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Masato Matsuo,1,2 Sho Ichioka,1 Akiko Harano,1 Yuji Takayanagi,1 Masaki Tanito1 1Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo, Japan; 2Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, JapanCorrespondence: Masato Matsuo, Department of Ophthalmology, Shimane University Faculty of Medicine, Enya 89-1, Izumo, Shimane, 693-8501, Japan, Tel +81-853-20-2284, Fax +81-853-20-2278, Email matsuondmc@gmail.comIntroduction: Although ab-interno trabeculotomy-related (goniotomy-related) surgeries has a favorable safety profile, cyclodialysis cleft refractory to conservative management could occur, thereby requiring additional surgical treatment. External and, more recently, internal cycloplexy have been attempted to treat cyclodialysis clefts with hypotony maculopathy, however the traditional methods require conjunctival or scleral incisions and have been inappropriate for glaucoma patients who need to undergo future trabeculectomy. Therefore, we report two cases who underwent a novel reliable technique for suture fixation of the detached ciliary body onto the original scleral bed directly through the intraocular approach without conjunctival or scleral incision, minimally invasive direct internal cyclopexy, in the management of goniotomy-related cyclodialysis cleft with hypotony maculopathy.Case Description: Goniotomy-related cyclodialysis cleft exceeded 45° and vision-threatening hypotony maculopathy was observed in two eyes in two patients with normal tension glaucoma and myopia gravis without a prior history of trauma who had undergone Kahook Dual Blade goniotomy combined with cataract surgery. The patients were followed conservatively for a while, however the cyclodialysis clefts and hypotony maculopathies did not resolve. Therefore, a 72-year-old man underwent minimally invasive direct internal cyclopexy on postoperative day 65 after the goniotomy, and another 67-year-old man underwent minimally invasive direct internal cyclopexy on postoperative day 149. In both cases, topical antibiotic and steroid eye drops were prescribed postoperatively. The cyclodialysis clefts were repaired successfully; however, the latter patient developed delayed-onset acute transient ocular hypertension 33 days after minimally invasive direct internal cyclopexy and required glaucoma medications. The hypotony maculopathies resolved approximately 3 months after suturing, and eventually visual acuity improved from preoperative levels and good intraocular pressure control was achieved in both. No further postoperative complications have been observed to date.Conclusion: We successfully managed two cases of goniotomy-related cyclodialysis cleft with hypotony maculopathy using minimally invasive direct internal cyclopexy.Keywords: cyclopexy, cyclodialysis cleft, hypotony maculopathy, ab-interno trabeculotomy, surgical complication

Masahito Katsuki,1,2 Maiko Nanri,3 Yuki Miyakoshi,4 Shuto Gobo,4 Akihito Koh,2 Shin Kawamura,2 Senju Tachikawa,2 Ryo Matsukawa,2 Kenta Kashiwagi,5 Mitsuhiro Matsuo,6 Fuminori Yamagishi7 1Department of Neurosurgery and Headache Outpatient, Japanese Red Cross Suwa Hospital, Nagano, Japan; 2Department of Neurosurgery, Itoigawa General Hospital, Niigata, Japan; 3Nurse-Senka, SMS Corporation, Tokyo, Japan; 4Creatone, Regnition, Saitama, Japan; 5Department of Neurology, Itoigawa General Hospital, Niigata, Japan; 6Department of Anesthesiology, Toyama University Hospital, Toyama, Japan; 7Department of Surgery, Itoigawa General Hospital, Niigata, JapanCorrespondence: Masahito Katsuki, Department of Neurosurgery, Japanese Red Cross Suwa Hospital, 5-11-50, Kogandori, Suwa, Nagano, 392-0027, Japan, Tel/Fax +81-0266-52-6111, Email ktk1122nigt@gmail.comIntroduction: Headache is a common public health problem, but its burden could be avoided by raising headache awareness and the appropriate use of acute medication and prophylactic medication. Few reports on raising headache awareness in the general public have been reported, and there are no reports on headache awareness campaigns through social networking services (SNS), or social media, in Japan. We prospectively performed a headache awareness campaign from March 2022 through 2 SNS, targeting nurse and wind instrumental musicians, because they are with high headache prevalence.Methods: Through the 2 SNS, the article and video were distributed, respectively. The article and video described the 6 important topics for the general public about headaches, which were described in the Clinical Practice Guideline for Headache Disorders 2021. Just after reading or watching them as e-learning, we performed online questionnaire sheets to investigate the awareness of the 6 topics through the 2 SNS. The awareness of the 6 topics before and after the campaign was evaluated.Results: In the SNS nurse-senka, we obtained 1191 responses. Women comprised 94.4%, and the median (range) age was 45 (20 to 71) years old. Headache sufferers were 63.8%, but only 35.1% had consulted doctors. In the SNS Creatone, we got the response from 134 professional musicians, with 77.3% of women. The largest number of respondents were in their 20s (range 18– 60 years old). Headache sufferers were 87.9%. Of them, 36.4% had consulted doctors, 24.2% were medication-overuse headache. The ratios of individuals who were aware of the 6 topics significantly increased from 15.2%-47.0% to 80.4– 98.7% after the online questionnaire in both SNS (p < 0.001, all).Conclusion: E-learning and online survey via SNS can improve headache awareness.Keywords: awareness, education, medication-overuse headache, migraine, online, prevention, social networking services, social media

