Serum brain natriuretic peptide levels may be a useful marker for early diagnosis of cardiomyopathy secondary to neuroblastoma: A case report.

Cardiomyopathy is a rare but serious complication associated with neuroblastoma. The brain natriuretic peptide level led to a diagnosis of secondary dilated cardiomyopathy before the worsening of heart failure symptoms.

Convergent mechanism underlying the acquisition of vertebrate scotopic vision.

High sensitivity of scotopic vision (vision in dim light conditions) is achieved by the rods' low background noise, which is attributed to a much lower thermal activation rate (kth) of rhodopsin compared with cone pigments. Frogs and nocturnal geckos uniquely possess atypical rods containing noncanonical cone pigments that exhibit low kth, mimicking rhodopsin. Here, we investigated the convergent mechanism underlying the low kth of rhodopsins and noncanonical cone pigments. Our biochemical analysis revealed that the kth of canonical cone pigments depends on their absorption maximum (λmax). However, rhodopsin and noncanonical cone pigments showed a substantially lower kth than predicted from the λmax dependency. Given that the λmax is inversely proportional to the activation energy of the pigments in the Hinshelwood distribution-based model, our findings suggest that rhodopsin and noncanonical cone pigments have convergently acquired low frequency of spontaneous-activation attempts, including thermal fluctuations of the protein moiety, in the molecular evolutionary processes from canonical cone pigments, which contributes to highly sensitive scotopic vision.

[Construction of a Temporary Radiological Image Viewing Network for Large-scale Disasters].

The Ministry of Health, Labor and Welfare mandated the creation of the business continuity plan (BCP) for disaster key hospitals on March 31, 2017. Supposing the hospital information system (HIS) failure occurred, the picture archiving and communication system (PACS) also suffers obstacles, we assumed building a new network was necessary for radiological examination images. The purpose of this study was to investigate whether building a new network for radiological examination images is necessary in an emergency. Using wireless fidelity (Wi-Fi), the new network consisting of one image server and two tablet terminals A and B was constructed. The study measured the portable image transfer time for various stages of the network. The results were as follows: Transfer time from the mobile X-ray unit to the image server was 4.12±0.86 s, that from the image server to the tablet device A was 5.14±0.71 s, and that from the image server to the tablet device B was 7.32±1.66 s. Therefore, the new network configuration can provide a reliable means of accessing radiological images during emergency situations when the HIS and PACS may experience obstacles or failures.

Impact of Excessive Increase in Systolic Blood Pressure after Exercise on Clinical Outcomes in Patients with ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: Although the clinical outcomes for patients with ST-elevation myocardial infarction (STEMI) have improved significantly, some patients still experience poor clinical outcomes. The available risk classifications focus on the short-term outcomes, and it remains important to find high-risk features among patients with STEMI. In Japan, the 200 m walk electrocardiogram (ECG) test is widely performed before discharge. The purpose of this study was to investigate the association between the excessive increase in systolic blood pressure (SBP) following a 200 m walk and the long-term clinical outcomes in patients with STEMI. METHODS: We included 680 patients with STEMI and divided those into an excessive increase in SBP group (n = 144) and a non-excessive increase in SBP group (n = 536) according to the SBP increase after a 200 m walk ECG test. We defined an excessive increase in SBP as SBP ≥ 20 mmHg either just after or 3 min after a 200 m walk ECG test. The primary endpoint consisted of major cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction, readmission for heart failure, and ischemia-driven target vessel revascularization. RESULTS: The median follow-up duration was 831 days. MACE was more frequently observed in the excessive increase in SBP group (24.3%) than in the non-excessive increase in SBP group (15.1%). Multivariate Cox hazard analysis revealed that the excessive increase in SBP was significantly associated with MACE (HR 1.509, 95% CI: 1.005-2.267, p = 0.047) after controlling for multiple confounding factors. CONCLUSION: An excessive increase in SBP after the 200 m walk ECG test was significantly associated with MACE in patients with STEMI. The 200 m walk ECG test is simple and low-cost, but may help to identify high-risk patients with STEMI.

Mammalian type opsin 5 preferentially activates G14 in Gq-type G proteins triggering intracellular calcium response.

