF) patients, implementation of cardiopulmonary exercise testing (CPX) is limited by its complex analysis. We aimed to develop a new bivariate predictor obtained without respiratory gas measurement, comparable to pVO2.Methods and Results:We studied 560 consecutive HF patients with ejection fraction (EF)

Macrophages play an important role in the regulation of inflammation and immune response as well as the pathogenesis of chronic inflammatory diseases and cancer. Therefore, targeted delivery of therapeutic reagents to macrophages is an effective method for treatment and diagnosis. We previously examined the therapeutic applications of polyrotaxanes (PRXs) comprised of multiple cyclodextrins (CDs) threaded on a polymer chain and capped with bulky stopper molecules. In the present study, we designed an &alpha, d-mannose-modified &alpha, CD/poly(ethylene glycol)-based PRX (Man-PRX). The intracellular uptake of Man-PRX through the interaction with macrophage mannose receptor (MMR) in macrophage-like RAW264.7 cells was examined. Intracellular Man-PRX uptake was observed in MMR-positive RAW264.7 cells but was negligible in MMR-negative NIH/3T3 cells. In addition, the intracellular Man-PRX uptake in RAW264.7 cells was significantly inhibited in the presence of free &alpha, d-mannose and an anti-MMR antibody, which suggests that MMR is involved in the intracellular uptake of Man-PRX. Moreover, the polarization of RAW264.7 cells affected the Man-PRX internalization efficiency. These results indicate that Man-PRX is an effective candidate for selective targeting of macrophages through a specific interaction with the MMR.

Air embolisms are rare life-threatening complications that develop under various conditions, including surgery. During segmentectomy for thoracic surgery, air is blown into the selected bronchus for segment margin detection. This may result in the formation of an air embolus. Herein, we report a case of successful recovery from sudden intraoperative cardiac arrest due to an air embolism in a patient undergoing left superior division segmentectomy via open thoracotomy. Intraoperatively, the patient was positioned head-down. Upon blowing air into the bronchus, the patient suddenly developed cardiac arrest. Open-chest cardiac massage and low-temperature therapy were commenced and the patient recovered. The head-down position prevents the air embolus from reaching the brain and thus prevents severe brain damage, whereas continuous open-chest massage and low temperature prevents severe body damage from anticipated cardiac air embolism. Thus, operation in the head-down position is useful in preventing severe brain damage from brain air embolisms.

Aims To investigate the clinical impact of T1 mapping for detecting myocardial impairment in takotsubo cardiomyopathy (TTC) over time. Methods and results In 23 patients with the apical ballooning type of TTC, the following 3T magnetic resonance (MR) examinations were performed at baseline and 3 months after TTC onset: T2-weighted imaging, T2 mapping, native T1 mapping, extracellular volume fraction (ECV), and late gadolinium enhancement. Eight healthy controls underwent the same MR examinations. Serial echocardiography was performed daily for ≥7 days and monthly until 3 months after onset. The median time from onset to MR examination was 7 days. During the acute phase, patients had, relative to controls, higher native T1 (1438 ± 162 vs. 1251 ± 90 ms, P < 0.001), ECV (35 ± 5% vs. 29 ± 4%, P < 0.001), and T2 (90 ± 34 vs. 68 ± 12 ms, P < 0.001) for the entire heart. Per-region analysis showed that higher native T1 and T2 in the basal region were correlated with lower left ventricular ejection fraction (r = −0.599, P = 0.004 and r = −0.598, P = 0.003, respectively). Receiver operator characteristic analysis showed that the area under the curve for native T1 (0.96) was significantly larger than that for T2 (0.86; P = 0.005) but similar to that for ECV (0.92; P = 0.104). At 3-month follow-up, native T1, ECV, and T2 in the apical region remained significantly elevated in all patients with TTC. The number of left ventricular (LV) segments with elevated native T1 (cut-off value 1339 ms) was significantly correlated with prolonged LV wall motion recovery time (r = 0.494, P = 0.027). Conclusion Characterization of myocardium with native T1 mapping is a promising method for predicting LV wall motion restoration in TTC.

