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BackgroundSurgical site infection (SSI) is one of the most important complications of surgery for gastroenterological malignancies because it leads to a prolonged postoperative hospital stay and increased inpatient costs. Furthermore, SSI can delay the initiation of postoperative treatments, including adjuvant chemotherapy, negatively affecting patient prognosis. Identifying the risk factors for SSI is important to improving intra- and postoperative wound management for at-risk patients.MethodsPatients with gastroenterological malignancies who underwent surgery at our institution were retrospectively reviewed and categorized according to the presence or absence of incisional SSI. Clinicopathological characteristics such as age, sex, body mass index, malignancy location, postoperative blood examination results, operation time, and blood loss volume were compared between groups. The same analysis was repeated of only patients with colorectal malignancies.ResultsA total of 528 patients (330 men, 198 women; mean age, 68 ± 11 years at surgery) were enrolled. The number of patients with diseases of the esophagus, stomach, small intestine, colon and rectum, liver, gallbladder, and pancreas were 25, 150, seven, 255, 51, five, and 35, respectively. Open surgery was performed in 303 patients vs. laparoscopic surgery in 225 patients. An incisional SSI occurred in 46 patients (8.7%). Multivariate logistic regression analysis showed that postoperative hyperglycemia (serum glucose level ≥140 mg/dl within 24 h after surgery), colorectal malignancy, and open surgery were independent risk factors for incisional SSI. In a subgroup analysis of patients with colorectal malignancy, incisional SSI occurred in 27 (11%) patients. Open surgery was significantly correlated with the occurrence of incisional SSI (P = 0.024).ConclusionsPostoperative hyperglycemia and open surgery were significant risk factors for SSI in patients with gastroenterological malignancies. Minimally invasive surgery could reduce the occurrence of incisional SSI.

Purpose: We previously reported that the expression of Aurora-A was frequently up-regulated in human esophageal squamous cell carcinoma (ESCC) tissues as well as cell lines and the up-regulation contributed to a poor prognosis. In this study, we assessed the possibility of Aurora-A suppression as a therapeutic target for ESCC using ESCC cell lines.Experimental Design: We established subclones using vector-based short hairpin RNA (shRNA). Then, we investigated the effect of Aurora-A suppression on proliferation and cell cycle changes in vitro. Next, chemosensitivity against docetaxel was investigated by tetrazolium salt–based proliferation assay (WST assay) and cell number determinations, and furthermore, the type of cell death induced by docetaxel was analyzed by flow cytometry. Finally, to examine the effect of Aurora-A shRNA on proliferation and chemosensitivity against docetaxel in vivo, a s.c. tumor formation assay in nude mice was done.Results: We established two genetically different stable cell lines (510 A and 1440 A) in which levels of Aurora-A were reduced. Cell growth was inhibited by 38.7% in 510 A and by 24.3% in 1440 A in vitro compared with empty vector–transfected controls (510 m and 1440 m), and this growth inhibition was mediated through G2-M arrest as confirmed by flow cytometry. Next, in a WST assay, the IC50 for Aurora-A shRNA-transfected cells was lower than that of empty vector–transfected cells (510 A, 2.7 × 10−7 mol/L; 510 m, 4.8 × 10−7 mol/L; 1440 A, 2.6 × 10−7 mol/L; 1440 m, 4.9 × 10−7 mol/L). In addition, 0.3 nmol/L docetaxel induced a notable level of apoptosis in Aurora-A shRNA-transfected cells compared with empty vector–transfected cells. In the assay of s.c. tumors in nude mice, tumor growth in 510 A was inhibited by 36.1% compared with that in 510 m, and in tumors treated with docetaxel, the suppression of Aurora-A resulted in 44.0% tumor growth suppression in vivo.Conclusions: These results indicated that Aurora-A might play an important role in chemosensitivity to docetaxel, and the suppression of its expression might be a potential therapeutic target for ESCC.