Masato Matsuo,1 Yotaro Matsuoka,2 Masaki Tanito1 1Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo City, Shimane, 693-8501, Japan; 2Division of Ophthalmology, Matsue Red Cross Hospital, Matsue, Shimane, 690-8506, JapanCorrespondence: Masato Matsuo, Department of Ophthalmology, Shimane University Faculty of Medicine, Enya 89-1, Izumo, Shimane, 693-8501, Japan, Tel +81-853-20-2284, Fax +81-853-20-2278, Email mmpeaceful@yahoo.ne.jpAbstract: Current therapeutic approaches for glaucoma aim to reduce intraocular pressure (IOP), which is the only available and reliable strategy proven to control the risk of disease development and progression. Omidenepag isopropyl (OMDI) is a novel topical ocular hypotensive agent that was launched onto the market for the treatment of glaucoma and ocular hypertension (OHT). After topical instillation and during corneal penetration, OMDI is converted into the active metabolite omidenepag (OMD), which behaves as a non-prostaglandin, selective E-prostanoid subtype 2 (EP2) receptor agonist. The topical administration of 0.002% OMDI once-daily (QD) possesses a 20– 35% IOP-lowering effect, comparable to that of prostaglandin analogs targeting F-prostanoid (FP) receptor QD, which are the current first-line for pharmaceutical reduction of IOP. However, the mechanism of action and adverse events (AEs) of OMDI are different from those of FP receptor agonists. OMDI reduces IOP by enhancing both conventional trabecular and uveoscleral outflow facilities without complications of prostaglandin-associated periorbitopathy (PAP) seen with FP receptor agonists. Moreover, OMDI was also effective and well-tolerated in non-/poor responders to latanoprost and showed a stable IOP-lowering effect for one year, and its concomitant use with timolol enhanced the IOP-lowering effect. OMDI demonstrated acceptable safety and tolerability with good adherence and can be used in almost every patient. However, OMDI has some AEs such as conjunctival hyperemia, corneal thickening, macular edema/cystoid macular edema and ocular inflammation. Moreover, OMDI is contraindicated in patients who are allergic to the product, in aphakic or pseudophakic eyes, and in combination with tafluprost eye drops. If used appropriately in the right patients, OMDI could be an effective treatment option for glaucoma and OHT as a first-line alternative to FP agonists. Here, we summarize the results of clinical studies of OMDI and discuss its efficacy and patient tolerability in glaucoma and OHT in this review.Keywords: omidenepag, EP2 receptor, intraocular pressure, adverse event, prostaglandin, glaucoma