AIM Balloon-occluded transcatheter arterial chemoembolization (B-TACE) was used to show the optimized duration of balloon occlusion to start injection of lipiodol in order to maximize lipiodol deposition in the nodule, and to reveal the endpoint of lipiodol injection. METHODS Of 29 consecutive patients who underwent balloon-occluded TACE between November 2013 and February 2014, we were able to measure stump pressure for 219 nodules in 27 patients. Tumors were counted, measured and could be visually assessed in 20 of these patients at 26 sites. Tumors with multiple feeders were found in eight patients. Arterial blood pressure was measured before, immediately after and 5 min after balloon occlusion prior to intra-arterial injection, as well as before and after balloon deflation after intra-arterial injection. Images were assessed qualitatively by two radiologists as well as quantitatively by calculating the contrast-to-noise ratio. RESULTS We found no significant difference in pressure between immediately after and 5 min after balloon occlusion. Mean stump pressure before balloon deflation after intra-arterial injection was 70.4 mmHg. We observed a significant increase in qualitative scores after balloon occlusion (P

The purpose of this study was to investigate clinical outcomes following stereotactic body radiotherapy (SBRT) for lung metastases as oligo-recurrence. From May 2003 to June 2014, records for 66 patients with 76 oligo-recurrences in the lungs treated with SBRT were retrospectively reviewed. Oligo-recurrence primary sites and patient numbers were as follows: lungs, 31; colorectal, 13; head and neck, 10; esophagus, 3; uterus, 3; and others, 6. The median SBRT dose was 50 Gy (range, 45–60 Gy) administered in a median of 5 (range, 5–9) fractions. All patients received SBRT, with no acute toxicity. Surviving patients had a median follow-up time of 36.5 months. The 3-year rates of local control, overall survival and disease-free survival were 90.6%, 76.0% and 53.7%, respectively. Longer disease-free interval from initial treatment to SBRT, and non-colorectal cancer were both associated with favorable outcomes. Disease progression after SBRT occurred in 31 patients, most with distant metastases (n = 24) [among whom, 87.5% (n = 21) had new lung metastases]. Among these 21 patients, 12 were judged as having a second oligo-recurrence. Additional SBRT was performed for these 12 patients, and all 12 tumors were controlled without disease progression. Three patients (4.5%) developed Grade 2 radiation pneumonitis. No other late adverse events of Grade ≥2 were identified. Thus, SBRT for oligo-recurrence achieved acceptable tumor control, with additional SBRT also effective for selected patients with a second oligo-recurrence after primary SBRT.

Transgenic mice that overexpress the red fluorescent protein tdTomato (tdTomato mice) are well suited for use in regenerative medicine studies. Cultured cells from this murine model exhibit strong red fluorescence, enabling real-time in vivo imaging through the body surface of grafted animals. Mesenchymal stem cells (MSCs) have marked potential for use in cell therapy and regenerative medicine; however, the mechanisms that regulate their dynamics in vivo are poorly understood. In the present study, an MSC line was derived from the submandibular gland fibroblasts of tdTomato mice. The fluorescent signal from this cell line was observed in organs throughout the body, as well as in salivary glands. Primary culture cells derived from the submandibular gland were immortalized with SV40 large T antigen (GManSV cells); these cells exhibited increased migratory ability, as compared with those isolated from the sublingual gland. GManSV cells were tdTomato-positive and exhibited spindle-shaped fibroblastic morphology; they also robustly expressed mouse MSC markers: Stem cell antigen-1 (Sca-1), CD44, and CD90. This cell line retained multipotent stem cell characteristics, as evidenced by its ability to differentiate into both osteogenic and adipogenic lineages. These results indicate that Sca-1+/CD44+/CD90+-GManSV cells may be useful for kinetic studies of submandibular gland-derived MSCs in the context of in vitro co-culture with other types of salivary gland-derived cells. These cells may also be used for in vivo imaging studies, in order to identify novel cell therapy and regenerative medicine for the treatment of salivary gland diseases.

Background Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody used as an immune checkpoint inhibitor, is commonly employed for its anti-tumor effects against various types of malignant tumors. However, its administration is complicated by immune-related adverse events (irAEs), including pneumonitis. Case presentation We present a case series of four patients with malignant melanoma, non-small cell lung cancer, and hypopharyngeal carcinoma who demonstrated pneumonitis induced by nivolumab, and further review clinicopathological characteristics of these patients in comparison with those of previously reported patients with nivolumab-induced pneumonitis. In our series, 20% of patients who were treated with nivolumab developed pneumonitis, all of which occurred approximately 2 weeks after the initiation of nivolumab treatment. Prompt recognition of the nivolumab-induced pneumonitis allowed for successful resolution. Computed tomography scan images of the patients demonstrated predominantly cryptogenic organizing pneumonia patterns. All patients were males, who had been heavily treated with antitumor drugs prior to nivolumab. Conclusions Our case series showed that nivolumab had a high incidence of drug-induced pneumonitis with early onset, supporting the need for renewed attention to nivolumab-induced pneumonitis, particularly in patients with a history of heavy antitumor treatments.

