The immune-stromal cell interactions play a key role in health and diseases.In periodontitis,the most prevalent infectious disease in humans,immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand(RANKL)expression in osteogenic cells such as osteoblasts and periodontal ligament cells.However,the detailed mechanism underlying immune-bone cell interactions in periodontitis is not fully understood.Here,we performed single-cell RNA-sequencing analysis on mouse periodontal lesions and showed that neutrophil-osteogenic cell crosstalk is involved in periodontitis-induced bone loss.The periodontal lesions displayed marked infiltration of neutrophils,and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production.Among the cytokines expressed in the periodontal neutrophils,oncostatin M(OSM)potently induced RANKL expression in the primary osteoblasts,and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss.Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells,and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism.These findings shed light on the role of neutrophils in bone regulation during bacterial infection,highlighting the novel mechanism underlying osteoimmune crosstalk.

Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%).Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions The present study demonstrated that ca-4F12-E6 was well-tolerated in nonOMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

A 62-year-old man presented with hemoptysis and hoarseness. He was diagnosed with an aortopulmonary fistula due to a thoracic aortic aneurysm rupture and was referred to our department. Emergency in-situ reconstruction of the aorta and pulmonary lobectomy were performed. Nine days postoperative, he developed empyema. Intrapleural urokinase and antibiotic therapy were selected as management instead of a video-assisted thoracoscopic debridement and decortication due to his worsening condition. The treatment was successful, and he was discharged from the hospital without any further complications. This study highlights the benefit of intrapleural administration of urokinase and antibiotics in patients with acute empyema, when surgical treatment is inappropriate.

Takayasu Arteritis causes annuloaortic ectasia and coronary ostial stenosis, which may necessitate open heart surgery. However, pseudoaneurysms are sometimes observed postoperatively, making subsequent treatment difficult. We report thoracic endovascular aortic repair of a pseudoaneurysm of the ascending aorta with an anastomosis of the great saphenous vein in a 61-year-old female with a history of multiple open-heart procedures. Thirty years earlier, she underwent aortic valve replacement and coronary artery bypass surgery for aortic regurgitation, and right coronary ostial stenosis. Eleven years after surgery, an ascending aortic aneurysm was found and Bentall's surgery was performed. Multiple open thoracotomies were subsequently performed. Postoperatively, a pseudoaneurysm was found at the anastomosis between the ascending aorta and the great saphenous vein. The patient was transferred to the emergency room owing to hemoptysis and was diagnosed with a ruptured pseudoaneurysm at the anastomosis of the ascending aorta and the great saphenous vein. By inserting a stent graft into the ascending aorta, we avoided further complications and her prognosis was good. She was discharged on postoperative day 18 and did not experience any end leak for a year. Thoracic endovascular aortic repair in the ascending aorta is a minimally invasive procedure that may be useful for high-risk patients.

In the 2022 revision of the Model Core Curriculum, a new "Educational Strategies and Assessment" section was added as a further development in outcome-based education. By adding a chapter on strategies and evaluation, which is an important element of the curriculum, and linking it to qualities and abilities, we have devised a way for learners and instructors to make use of the Core Curriculum more easily. In addition, 11 example of strategy and assessment cases are included as Good Practice to encourage practical application. However, since these are only examples, we hope this chapter will be further developed as universities create strategies and evaluations that make the most of their unique characteristics.

Low back pain is ranked number one burden of disease and a symptom that afflicts people worldwide. Although many cases of low back pain are considered non-specific, there is no unified agreement on the classification method. Furthermore, the biopsychosocial model is used as an interpretation model for understanding low back pain. Therefore, the effectiveness of acupuncture treatment for low back pain must be verified while clearly identifying the perspective from which low back pain is viewed and considering psychological factors. In this symposium, lectures were given by Akasaka, Inoue, Kikuchi, and Kondo. Akasaka explained specific and non-specific low back pain from the perspective of a physical therapist. Specifically, he presented the classification of low back pain based on structural anatomy of the musculoskeletal system such as facet joint, myofascial, and intervertebral discogenic pain as non-specific low back pain, and explained about the effectiveness of physical therapy. Inoue presented the results of randomized controlled trials of acupuncture treatment in patients with low back and lower limb pain that he had conducted. He also discussed the importance of needling at specific points such as the erector spinae group of muscles after carefully palpating these points. Furthermore, Inoue outlined the effects of needling along nerve pathways in patients with lower limb symptoms. Kikuchi reported the results of a retrospective observational study on the effectiveness of acupuncture in treatment of low back pain by classifying patients according to their movement reproducibility. He well stated that patients with movement reproducibility showed more improvement in low back pain-related quality of life. Kondo elaborated on how psychosocial factors in patients with low back pain could affect the effectiveness of acupuncture treatment. He also reported that the less catastrophic thinking about pain was, the greater effectiveness of acupuncture treatment was. In addition, Kondo also indicated that the lower risk on the Subgrouping for Targeted Treatment Back Screening Tool was, the more easily reduced pain was.We hope that the content of this symposium would serve as a valuable resource for clinical, research, and educational activities starting tomorrow.

