Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

BACKGROUND: Meals are provided at nursery schools for Japanese preschool children, and this may result in different energy and nutrient intakes on weekdays and weekends. The purpose of this study was to obtain basic information for public nutrition policies in early childhood by examining differences in energy and nutrient intakes of preschool children between weekdays and weekends using meal categories such as breakfast, lunch, dinner, and snacks. METHODS: Energy and nutrient intakes were examined in 761 Japanese preschool children (423 boys, 338 girls) aged 3-6 years attending childcare facilities in seven regions in Japan. Data collection was based on non-consecutive four-day dietary records (two weekdays, two weekend days) in 2019 or 2020. Energy and nutrient intake by meal category were compared using a generalized linear mixed model adjusted for demographic factors. RESULTS: Total energy intake was significantly higher on weekdays for boys (1,478 vs. 1,415 kcal) and girls (1,349 vs. 1,296 kcal) (both P < 0.001). Weekday lunches had higher protein content and essential micronutrients such as potassium, iron, vitamins, and lower fat, saturated fatty acids, and salt, compared to weekend lunches. Similarly, weekday snacks also had significantly higher nutritional consumption for most nutrients compared to weekend equivalents. CONCLUSION These findings suggest that meals at nursery schools, particularly lunch and snacks, result in more desirable nutrient intake in preschool children. On weekdays, children consume meals with higher nutrient density, possibly due to the role of dietitians in menu planning. However, some children still fail to meet the Dietary Reference Intakes for Japanese, indicating a need for improvements in nursery school and home meals. More communication is needed between nursery schools and families, including sharing menus and recipes is essential. The results of this study are of value for development of public health nutrition strategies targeting early childhood.
Humans ; Child, Preschool ; Male ; Japan ; Female ; Energy Intake ; Meals ; Child ; Nutrients/analysis* ; Diet/statistics & numerical data* ; East Asian People

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.

The Trail Making Test (TMT) is a widely used measure of attention impairment. The time needed to complete the TMT (TMT score) is longer with greater impairment of attention in patients with brain diseases. TMT score becomes large in a proportion of patients with minor ischemic stroke. The Japanese version of the TMT- (TMT-J) was published in 2019. The purpose of this study was to clarify serial changes in TMT-J scores in patients with minor ischemic stroke. We retrospectively reviewed the TMT-J scores in those patients who completed the test both 8-14 days and 29-35 days after stroke onset. On initial evaluation, 1 of 21 patients could not complete TMT-J Part A. TMT-J Part A scores had a mean of 67 s and were abnormally large in 45% of the 20 patients who completed this part. Two of these 20 patients could not complete TMT-J Part B. TMT-J Part B scores had a mean of 135 s and were abnormally large in 61% of the 18 patients who completed this part. On second evaluation, scores on Part A and Part B improved in 76% and 73% of patients, respectively. This study demonstrated that abnormal TMT-J scores 8-14 days after onset of minor ischemic stroke improved over time in most patients.

Oxycodone controlled-release (CR) tablets are used as a first-line opioid analgesic for cancer pain. However, use of oxycodone CR tablets is associated with toxicities such as drowsiness and constipation, leading to deterioration of the quality of life (QOL), especially in patients with gynecologic cancer. In contrast, fentanyl has a superior toxicity profile while still showing a strong analgesic effect. Although fentanyl has been approved for switching from opioid, there have been no Japanese studies of patients with gynecologic cancer who were switched to transdermal fentanyl after experiencing toxicity during therapy with oxycodone CR. More importantly early introduction of palliative therapy for pain has not been adopted routinely in the management of gynecologic cancer. Thus, it appears that treatment for patients with gynecologic cancer remains unsatisfactory at present. We conducted research into improvement of the toxicity profile and pain control with the aim of improving QOL for patients with gynecologic cancer. We showed that pain, drowsiness, and constipation could be significantly improved in gynecologic cancer patients as a result of switching to transdermal fentanyl therapy at an early stage.