The efficacy of thiopurines, including azathioprine (AZA) and 6-mercaptopurine (6MP), has been demonstrated for the treatment of inflammatory bowel disease (IBD). The most common and serious adverse event of treatment with thiopurines altered by doctors is leukopenia. Hair loss is also a serious event that could be a critical reason for patients to decline thiopurine treatment. Thiopurine-induced severe hair loss causes cosmetic problems, and it takes a long time to recover. In a recent study, NUDT15 R139C was strongly associated with thiopurine-induced leukopenia in Korean and Caucasian populations. In this study, we performed an association study to investigate and replicate the association of R139C with adverse events of thiopurines in Japanese patients. A total of 142 Japanese patients with IBD, with histories of thiopurine treatment, were examined. NUDT15 R139C was genotyped using a custom TaqMan genotyping assay. Adverse events including leukopenia were reviewed from medical records. The 6MP dose was adjusted to AZA equivalents by multiplying with 2 as a thiopurine dose. Five patients developed severe hair loss and all of them were risk homozygous (T/T) for R139C. No early severe hair loss was observed in patients with the C/T or C/C genotype (P=3.82 × 10(-16), odds ratio=212). The association of R139C with early (<8 weeks) leukopenia (white blood cells<3000 mm(-3)), which was previously reported in Korean patients, was replicated in our Japanese IBD cohort (P=1.92 × 10(-16), odds ratio=28.4). However, we could not confirm the association with late leukopenia in the Japanese subjects. Patients with the C/T genotype discontinued treatment or required thiopurine dose reduction significantly earlier than patients with the C/C genotype (P=1.45 × 10(-4)); however, on manipulating the doses, there was no significant difference in the thiopurine continuation rates between the groups. In the maintenance period, the frequencies of 6MP usage were higher, and the doses of thiopurines were significantly lower in patients with the C/T genotype than in those with the C/C genotype (0.574±0.316 mg kg(-1) per day vs 1.03±0.425 mg kg(-1) per day, P=6.21 × 10(-4)). NUDT R139C was significantly associated with early severe hair loss in Japanese patients with IBD. We also verified the previously reported association of R139C with early leukopenia in a different East Asian population. It is recommended that treatment with thiopurines should be avoided for patients with the T/T genotype. Low-dose 6MP (0.2-0.3 mg kg(-1) per day) could be used rather than AZA for the patients with C/T genotype to continue thiopurine treatments. However, late leukopenia and other several adverse events could not be completely predicted by R139C genotypes.

Our results, showing downregulation of the cornified envelope genes and upregulation of the alternative keratinization pathway, are the first to suggest abnormal epidermal differentiation and defective defences as key abnormalities in AD.

Child development is seriously affected by social interactions with caregivers, which may lead to forming social minds in our daily life afterward. However, the underlying neural mechanism for such interactions has not yet been revealed. This article introduces a magnetoencephalographic (MEG) hyperscanning system to examine brain-to-brain interactions between a mother and her child. We used two whole-head MEG systems placed in the same magnetically-shielded room. One is a 160-channel gradiometer system for an adult and the other is a 151-channel gradiometer system for a child. We developed an audio-visual presentation system, which enabled a mother and her child to look at each other in real time. In each MEG system, a video camera was placed behind a half-mirror screen for visual presentation to obtain the subjects' facial expressions. The visual presentation system is capable of displaying not only real-time facial expression but also processed facial expression such as a still face or delayed facial expressions. A projector system displays the side-by-side face images of the mother and child, and the images are divided into each face using splitting mirrors and each face is displayed on the half-mirror screen in front of the other subject. To the best of our knowledge, our system is the first MEG hyperscanning system in a single shielded room, and may contribute to elucidating brain-to-brain interactions not only between a mother and her child but also in general inter-individual, brain-to-brain interactions.

MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection.

