Maternal multivitamin intake and orofacial clefts in offspring: Japan Environment and Children's Study (JECS) cohort study

Objectives: Orofacial clefts are common birth defects with a lack of strong evidence regarding their association with maternal nutrition. We aimed to determine whether a relationship exists between maternal nutrient or multivitamin intake and orofacial clefts. Design: This is a prospective, population-based nationwide cohort study. Setting: The study was conducted in 15 regional centres, consisting of local administrative units and study areas. Participants: A total of 98 787 eligible mother–child pairs of the Japan Environment and Children’s Study were included. Intervention: Exposures were maternal nutrition and the use of supplemental multivitamins in mothers. Primary and secondary outcome measures: Outcomes were the occurrence of any orofacial cleft at birth. Multinomial logistic regression analyses were used to evaluate the association between maternal multivitamin intake and the incidence of orofacial clefts. Results: Of the 98 787 children, 69 (0.07%) were diagnosed with cleft lip alone, 113 (0.11%) were diagnosed with cleft lip and palate, and 52 (0.05%) were diagnosed with cleft palate within 1 month after birth. Regarding the total orofacial cleft outcome, statistically significant point estimates of relative risk ratios (RR) were determined for multivitamin intake before pregnancy (RR=1.71; 95% CI 1.06 to 2.77) and during the first trimester (RR=2.00; 95% CI 1.18 to 3.37), but the association was not significant for multivitamin intake after the first trimester (RR=1.34; 95% CI 0.59 to 3.01). Maternal micronutrient intake via food was not associated with the incidence of orofacial clefts in offspring. Conclusions: Intake of multivitamin supplements shortly before conception or during the first trimester of pregnancy was found to be associated with an increased incidence of orofacial clefts at birth. Pregnant women and those intending to become pregnant should be advised of the potential risks of multivitamin supplementation

A case of follicular lymphoma complicated with mesenteric panniculitis

Mesenteric panniculitis (MP) is a rare disease occasionally complicated with lymphoma. A 55-year old female presented with MP accompanied by malignant lymphoma. This patient was first treated for follicular lymphoma and subsequently for panniculitis. After 6 courses of R-CHOP chemotherapy, the treatment response was partial. An additional course of salvage chemotherapy led to a complete response. Since the mesenteric mass progressed simultaneously with the regression of other lymphoma lesions, we performed a biopsy of the mesenteric mass and pathologically confirmed an MP lesion without lymphoma. Subsequent high-dose chemotherapy led to CR and the MP lesion remained stable. In the present case, MP progressed with chemotherapy. We concluded that mesenteric lesions suspected of progressing or recurring should be diagnosed pathologically even if asymptomatic

Locating and Stabilizing Unstable Periodic Orbits

Based on the theory of symbolic dynamical systems, we propose a novel computation method to locate and stabilize the unstable periodic points (UPPs) in a two-dimensional dynamical system with a Smale horseshoe. This method directly implies a new framework for controlling chaos. By introducing the subset based correspondence between a planar dynamical system and a symbolic dynamical system, we locate regions sectioned by stable and unstable manifolds comprehensively and identify the specified region containing a UPP with the particular period. Then Newton’s method compensates the accurate location of the UPP with the regional information as an initial estimation. On the other hand, the external force control (EFC) is known as an effective method to stabilize the UPPs. By applying the EFC to the located UPPs, robust controlling chaos is realized. In this framework, we never use ad hoc approaches to find target UPPs in the given chaotic set. Moreover, the method can stabilize UPPs with the specified period regardless of the situation where the targeted chaotic set is attractive. As illustrative numerical experiments, we locate and stabilize UPPs and the corresponding unstable periodic orbits in a horseshoe structure of the Duffing equation. In spite of the strong instability of UPPs, the controlled orbit is robust and the control input retains being tiny in magnitude

Attaining Complete Remission May Confer a Better Outcome after Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute B-cell Lymphoblastic Leukemia

Introduction : Treatment outcome of adult patients with acute B-cell lymphoblastic leukemia (ALL) is suboptimal even after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To maximize the efficacies of this treatment strategy, risk stratification is crucial. Methods : We retrospectively collected clinical data of the adult patients with allo-HSCT for ALL at a single insitiution in Japan between 2003 and 2022. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS), progression-free survival (PFS) and GVHD-free-and-relapse-free survival (GRFS) at 3 years. Results : A total of 58 patients were included with 34 females and a median age of 39. Sixty-two percent of patients harbored high-risk cytogenetic features or Philadelphia chromosome (Ph). Hematologic complete response (CR) rate was 93 ％ after a first induction, but 75.9 ％ were in CR at allo-HSCT. Blinatumomab was used in 1.7 ％ of patients. A chimeric mRNA had been detected in 4 of 26 patients at allo-HSCT. The 3-year OS, PFS and GRFS were 72.7 ％, 54.7 ％ and 46.2 ％, respectively. Pre-transplantation CR was an independent risk factor. Discussion/Conclusions : Our results imply that a better OS may potentially be achieved by improved pretransplantation CR rate with more frequent application of novel agents.Article信州医学雑誌 71(5) : 257-267, (2023)journal articl