Background: The aim of this study was to investigate whether the combination of QRS duration ≥120 ms (wide QRS duration [wQRS]) and late gadolinium enhancement (LGE) is a precise prognostic indicator for dilated cardiomyopathy. Methods and Results: We investigated the association between the combination of LGE plus wQRS and the primary end point (all-cause death) and a composite of sudden cardiac death (SCD) or aborted SCD in 531 patients with dilated cardiomyopathy. We also analyzed the association between the combination of LGE and wQRS and these end points among patients with a class I indication for implantable cardioverter defibrillator implantation. We divided study patients into 3 groups according to LGE status and QRS duration: 2 negative indices (LGE negative and narrow QRS), 1 positive index (LGE positive or wQRS), or 2 positive indices (LGE positive and wQRS), and followed them for 3.8 years. Multivariable Cox regression analysis identified 2 positive indices as a significant predictor of all-cause death (hazard ratio, 4.29 [1.19–15.47]; P =0.026). Among 317 patients with a class I indication for implantable cardioverter defibrillator, the 5-year event rate of SCD or aborted SCD was the lowest in the 2 negative indices group (1.4%). With propensity score–matching cohorts, the 2 negative indices group had a significantly lower event rate of SCD or aborted SCD than the other 2 groups (hazard ratio, 0.12 [0.01–0.97]; P =0.046). Conclusions: The combination of LGE and wQRS provides additional prognostic stratification compared with LGE status alone and might improve the appropriate use of implantable cardioverter defibrillator therapy in patients with dilated cardiomyopathy.

BACKGROUND Acute decompensated heart failure (ADHF) is generally considered to be a problem of fluid volume overload, therefore accurately quantifying the degree of fluid accumulation is of critical importance in assessing whether adequate decongestion has been achieved. The aim of this study was to develop and validate a method to quantify the degree of fluid accumulation in patients with ADHF. METHODS AND RESULTS Using multi-frequency bioelectrical impedance analysis (BIA), we measured extracellular water (ECW) volume in 130 ADHF patients on admission and at discharge. We also predicted optimal ECW volume using original equations based on data from 60 control subjects without the signs of HF. Measured/predicted (M/P) ratio of ECW in ADHF patients was observed to decrease from 1.26±0.25 to 1.04±0.17 during hospitalization (P

Background The periodontal ligament (PDL), which maintains homeostasis in the periodontium, is a group of specialized connective tissue fibers attached to both the cementum and alveolar bone. Regeneration of periodontium with PDL cells has been investigated, and the chemical and molecular structures of scaffolds control the adhesion and differentiation of cells. Therefore, the development of adequate materials for PDL-derived cells is essential to regenerate the periodontium. Objective We evaluated the suitable passage time for PDL-derived cells and investigated the behaviors of PDL-derived cells grown on hydroxyapatite (HAp) scaffolds coated with type I and type III collagen. Methods PDL-derived cells were isolated with enzyme from the upper molars of male Wister rats. After characterization of HAp, type I collagen, and type III collagen, PDL-derived cells at passage 2 were seeded onto collagen-coated HAp. Cell adhesion, proliferative potential, and osteoconductivity were analyzed with immunostaining, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, Alizarin S staining, and real-time polymerase chain reaction. Results Type I and III collagens were successfully coated on HAp. Gene expression analysis revealed that passage 2 was suitable for maintaining differentiation potential. Proliferative potential and cell adhesion were significantly higher on type III collagen than on HAp alone or type I collagen. In contrast, the osteoconductivity of type III collagen was significantly lower than those of HAp and type I collagen. Conclusion PDL-derived cells on type I collagen differentiated into osteogenic cells and formed hard tissues. However, type III collagen enhanced the adhesion of PDL-derived cells and inhibited mineralization.