Supplementary Figure S3 from The Suppression of Aurora-A/STK15/BTAK Expression Enhances Chemosensitivity to Docetaxel in Human Esophageal Squamous Cell Carcinoma

Supplementary Figure S1 from The Suppression of Aurora-A/STK15/BTAK Expression Enhances Chemosensitivity to Docetaxel in Human Esophageal Squamous Cell Carcinoma

Supplementary Figure S2 from The Suppression of Aurora-A/STK15/BTAK Expression Enhances Chemosensitivity to Docetaxel in Human Esophageal Squamous Cell Carcinoma

Supplementary Figure Legend from The Suppression of Aurora-A/STK15/BTAK Expression Enhances Chemosensitivity to Docetaxel in Human Esophageal Squamous Cell Carcinoma

Claviceps humidiphila [≡ C. purpurea var. phalaridis] was previously typified with the holotype collected by Tanda in Japan and an epitype from Bavaria, Germany. Phylogenetic analyses based on translation elongation factor 1-α (TEF1-α) and RNA polymerase II second largest subunit (RPB2) indicated that the previously designated epitype from Germany was not conspecific with the Japanese species. The German specimen is proposed as a new species, C. bavariensis, and a specimen collected from the type location (Chiba, Japan) is designated as a neotype for C. humidiphila, replacing the lost holotype.

ASO Visual Abstract

Internal hernia (IH) is one of the critical complications after gastrectomy with Roux-en-Y reconstruction, which can be prevented by closing mesenteric defects. However, only few studies have investigated the incidence of IH after laparoscopic total gastrectomy (LTG) with Roux-en-Y reconstruction for gastric cancer till date. This study aimed to assess the efficacy of defect closure for the prevention of IH after LTG. This multicenter, retrospective cohort study collected data from 714 gastric cancer patients who underwent LTG with Rou-en-Y reconstruction between 2010 and 2016 in 13 hospitals. We evaluated the incidence of postoperative IH by comparing closure and non-closure groups of Petersen’s defect, jejunojejunostomy mesenteric defect, and transverse mesenteric defect. The closure group for Petersen’s defect included 609 cases, while the non-closure group included 105 cases. The incidence of postoperative IH in the closure group for Petersen’s defect was significantly lower than it was in the non-closure group (0.5% vs. 4.8%, p

Background and Overview The authors successfully treat a case of hemifacial microsomia involving unilateral condylar hypoplasia using conventional orthodontic techniques followed by long-term retention. Case Description A girl aged 10 years and 2 months received a diagnosis of hemifacial microsomia resulting from unilateral condylar hypoplasia. During a growth period, premature incisal contact was abolished. After her growth was complete, she received conventional orthodontic treatment with preadjusted edgewise appliances. After 27 months of multibracket treatment, acceptable occlusion with a class I canine and molar relationship was achieved. The occlusion remained stable throughout the 15-year retention period, although there was a slight facial change. Conclusions and Practical Implications Early orthodontic management only can have some limitations but could be one of the treatment options for hemifacial microsomia.

Cancer-related systemic inflammation influences postoperative outcomes in cancer patients. Although the relationship between inflammation-related markers and postoperative outcomes have been investigated in many studies, their clinical significance remains to be elucidated in rectal cancer patients. We focused on the lymphocyte count/C-reactive protein ratio (LCR) and its usefulness in predicting short- and long-term outcomes after rectal cancer surgery. Patients with rectal cancer who underwent curative resection at our institution between 2010 and 2018 were enrolled in this study. We comprehensively compared the effectiveness of 11 inflammation-related markers, including LCR and other clinicopathological characteristics, in predicting postoperative complications and survival. Receiver operating characteristic curve analysis indicated that LCR had the highest area under the curve value for predicting the occurrence of postoperative complications. In the multivariate analysis, male sex (odds ratio [OR]: 2.21, 95% confidence interval [CI] 1.07–4.57, P = 0.031), low tumor location (OR: 2.44, 95% CI 1.23–4.88, P = 0.011), and low LCR (OR: 3.51, 95% CI 1.63–7.58, P = 0.001) were significantly and independently associated with the occurrence of postoperative complications. In addition, multivariate analysis using Cox’s proportional hazard regression model for the prediction of survival showed that low LCR (≤ 12,600) was significantly associated with both poor overall survival (hazard ratio [HR]: 2.07, 95% CI 1.03–4.15, P = 0.041) and recurrence-free survival (HR: 2.21, 95% CI 1.22–4.01, P = 0.009). LCR is a useful marker for predicting both short- and long-term postoperative outcomes in rectal cancer patients who underwent curative surgery.

