Preparation and antibacterial evaluation of silver-doped zirconia for enhanced dental restoration performance.

Because of its superior strength, esthetic properties, and excellent biocompatibility, zirconia is preferred for dental prosthetic such as crowns and bridges. However, zirconia crowns and bridges are susceptible to secondary caries owing to margin leakage. Silver is a well-known antibacterial agent, making it a desirable additive to zirconia crowns and bridges for secondary caries prevention. This study focuses on imparting zirconia composite with antibacterial properties to enhance its protective capacity in dental restorations. We used the sol-gel method to dope Ag into zirconia. Silver-doped zirconia powders were prepared at Zr:Ag molar ratios of 100:0,100:0.1, 100:0.5, 100:1, 100:3, and 100:5 (respective samples denoted as Ag-0, Ag-0.1, Ag-0.5, Ag-1, Ag-3, and Ag-5) and were subjected to firing at various temperatures (400 °C-1000 °C). We performed x-ray diffraction to investigate the crystal phase of these powders and x-ray fluorescence and field emission scanning electron microscopy to analyze their elemental composition and surface morphology, respectively. Moreover, we performed spectrophotometry to determine theL*a*b* color values, conducted dissolution tests, and quantified the Ag content through inductively coupled plasma optical emission spectroscopy. In addition, we studied the antibacterial activity of the samples. Analyses of the samples fired at ⩽600 °C revealed a predominantly white to grayish-white coloration and a tetragonal crystal phase. Firing at ⩾700 °C resulted in gray or dark gray coloration and a monoclinic crystal phase. The Ag content decreased after firing at 900 °C or 1000 °C. Ag-0.5 and above exhibited antibacterial activity against bothEscherichia coliandStaphylococcus aureus. Therefore, the minimum effective silver-doped zirconia sample was found to be Ag-0.5. This study allows the exploration of the antimicrobial potential of silver-doped zirconia materials in dental applications such as prosthdontical lining materials, promoting the development of innovative restorations with protective capacity against secondary caries.

Adsorption of oral antibacterial agents on zirconia surfaces with different crystal systems.

Zirconia ceramics are widely used as dental prosthetics owing to their high biocompatibility, excellent mechanical strength, and aesthetic properties similar to color tones of natural teeth. However, there exists a growing demand for the facile attachment of antibacterial properties in long-term dental restoration. Thus, in this study, we evaluated the adsorption ability of cetylpyridinium chloride (CPC) and benzalkonium chloride (BKC)-quaternary amines widely used as antibacterial substances in commercial toothpaste and other oral care products-onto zirconia surfaces with tetragonal and monoclinic crystal structures. Although tetragonal zirconia has been widely used in dental prosthetic materials such as crowns etc., monoclinic zirconia has also been used under oral conditions because of long-term implantation. When antibacterial molecule loading on zirconia powders under simulated oral conditions, it was revealed that monoclinic zirconia adsorbed approximately five times more CPC and BKC per unit area compared with that of tetragonal zirconia. Moreover, in tetragonal zirconia, the adsorption amounts of both CPC and BKC increased slightly with growing Y2O3 content as a stabilizer. This phenomenon was attributable to the formation of complexes between rare earth elements (REE) such as Y2O3 in zirconia and quaternary amines such as CPC and BKC. In this study, the antibacterial molecular adsorption ability of dental zirconia was observed, and new advantages of zirconia in dental applications were discovered.

Physical properties of experimental light-curing pattern resins based on poly (n-butyl methacrylate) or poly(iso-butyl methacrylate).

Experimental light-curing pattern resins were fabricated to produce pattern resin materials with adequate dimensional stability. The light-curing pattern resins consisted of poly(n-butyl methacrylate) or poly(iso-butyl methacrylate) (PiBMA) polymers and methacrylate monomers. The physical properties, amount of residual ash after burning, Vickers hardness, flexural strength, and volumetric polymerization shrinkage of each material were determined. The data obtained for the prepared resins were compared with those of a commercially available pattern resin, Palavit G (PG). A lower amount of residual ash was observed for some of the prepared resins than for PG. The Vickers hardness and flexural strength values of all experimental resins were lower than those of PG. The volumetric polymerization shrinkage of all the experimental resins based on PiBMA was lower than that of PG. These results suggest that acrylic light-curing resin materials based on PiBMA may be useful for patterning and indexing during soldering.