Aims Coronary high-intensity plaques (HIPs) with a high plaque-to-myocardial signal intensity ratio (PMR) on non-contrast T1-weighted imaging in patients with stable coronary artery disease (CAD) are associated with future coronary events. To characterize the morphological substrate of HIP, we performed a correlative optical coherence tomography (OCT) study. Methods and results We examined 137 lesions in 105 patients with stable angina pectoris or silent myocardial ischaemia scheduled for percutaneous coronary intervention (PCI) using a 3 T magnetic resonance scanner. Pre-interventional OCT was performed for PCI target lesions. HIP was defined as PMR ≥ 1.4. Of the 137 lesions, 34% were HIP and 66% were non-HIP. The prevalence of lipid-rich plaque (96% vs. 70%, P

The ethylene glycol-based dimethacrylates are commonly used in biomaterials and dental restorative materials as a cross-linking agent. In this study, toxic effect of triethylene glycol dimethacrylate (TEGDMA) and poly(ethylene glycol) dimethacrylates (PEG-DMAs) with various ethylene glycol repeating units was investigated in terms of cytotoxicity, oxidative stress, and the expression of co-stimulatory factors in human leukemia cell line (THP-1 cells) to verify the effect of ethylene glycol repeating units. Note that the 1-octanol/water partition coefficient of PEG-based dimethacrylates decreased with increasing the ethylene glycol repeating units, indicating that the hydrophilicity of PEG-DMAs increased with ethylene glycol repeating units. The toxic effect of PEG-DMAs such as cytotoxicity, oxidative stress, and the expression of CD86 in treated THP-1 cells are reduced with increasing the ethylene glycol repeating units in PEG-DMAs. However, the expression of CD54 in treated THP-1 cells was not influenced with the ethylene glycol repeating units and the maximal expression level of CD54 was observed at the concentration range of 2-4 mM for all samples. Accordingly, hydrophilic character of PEG-DMAs with long ethylene glycol chains definitely alleviates the some toxic aspect of PEG-based DMAs. This finding would provide important insight into the design of new biomaterials and dental materials with superior biocompatibility.

The purpose of this study was to investigate the relationship between tumor size and blood volume for patients with lung tumors, using dual-energy computed tomography (DECT) and a gemstone spectral imaging (GSI) viewer. During the period from March 2011 to March 2013, 50 patients with 57 medically inoperable lung tumors underwent DECT before stereotactic body radiotherapy (SBRT) of 50-60 Gy in 5-6 fractions. DECT was taken for pretreatment evaluation. The region-of-interest for a given spatial placement of the tumors was set, and averages for CT value, water density and iodine density were compared with tumor size. The average values for iodine density in tumors of ≤ 2 cm, 2-3 cm, and >3 cm maximum diameter were 24.7, 19.6 and 16.0 (100 µg/cm(3)), respectively. The average value of the iodine density was significantly lower in larger tumors. No significant correlation was detected between tumor size and average CT value or between tumor size and average water density. Both the average water density and the average CT value were affected by the amount of air in the tumor, but the average iodine density was not affected by air in the tumor. The average water density and the average CT value were significantly correlated, but the average iodine density and the average CT value showed no significant correlation. The blood volume of tumors can be indicated by the average iodine density more accurately than it can by the average CT value. The average iodine density as assessed by DECT might be a non-invasive and quantitative assessment of the radio-resistance ascribable to the hypoxic cell population in a tumor.

Incidental 18F-fluorodeoxyglucose (18F-FDG) uptake in the prostate is often experienced in clinical practice; however, it is difficult to determine whether incidental uptake is indicative of a malignancy or benign state based on the maximum standardized uptake value (SUVmax). In the present study, we investigated the clinical significance of incidental prostate uptake by 18F-FDG positron emission tomography (PET)/CT, and examined the differences between malignant and benign uptake from a clinicopathological viewpoint. We reviewed 3,236 male subjects who underwent 18F-FDG PET/CT scans at Hirosaki University Hospital (Japan) from 2008 to 2012 in order to identify cases of incidental prostate FDG uptake. The final diagnosis was made by serum prostate-specific antigen (PSA) levels, biopsy, imaging studies and clinical follow-up with PET findings. Incidental FDG uptake of the prostate was observed in 53 cases (2%). Four cases were excluded due to insufficient clinical data, and 49 cases were included in the present study. Of the 49 cases, 8 (16%) had prostate cancer, while 41 (84%) were benign. All 8 malignant cases had high uptake areas, e.g. in the prostate peripheral zone, where there was no coexistence of calcification or FDG uptake. Of the 41 benign cases, 19 had high uptake in the inner zone, 17 in the peripheral zone, and 5 in both the inner and peripheral zones. Of the 41 cases, 18 (44%) showed FDG uptake coexisting with prostatic calcification. Incidental prostate 18F-FDG uptake infrequently signifies prostate cancer; however, FDG uptake not coexisting with calcification indicates the possibility of prostate cancer and should be included in the differential diagnosis for performing other clinical examinations.