The basis of clinicopathological heterogeneity in TDP-43 proteinopathy

Transactive response DNA-binding protein 43 kDa (TDP-43) was identified as a major disease-associated component in the brain of patients with amyotrophic lateral sclerosis (ALS), as well as the largest subset of patients with frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U), which characteristically exhibits cytoplasmic inclusions that are positive for ubiquitin but negative for tau and α-synuclein. TDP-43 pathology occurs in distinct brain regions, involves disparate brain networks, and features accumulation of misfolded proteins in various cell types and in different neuroanatomical regions. The clinical phenotypes of ALS and FTLD-TDP (FTLD with abnormal intracellular accumulations of TDP-43) correlate with characteristic distribution patterns of the underlying pathology across specific brain regions with disease progression. Recent studies support the idea that pathological protein spreads from neuron to neuron via axonal transport in a hierarchical manner. However, little is known to date about the basis of the selective cellular and regional vulnerability, although the information would have important implications for the development of targeted and personalized therapies. Here, we aim to summarize recent advances in the neuropathology, genetics and animal models of TDP-43 proteinopathy, and their relationship to clinical phenotypes for the underlying selective neuronal and regional susceptibilities. Finally, we attempt to integrate these findings into the emerging picture of TDP-43 proteinopathy, and to highlight key issues for future therapy and research

Limits on monopole fluxes from KFG experiment

The nucleon decay experiment at KGF at a depth of 2.3 Km is eminently suited for the search of Grand Unified theory (GUT) monopoles, whose velocities at the present epoch are predicted to be around 0.001C. At this depth the cosmic ray background is at a level 2/day in the detector of size 4m x 6m x 3.7m and one can look for monopoles traversing the detector in all directions, using three methods, i.e., (1) dE/dx (ionization); (2) time of flight and (3) catalysis of nucleon decay. The detector is composed of 34 layers of proportional counters arranged in horizontal planes one above the other in an orthogonal maxtrix. Each of the 1594 counters are instrumented to measure ionization in the gas (90% Argon + 10% Methane) as well as the time of arrival of particles

Association between maternal heavy metal exposure and Kawasaki Disease, the Japan Environment and Children’s Study (JECS)

妊婦の⾎中重⾦属濃度と⽣まれた子どもの川崎病発症との関連について 子どもの健康と環境に関する全国調査（エコチル調査）.京都大学プレスリリース. 2024-07-01.Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting young children, with an unclear etiology. We investigated the link between maternal heavy metal exposure and KD incidence in children using the Japan Environment and Children’s Study, a large-scale nationwide prospective cohort with approximately 100, 000 mother–child pairs. Maternal blood samples collected during the second/third trimester were analyzed for heavy metals [mercury (Hg), cadmium (Cd), lead (Pb), selenium (Se), manganese (Mn)], divided into four quartiles based on concentration levels. KD incidence within the first year of life was tracked via questionnaire. Among 85, 378 mother–child pairs, 316 children (0.37%) under one year were diagnosed with KD. Compared with the lowest concentration group (Q1), the highest (Q4) showed odds ratios (95% confidence interval) for Hg, 1.29 (0.82–2.03); Cd, 0.99 (0.63–1.58); Pb, 0.84 (0.52–1.34); Se, 1.17 (0.70–1.94); Mn, 0.70 (0.44–1.11), indicating no concentration-dependent increase. Sensitivity analyses with logarithmic transformation and extended outcomes up to age 3 yielded similar results. No significant association was found between maternal heavy metal levels and KD incidence, suggesting that heavy metal exposure does not increase KD risk

Dual-alkylator Conditioning Regimen with Busulfan and Melphalan for Bone Marrow Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelofibrosis : The Results of a Retrospective Study at a Single Institution in Japan

Myelofibrosis (MF) is a myeloproliferative neoplasm associated with significant morbidity and mortality, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative approach. While the optimal conditioning regimen before allo-HSCT for MF patients remains to be determined, recent studies have suggested that a thiotepa-busulfan-containing dual-alkylator regimen, FBT regimen, may be associated with favorable outcomes. In Japan, however, thiotepa is not indicated for MF. Here we describe the results of 6 cases of MF treated with melphalan-busulfan containing dual-alkylator regimen, FBM regimen, followed by their first allo-HSCT at a single institution. Neutrophil and platelet engraftment was achieved in all patients. And a full donor chimerism was confirmed in all patients at ＋30 days after allo-HSCT. The relatively small size and short observation period of our study make it difficult to draw a definitive conclusion ; however, our results suggest that a dualalkylator regimen of FBM may be a candidate for an conditioning for allo-HSCT for MF, which should be verified with a large cohort of patients.Article信州医学雑誌 71(6) : 393-402, (2023)journal articl

Results on nucleon life-time from the Kolar gold field experiment

The KGF nucleon decay experiment has been in operation since October 1980 with a 140 ton calorimetric detector at a depth of 2.3 Km underground. The detector comprises 34 layers of proportional counters arranged in an orthogonal geometry with 12 mm thick iron plates in between successive layers. The proportional counters are made up of square (10 x 10 square centimeters) iron plates of wall thickness 2.3 mm. Each of the 1600 counters is instrumented to provide data on ionization, DE/dx and arrival time. The visible energy of a particle is determined to an accuracy of approximately 20% from the ionization and range of its track. The end point ionization of a stopping track provides the direction of motion as well as the nature of the particle (mu/pi,k,p). Decay of mu is recorded with an overall efficiency of only 20% in view of the thickness of 13 g/square centimeters between successive layers

Data acquisition system for phase-2 KGF proton decay experiment

Phase-2 of KGF proton decay experiment using 4000 proportional counters will start operating from middle of 1985. The detection systems, in addition to measuring the time information to an accuracy of 200 n see, also records ionization in the hit counters. It also monitors different characteristics of the counters like pulse height spectrum, pulse width spectrum and counting rate. The acquisition system is discussed