The Paper introduces the centrifuge research activities undertaken by the soil mechanics group at the Tokyo Institute of Technology during the past ten years and focuses on the bearing capacity of shallow foundations in dense sand. A series of experiments was conducted to explain de Beer's scale effect and to investigate the effect of the roughness of the footing base, the anisotropy in dense sand, the embedment of footings and the effect of slopes near footings. Measurements of deformations were attempted during loading tests using an automatic tracking device developed by the group and radiographs were used to detect slip lines. Progressive failure was found to be more marked for wider footings, which is considered to be the main cause of the scale effect; the smaller bearing capacity factors occur for wider footings. It is shown that strong anisotropy in dense sand is also responsible for the scale effect. A smooth footing, made by lubricating the base with a greased membrane, yielded two symmetrical wedges beneath the base and a smaller bearing capacity than that obtained with a rough footing, as theory predicts. A simple expression for predicting the effect of embedment of footings is deduced from the results of the experiments. With respect to the bearing capacity of foundations near slopes, a satisfactory agreement was found between the results of the centrifuge experiments and those of model tests on a prototype scale. Cet article décrit les recherches faites à l'aide des centrifugeuses depuis dix années par le département de mécanique des sols de I'Institut de Technologie de Tokyo et examine plus particulierement la charge portante des fondations superficielles dans du sable dense. Une série d'essais a été effectuée pour expliquer l'effet d'éechelle (de Beer) et aussi pour étudier I'effet de la ruguosité de la base de la semelle, de l'anisotropie du sable dense, de l'encastrement des semelles et I'effet des gradients dans le voisinage des semelles. On a essayé de faire des mesures des déformations à l'aide d'un dispositif automatique de tragage développé par la faculté, en employant des radiographies pour découvrir les lignes de glissement. On a trouvé une rupture progressive plus poussée dans le cas des larges semelles, ce qui doit être la cause principale de l'effet d'échelle; les coefficients de capacité portante les plus faibles correspondent aux semelles les plus larges. On a démontré aussi que l'effet d'échelle est due à une forte anisotropie du sable dense. Un semelle lisse, obtenue en lubrifiant la base avec une membrane graissée, a donné comme résultat deux coins symétriques au-dessous de la base et une charge portante plus faible que celle obtenue avec une semelle rugueuse, comme prévu par la théorie. Des résultats expérimentaux on peut déduire une expression très simple pour prévoir l'effet de l'encastrement des semelles. En ce qui concerne la charge portante de fondations dans le voisinage des gradients on a découvert que les résultats des expériences à la centrifugeuse s'accordaient de façon satisfaisante avec ceux des essais-modèles sur une échelle prototype.

Background/Aims. Antitumor necrosis factor antibodies and calcineurin inhibitors have shown good therapeutic efficacy for steroid-refractory ulcerative colitis (UC). Although some studies have compared the efficacy of infliximab (IFX) and cyclosporin A, there are no published studies comparing IFX and tacrolimus (Tac). This study aimed to compare therapeutic efficacies between IFX- and Tac-based strategies for steroid-refractory UC. Methods. Between July 2009 and August 2013, 95 patients with steroid-refractory UC received either IFX (n = 48) or Tac (n = 47) in our hospital. In the IFX group, the patients continued to receive maintenance treatment with IFX. In the Tac group, patients discontinued Tac treatment up to 3 months and subsequently received thiopurine. We retrospectively compared the therapeutic outcomes between the groups. Results. There was no significant difference in the colectomy-free rate, clinical remission rate, and clinical response rate at 2 months between the groups. However, relapse-free survival was significantly higher in the IFX group than in the Tac group (p < 0.001; log-rank test). The proportions of serious adverse events did not differ between the groups. Conclusion. The findings of our study showed that IFX and Tac have similar short-term therapeutic efficacy for steroid-refractory UC. Maintenance treatment with IFX, however, yields better long-term outcomes than Tac-thiopurine bridging treatment.

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