The Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine (founding director; CEO Hideoki Ogawa), was founded in 2002, supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. Since 2013, we have been focusing on intractable itch supported by Strategic Research Foundation Grant-aided Project for Private Universities from MEXT. We have been conducting research on elucidating the pathogenesis of intractable itch and developing preventive and therapeutic methods, and the results of our research have been highly evaluated both in Japan and overseas. After the end of the above support project, Asia’s first itch research center, Juntendo Itch Research Center (JIRC), was established at our institute to promote research in this field and to return the results of our research to society. In addition, our institute has held four academic symposiums about “Aiming to overcome intractable itch” since 2014 in order to develop itch research in Japan. The 5 ^th Symposium, which was the first since JIRC was established, was held on December 7, 2019. In this “What’s New from Juntendo University, Tokyo”, we report selected aspects of the 5 ^th Symposium and advances in the field of itch research.

　The Department of Neurosurgery at Juntendo University was established in 1968 by Prof. Shozo Ishii. This was followed by the appointment of Prof. Kiyoshi Sato as the second professor in 1988, and then Prof. Hajime Arai as the third in 2002. Currently, nearly 1,000 surgeries are performed at the neurosurgical department only, with the total number performed by Juntendo-affiliated hospitals amounting to approximately 4,300. At present, the Neurosurgical Group of Juntendo University has 197 members, of whom 186 are board certified neurosurgeons. Ever since the time of Prof. Ishii, our institution has been accepting many new members every year without interruption, and they continued to carry out the main three domains of neurosurgical activities: clinical work, research, and education in a well-balanced manner, and moving forward with a spirit of continued progress into the next 50 years.

　Antimicrobial peptides (AMPs) represent the first line of host defense against invading microorganisms. Cathelicidin family of AMPs has been identified in various mammalian species, and LL-37 is the only cathelicidin identified in humans. In addition to its antimicrobial and lipopolysaccharide (LPS)-neutralizing activities, LL-37 exhibits diverse biological activities, including regulation of inflammatory responses. Recently, we have evaluated the effect of LL-37 on a murine cecal ligation and puncture (CLP) septic model. The results indicated that LL-37 exhibits multiple protective actions on septic mice; firstly, LL-37 improves the survival of CLP mice by suppressing the macrophage pyroptosis that induces the release of pro-inflammatory cytokines (such as IL-1β) and augments inflammatory reactions in sepsis; secondly, LL-37 induces the release of neutrophil extracellular traps (NETs) with potent bactericidal activity, and protects mice from CLP-induced sepsis; thirdly, LL-37 stimulates neutrophils to release antimicrobial microvesicles (ectosomes), thereby improving murine sepsis. These observations suggest that LL-37 protects CLP septic mice through at least three mechanisms, i.e., the suppression of pro-inflammatory macrophage pyroptosis and the release of antimicrobial NETs (induction of NETosis) and ectosomes from neutrophils. Thus, LL-37 can be a promising therapeutic candidate for sepsis because of its multiple functions, including the modulation of cell death (pyroptosis and NETosis) and release of antimicrobial NETs and ectosomes as well as its own bactericidal and LPS-neutralizing activities.

　I divide my career as a neurosurgeon into three stages.

　The first stage is from entering Professor Dr. Shozo Ishi’s department of Neurosurgery, Juntendo University till becoming a board certified neurosurgeon. During this stage I did research on delayed neuronal death in hippocampus CA1 after short-term ischemia at National Institutes of Health in the United States. I reported that disinhibition to the CA1 neurons induced by derangement in GABA metabolism was related to delayed neuronal death in the hippocampus CA1.

　The second stage is Matsumura General Hospital. I developed my neurosurgical techniques at this stage under Professor Dr. Kiyoshi Sato’s direction. Dr. Sato also offered me opportunities to do clinical and experimental researches at Juntendo University. I assumed the post of the director of Matsumura General Hospital and had a very hard time maintaining functions of the hospital because the new doctor clinical training system just started.

　The third stage is Juntendo University Urayasu Hospital. Since Dr. Masanori Ito, former professor of Neurosurgery and I moved to Juntendo University Urayasu Hospital, new surgical equipment and techniques have been introduced. Dr. Ito started spinal surgery under microscope. Dr. Senshu Nonaka, an endovascular specialist introduced coil embolization for cerebral aneurysms and thrombectomy for acute stroke. Dr. Hisato Ishii, associate professor began endoscopic transnasal removal for pituitary adenomas. Dr. Takamoto Suzuki, assistant professor started endoscopic third ventriculostomy for non-communicating hydrocephalus. Advances in surgical technology have made us develop the quality in neurosurgical practices. I was given opportunities to work for the doctor clinical training center and the medical safety. I was impressed by the young residents growing well through clinical training. We proposed “Medical Team Approach” for the trouble cases that are difficult to solve by only the medical staffs in charge. I started Brain Dock in the department of General Medicine in 2017 and wish to spread Brain Dock in order to prevent stroke and dementia.