Masato Matsuo, Yuina Inomata, Nana Kozuki, Masaki Tanito Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo, Shimane, 693-8501, JapanCorrespondence: Masato MatsuoDepartment of Ophthalmology, Shimane University Faculty of Medicine, Enya 89-1, Izumo, Shimane, 693-8501, JapanTel +81-853-20-2284Fax +81-853-20-2278Email matsuohp@med.shimane-u.ac.jpPurpose: To investigate the prevalence, locations, and characteristics of peripheral anterior synechiae (PAS) formation after microhook ab-interno trabeculotomy (μLOT), a minimally invasive glaucoma surgery, using a 360-degree gonio-camera, gonioscope GS-1 (NIDEK Co., Gamagori, Japan).Subjects and Methods: A total of 105 consecutive eyes of 75 subjects with open-angle glaucoma were analyzed. The eyes had undergone μLOT or combined μLOT and cataract surgery as an initial glaucoma surgery. Postoperative PAS formation was evaluated in 16 iridocorneal angle images with the best focus covering 360 degrees in each eye.Results: Compared to baseline, at 225± 226 days postoperatively, the intraocular pressure and number of antiglaucoma medications decreased significantly (p< 0.01, respectively). PAS developed in 86% of eyes. The mean number of iridocorneal angle images that showed PAS in all eyes was 4.1 (26%) in the total circumference, 3.1 (39%) within the μLOT incision, and 1.0 (13%) outside of the μLOT incision; the rate was significantly (p< 0.0001) higher within the incision than outside of the incision. Moreover, the higher total PAS rate and that within the incision may be associated with later postoperative days (p=0.01 and 0.004, respectively), that outside of the incision with μLOT alone rather than the combined surgery, and with shallower preoperative central anterior chamber depth (p=0.048 and 0.04, respectively), calculated by the mixed-effect model.Conclusion: The current results showed the characteristics of PAS formation after μLOT using 360-degree gonio-images, and the formation rate was significantly higher within the μLOT incision. The PAS within and outside of the incision had different causes.Keywords: peripheral anterior synechiae, microhook ab-interno trabeculotomy, minimally invasive glaucoma surgery, open-angle glaucoma, 360-degree gonio-camera

The cell population within the periodontal ligament (PDL) tissue is remarkably heterogeneous1. Fibroblasts, a mixed population of cells, are the main cellular component of the PDL and the cell type most often studied for periodontal regeneration. Osteoblasts and osteoclasts are found on the bone side, while fibroblasts, macrophages, undifferentiated adult/mesenchymal stem cells, neural elements, and endothelial cells are found throughout the PDL. Epithelial rests of Malassez cells and cementoblasts are focused near the root surface. PDL tissue also includes loose connective tissue between dense fiber bundles that contain branches of the periodontal blood vessels and nerves2. The complexity of the PDL tissue, with its various cell types and cell progenitor components, explains the challenges involved in therapies to restore tissue following periodontal disease. Cementoblasts, osteoblasts, and endothelial cells must migrate, differentiate, and coordinately interact with a variety of soluble mediators to regenerate the periodontium3. Stem cells located in the PDL tissue are key contributors to this process4. Stem cells in the PDL are important not only for formation and maintenance of the tissue but also for repair, remodeling, and regeneration of adjacent alveolar bone and cementum5. Our laboratory has shown that progenitor cells isolated from PDL tissue by selection with cell surface markers STRO-1+ and CD146+ are capable of differentiating into chondrogenic, osteogenic, and adipogenic phenotypes under appropriate culture conditions

The cell population within the periodontal ligament (PDL) tissue is remarkably heterogeneous1. Fibroblasts, a mixed population of cells, are the main cellular component of the PDL and the cell type most often studied for periodontal regeneration. Osteoblasts and osteoclasts are found on the bone side, while fibroblasts, macrophages, undifferentiated adult/mesenchymal stem cells, neural elements, and endothelial cells are found throughout the PDL. Epithelial rests of Malassez cells and cementoblasts are focused near the root surface. PDL tissue also includes loose connective tissue between dense fiber bundles that contain branches of the periodontal blood vessels and nerves2. The complexity of the PDL tissue, with its various cell types and cell progenitor components, explains the challenges involved in therapies to restore tissue following periodontal disease. Cementoblasts, osteoblasts, and endothelial cells must migrate, differentiate, and coordinately interact with a variety of soluble mediators to regenerate the periodontium3. Stem cells located in the PDL tissue are key contributors to this process4. Stem cells in the PDL are important not only for formation and maintenance of the tissue but also for repair, remodeling, and regeneration of adjacent alveolar bone and cementum5. Our laboratory has shown that progenitor cells isolated from PDL tissue by selection with cell surface markers STRO-1+ and CD146+ are capable of differentiating into chondrogenic, osteogenic, and adipogenic phenotypes under appropriate culture conditions