Eichner classification based on panoramic X-ray images using deep learning: A pilot study.

BACKGROUND: Research using panoramic X-ray images using deep learning has been progressing in recent years. There is a need to propose methods that can classify and predict from image information. OBJECTIVE: In this study, Eichner classification was performed on image processing based on panoramic X-ray images. The Eichner classification was based on the remaining teeth, with the aim of making partial dentures. This classification was based on the condition that the occlusal position was supported by the remaining teeth in the upper and lower jaws. METHODS: Classification models were constructed using two convolutional neural network methods: the sequential and VGG19 models. The accuracy was compared with the accuracy of Eichner classification using the sequential and VGG19 models. RESULTS: Both accuracies were greater than 81%, and they had sufficient functions for the Eichner classification. CONCLUSION: We were able to build a highly accurate prediction model using deep learning scratch sequential model and VGG19. This predictive model will become part of the basic considerations for future AI research in dentistry.

Risk Factors for Residual Back Pain After Balloon Kyphoplasty for Osteoporotic Vertebral Fracture.

Background: Balloon kyphoplasty (BKP) is a method for the management of osteoporotic vertebral body fracture (OVF). However, improvement in back pain (BP) is poor in some patients, also previous reports have not elucidated the exact incidence and risk factors for residual BP after BKP. We clarified the characteristics of residual BP after BKP in patients with OVF. Hypothesis: In this study, we hypothesize that some risk factors may exist for residual BP 2 years after the treatment of OVF with BKP. Patients and Methods: A multicenter cohort study was performed where patients who received BKP within 2 months of OVF injury were followed-up for 2 years. BP at 6 months after surgery and final observation was evaluated by Visual Analog Scale (VAS) score. Patients with a score of 40 mm or more were allocated to the residual BP group, and comparisons between the residual back pain group and the improved group were made for bone density, kyphosis, mobility of the fractured vertebral body, total spinal column alignment, and fracture type (fracture of the posterior element, pedicle fracture, presence or absence of posterior wall damage, etc.). Also, Short Form 36 (SF-36) for physical component summary (PCS) and mental component summary (MCS) at the final follow-up was evaluated in each radiological finding. Results: Of 116 cases, 79 (68%) were followed-up for 2 years. Two years after the BKP, 26 patients (33%) experienced residual BP. Neither age nor sex differed between the groups. In addition, there was no difference in bone mineral density, BKP intervention period (period from onset to BKP), and osteoporosis drug use. However, the preoperative height ratio of the vertebral body was significantly worse in the residual BP group (39.8% vs. 52.1%; p = 0.007). Two years after the operation, the vertebral body wedge angle was significantly greater in the residual BP group (15.7° vs. 11.9°; p = 0.042). In the multiple logistic regression model with a preoperative vertebral body height ratio of 50% or less [calculated by receiver operating characteristic (ROC) curve], the adjusted odds ratio for residual BP was 6.58 (95% confidence interval 1.64-26.30; p = 0.007); similarly, patients with vertebral body height ratio less than 50% had a lower score of SF-36 PCS 24.6 vs. 32.2 p = 0.08. Conclusion: The incidence of residual BP 2 years after BKP was 33% in the current study. The risk factor for residual BP after BKP was a preoperative vertebral body height ratio of 50% or less, which should be attentively assessed for the selection of a proper treatment scheme and to provide adequate stabilization. Level of Evidence: III.

Rikkunshito increases peripheral incretin-hormone levels in humans and rats.