　I feel very happy to be back to Juntendo and reach retirement at Urayasu Hospital which is one of the hospitals in my alma mater, Juntendo University. I wish further development of Juntendo University in the medical service and research.

　Since its approval for reimbursement in 1974 in Japan, the artificial pacemaker (PM) for the treatment of bradycardia has come into wide clinical use. In the years that have followed, remarkable structural and functional progress has been made with PMs and the associated lead systems, and the reliability of the PM as an implanted artificial device has been established. In 1996, the implantable cardioverter-defibrillator (ICD) became the next reimbursed device, approved as a therapy for fatal ventricular arrhythmias. ICD have contributed to improved prognosis in patients with these arrhythmias through preventing sudden cardiac death. Cardiac resynchronization therapy (CRT) was recognized as the next effective modality for drug-refractory chronic heart failure. CRT became reimbursable in 2004, followed by CRT with defibrillator function in 2006. Large-scale randomized trials and meta-analyses have confirmed the reduced overall mortality with CRT. Currently, these implanted devices are essential therapeutic modalities, collectively known as cardiac implantable electrical devices (CIEDs), for indications from symptomatic bradycardia and fatal ventricular tachyarrhythmia to severe chronic heart failure. As CIEDs continue to evolve, we should always be updating relevant knowledge and ensuring appropriate indications for CIED implantation.

Objective: This study examined the prevalence of and factors affecting normal weight obesity (NWO) among women aged under 40 years old. NWO was having a normal BMI but a high body-fat percentage (BFP).

Materials and Methods: We recruited 399 participants aged 18-39 during a health checkup and surveyed them about lifestyle patterns, height, weight, body composition, and girth and visceral fat area. Participants were divided into three. Those with a BMI of <25 and a BFP of <30 were classified as non-obese, a BMI of <25 and a BFP of ≥30 as NWO, a BMI of ≥25 and a BFP of ≥30 as obese. The analysis was conducted on NWO (97) and non-obese (262) groups.

Results: NWO prevalence ranged from 20% to 30% across the three age groups. NWO participants had lower values for segmental lean body mass, particularly in lower limb, and higher values for abdominal girth and visceral fat area. Among participants aged 30-39, those with NWO had higher values for triglycerides and LDL cholesterol and lower values for HDL cholesterol. Regarding lifestyle factors, among those aged 30-39, NWO was associated with past weight fluctuation, respectively. In the latter age group, a gain of more than 10 kg since the age of 20 was associated with a 13-fold increase in the odds for NWO.

Conclusions: Results suggest that for women under 40 years, detecting NWO early and guidance on effective lifestyle and exercise are necessary.

Objective: Recently, there has been a worldwide increase in non-B and non-C hepatocellular carcinoma (NBNC-HCC), which are negative for both markers of hepatitis B and C virus infection. Here, we investigated the role of phosphatase and tensin homolog (PTEN), a negative regulator of the phosphatidylinositol-3 kinase pathway in the development of NBNC-HCC.

Materials: A total of 14 patients who received hepatectomy because of NBNC-HCC (NBNC group) were analyzed retrospectively. Nine patients who underwent hepatectomy for liver metastasis of colorectal cancer, were analyzed as the control.

Methods: Expression of PTEN and p62, which is a marker of autophagic degradation, was evaluated in background liver, peritumoral region, and tumor by immunohistochemical analysis. Recurrence rate up to 7 years post-surgery was evaluated.

Results: The expression of PTEN in the NBNC group was significantly decreased in all regions compared to the control, and it was notably reduced in the tumor. In contrast, the expression of P62 in the tumor of patients of the NBNC group was significantly increased. Recurrence rate at 7 years in NBNC group reached 85%, and recurrence time post-surgery was significantly longer in survivors with strong expression of PTEN in the peritumoral region.

Conclusions: These findings indicate that the expression of PTEN decreases in NBNC chronic liver injury, which is possibly related to inhibition of autophagy as a trigger of carcinogenesis and the intrahepatic recurrence of NBNC-HCC.