The purpose of this study was to evaluate the surface strain of zirconia fixed partial denture frameworks and their abutment roots when restored with two types of post and core materials. Artificial mandibular first premolars and second molars were used as the abutment teeth. Posts and cores were of two types: resin composite with glass fiber posts (RC) and cast platinum gold alloy (MC). The cores and 4-unit zirconia frameworks were bonded to the specimens. Static loading was applied to the occlusal surfaces, and the surface strain of the frameworks and roots (distal premolar and mesial molar) was measured by strain gauge method. Premolar root showed a significantly higher magnitude of principal strain than molar root. RC showed a significantly higher magnitude of principal strain than MC. The results suggest that MC restrain the surface strain compared to RC when the missing teeth are replaced by a 4-unit zirconia framework.

This study evaluated the fracture strength and mode of failure of structurally compromised teeth with flared root canals restored using composite resin with four different systems.Sixty endodontically treated bovine teeth were uniformly shaped to simulate human mandibular premolars with flared root canals. The roots were divided into four groups of 15 specimens each based on the type of restoration: composite resin core only (control), glass fiber post, cylindroid glass fiber ribbons, and glass fiber post and ribbons. All specimens were loaded until fracture occurred using a universal testing machine. Average fracture loads were compared with a one-way ANOVA and Tukey HSD test (α=.05). The modes of failure were observed and the Fisher exact test and Bonferroni correction were used for statistical analysis.The fiber post and ribbon group (1035.70N) and the fiber ribbon group (881.77N) showed significantly higher fracture strength than the controls (567.97N) (p.05). The fiber post and ribbon group also showed significantly higher fracture strength than the fiber post group (769.40N). Almost all specimens showed unrestorable root fractures (p.008). The control group had a significantly higher ratio of core sectional fractures (p.017).Cylindroid glass fiber ribbons significantly increased the fracture strength of the composite resin post and cores in the case of the dentin within the thin root canal wall. Based on the results, this study recommends the combined use of glass fiber post and ribbons.

We report a very unusual cytologic feature, intranuclear inclusion bodies, in mesothelioma of a predominantly adenomatoid type. The patient, a 57-year-old woman, was presented with dyspnea and right pleural effusion. Pleural aspiration cytology revealed many cohesive ball-like clusters, with a tubular pattern, composed of small atypical cells displaying a high-nuclear-cytoplasmic ratio. They had a nuclear groove and irregular intranuclear inclusion bodies. Right lung partial resection with thoracoscopy revealed that a white tumor had proliferated along the pleural surface at S(8) . Histology revealed nodular tumor cells forming dilated structures mixed with small tubular or glandular structures similar to those seen in benign adenomatoid tumors. These tumor cells had invaded peripheral lung tissues. Such inclusion bodies have not been reported earlier in mesothelioma. On the basis of this observation, we propose that the adenomatoid type of malignant mesothelioma be added to the differential diagnosis of malignant effusions when tumor cells with nuclear grooves and intranuclear inclusions are found in pleural aspiration cytology.

Background: In prosthodontic treatment, the occlusal form should be designed such that bite force is applied at the position that has higher load-bearing capacity and is comfortable for the patient. The purpose of this study was to clarify the differences in bite force and occlusal sensation with different loading positions on the occlusal surface. Methods: Twelve healthy subjects were recruited for this study. Bite force and occlusal sensation were measured at five loading points on the upper and lower left first molars. Occlusal sensation was evaluated using a Visual Analogue Scale (VAS). Results: Bite forces on the lingual side of the upper first molar and the buccal side of the lower first molar were significantly higher and VAS scores were significantly lower, i.e. the subjects felt less discomfort during biting on the buccal side of the upper first molar and the lingual side of the lower first molar compared to the other side of each molar. Conclusions: Loading on the occlusal surfaces of the functional cusps of the upper and lower first molars produces more load-bearing capacity and is more comfortable than loading on the non-functional cusps.