BACKGROUND: It was reported that rikkunshito (TJ-43) improved the cisplatin-induced decreases in the active form of ghrelin in plasma; however, other effects on gastrointestinal hormones have not been investigated. AIM: To investigate the effects of TJ-43 on peripheral levels of incretin hormones, including gastric inhibitory polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1), in humans and rats. METHODS: Patients were divided into two groups, namely patients who received TJ-43 immediately following surgery [TJ-43(+) group] and those who received TJ-43 on postoperative day 21 [TJ-43(-) group], and the plasma levels of active GIP and active GLP-1 were assessed. In animal experiments, rats were treated with TJ-43 [rat (r)TJ-43(+) group] or without [rTJ-43(-) group] by gavage for 4 wk, and the plasma active GIP and active GLP-1 levels were measured. The expression of incretin hormones in the gastrointestinal tract and insulin in the pancreas were investigated by immunohistochemistry. Furthermore, the cyclic adenosine monophosphate activities were assessed in pancreatic tissues from rats treated with or without TJ-43 in vivo, and the blood glucose levels and plasma insulin levels were measured in rats treated with or without TJ-43 in oral glucose tolerance tests. RESULTS: In humans, the active incretin hormone levels increased, and values were significantly greater in the TJ-43(+) group compared those in the TJ-43(-) group. In rats, the plasma active incretin levels significantly increased in the rTJ-43(+) group compared with those in the rTJ-43(-) group. GIP and GLP-1 expressions were enhanced by TJ-43 treatment. Moreover, plasma insulin levels increased and blood glucose levels were blunted in the rTJ-43(+) group. CONCLUSION: The results show that TJ-43 may be beneficial for patients who undergo pancreatic surgery.

PaCS-Toolkit: Optimized Software Utilities for Parallel Cascade Selection Molecular Dynamics (PaCS-MD) Simulations and Subsequent Analyses.

Parallel cascade selection molecular dynamics (PaCS-MD) is an enhanced conformational sampling method conducted as a "repetition of time leaps in parallel worlds", comprising cycles of multiple molecular dynamics (MD) simulations performed in parallel and selection of the initial structures of MDs for the next cycle. We developed PaCS-Toolkit, an optimized software utility enabling the use of different MD software and trajectory analysis tools to facilitate the execution of the PaCS-MD simulation and analyze the obtained trajectories, including the preparation for the subsequent construction of the Markov state model. PaCS-Toolkit is coded with Python, is compatible with various computing environments, and allows for easy customization by editing the configuration file and specifying the MD software and analysis tools to be used. We present the software design of PaCS-Toolkit and demonstrate applications of PaCS-MD variations: original targeted PaCS-MD to peptide folding; rmsdPaCS-MD to protein domain motion; and dissociation PaCS-MD to ligand dissociation from adenosine A2A receptor.

Investigating Cytoglobin Expression in Colon Cancer: Clinicopathological Insights from Immunohistochemical Analysis.

BACKGROUND/AIM: Cytoglobin (Cygb), a protein involved in cellular oxygen metabolism and protection, has garnered attention owing to its potential role in the initiation and progression of cancer, particularly colon cancer (CC). This study investigated the expression and significance of Cygb in CC. PATIENTS AND METHODS: This study included 145 patients who underwent R0 surgery for CC (clinical stage II/III) at our institution between January 2007 and December 2014. Immunohistochemical analysis was performed to evaluate the Cygb expression patterns in CC tissues. Additionally, the correlation between Cygb expression levels and the clinicopathological characteristics of patients with CC was investigated. RESULTS: Colon cancer tissues were categorized into high-expression (95 cases) and low-expression (50 cases) groups. Cygb was highly expressed in well-differentiated cases, whereas its expression decreased in poorly differentiated cases. No significant differences in other clinicopathological factors were observed between the two groups. Cygb expression had no significant effect on recurrence-free survival or overall survival. CONCLUSION: This study contributes to the growing understanding of Cygb expression and its significance in CC. The expression of Cygb in CC was found to be unrelated to the recurrence rate and prognosis, but showed a correlation with differentiation status.

Mechanochemical synthesis of cerium chlorapatite from a mixture of cerium chloride heptahydrate, dicalcium phosphate dihydrate, and calcium hydroxide for biomedical application.