Porcine reproductive and respiratory syndrome (PRRS) is an infectious swine disease caused by the PRRS virus (PRRSV) that results in economic loss to the pig-rearing industry. To study PRRSV infection in wild boars and pigs, we conducted a serological survey in Gifu Prefecture, Japan, from 2020 to 2021. Three out of 453 (0.7%) wild boar sera were positive for PRRSV antibodies in a commercial ELISA. However, given that PRRSV RNA was not detected in these three wild boars and the specificity and sensitivity of the test kit, these are considered as false positives. Although seropositive pigs were found in multiple pig farms in the study area, the role of wild boars as a source of PRRS to pig farms appeared to be minimal.

Background The treatment strategy for metastatic lesions of primary malignant melanoma of the esophagus (PMME) is currently determined on a case-by-case basis, based on the National Comprehensive Cancer Network (NCCN) guidelines for cutaneous melanoma. The NCCN guidelines state that resection should be considered in patients with resectable metastatic recurrence. Herein, we report a case of long-term survival treated with three metastasectomies and two subsequent adjuvant nivolumab therapies for the metastatic recurrence of PMME. Case presentation A 65-year-old female patient with PMME underwent thoracoscopic subtotal esophagectomy, gastric tube reconstruction via the posterior mediastinal route, and cervical esophagogastric anastomosis. Histopathological examination of the resected specimen revealed that the tumor was PMME with tumor invasion into the muscularis propria and no lymph node metastasis. At the age of 68 years, she developed intestinal invagination due to jejunal metastasis of malignant melanoma and underwent resection of the jejunum. Histopathological examination of the resected specimen revealed two metastases of malignant melanoma in the jejunum and one metastasis to the mesenteric lymph node. At the age of 75 years, a recurrence of malignant melanoma was found in the cervical esophagus. She underwent thoracoscopic mobilization of the gastric tube and esophagus followed by cervical esophagectomy and reconstruction with a free jejunum flap. She received 24 courses of nivolumab therapy for 1 year as a postoperative adjuvant therapy. Subsequently, at the age of 78 years, an enlarged left cervical lymph node and a mass in the right lower lobe of the lung were found. She underwent left cervical lymph node dissection and thoracoscopic wedge resection of the right lung. Histopathological examination of the resected specimens revealed that both tumors were metastases of malignant melanoma. At age 79 years, she received eight courses of nivolumab therapy as a second postoperative adjuvant therapy, with no sign of recurrence in a 9-month follow-up period after the third metastasectomy. Conclusion In cases of metastatic recurrence of PMME, aggressive resection of oligometastasis with postoperative adjuvant nivolumab therapy may result in long-term survival.

Sleep is a crucial component of health, and insomnia is among the most common and vexing of life-habit-related disorders. While dietary sleep-support supplements can improve sleep, choosing an effective dietary supplement can be challenging for users due to the wide variety of options available and the varying effects experienced by different individuals. In this study, to identify new criteria for estimating the effects of dietary supplements, we examined the relationships among the dietary supplements, the pre-conditions (PCs; defined as the life habits and sleep conditions before supplementation), and the sleep problems of subjects before supplementation. An open, randomized, cross-over intervention trial enrolling 160 subjects was conducted to test the efficacy of each dietary supplement (Analysis 1) and the relationships among dietary supplements, the PCs, and sleep problems (Analysis 2). To this end, l-theanine (200 mg/day), γ-aminobutyric acid (GABA) (111.1 mg/day), Apocynum venetum leaf extract (AVLE) (50 mg/day), and l-serine (300 mg/day) were administered to subjects. Before the first intervention period, life habits and sleep conditions were surveyed to identify each subject’s PCs. For each combination of supplements and sleep problems, PCs were compared between subjects whose sleep problems were improved and subjects whose sleep problems were not improved via supplementation. All the tested supplements were found to ameliorate sleep problems significantly (Analysis 1). In Analysis 2, the PCs specific to improved subjects were found to differ depending on the dietary supplements and sleep problems. In addition, subjects who consumed dairy products often showed improvement in their sleep problems with all the tested supplements. This study suggests the possibility of personalizing sleep-support supplementation based on personal life habits, sleep conditions, and sleep problems, in addition to the known efficacy of dietary supplements.

Infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis (IB) in chickens. There is a correlation between cross-protection and percentage of similarity between nucleotide sequences encoding the S1 subunit, which is responsible for generating neutralizing and serotype-specific antibodies. Therefore, RT-PCR is commonly used to amplify the IBV-S1 gene following DNA sequencing in order to predict the efficacy of vaccines against IBV strains. We successfully enhanced the sensitivity for detection of the IBV-S1 gene by second PCR after purification of the 1st RT-PCR product. Using that method, we obtained detailed information on the prevalence of IBV on poultry farms in Gifu Prefecture, Japan. The IBV-S1 gene detection method used in the current study will enable accurate information on the prevalence of IBV in Japan to be obtained.

Minimally invasive esophagectomy (MIE) is increasingly performed to expect lower complication rate compared to open esophagectomy. Studies of minimally invasive Ivor Lewis esophagectomy (MIILE) with circular staplers have reported better outcomes compared to MIE with cervical anastomosis, but frequent anastomotic complications have also been reported. MIILE with linear staplers is a promising alternative, but the long-term functional and oncological outcomes are uncertain. To evaluate the functional and oncological outcomes of MIILE with linear stapled anastomosis, a retrospective cohort study was performed in 104 patients who underwent MIILE with linear stapled anastomosis for esophageal malignant tumors. The primary endpoints were the overall complication and anastomotic leak rates. The secondary endpoints were late complications, overall and disease-free survival, and nutritional status at 6 and 12 months after MIILE. Anastomotic leak occurred in 4 patients (3.8%). The short-term complication rate of grade IIIb or higher was 6.7%. During a median 57-month follow-up period, anastomotic stricture occurred in one patient, 7 required hiatal hernia repair, and 2 underwent conduit revision surgery. The 5-year overall survival and disease-free survival rates were 69.3% and 59.5%, respectively. Status of reflux esophagitis at the time of most recent evaluation was grade N/A/B/C/D in 52/10/10/13/8 among 93 patients who had follow-up endoscopy. The mean body weight loss at 6 and 12 months after MIILE was 11.3 and 11.8% with maintenance of the serum albumin level. MIILE with linear stapled anastomosis is a safe procedure with a low anastomotic complication rate and favorable long-term functional and survival outcomes.

Aim To present a case of skeletal mandibular protrusion with multiple impacted ankylosed teeth, which were treated with conventional orthognathic surgery and alveolar corticotomy, respectively. Background Tooth ankylosis is characterized by the fusion of a root surface with the surrounding alveolar bone. Various treatment modalities for tooth ankylosis have been developed and are used commonly in the clinic. Corticotomy is defined as the application of intentional surgical injury to the cortical bone to mobilize a tooth with the adjacent bone and soft tissues. The corticotomy technique has been improved in recent years to avoid possible risks such as periodontal damage, tooth devitalization, and osseous necrosis due to an inadequate blood supply. Case description A female patient aged 16 years and 3 months was diagnosed with anterior crossbite and the impaction and ankylosis of multiple canines. After the confirmation of ankylosis, alveolar corticotomy was performed on the maxillary left and mandibular right canines. After 6 months of traction (patient age, 19 years and 7 months), both canines had extruded successfully. After the completion of preoperative treatment, bilateral intraoral vertical ramus osteotomy was performed to correct the anterior crossbite involving a skeletal mandibular protrusion. The amounts of mandibular setback on the right and left sides were approximately 7 and 5 mm, respectively. The total treatment period was 55 months. Acceptable occlusion with a balanced profile was maintained over a 5-year retention period, indicating the long-term stability and success of the treatment. Conclusion Our results indicate that alveolar corticotomy should be considered to facilitate the treatment of multiple impacted ankylosed teeth. Clinical significance This report proposes an efficacy of alveolar corticotomy for extrusion of impacted ankylosed teeth.