Objective: Transvaginal removal of large specimens during laparoscopic hysterectomy can be a complex surgical procedure that poses a risk of organ injury and tissue spillage into the abdominal cavity and is associated with extraction of the specimen and manual morcellation. Our objective was to demonstrate a technique for transvaginal removal of large specimens using the Alexis Contained Extraction System (CES) in laparoscopic hysterectomy. Methods: The technique used for transvaginal removal of large specimens using the Alexis CES was presented in this video. Surgery was performed at a tertiary hospital. Results: Following resection of the specimen during laparoscopic hysterectomy, the Alexis CES was inserted into the abdominal cavity through the umbilical trocar wound. The specimen was placed in a bag to prevent tissue spillage. The ring retractor was guided to the vagina and pulled out transvaginally. By repeatedly turning the ring retractor, tension was applied to the specimen bag, and the vaginal wall was unfolded all around to enable a secure surgical field. During manual morcellation of the specimen in the bag, the retractor was pulled and additionally turned to roll and re-tension the specimen bag when the bag was loosened. The specimen was pushed out of the vagina and safely and effectively extracted without concerns about tissue spillage in the abdominal cavity or related organ injuries. Conclusion The technique for transvaginal removal of large specimens using the Alexis CES enables simple, effective, and safe tissue extraction with contained manual morcellation during laparoscopic hysterectomy.

Objective: There have been reports of health hazards caused by medical devices, cosmetics, quasi-drugs, daily necessities, hygiene products, etc. (health-related products) sold in pharmacies and drugstores. However, the role pharmacists play in dealing with the health hazards caused by health-related products has not been clarified. Therefore, we conducted a survey on the cases of health hazards related to health-related products and the views of pharmacists.Methods: A questionnaire was administered anonymously by email to 601 pharmacists working in community pharmacies or drugstores between December 11 and 20, 2019.Results: The number of valid responses was 585. The breakdown of health hazard cases where pharmacists counseled customers were 60 for medical devices, 31 for cosmetics, 18 for quasi-drugs, 9 for hygiene products, and 20 for daily necessities and others. Of those 138 cases, 19 cases of medical devices were estimated to have an intermediate risk as a health hazard, and the other 119 cases were all classified as low. Of the cases that the pharmacists were not approached for help, but were aware of, 57 were medical devices (21 high, 31 intermediate, 5 low), 44 were cosmetics (12 intermediate, 32 low), 12 were quasi-drugs (7 intermediate, 5 low), 7 were hygiene products (7 low), and 64 were daily necessities and others (26 high, 34 intermediate, 4 low). With regard to health-related products, 95% of the respondents indicated that they had responded to customer questions with advice.Conclusion: Our results show that there are various cases that could develop into health hazards due to health-related products, and most respondents felt a need to alert the public. As such, pharmacists and other staffs in drugstores will continue to provide health support functions to their customers by advising them on not only pharmaceuticals but also these health-related products.

INTRODUCTION: The pathophysiology and mechanism of in-stent restenosis (ISR) after implantation of second-generation drug-eluting stents (DESs) are not fully clear. We compared the morphological characteristics of ISR between first- and second-generation DESs using frequency domain optical coherence tomography (OCT). METHODS: Patients who underwent follow-up coronary angiography (CAG) after first-generation (CYPHER™ and TAXUS™) and second-generation (Nobori®, PROMUS Element™, Resolute Integrity and XIENCE) DES implantations were examined. ISR was defined as lesions of over 50% diameter stenosis at follow-up CAG. Frequency domain OCT was performed at the time of revascularisation of ISR. Tissue morphology was assessed at minimum lumen area. OCT images of DESs at both early (≤ 1 year) and late (> 1 year) phase follow-up were compared. RESULTS: On qualitative OCT assessment, the ratios of homogeneous, layered, heterogeneous without-attenuation and heterogeneous with-attenuation morphologies were 57.1%, 17.1%, 20.0% and 5.7%, respectively, for second-generation DES ISR (n = 35), and 16.7%, 25.0%, 25.0% and 33.3%, respectively, for first-generation DES ISR (n = 36). At late phase follow-up, homogeneous morphology was significantly more common for second-generation DES ISR compared to first-generation DES ISR (first-generation: 8.0% vs. second-generation: 50.0%; p < 0.01) while heterogeneous with-attenuation morphology was significantly more common for first-generation DES ISR (first-generation: 44.0% vs. second-generation: 5.6%; p < 0.01). CONCLUSION Homogeneous tissue morphology was more frequently found for second-generation than first-generation DES ISR, especially in the late phase. This suggested that neointimal hyperplasia was the main mechanism in second-generation DES ISR, and that the neointima was stabilised, much like in bare metal stent implantation.
Aged ; Constriction, Pathologic ; pathology ; Coronary Angiography ; Coronary Restenosis ; diagnostic imaging ; pathology ; Coronary Vessels ; diagnostic imaging ; pathology ; surgery ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Incidence ; Male ; Metals ; Middle Aged ; Neointima ; Retrospective Studies ; Tomography, Optical Coherence

We previously described a rare case of anaphylaxis presumably induced by carminic acid in cochineal dye used as a food additive. In this study, highly pure carminic acid was added to an albumin-containing buffer at various concentrations, followed by serial dilution. Varying the mixing ratio of carminic acid and albumin affected the extent of histamine release from passively sensitized basophils. Similar basophil histamine release occurred with carminic acid-globulin solutions. These results provide experimental evidence indicating that basophil activation is dependent on hapten (carminic acid) and carrier (protein) interaction.
Anaphylaxis ; Basophils ; Carmine ; Food Additives ; Histamine Release ; Hypersensitivity ; In Vitro Techniques