BACKGROUND: Cerium ions promote osteoclastogenesis and activate bone metabolism, while cerium oxide nanoparticles exhibit potent anti-inflammatory properties, making them promising for biomedical applications. OBJECTIVE: The purpose of this study was to develop and evaluate a synthesis method for sustained-release cerium-ion bioceramics containing apatite. Substituted apatite was found to be an effective biomaterial. METHODS: Cerium-containing chlorapatite was synthesized using a mechanochemical method employing dicalcium phosphate, cerium chloride heptahydrate, and calcium hydroxide as raw materials. The synthesized samples were characterized using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Raman spectroscopy. RESULTS: Cerium chlorapatite was successfully synthesized in the 10.1% and 20.1% samples. However, at Ce concentrations higher than 30.2%, the samples consisted of three or more phases, indicating the instability of a single phase. CONCLUSION: The method used in this study was found to be more efficient and cost-effective than the precipitation method for producing substituted apatite and calcium phosphate-based biomaterials. This research contributes to the development of sustained-release cerium-ion bioceramics with potential applications in the field of biomedicine.

Postoperative Remission of Diabetes Mellitus After Gastrectomy in Patients With Diabetes Mellitus and Gastric Cancer.

BACKGROUND/AIM: We investigated the postoperative treatment status for diabetes mellitus and perioperative HbA1c levels in patients with diabetes mellitus and examined the effects of clinical factors on the remission of diabetes mellitus. PATIENTS AND METHODS: In this study, 126 patients with gastric cancer were considered to have diabetes mellitus preoperatively, of whom 79 were treated with oral antidiabetic drugs and/or insulin treatment. We compared diabetic treatment status and HbA1c values between the preoperative and postoperative periods in patients who underwent gastrectomy and examined the effects of clinical factors on improving diabetes mellitus. RESULTS: Of the 79 patients treated preoperatively for diabetes mellitus, 34 (43%) discontinued all medications for diabetes mellitus and for 37 (47%) the therapeutic dose was reduced or switched from insulin to oral antidiabetic drugs. Total gastrectomy was an independent factor for remission of antidiabetic treatments after gastrectomy. Concerning HbA1c levels, only the absence of preoperative insulin use was an independent factor for improvement. However, reconstruction was not a significantly correlated factor for the improvement of postoperative HbA1c levels and reduction of antidiabetic medications after distal gastrectomy. CONCLUSION: Almost all patients discontinued or had their dose of antidiabetic medications reduced after gastrectomy in clinical practice, and special attention should be paid in the management methods for diabetes mellitus in patients who underwent total gastrectomy for gastric cancer.

Detection of Abdominal Lymph Node Metastasis from Pancreatic Neuroendocrine Tumor by Somatostatin Receptor Scintigraphy: Comparison with Somatostatin Receptor Type 2 Immunostaining.

We report a 58-year-old male with a histopathologically proven grade 2 (G2) pancreatic neuroendocrine neoplasm and multiple abdominal node metastases by use of a laparoscopic pancreatic body and tail resection procedure, plus abdominal lymph node dissection. A primary pancreatic tail neuroendocrine tumor sized 20 × 25 mm was detected by contrast-enhanced computed tomography, somatostatin receptor scintigraphy (SRS), and fluorodeoxyglucose positron emission tomography (FDG-PET) examinations and pathologically diagnosed as a pancreatic neuroendocrine tumor (PNET, G2) based on positive immunostaining for somatostatin receptor (SSTR) type 2. Of three metastatic histopathological lymph nodes, two measured 18 × 21 and 10 × 12 mm, respectively, with whole strong SSTR immunostaining showing moderate uptake in SRS findings, whereas the other node, sized 8 × 10 mm, had strong SSTR immunostaining only in a small 6 × 6-mm-sized portion and showed no uptake in SRS findings, likely because of the limited spatial resolution of scintigraphy. On the other hand, only the largest node (18 × 21 mm) was visualized by FDG-PET. SRS may be useful for metastatic lymph node diagnosis based on SSTR immunostaining, though a disadvantage is the spatial resolution limitation.

Rikkunshito increases appetite by enhancing gastrointestinal and incretin hormone levels in patients who underwent pylorus-preserving pancreaticoduodenectomy: A retrospective study.