Mammalian type opsin 5 (Opn5m), a UV-sensitive G protein-coupled receptor opsin highly conserved in vertebrates, would provide a common basis for UV sensing from lamprey to humans. However, G protein coupled with Opn5m remains controversial due to variations in assay conditions and the origin of Opn5m across different reports. Here, we examined Opn5m from diverse species using an aequorin luminescence assay and Gα-KO cell line. Beyond the commonly studied major Gα classes, Gαq, Gα11, Gα14, and Gα15 in the Gq class were individually investigated in this study, as they can drive distinct signaling pathways in addition to a canonical calcium response. UV light triggered a calcium response via all the tested Opn5m proteins in 293T cells, which was abolished by Gq-type Gα deletion and rescued by cotransfection with mouse and medaka Gq-type Gα proteins. Opn5m preferentially activated Gα14 and close relatives. Mutational analysis implicated specific regions, including α3-ß5 and αG-α4 loops, αG and α4 helices, and the extreme C terminus, in the preferential activation of Gα14 by Opn5m. FISH revealed co-expression of genes encoding Opn5m and Gα14 in the scleral cartilage of medaka and chicken eyes, supporting their physiological coupling. This suggests that the preferential activation of Gα14 by Opn5m is relevant for UV sensing in specific cell types.

Diversification processes of teleost intron-less opsin genes.

Opsins are universal photosensitive proteins in animals. Vertebrates have a variety of opsin genes for visual and non-visual photoreceptions. Analysis of the gene structures shows that most opsin genes have introns in their coding regions. However, teleosts exceptionally have several intron-less opsin genes that are presumed to have been duplicated by an RNA-based gene duplication mechanism, retroduplication. Among these retrogenes, we focused on the Opn4 (melanopsin) gene responsible for non-image-forming photoreception. Many teleosts have five Opn4 genes including one intron-less gene, which is speculated to have been formed from a parental intron-containing gene in the Actinopterygii. In this study, to reveal the evolutionary history of Opn4 genes, we analyzed them in teleost (zebrafish and medaka) and non-teleost (bichir, sturgeon, and gar) fishes. Our synteny analysis suggests that the intron-less Opn4 gene emerged by retroduplication after the branching of the bichir lineage. In addition, our biochemical and histochemical analyses showed that, in the teleost lineage, the newly acquired intron-less Opn4 gene became abundantly used without substantial changes in the molecular properties of the Opn4 protein. This stepwise evolutionary model of Opn4 genes is quite similar to that of rhodopsin genes in the Actinopterygii. The unique acquisition of rhodopsin and Opn4 retrogenes would have contributed to the diversification of the opsin gene repertoires in the Actinopterygii and the adaptation of teleosts to various aquatic environments.

Chromophore Structure in an Inactive State of a Novel Photosensor Protein Opn5L1: Resonance Raman Evidence for the Formation of a Deprotonated Adduct at the 11th Carbon Atom.

Opsins are photosensitive G protein-coupled receptor proteins and are classified into visual and nonvisual receptors. Opn5L1 is a nonvisual opsin that binds all-trans retinal as a chromophore. A unique feature of Opn5L1 is that the protein exhibits a photocyclic reaction upon photoexcitation. Determining the chromophore structures of intermediates in the photocycle is essential for understanding the functional mechanism of Opn5L1. A previous study revealed that a long-lived intermediate in the photocycle cannot activate the G protein and forms a covalent bond between the retinal chromophore and a nearby cysteine residue. However, the position of this covalent bond in the chromophore remains undetermined. Here, we report a resonance Raman study on isotopically labeled samples in combination with density functional theory calculations and reveal that the 11th carbon atom of the chromophore of the intermediate forms a covalent linkage to the cysteine residue. Furthermore, vibrational assignments based on the isotopic substitutions and density functional theory calculations suggested that the Schiff base of the intermediate is deprotonated. The chromophore structure determined in the present study well explains the mechanism of the photocyclic reaction, which is crucial to the photobiological function of Opn5L1.

Talar component subsidence correlates with periprosthetic osteolysis after total ankle arthroplasty.

PURPOSE: This study aimed to investigate the relationship between periprosthetic osteolysis around the talar component and the amount of talar component subsidence after total ankle arthroplasty (TAA). METHODS: This study included forty patients who underwent TAA with a mean follow-up of 67.5 ± 17.0 months. The patients were divided into two groups based on the amount of osteolysis around the talar component, as measured by computed tomography at the latest clinic visit: none to 2 mm (N group, n = 20) and greater than or equal to 2 mm (O group, n = 20). The average amount of talar component subsidence, clinical outcomes, and complications were compared between the two groups. In the O group, the correlation between osteolysis and talar component subsidence was evaluated. RESULTS: The average talar component subsidence was significantly different between the N (0.22 ± 0.94 mm) and O groups (2.12 ± 2.28 mm). Five out of 20 ankles in the O group required revision surgery owing to talar component subsidence. The Japanese Society for Surgery of the Foot scores in the N and O groups were significantly different: 93.5 ± 7.7 and 85.3 ± 15.4, respectively. In the O group, we found that osteolysis tended to develop on the lateral side, and the amount of osteolysis was positively correlated with the talar component subsidence (r = 0.59, P = .007). CONCLUSION: In the O group, a positive correlation between osteolysis and talar component subsidence was found, and five patients required revision surgery.