Objective We aimed to identify the immunoregulatory role of the cyclin‐dependent kinase inhibitor p21 in the homeostasis of mandibular condylar cartilage affected by mechanical stress. Materials and methods Ten C57BL/6 wild‐type (WT) and ten p21−/− mice aged 8 weeks were divided into the untreated and treated groups. In the treated groups, mechanical stress was applied to the temporomandibular joint (TMJ) through forced mouth opening for 3 hr/day for 7 days. The dissected TMJs were assessed using micro‐CT, histology, and immunohistochemistry. Results Treated p21−/− condyles with mechanical stress revealed more severe subchondral bone destruction, with thinner cartilage layers and smaller proteoglycan area relative to treated WT condyles; untreated WT and p21−/− condyles had smoother surfaces. Immunohistochemistry revealed significant increases in the numbers of caspase‐3, interleukin‐1β, matrix metalloprotease (MMP)‐9, and MMP‐13 positive cells, and few aggrecan positive cells, in treated p21−/− than in treated WT samples. Moreover, the number of TUNEL positive cells markedly increased in p21−/− condyles affected by mechanical stress. Conclusions Our findings indicate that p21 in chondrocytes contributes to regulate matrix synthesis via the control ofm aggrecan and MMP‐13 expression under mechanical stress. Thus, p21 might regulate the pathogenesis of osteoarthritis in the TMJ.

Advancements in dental cements have considerably improved their bond strengths. However, high bond strength often makes the removal of restorations difficult. Thus, smart dental cements that show controllable bond strength are required. A conventional resin-modified glass-ionomer-cement demonstrated a significant reduction in the bond strength after current application. However, for this system, the ions in the cement are released into the oral cavity, resulting in a reduction of the electrical conductivity and in losses of the expected on-demand debonding property. Herein, the effects of immersion in 0.9 and 15% NaCl solutions on the electrical conductivity and debonding properties were investigated. The cement immersed in 0.9% NaCl solution from 1 to 28 days maintained similar bond strength reductions after current application, whereas that in 15% NaCl solution initially showed no bond strength reduction after 1 day but exhibited an increase in the bond strength reduction after immersion for 28 days.

Background: Idiopathic condylar resorption (ICR) is an aggressive degenerative disease of the temporomandibular joint that is most frequently observed in teenage girls. However, no specific cause of ICR has been identified. To explore the specific causes of the onset and progression of ICR, we performed a survey-based study on ICR in orthodontic patients and described its subjective symptoms, clinical signs, and condylar morphological features. Methods: A total of 1735 participants were recruited from 2193 orthodontic patients. For each participant, subjective symptoms and clinical signs of temporomandibular disorders (TMDs) were evaluated through clinical examination and a questionnaire. Furthermore, three-dimensional computed tomography (CT) was performed to diagnose ICR. Results: Among the 1735 patients evaluated, ICR was present in two male and ten female patients. All 12 patients had maxillary protrusion and an anterior open bite. Four patients with ICR underwent orthodontic treatment. Based on CT findings, patients with ICR had significantly different condylar sizes and shapes from patients with TMDs alone. Conclusions: The coexistence of intrinsic and extrinsic factors, such as sex-hormone imbalance and a history of orthodontic treatment, might lead to the onset of ICR. We suggest that growing patients suspected of having ICR should undergo CT evaluation because CT findings may precede clinical symptoms and signs.

Following liver transplantation (LT), allograft liver failure can be developed by various causes and requires re-LT. Hence, this study aimed to clarify the characteristics and prognostic factors of patients with allograft liver failure awaiting deceased donor LT (DDLT) in Japan.Of the 2686 DDLT candidates in Japan between 2007 and 2016, 192 adult patients listed for re-LT were retrospectively enrolled in this study. Factors associated with waitlist mortality were assessed using the Cox proportional hazards model. The transplant-free survival probabilities were evaluated using the Kaplan-Meier analysis and log-rank test.The median period from the previous LT to listing for re-LT was 1548 days (range, 4-8449 days). Primary sclerosing cholangitis (PSC), which was a primary indication, showed a higher listing probability for re-LT as compared with other primary etiologies. Recurrent liver disease was a leading cause of allograft failure and was more frequently observed in the primary indication of hepatitis C virus (HCV) infection and PSC in contrast with other etiologies. Multivariate analysis identified the following independent risk factors associated with waitlist mortality: age, Child-Turcotte-Pugh (CTP) score, mode for end-stage liver disease (MELD) score, alanine aminotransferase (ALT), and causes of allograft failure.Recurrent HCV and PSC were major causes of allograft liver failure in Japan. In addition to CTP and MELD scores, either serum ALT levels or causes of allograft failure should be considered as graft liver allocation measures.

