Is the progression of treatment for patients with hemophilia leading to improvements in school or social life?: A questionnaire survey for mothers of children or adolescents who chiefly receive prophylactic treatment for hemophilia.

【背景】血友病患者の治療は進歩した。そこで治療の進歩による患者の学校・社会生活の詳細を明らかにするために，母親を対象に，若年世代の患者の学校・社会生活，母親の困り事について実態調査した。 【方法】血友病患者の母親を対象に，無記名自記式の質問紙調査を実施した。 【結果】母親27人の回答が得られ，息子である患者は30人だった。定期輸注実施は23人で，そのうち家庭で輸注を行う者は22人だった。通園経験のある者は27人だった。全ての行事に参加させた者が18人だった。宿泊行事中の定期輸注の実施について，中学生までは学校に支援依頼していた。患者８人は自己注射し，高校生以降の患者４人は，自室で一人の時に注射をしたという回答だった。母親の困り事は「血管確保の失敗と焦り」だった。 【結論】治療の進歩は患者の学校・社会生活を改善した。しかし継続的治療を支える家族の負担のもとに成立する。今後必要な医療支援として，患者の宿泊行事中の輸注において，患者が安心して注射できる場所についての助言が示された。Background: Hemostatic treatment for patients with hemophilia（ PWH） has improved. The aim of this study was to clarify school status and social life among young boys with hemophilia, as well as their mothers’ frustrations. Methods: A questionnaire survey was completed anonymously by mothers of hemophilic boys. Results: A total of 27 mothers of 30 PWHs completed the survey. Twenty-three PWHs had received prophylactic treatment, and 22 received home infusion therapy. Twenty-seven PWHs had attended preschool, and 18 had participated in all preschool/school events. When factor concentrates needed to be infused during overnight events, many mothers requested the assistance of medical staff until the PWHs were junior high school students. When they were high school students, eight PWHs were able to infuse themselves. Four PWHs were reported to infuse alone, hiding from the public eye. Mothers’ chief source of frustration was“ infusion failure on busy mornings.” Conclusion: This study indicates that the progress of treatment for PWHs may improve the school or social life of patients. However, these patients’ family support is also essential for the patients’ treatment. Medical support, such as advice about where to self-infuse during overnight events is needed for PWHs

Expression analyses of CUP-SHAPED COTYLEDON and SHOOT MERISTEMLESS in the one-leaf plant Monophyllaea glabra reveal neoteny evolution of shoot meristem

Abstract The one-leaf plant Monophyllaea glabra exhibits a unique developmental manner in which only one cotyledon continues growing without producing new vegetative organs. This morphology is formed by specific meristems, the groove meristem (GM) and the basal meristem (BM), which are thought to be modified shoot apical meristem (SAM) and leaf meristem. In this study, we analysed the expression of the organ boundary gene CUP-SHAPED COTYLEDON (CUC) and the SAM maintenance gene SHOOT MERISTEMLESS (STM) orthologs by whole-mount in situ hybridisation. We found that CUCs did not show clear border patterns around GM and BM during the vegetative phase. Furthermore, double-colour detection analysis at the cellular level revealed that CUC and STM expression overlapped in the GM region during the vegetative phase. We also found that this overlap is dissolved in the reproductive phase when normal shoot organogenesis is observed. Since co-expression of these genes occurs during SAM initiation under embryogenesis in Arabidopsis, our results demonstrate that GM is a prolonged stage of pre-mature SAM. Therefore, we propose that neotenic meristems could be a novel plant trait acquired by one-leaf plants

Usefulness of a New Therapy Using Rebamipide Eyedrops in Patients with VKC/AKC Refractory to Conventional Anti-Allergic Treatments

Background: Rebamipide, a gastroprotective drug, has been reported to suppress gastric mucosal inflammation. In Japan, rebamipide eyedrops have recently been approved for the treatment of dry eye disease. Some patients with allergic conjunctival diseases such as vernal keratoconjunctivitis (VKC) or atopic keratoconjunctivitis (AKC) manifest dry eye with decreased tear break-up time only. We report patients with VKC/AKC refractory to anti-allergic treatments who responded to the combination of rebamipide eyedrops and conventional anti-allergic treatments with anti-allergic- and/or immunosuppressive/steroid eyedrops. Methods: Four patients with allergic conjunctival diseases with giant papillae (VKC or AKC) instilled rebamipide eyedrops three or four times a day for varying periods. All had dry eye with decreased tear break-up time. We evaluated changes in the size of their giant papillae using Image J software. Results: We observed attenuation of the giant papillae in all 4 patients. In 2 patients with severe disease, whose giant papillae had become larger despite the administration of tacrolimus and steroids, the addition of rebamipide contributed to their attenuation. In 2 patients with mild disease, the giant papillae had become larger or remained the same size despite the administration of anti-allergy drugs; the addition of rebamipide eyedrops also resulted in the attenuation of their giant papillae. Conclusions: Our findings suggest that rebamipide eyedrops might attenuate giant papillae in patients with allergic conjunctival diseases and that these eyedrops may be useful for the treatment of not only dry eye but also of allergic conjunctival diseases