BACKGROUND: Rikkunshito (TJ-43) relieves gastrointestinal disturbance by increases in the levels of acylated ghrelin. AIM: To investigate the effects of TJ-43 in patients undergoing pancreatic surgery. METHODS: Forty-one patients undergoing pylorus-preserving pancreaticoduodenectomy (PpPD) were divided into two groups; patients took daily doses of TJ-43 after surgery or after postoperative day (POD) 21. The plasma levels of acylated and desacylated ghrelin, cholecystokinin (CCK), peptide YY (PYY), gastric inhibitory peptide (GIP), and active glucagon-like peptide (GLP)-1 were evaluated. Oral calorie intake was assessed at POD 21 in both groups. The primary endpoint of this study was the total food intake after PpPD. RESULTS: The levels of acylated ghrelin were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 administration at POD 21, and oral intake was significantly increased in patients treated with TJ-43. The CCK and PYY levels were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 treatment. Furthermore, the GIP and active GLP-1 levels increased and values at POD 21 were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 administration. Insulin secretion tended to increase in patients treated with TJ-43. CONCLUSION: TJ-43 may have advantages for oral food intake in patients in the early phase after pancreatic surgery. Further investigation is needed to clarify the effects of TJ-43 on incretin hormones.

Metastasis of Hepatocellular Carcinoma in the Pouch of Douglas Successfully Treated by Radiation Therapy: A Case Report.

Metastasis of hepatocellular carcinoma (HCC) in the pouch of Douglas is relatively rare. A 65-year-old man with liver cirrhosis was admitted for detailed examination of a pelvic tumor. He had a previous history of ruptured HCC, and received emergent hemostasis with transcatheter arterial embolization followed by curative ablation. His blood tests showed an increase in des-gamma-carboxy prothrombin (DCP). Contrast-enhanced computed tomography (CE-CT) revealed a heterogeneously enhanced large pelvic tumor, but no additional tumorous lesions were detected in other organs, including the lungs, liver and abdominal lymph nodes. The colonoscopy showed compression by an extra-luminal/submucosal tumor, and computed tomography-guided percutaneous needle biopsy revealed that the pelvic tumor was metastasis of HCC. Because of the poor liver function, the solitary pelvic tumor was treated with three-dimensional conformal radiation therapy (3D-CRT). The tumor size and the DCP value were markedly decreased after radiation therapy. Nine months later, occasional mild bloody stool due to radiation proctitis was observed; however, no serious side effects occurred. Our case suggests that radiation therapy may be a therapeutic option for a solitary metastatic lesion of HCC in the pouch of Douglas.

The Prognostic Implications of Perioperative Serum Cholesterol Levels in Patients With Gastric Cancer.

BACKGROUND/AIM: Although cholesterol is an important indicator of nutritional status, it is also involved in cancer progression. In this study, we investigated the clinical significance of the dynamics of perioperative total cholesterol (T-Cho) levels in patients with gastric cancer (GC). PATIENTS AND METHODS: A total of 212 patients with pathological stage II/III disease who underwent gastrectomy between 2004 and 2020 were enrolled in this retrospective study. The preoperative and postoperative serum T-Cho levels were measured in these patients. RESULTS: Increased serum T-Cho levels were significantly correlated with low preoperative serum albumin levels (p<0.001). Patients with increased serum T-Cho levels after surgery had significantly lower overall and recurrence-free survival rates (p=0.030 and p=0.013, respectively; log-rank test). Cox proportional hazards model revealed that increased serum T-Cho levels (p=0.040), advanced pathological stage (p<0.001), and the provision of adjuvant chemotherapy (p=0.006) were independent prognostic factors for recurrence-free survival in patients with GC. CONCLUSION: Increased serum T-Cho levels after gastrectomy may be an independent prognostic factor in patients with GC.

Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats.

