Background: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe. Methods: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass. Results: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass. Conclusion This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.

Objective: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. Methods: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30–30.6 Gy in 15–17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50–50.4 Gy in 25–28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. Results: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9–52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%–88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. Conclusion The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

Objective: In this study, we investigated the occurrence of skin damage following the initiation of low-dose lamotrigine.Methods: We retrospectively analyzed the incidence of skin disorders within 8 weeks of the start of lamotrigine administration, prescribing for 3 years from July 2014 to June 2016.In addition, we also confirmed the onset time of skin disorders in the low- and normal-dose groups.Results: The incidence of skin damage was 7.7 and 24.6 % in the low- and normal-dose lamotrigine start groups, respectively. The onset of skin disorders was relatively early in the normal-dose lamotrigine start group.On the other hand, no tendency was found in the low-dose lamotrigine start group because the number of cases was small.Conclusion: The initiation of low-dose lamotrigine and extension of introduction period might reduce the onset of early skin damage.

Objective：We aimed to examine the clinical validity of the Wechsler Adult Intelligence Scale (WAIS)-III for resuming automobile driving in patients with brain injury.Methods：A total of 71 patients who requested to resume driving after brain injuries were included, with 43 and 28 patients categorized in the resumed and non-resumed driving groups, respectively. Statistical analysis was performed by comparing the sub-items of the WAIS-III between the groups. The reference value of accurate determinants was estimated using receiver operating characteristic (ROC) curve analysis.Results：The results of the ROC curve analysis showed that the areas under the curves for full-scale intelligence quotient (FIQ), performance IQ (PIQ), and perceptual organization index (POI) were higher than 0.7 (with moderate predictive accuracy). The cutoff values were as follows with high specificity and low sensitivity：PIQ, 98.5；FIQ, 107；and PO, 107.Conclusion：The cutoff values of the FIQ, PIQ, and POI of the WAIS-III were inadequate predictors for resumption of driving in patients with brain injury. However, if patients had all three scores less than 70, it was suggested that they refrain from driving.

Objective：We aimed to examine the clinical validity of the Wechsler Adult Intelligence Scale (WAIS)-III for resuming automobile driving in patients with brain injury.Methods：A total of 71 patients who requested to resume driving after brain injuries were included, with 43 and 28 patients categorized in the resumed and non-resumed driving groups, respectively. Statistical analysis was performed by comparing the sub-items of the WAIS-III between the groups. The reference value of accurate determinants was estimated using receiver operating characteristic (ROC) curve analysis.Results：The results of the ROC curve analysis showed that the areas under the curves for full-scale intelligence quotient (FIQ), performance IQ (PIQ), and perceptual organization index (POI) were higher than 0.7 (with moderate predictive accuracy). The cutoff values were as follows with high specificity and low sensitivity：PIQ, 98.5；FIQ, 107；and PO, 107.Conclusion：The cutoff values of the FIQ, PIQ, and POI of the WAIS-III were inadequate predictors for resumption of driving in patients with brain injury. However, if patients had all three scores less than 70, it was suggested that they refrain from driving.

Objective: The practices pertaining to hereditary breast and ovarian cancer (HBOC) in Japan have been rapidly changing owing to the clinical development of poly(ADP-ribose) polymerase inhibitors, the increasing availability of companion diagnostics, and the broadened insurance coverage of HBOC management from April 2020. A questionnaire of gynecologic oncologists was conducted to understand the current status and to promote the widespread standardization of future HBOC management. Methods: A Google Form questionnaire was administered to the members of the Japan Society of Gynecologic Oncology. The survey consisted of 25 questions in 4 categories: respondent demographics, HBOC management experience, insurance coverage of HBOC management, and educational opportunities related to HBOC. Results: A total of 666 valid responses were received. Regarding the prevalence of HBOC practice, the majority of physicians responded in the negative and required human resources, information sharing and educational opportunities, and expanded insurance coverage to adopt and improve HBOC practice. Most physicians were not satisfied with the educational opportunities provided so far, and further expansion was desired. They remarked on the psychological burdens of many HBOC managements. Physicians reported these burdens could be alleviated by securing sufficient time to engage in HBOC management, creating easy-to-understand explanatory material for patients, collaboration with specialists in genetic medicine, and educational opportunities. Conclusion Gynecologic oncologists in Japan are struggling to deal with psychological burdens in HBOC practice. To promote the clinical practice of HBOC management, there is an urgent need to strengthen human resources and improve educational opportunities, and expand insurance coverage for HBOC management.