Background: The monocyte-to-lymphocyte ratio (MLR) has been reported as a useful prognosticator in various types of cancers. We studied the usefulness of MLR as a prognosticator for head and neck squamous cell carcinoma (HNSCC) in patients with oropharyngeal, hypopharyngeal, and laryngeal cancer who received radical concurrent chemoradiotherapy (CRT) or bioradiotherapy (BRT). Materials and Methods: This study included 76 HNSCC patients diagnosed between January 2015 and April 2020. We obtained their haematological records within one month before radiotherapy and calculated the MLR. Kaplan-Meier method and Cox proportional hazard model were performed to evaluate the association of MLR with locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS). Results: The Kaplan-Meier survival analysis for MLR showed a significant difference (p = 0.0326) in OS. Univariate and multivariate analysis revealed that the lower MLR group was associated with better OS (hazard ratio [HR] = 0.345, 95 % confidence interval [CI] = 0.124-0.960, p = 0.042 and HR = 0.305, 95% CI = 0.102-0.916, p = 0.034, respectively). Multivariate analysis also revealed that N 2-3 was significant independent predictor of LFRS and PFS (HR = 4.47, 95% CI = 1.43-14.0, p = 0.0286 and HR = 4.94, 95% CI = 1.84-13.2, p < 0.01, respectively). Conclusion: MLR was useful as a prognostic predictor for OS in patients with HNSCC who received radical concurrent CRT or BRT. MLR may be more reflective of OS than of LRFS or PFS. [ABSTRACT FROM AUTHOR]

We examined the role of spatiotemporal visualization of stereotactic body radiotherapy (SBRT) for cardiac radioablation to the cavotricuspid isthmus (CTI) based on both 13C labeled pyruvate metabolic imaging by Dynamic Nuclear Polarized (DNP) and redox reaction by in vivo DNP MRI compared with routine MRI. First, four mini pigs underwent electrophysiology assessment using electroanatomical mapping (EAM) before and 3 months after SBRT with single-fraction doses of 25Gy. Routine MR examination, including diffusion-weighted, dynamic Gd-enhanced, spectroscopy, and T2-weighted images were performed before and 3 months after SBRT. Second, the dynamics of 13C compound pyruvate for metabolic imaging by DNP MRI (SpinAligner), free radical imaging by low filed type of in vivo DNP MRI and routine MR (1.5T) were performed on the four mice before and 3 days and 7 days after single-fraction doses of 25Gy and 10Gy to whole heart. EAM visualized the irradiated site and confirmed clockwise conduction block across the CTI after SBRT. Both Abnormal signals which reflect the damaged myocardium on T2WI and DWI images and late gadolinium enhancement which reflects fibrosis could not be detected by routine MRI in four mini pigs. Pyruvate metabolic imaging by DNP MRI showed a significant increase in 13C lactate/pyruvate ratio after SBRT at all time points compared to before SBRT. In vivo DNP MRI signals were decreased depending on prescribed irradiation dose and days after SBRT. The mice treated by 10Gy irradiation showed a decrease on day 3 in whole heart. The mice treated by 25Gy irradiation showed a marked decrease on day 3 and a further decrease on day 7 in whole heart. Pyruvate metabolic imaging by DNP and redox reaction by in vivo DNP MRI could be useful for the evaluation of early response to the cardiac damaged after SBRT for cardiac radioablation to CTI. [ABSTRACT FROM AUTHOR]

Tomohiro Matsuo, Yasuyoshi Miyata, Yuji Sagara, Yoshikazu Higami, Shohei Tobu, Manabu Matsuo, Mitsuru Noguchi, Isao Shimokawa, Hiroshi Kanetake, Hideki Sakai Department of Nephro-Urology, Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan Purpose: The renoprotective function of the angiotensin II type 1 receptor blocker (ARB) is well-known in various studies, including the animal model of renal failure. However, detailed temporal changes of pathological and molecular findings after unilateral nephrectomy are not fully understood. The main purpose of this study was to clarify the renoprotective effects and pathological changes induced by the ARB in rat-remnant kidney (RK) tissues after unilateral nephrectomy, but not after a 5/6 nephrectomy. Methods: Telmisartan, which is structurally and functionally unique among ARB, was used in this study. Three rat groups were examined: A) no ARB administrated (RK, n=21); B) continuous subcutaneous infusion of an ARB administrated (RK-ARB, n=21); and C) a sham-operated group (Sham). Renal function was evaluated by blood urea nitrogen (BUN) levels and creatinine clearance (Ccr). Fibrosis was evaluated by hydroxyproline levels and Masson's trichrome staining. Expressions of angiotensin II type 1 receptor (AT1R) and transforming growth factor beta (TGF-ß) were investigated by real-time polymerase chain reaction and Western blotting. Results: There was no significant difference regarding body and kidney weight or pathological features evaluated by hematoxylin and eosin staining between the RK and RK-ARB groups. The Ccr in the RK group was significantly lower than that in the Sham group (P