A female patient, aged 32 years 11 months, had a chief complaint of facial asymmetry, which initiated about 10 years ago. She was diagnosed with facial asymmetry with a skeletal Class III jaw-base relationship caused by unilateral mandibular condylar osteochondroma. After surgical orthodontic treatment, including unilateral condylectomy, an ideal occlusion with an adequate interincisal relationship was achieved, and facial asymmetry and mandibular protrusion were dramatically improved. At 5 years 10 months postretention, the patient had no masticatory disturbance and functional problems. Overall, the facial balance was maintained well, and no recurrence of facial asymmetry was observed; however, the panoramic radiograph revealed a minor change in condylar shape, which may be caused by bone remodeling and/or resorption. In conclusion, our results indicated the necessity of long-term monitoring in this patient who underwent unilateral condylectomy, especially because of the persistent condylar remodeling.

Aim To clarify the outcome and predictive factors in patients with acute liver failure (ALF) awaiting deceased donor liver transplantation (DDLT) in Japan. Methods Of the DDLT candidates in Japan between 2007 and 2016, 264 adult patients with ALF were retrospectively enrolled in this study. Factors associated with DDLT and waiting-list mortality were assessed using the Cox proportional hazard model. The DDLT and transplant-free survival probabilities were evaluated using Kaplan-Meier analysis and the log-rank test. Results The waiting-list registration year after the Transplant Law revision in 2010 was a significant factor associated with DDLT. The adjusted hazard ratio indicated that DDLT probability after 2010 was four times higher than that before, and the 28-day cumulative DDLT probability was more than 35%. The median survival time of the entire cohort was 40 days. Multivariate analysis identified the following three factors associated with waiting-list mortality: age, coma grade, and international normalized ratio. The transplant-free survival probabilities were significantly stratified by the number of risks, and patients with all three risks showed extremely poor short-term prognosis (median survival time = 23 days). Conclusions The DDLT probability of ALF patients increased after the law revision in 2010; however, patients at high risk of short-term waiting-list mortality might need emergent living donor transplantation.

It remains unclear whether laparoscopic gastrectomy (LG) for gastric cancer is a suitable treatment for very elderly (VE) patients. We aimed to assess the safety and feasibility of LG for gastric cancer in VE patients. We reviewed 226 consecutive patients who underwent LG between January 2010 and December 2016. We compared VE patients (age ≥ 80, n = 38) with non-elderly patients (age ≤ 79, n = 188). An ASA-PS score ≥ 2 was more common in VE group (86.8 vs. 48.9%; P

The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology published the first version of the Guidelines for the Management of Hepatitis B in 2013 (first English version in 2014), and has since been publishing updates to the Guidelines as new drugs become available, with the latest original Japanese version being Version 3.1. Herein, the Drafting Committee publishes the second English version that contains all the changes made since the first English version of the guidelines was published in 2014. This 2019 version covers: (i) the nucleos(t)ide analogs, tenofovir disoproxil fumarate and tenofovir alafenamide; (ii) updates to treatment recommendations and management of drug-resistant hepatitis B virus that reflect the new availability of these drugs; and (iii) new information about hepatitis B virus reactivation with each update. This latest update also contains information about treatment goals, indications for treatment and cessation of nucleos(t)ide analog therapy, most of which were covered by the first version.

Loading is indispensable for the growth, development, and maintenance of joint tissues, including mandibular condylar cartilage, but excessive loading or reduced host adaptive capacity can considerably damage the temporomandibular joint (TMJ), leading to temporomandibular joint osteoarthritis (TMJ-OA). TMJ-OA, associated with other pathological conditions and aging processes, is a highly degenerative disease affecting the articular cartilage. Many treatment modalities for TMJ-OA have been developed. Traditional clinical treatment includes mainly nonsurgical options, such as occlusal splints. However, non-invasive therapy does not achieve joint tissue repair and regeneration. Growing evidence suggests that low-intensity pulsed ultrasound (LIPUS) accelerates bone fracture healing and regeneration, as well as having extraordinary effects in terms of soft tissue repair and regeneration. The latter have received much attention, and various studies have been performed to evaluate the potential role of LIPUS in tissue regeneration including that applied to articular cartilage. The present article provides an overview of the status of LIPUS stimulation used to prevent the onset and progression of TMJ-OA and enhance the tissue regeneration of mandibular condylar cartilage. The etiology and management of TMJ-OA are explained briefly, animal models of TMJ-OA are described, and the effectiveness of LIPUS on cell metabolism and tissue regeneration in the TMJ is discussed.