Ninety percent of the crude drugs consumed in Japan depend on imports. Recently, the Japanese government has been promoting the domestic production of crude drugs. We investigated the history and current situation of the cultivation of medicinal plants and the production of crude drugs in the Tohoku region, where the 71st annual meeting of the Japan Society for Oriental Medicine was held in August 2021. In the Tohoku region, the cultivation of medicinal plants expanded after the Kyoho era of the Edo period. Several medicinal plants in this region have been successfully cultivated and distributed as local specialty products and are being preserved (e.g., Panax ginseng in Aizu, Carthamus tinctorius in Dewa). In some other areas, cultivation has just begun. In each cultivation area, a contractual relationship was established in which local governments, cultivation experts, farmers, Kampo-related associations, and pharmaceutical companies collaborated to continue and expand the cultivation business. To generate revenue, they have been trying to find sales channels not only for crude drugs but also for foods, cosmetics, textiles, and processed products. Although many issues remain to be solved in the distribution of medicinal plants as the source of crude drugs, this survey clarified the ingenuity of medicinal plant cultivation in various areas of the Tohoku region. The results of the investigation are available as videos on the website for members of the Japan Society for Oriental Medicine.

Objective: Two types of symbols have been established as industry standards in terms of two-dimensional (2D) symbols with prescription information: one for objects to be printed on prescriptions and the other for electronic versions of medication diaries. However, no studies have investigated the system for using 2D symbols in pharmacies and hospitals/clinics as well as the quality of the information actually stored in these 2D symbols. Therefore, we conducted a survey to clarify the current status and problems pertaining to prescription information sharing via 2D symbols.Methods: We distributed questionnaires to community pharmacies through the Fukui Pharmaceutical Association and asked them to cooperate with us during the survey. The list of items in the survey　included the installation status of devices necessary for reading 2D symbols at each pharmacy, receipt computer in use, and status of the support issued by hospitals/clinics for reading 2D symbols. At the same time, we received 2D symbols created by community pharmacies and conducted reading tests to examine issues related to the collection of prescription information via 2D symbols at medical institutions.Results: The response rate for the survey was 21.8%. Among the 57 stores that responded to the survey, 26 (45.6%) answered that they could read prescription symbols, and 22 of them had actually used the system till date. In addition, 38 community pharmacies were able to provide the 2D symbols for medication diaries. Of the 30 provided symbols for medication diaries, 16 (53.3%) could be read as Japanese data by the barcode reader used.Conclusions: It has become clear that the 2D symbols with stored prescription information are not being completely utilized at present, as both community pharmacies and hospitals/clinics face several issues such as hardware maintenance, software updates, and time and effort required for the usage.

This study aimed to clarify the effects of carbohydrate mouth rinse on exercise performance. We examined the effect of mouth rinse on fatigability. Thirty healthy male college students completed three trials with non mouth rinse (CON), mouth rinse intervention of 6% glucose (GMR), and artificial sweetener (PLA). Handgrip exercise was performed as a fatigue task. The subjects performed a 10-seconds maximal voluntary contraction (MVC) followed by a 40% MVC rhythmic grasping movement for 14 per minutes, followed by a 4-seconds rest. This set of exercises was performed for a total of ten sets. Mouth rinse was performed from the 5th set to the 10th set. The subjects were divided into three groups: L, M, and S, according to the degree of decrease in MVC due to fatigue in CON. The effect was evaluated using the rate of change in MVC after the mouth rinse. The evaluation was performed for each trail and group. In the L group, mouth rinse significantly improved the rate of change of MVC compared with the other trials (GMR vs. CON: P = 0.002; PLA vs. CON: P = 0.042). A significant trend was observed in the M (GMR vs. CON: P = 0.062), but not in the S. In conclusion, the effects of mouth rinse differed depending on fatigability in isometric hand grip performance, with mouth rinse inhibiting the decrease of motor fatigue. In addition, it was suggested that the sweetness of carbohydrates may have an effect on mouth rinse.