Association of Plasma Lipopolysaccharide-Binding Protein Concentration with Dietary Factors, Gut Microbiota, and Health Status in the Japanese General Adult Population: A Cross-Sectional Study.

The influx of intestinal bacteria-derived lipopolysaccharide (LPS) into the blood has attracted attention as a cause of diseases. The aim of this study is investigating the associations between the influx of LPS, dietary factors, gut microbiota, and health status in the general adult population. Food/nutrient intake, gut microbiota, health status and plasma LPS-binding protein (LBP; LPS exposure indicator) were measured in 896 residents (58.1% female, mean age 54.7 years) of the rural Iwaki district of Japan, and each correlation was analyzed. As the results, plasma LBP concentration correlated with physical (right/left arms' muscle mass [ß = -0.02, -0.03]), renal (plasma renin activity [ß = 0.27], urine albumin creatinine ratio [ß = 0.50]), adrenal cortical (cortisol [ß = 0.14]), and thyroid function (free thyroxine [ß = 0.05]), iron metabolism (serum iron [ß = -0.14]), and markers of lifestyle-related diseases (all Qs < 0.20). Plasma LBP concentration were mainly negatively correlated with vegetables/their nutrients intake (all ßs ≤ -0.004, Qs < 0.20). Plasma LBP concentration was positively correlated with the proportion of Prevotella (ß = 0.32), Megamonas (ß = 0.56), and Streptococcus (ß = 0.65); and negatively correlated with Roseburia (ß = -0.57) (all Qs < 0.20). Dietary factors correlated with plasma LBP concentration correlated with positively (all ßs ≥ 0.07) or negatively (all ßs ≤ -0.07) the proportion of these bacteria (all Qs < 0.20). Our results suggested that plasma LBP concentration in the Japanese general adult population was associated with various health issues, and that dietary habit was associated with plasma LBP concentration in relation to the intestinal bacteria.

The medaka mutant deficient in eyes shut homolog exhibits opsin transport defects and enhanced autophagy in retinal photoreceptors.

Eyes shut homolog (EYS) encodes a proteoglycan and the human mutation causes retinitis pigmentosa type 25 (RP25) with progressive retinal degeneration. RP25 most frequently affects autosomal recessive RP patients with many ethnic backgrounds. Although studies using RP models have facilitated the development of therapeutic medications, Eys has been lost in rodent model animals. Here we examined the roles for Eys in the maintenance of photoreceptor structure and function by generating eys-null medaka fish using the CRISPR-Cas9 system. Medaka EYS protein was present near the connecting cilium of wild-type photoreceptors, while it was absent from the eys-/- retina. The mutant larvae exhibited a reduced visual motor response compared with wild-type. In contrast to reported eys-deficient zebrafish at the similar stage, no retinal cell death was detected in the 8-month post-hatching (8-mph) medaka eys mutant. Immunohistochemistry showed a significant reduction in the length of cone outer segments (OSs), retention of OS proteins in the inner segments of photoreceptors, and abnormal filamentous actin network at the base of cone OSs in the mutant retina by 8 mph. Electron microscopy revealed aberrant structure of calyceal processes, numerous vesiculation and lamellar interruptions, and autophagosomes in the eys-mutant cone photoreceptors. In situ hybridization showed an autophagy component gene, gabarap, was ectopically expressed in the eys-null retina. These results suggest eys is required for regeneration of OS, especially of cone photoreceptors, and transport of OS proteins by regulating actin filaments. Enhanced autophagy may delay the progression of retinal degeneration when lacking EYS in the medaka retina.