Biological Effects of β-Glucans on Osteoclastogenesis

Although the anti-tumor and anti-infective properties of β-glucans have been well-discussed, their role in bone metabolism has not been reviewed so far. This review discusses the biological effects of β-glucans on bone metabolisms, especially on bone-resorbing osteoclasts, which are differentiated from hematopoietic precursors. Multiple immunoreceptors that can recognize β-glucans were reported to be expressed in osteoclast precursors. Coordinated co-stimulatory signals mediated by these immunoreceptors are important for the regulation of osteoclastogenesis and bone remodeling. Curdlan from the bacterium Alcaligenes faecalis negatively regulates osteoclast differentiation in vitro by affecting both the osteoclast precursors and osteoclast-supporting cells. We also showed that laminarin, lichenan, and glucan from baker’s yeast, as well as β-1,3-glucan from Euglema gracilisas, inhibit the osteoclast formation in bone marrow cells. Consistent with these findings, systemic and local administration of β-glucan derived from Aureobasidium pullulans and Saccharomyces cerevisiae suppressed bone resorption in vivo. However, zymosan derived from S. cerevisiae stimulated the bone resorption activity and is widely used to induce arthritis in animal models. Additional research concerning the relationship between the molecular structure of β-glucan and its effect on osteoclastic bone resorption will be beneficial for the development of novel treatment strategies for bone-related diseases

Antioxidant capacity of wheat bran fermented with gut indigenous Bifidobacterium and its antagonistic effect on food‐related pathogens in vitro

Abstract Wheat bran (WB) has several health‐promoting effects. This study aimed to identify gut bacteria that increase after WB consumption and assess their functionality. Human stool samples obtained from healthy volunteers were inoculated into culture broth with or without 2% (w/v) WB and incubated under anaerobic conditions for 24 h. The microbiota in the cultures was analysed using 16S rRNA (V4) gene amplicon sequencing. The addition of WB decreased the pH from 6.9 to 5.9 (p < 0.05) and increased the acetate level by 1.6 times. Although the microbiota differed across individuals, butyrate‐producing genera (Faecalibacterium and Roseburia), Blautia, and Bifidobacterium spp. were abundant in cultures supplemented with WB. Bifidobacterium pseudocatenulatum and B. adolescentis, isolated as WB‐responsible gut indigenous bacteria (WB‐RIBs), were found to ferment WB. The WB‐RIBs increased the 1,1‐diphenyl‐picrylhydrazyl and superoxide anion radical‐scavenging capacities of WB‐supplemented cultures. Further, these WB‐RIBs suppressed the growth of Salmonella Typhimurium, Staphylococcus aureus, and Bacillus cereus in WB‐supplemented brain heart infusion broth. These results suggest that compounds present in WB, along with WB‐RIBs, affect the gut environment. Further studies should be conducted to elucidate the mechanisms underlying the interactions between WB and WB‐RIBs

p53 Regulates Toll-Like Receptor 3 Expression and Function in Human Epithelial Cell Lines▿

Toll-like receptors (TLRs) are important sensors of microbial pathogens and mediators of innate immune responses. Although the signal transduction of TLRs is well elucidated, their basal regulation is largely unexplored. Here we show that the tumor suppressor p53 positively regulates the transcription of TLR3, a receptor for viral double-stranded RNA and poly(I-C), by binding to the p53 site in the TLR3 promoter. TLR3 expression was lower in HCT116 p53−/− cells than in HCT116 p53+/+ cells. Activation of p53 by 5-fluorouracil increased the TLR3 mRNA in epithelial cell lines with wild-type p53 but not in cell lines harboring mutant p53. Knockdown of p53 by small interfering RNA decreased the TLR3 expression. TLR3 mRNA was also lower in liver and intestine of p53−/− mice than in p53+/+ mice. Furthermore, the poly(I-C)-induced phosphorylation of IκB-α, nuclear translocation of NF-κB, and phosphorylation of interferon regulatory transcription factor 3, were drastically reduced in HCT116 p53−/− cells, indicating a dysregulation of the two signaling pathways governed by TLR3. Consequently, induction of interleukin-8 and beta interferon after poly(I-C) stimulation was impaired in HCT116 p53−/− cells. These results suggest that p53 influences TLR3 expression and function and highlight a role of p53 in innate immune response in epithelial cells

Paraneoplastic Syndrome Presenting with Polymyalgia Rheumatica-like Accumulations on 18F-fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography

A 70-year-old woman presented with a fever and pain in both lower extremities and the right shoulder and right upper arm continuously for approximately 3 months. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG/PET-CT) revealed the accumulation of FDG in the right shoulder, lumbar spinous processes, both ischial tuberosities, and both hips and greater trochanters, indicating polymyalgia rheumatica (PMR). In addition, upper gastrointestinal endoscopy revealed esophageal carcinoma.After endoscopic submucosal dissection was performed, her musculoskeletal symptoms spontaneously improved,and the 18F-FDG/PET-CT findings decreased. In light of these findings, she was diagnosed with paraneoplastic syndrome. When atypical features of PMR, such as asymmetric symptoms occur, we should search for malignancies