This study aimed to investigate the therapeutic effects of recombinant human thrombomodulin (rhTM) on acute lung injury (ALI) caused by sepsis in rats. Rats that underwent cecal ligation and puncture (CLP) were treated with or without rhTM, and then mortality was analyzed. In another set of experiments, ALI was assessed. Furthermore, microthrombosis in the lungs was investigated by immunohistochemistry. Moreover, plasma inflammatory and anti-inflammatory cytokines, such as TNF-α, high-mobility group box chromosomal protein 1 (HMGB-1), and IL-10, were evaluated by ELISA. Production of TNF-α and HMGB-1 by isolated tissue macrophages (Mφs) was assessed in vitro. Mortality after CLP was significantly improved by rhTM treatment. In addition, rhTM treatment improved the wet/dry weight ratio of the lungs, the pulmonary microvascular permeability, and the lung injury scores in animals that underwent CLP. Microthrombosis was detected in the lungs after CLP. These pathophysiological changes were blunted by rhTM treatment. Increased plasma TNF-α and HMGB-1 levels were blunted by rhTM treatment; however, the anti-inflammatory cytokine IL-10 was significantly greater in the rhTM(+) group than in the rhTM(-) group. Increased TNF-α and HMGB-1 production by the tissue Mφs stimulated with LPS were significantly blunted by rhTM treatment in vitro, but the production of IL-10 by the tissue Mφs was not changed in the cells incubated with rhTM. Overall, rhTM improved the mortality caused by septic peritonitis. The possible mechanisms are most likely anti-inflammatory and anticoagulant effects, which lead to the prevention of ALI.

Periostin increased by mechanical stress upregulates interleukin-6 expression in the ligamentum flavum.

Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long-term mechanical stress were analyzed using RNA-seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor-ß1, α-smooth muscle actin, collagen type 1 alpha 1, and interleukin-6 (IL-6) in LF cells. Periostin blockade suppressed the mechanical stress-induced gene expression of IL-6 while periostin treatment increased IL-6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL-6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.

Carcinoembryonic antigen levels in pancreatic juice are associated with histological subtypes of intraductal papillary mucinous neoplasm of the pancreas.

Background: The present study aimed to examine the correlation between preoperative carcinoembryonic antigen levels in pancreatic juice (PJ-CEA) and the histological subtype of intraductal papillary mucinous neoplasm (IPMN). Methods: We enrolled IPMN patients who underwent endoscopic retrograde pancreatography between March 2002 and March 2018. Clinical factors associated with IPMN histological subtypes of 67 patients who underwent surgery were analyzed. Furthermore, the relationship between CEA immunohistochemistry findings and histological subtypes was investigated. Results: Median PJ-CEA were 15 ng/ml in the gastric type, 150 ng/ml in the intestinal type, and 175 ng/ml in the pancreatobiliary type. Both intestinal and pancreatobiliary types had significantly higher PJ-CEA than the gastric type (p = 0.001). In the analysis of histological subtype predictors, high PJ-CEA (≥63 ng/ml) only showed a significant difference in multivariate analyses (95% confidence interval 4.8-70.2; p < 0.001). Immunohistochemistry findings revealed significantly higher CEA expression in the non-gastric type than in the gastric type (p < 0.001). The non-gastric type showed a significantly worse prognosis than the gastric type (p = 0.017). Conclusion: PJ-CEA was an independent predictor of IPMN histological subtypes in a preoperative setting. High PJ-CEA predict the non-gastric type, while low PJ-CEA predict the gastric type.

[Long-Term Prognosis of Patients with Biliary Tract Cancer Undergoing Pancreaticoduodenectomy].

We divided the patients with biliary tract cancer who underwent pancreaticoduodenectomy(PD)at our hospital into the 5-year recurrence-free and recurrence groups and investigated the prognostic factors. Additionally, we investigated the efficacy of adjuvant chemotherapy in patients with and without lymph node (LN) metastasis. There was no significant difference between the two groups for patient characteristics and perioperative factors. However, patients with LN metastasis tended to have a higher recurrence rate. For patients without LN metastasis, the median overall survival(OS)was not significantly different between the patients who received and did not receive adjuvant chemotherapy. For patients with LN metastasis, although it was not significantly different(p=0.234), the OS of patients who received adjuvant therapy was more than 3 times than that of patients who did not(58.6 months and 18.4 months, respectively). For patients with biliary tract cancer who underwent PD, positive LN metastasis may be a poor prognostic factor, and adjuvant therapy may possibly improve prognosis.