Factors associated with perioperative deep vein thrombosis in arthroscopic anterior cruciate ligament reconstruction.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) is reportedly associated with a higher incidence of deep vein thrombosis (DVT) incidence than other arthroscopic surgical procedures. The aim of this study is to retrospectively investigate the incidence and type of DVT and evaluate the relationship between DVT and risk factors among all patients who underwent ACLR under uniform conditions consisting of mechanical prophylaxis, no medical prophylaxis, and preoperative and postoperative lower extremity venous ultrasonography. METHODS: Of the 114 patients who underwent arthroscopic primary ACLR at our hospital who did not have a compound ligament injury or revision surgery, 112 patients were included. Two patients were not examined. DVT evaluation consisted of whole-leg ultrasonography at 1 week after surgery. We evaluated age, sex, body mass index, comorbidities, operative time, tourniquet time, presence of concurrent surgery (meniscus repair/resection or osteochondral column grafting), and non-weight-bearing status at 1 week after surgery as risk factors for DVT. RESULTS: DVT was found in 33 (29.5%) of 112 patients. Of these, 22 (19.6%) had distal DVT and 11 (9.8%) had proximal DVT. Non-weight-bearing status at 1 week after surgery was a statistically significant risk factor for proximal DVT (P = .034). CONCLUSIONS: Non-weight-bearing status is an independent risk factor for DVT, suggesting that early weight bearing may reduce the occurrence of DVT.

3D Printed lattice-structured metal electrodes for enhanced current production in bioelectrochemical systems.

Bioelectrochemical systems (BESs) are emerging techniques that use biological production of current for versatile activities, including energy recovery and bioremediation. The development of high-performance three-dimensional (3D) electrodes has attracted attention for facilitating current production in BESs. Carbon-based electrodes have been commonly used in BESs, but metal electrodes are not generally employed because of their low biocompatibility with microbes. In this study, 3D stainless-steel electrodes, composed of octahedral lattice, were fabricated using the 3D printing technique. Heat treatment was conducted to form an iron-oxide layer on the electrode surface for increasing biocompatibility. Another crucial parameter that determines current production is the pitch length of a lattice electrode as it affects the surface area and substrate diffusion. The pitch length was optimized by testing the lattice electrodes with pitches ranging from 1.5 mm to 6.0 mm. The highest current, obtained with the 3.0 mm-pitch electrode, was 50% higher than that obtained with common 3D carbon-felt electrodes. These results demonstrate the usefulness of 3D lattice-structured metal electrodes in BESs.

Short-Term Clinical Outcomes Following Total Ankle Arthroplasty Without Concomitant Osteotomy in Ankles with Severe Preoperative Varus Deformity: Comparison to Ankles with Preoperative Neutral Alignment.

BACKGROUND: It remains controversial whether satisfactory outcomes can be obtained following total ankle arthroplasty (TAA) without osteotomy in patients with severe varus ankle deformities. This study aimed to examine outcomes following TAA without concomitant osteotomies in patients with severe varus ankle alignment by comparing them with those in patients with neutral alignment. METHODS: Fifty-one patients (53 ankles; mean age, 71.4 ± 5.6 years) who underwent TAA using the TNK ankle prosthesis were examined (mean follow-up, 36.8 ± 17.8 months). Patients were allocated into groups according to the preoperative talar tilt (TT) angle: the neutral group (preoperative TT angle <10°; n = 37) and the varus group (preoperative TT angle ≥10°; n = 16). Outcome measures, including the Japanese Society for Surgery of the Foot scale, Self-Administered Foot Evaluation Questionnaire, ankle range of motion, and radiographic parameters, were assessed before surgery and at the final follow-up. RESULTS: Significant improvements were observed in clinical and radiographic outcomes in both groups after surgery. Postoperative Japanese Society for Surgery of the Foot scale and subscale scores of pain and shoes in the Self-Administered Foot Evaluation Questionnaire were not significantly different between the groups, whereas subscale scores of function, social, and health were greater in the varus group than in the neutral group at the final follow-up. Radiographic parameters, including TT angle and tibial axis-medial malleolus (TMM) angle, improved postoperatively and were not significantly different between the neutral (mean TT angle, 0.5 ± 0.7°; mean TMM angle, 16.0 ± 4.6°) and varus (meanTT angle, 0.4 ± 0.7°; meanTMM angle, 17.0 ± 5.3°) groups at the final follow-up. To achieve neutral alignment, adjunctive procedures were required more often in the varus group. CONCLUSIONS: Outcomes of TAA using the TNK ankle prosthesis were favorable in patients with severe varus ankle and in those with neutral ankle without concomitant osteotomy. Satisfactory outcomes could be achieved in patients with severe varus ankle alignment after TAA without concomitant osteotomy.