Summary Objective Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression. Design To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model. Results SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1β, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration. Conclusions Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA.

A fungus causing false smut in the flowers of Murdannia keisak (Commelinaceae, Commelinales, Monocots) in Japan was morphologically identical to Ustilago aneilematis. The fungus infected ovaries of most flowers of host plants. Infected flowers were filled with yellow to orange thick-walled conidia that became olivaceous green at maturity. However, multilocus phylogenetic analysis of DNA sequences (18S, 28S, translation elongation factor 1α [TEF], the largest [RPB1] and the second largest [RPB2] subunit of RNA polymerase II) showed that the fungus belonged to the tribe Ustilaginoideae (Clavicipitaceae, Hypocreales, Ascomycota). Microscopic examination showed that the fungus developed conidia at the apex of conidiogenous cells, in contrast to other species in the Ustilaginoideae that develop conidia pleurogenously. A new genus, Commelinaceomyces, is formally proposed in the Ustilaginoideae to accommodate this fungus. Four species previously misplaced in Ustilago (Ustilaginales, Basidiomycota) are transferred to Commelinaceomyces, including the type of the genus, C. aneilematis, on Murdannia keisak. This is the first report of a clavicipitaceous species infecting host plants in the Commelinaceae.

WNT molecules are the regulators of various biological functions, including body axis formation, organ development, and cell proliferation and differentiation. WNTs have been extensively studied as causative genes for an array of diseases. WNT10A and WNT10B, which are considered to be genes of the same origin, have been identified as causative genes for tooth deficiency in humans. However, the disrupted mutant of each gene does not show a decrease in teeth number. A negative feedback loop, interacting with several ligands based on a reaction–diffusion mechanism, was proposed to be important for the spatial patterning of tooth formation, and WNT ligands have been considered to play a pivotal role in controlling tooth patterning from mutant phenotypes of LDL receptor-related proteins (LRPs) and WNT co-receptors. The Wnt10a and Wnt10b double-mutants demonstrated severe root or enamel hypoplasia. In Wnt10a−/− and Wnt10a+/−;Wnt10b−/− mice, changes in the feedback loop may collapse the modulation of fusion or split a sequence of tooth formation. However, in the double-knockout mutant, a decrease in the number of teeth was observed, including the upper incisor or third molar in both jaws. These findings suggest that there may be a functional redundancy between Wnt10a and Wnt10b and that the interaction between the two genes functions in conjunction with other ligands to control the spatial patterning and development of teeth.

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine catabolism that acts as a novel regulator of adipogenesis. In pathological states, xanthine oxidoreductase activity increases to produce excess reactive oxygen species (ROS). The nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical inducer of antioxidants, which is bound and repressed by a kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm. The Keap1-Nrf2 axis appears to be a major mechanism for robust inducible antioxidant defenses. Here, we demonstrate that febuxostat, a xanthine oxidase inhibitor, alleviates the increase in adipose tissue mass in obese mouse models with a high-fat diet or ovariectomy. Febuxostat disrupts in vitro adipocytic differentiation in adipogenic media. Adipocytes appeared at day 7 in absence or presence of febuxostat were 160.8 ± 21.2 vs. 52.5 ± 12.7 (p < 0.01) in 3T3–L1 cells, and 126.0 ± 18.7 vs. 55.3 ± 13.4 (p < 0.01) in 10T1/2 cells, respectively. Adipocyte differentiation was further enhanced by the addition of hydrogen peroxide, which was also suppressed by febuxostat. Interestingly, febuxostat, but not allopurinol (another xanthine oxidase inhibitor), rapidly induced the nuclear translocation of Nrf2 and facilitated the degradation of Keap1, similar to the electrophilic Nrf2 activator omaveloxolone. These results suggest that febuxostat alleviates adipogenesis under oxidative conditions, at least in part by suppressing ROS production and Nrf2 activation. Regulation of adipocytic differentiation by febuxostat is expected to inhibit obesity due to menopause or overeating.