Development of a system to analyze oral frailty associated with Alzheimer's disease using a mouse model.

The rapid aging of the population makes the detection and prevention of frailty increasingly important. Oral frailty has been proposed as a novel frailty phenotype and is defined as a decrease in oral function coexisting with a decline in cognitive and physical functions. Oral frailty has received particular attention in relation to Alzheimer's disease (AD). However, the pathomechanisms of oral frailty related to AD remain unknown. It is assumed that the mesencephalic trigeminal nucleus (Vmes), which controls mastication, is affected by AD pathology, and as a result, masticatory function may be impaired. To investigate this possibility, we included male 3 × Tg-AD mice and their non-transgenic counterpart (NonTg) of 3-4 months of age in the present study. Immunohistochemistry revealed amyloid-ß deposition and excessive tau phosphorylation in the Vmes of 3 × Tg-AD mice. Furthermore, vesicular glutamate transporter 1-immunopositive axon varicosities, which are derived from Vmes neurons, were significantly reduced in the trigeminal motor nucleus of 3 × Tg-AD mice. To investigate whether the AD pathology observed in the Vmes affects masticatory function, we analyzed electromyography of the masseter muscle during feeding. The 3 × Tg-AD mice showed a significant delay in masticatory rhythm compared to NonTg mice. Furthermore, we developed a system to simultaneously record bite force and electromyography of masseter, and devised a new method to estimate bite force during food chewing in mice. Since the muscle activity of the masseter showed a high correlation with bite force, it could be accurately estimated from the muscle activity. The estimated bite force of 3 × Tg-AD mice eating sunflower seeds was predominantly smaller than that of NonTg mice. However, there was no difference in masseter weight or muscle fiber cross-sectional area between the two groups, suggesting that the decreased bite force and delayed mastication rhythm observed in 3 × Tg-AD mice were not due to abnormality of the masseter. In conclusion, the decreased masticatory function observed in 3 × Tg-AD mice was most likely caused by AD pathology in the Vmes. Thus, novel quantitative analyses of masticatory function using the mouse model of AD enabled a comprehensive understanding of oral frailty pathogenesis.

Intended preoperative trans-arterial embolization for large hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: Generally, a large tumor size of hepatocellular carcinoma (HCC) is associated with poor visibility and uncertainty in the surgical field which results in increased surgical difficulty as well as unfavorable postoperative outcomes. We performed intended preoperative trans-arterial embolization (TAE) in patients with a large HCC. In this study, we investigated the oncological significance of intended preoperative TAE for a large HCC, using a comparison between patients with and without TAE, and detailed analyses for pre- and post-TAE status. METHODS: A total of 411 patients who underwent hepatectomy for primary HCC at the University of Yamanashi Hospital between January 2007 and December 2018 were included in this study. The patients were divided into two groups: patients with larger HCCs (≥50 mm, n=51) and those with smaller HCC (<50 mm, n=360) according to the size of their HCCs. Comparison of clinicopathological features between these groups and clinical outcomes between the TAE and non-TAE groups were compared. In addition, a detailed analysis of each case in the TAE group was conducted, comparing clinicopathological factors between pre- and post-TAE status. RESULTS: The clinical unfavorable short- and long-term outcomes of patients with large HCCs (≥50 mm) were revealed compared to those with small HCCs (<50 mm). The prognostic analyses showed that a large tumor size and increased tumor markers, multiple tumor numbers, and others were adverse prognostic factors, and vascular invasions and residual tumors were included in the multivariate analysis. Further detailed analyses revealed that the average rates of change in tumor size and tumor shrinkage after TAE were - 48.6±35.6 mm and - 30.7±17.0%, respectively. Pathological high necrotic changes in the tumor, after multiple-times TAE aiming to a better effect, were related to a better prognosis in patients with large HCC. Poor prognostic factors became less common in patients who underwent intended preoperative TAE, and these patients had better prognoses. CONCLUSIONS: The large tumor size of HCC is associated with unfavorable outcomes; the intended preoperative TAE for large HCC patients performed multiple times aiming to affect the tumor as much as possible might improve their prognoses.