Background and Overview Previous studies have suggested that occlusal discrepancy is a risk factor contributing to periodontal disease. Occlusal discrepancy could increase the risk of developing infrabony defects. The authors present a case of a patient with severe periodontitis who exhibited many infrabony defects in the molar region due to malocclusion-induced trauma. They report the 7-year treatment outcomes of the patient after periodontal regenerative and comprehensive orthodontic therapies for functional recovery with implant prosthodontics. Case Description A 56-year-old woman sought treatment with the chief symptom of masticatory disturbance. In the molar region, excessive tooth mobility, deep periodontal pockets, and infrabony defects were observed. She had excessive overjet, resulting in collapse of anterior guidance. Malocclusion was considered to be an exacerbating factor of the infrabony defects. After initial periodontal therapy, the authors performed periodontal regenerative therapy in the mandibular molar regions. The authors carefully placed implants in a position in the maxillary molar region that would ensure an appropriate anterior dental relationship after orthodontic treatment. Comprehensive orthodontic treatment was subsequently performed, using implants as anchoring units. Definitive surgery was then performed on the mandibular molars before placing the final prosthesis. Favorable periodontal condition and stable occlusion have been maintained for the 7-year posttreatment period. Conclusions and Practical Implications Comprehensive and interdisciplinary treatment enables stable occlusion and establishment of periodontal and peri-implant tissues with high cleansability, even in patients with severe periodontitis and malocclusion. In this case, a favorable long-term treatment outcome can be expected.

The safety of robotic gastrectomy (RG) for gastric cancer in daily clinical settings and the process by which surgeons are introduced and taught RG remain unclear. This study aimed to evaluate the safety of RG in daily clinical practice and assess the learning process in surgeons introduced to RG.Patients who underwent RG for gastric cancer at Kyoto University and 12 affiliated hospitals across Japan from January 2017 to October 2019 were included. Any morbidity with a Clavien-Dindo classification grade of II or higher was evaluated. Moreover, the influence of the surgeon's accumulated RG experience on surgical outcomes and surgeon-reported postoperative fatigue were assessed.A total of 336 patients were included in this study. No conversion to open or laparoscopic surgery and no in-hospital mortality were observed. Overall, 50 (14.9%) patients developed morbidity. During the study period, 14 surgeons were introduced to robotic procedures. The initial five cases had surprisingly lower incidence of morbidity compared to the following cases (odds ratio 0.29), although their operative time was longer (+ 74.2 min) and surgeon's fatigue scores were higher (+ 18.4 out of 100 in visual analog scale).RG was safely performed in actual clinical settings. Although the initial case series had longer operative time and promoted greater levels of surgeon fatigue compared to subsequent cases, our results suggested that RG had been introduced safely.

Interval appendectomy or non-operative management is commonly performed for complicated appendicitis in adult patients. However, these treatments are still controversial because the incidence rate of appendiceal tumors recognized after interval appendectomy is reportedly higher than that after emergency appendectomy. Thus, this study aimed to compare the appendiceal tumor rates between uncomplicated and complicated appendicitis.This study was a retrospective review of patients with appendicitis who underwent surgical removal at a single institution over 7.5 years. The primary objective was the comparison of the incidence rate of appendiceal tumors using propensity score matching, and the secondary objective was the same comparison among older patients, defined as patients aged ≥ 60 years.A total of 1277 patients were included. Of these patients, 297 (23.3%) were preoperatively diagnosed with complicated appendicitis. Moreover, 22 (1.7%) patients, including 14 cases of complicated appendicitis and 8 cases of uncomplicated appendicitis, were diagnosed with appendiceal tumors based on pathological examination. No significant difference was found in the incidence rate of appendiceal tumors between the two groups after matching for patients' background, including age, sex, and history of appendicitis by propensity score matching (P = 0.073). However, among patients aged ≥ 60 years, the incidence of appendiceal tumors was significantly higher in complicated than in uncomplicated appendicitis (P = 0.006).Although the overall risk of appendiceal tumors did not differ between complicated and uncomplicated appendicitis when analyzed by the propensity score matching, in older patients aged ≥ 60 years, the risk increased among those with complicated appendicitis. Therefore, although the incidence is low, complicated appendicitis, particularly, among older patients, should be examined carefully and be performed IA when unusual findings exist.