Dietary patterns before and during pregnancy and small for gestational age in Japan: a prospective birth cohort study.

BACKGROUND: Although small for gestational age (SGA) is a serious problem worldwide, the association of dietary patterns before and during pregnancy with SGA risk is unclear. We evaluated this association among Japanese pregnant women using three methods: reduced rank regression (RRR) and partial least squares (PLS), methods for extracting dietary patterns that can explain the variation of response variables, and principal component analysis (PCA), a method for extracting dietary patterns of the population. METHODS: Between July 2013 and March 2017, 22,493 pregnant women were recruited to the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a population-based prospective birth cohort study in Japan. Information on dietary intake was obtained using food frequency questionnaires, and dietary patterns were extracted using RRR, PLS, and PCA. Information on birth weight was obtained from obstetric records, and the birth weight SD score and SGA were defined by the method of the Japan Pediatric Society. The associations of dietary patterns with birth weight SD score and SGA risk were investigated using multiple linear regression and multiple logistic regression, respectively. RESULTS: A total of 17,728 mother-child pairs were included. The birth weight SD score was 0.15 ± 0.96, and the prevalence of SGA was 6.3%. The dietary patterns extracted by RRR and PLS were similar and characterized by a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages in both pre- to early pregnancy and from early to mid-pregnancy. Higher adoption of the RRR and PLS patterns in both periods was associated with an increased birth weight SD score and lower risk of SGA. In contrast, the PCA1 pattern was not associated with birth weight SD score or SGA risk in either period. Although the PCA2 pattern was associated with increased birth weight SD score from early to mid-pregnancy, no other associations with birth weight SD score or SGA risk were observed. CONCLUSIONS: The dietary pattern with a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages before and during pregnancy was associated with a decreased SGA risk in Japan.

Convergent evolutionary counterion displacement of bilaterian opsins in ciliary cells.

Opsins are universal photoreceptive proteins in animals. Vertebrate rhodopsin in ciliary photoreceptor cells photo-converts to a metastable active state to regulate cyclic nucleotide signaling. This active state cannot photo-convert back to the dark state, and thus vertebrate rhodopsin is categorized as a mono-stable opsin. By contrast, mollusk and arthropod rhodopsins in rhabdomeric photoreceptor cells photo-convert to a stable active state to stimulate IP3/calcium signaling. This active state can photo-convert back to the dark state, and thus these rhodopsins are categorized as bistable opsins. Moreover, the negatively charged counterion position crucial for the visible light sensitivity is different between vertebrate rhodopsin (Glu113) and mollusk and arthropod rhodopsins (Glu181). This can be explained by an evolutionary scenario where vertebrate rhodopsin newly acquired Glu113 as a counterion, which is thought to have led to higher signaling efficiency of vertebrate rhodopsin. However, the detailed evolutionary steps which led to the higher efficiency in vertebrate rhodopsin still remain unknown. Here, we analyzed the xenopsin group, which is phylogenetically distinct from vertebrate rhodopsin and functions in protostome ciliary cells. Xenopsins are blue-sensitive bistable opsins that regulate cAMP signaling. We found that a bistable xenopsin of Leptochiton asellus had Glu113 as a counterion but did not exhibit elevated signaling efficiency. Therefore, our results show that vertebrate rhodopsin and L. asellus xenopsin regulate cyclic nucleotide signaling in ciliary cells and displaced the counterion position from Glu181 to Glu113 via convergent evolution, whereas subsequently only vertebrate rhodopsin elevated its signaling efficiency by acquiring the mono-stable property.

Creation of photocyclic vertebrate rhodopsin by single amino acid substitution.

Opsins are universal photoreceptive proteins in animals and can be classified into three types based on their photoreaction properties. Upon light irradiation, vertebrate rhodopsin forms a metastable active state, which cannot revert back to the original dark state via either photoreaction or thermal reaction. By contrast, after photoreception, most opsins form a stable active state which can photoconvert back to the dark state. Moreover, we recently found a novel type of opsins whose activity is regulated by photocycling. However, the molecular mechanism underlying this diversification of opsins remains unknown. In this study, we showed that vertebrate rhodopsin acquired the photocyclic and photoreversible properties upon introduction of a single mutation at position 188. This revealed that the residue at position 188 contributes to the diversification of photoreaction properties of opsins by its regulation of the recovery from the active state to the original dark state.

Effects of organic carbon and sulfide on the anammox reaction in the anoxic column in the SRDAPN process for treating high-strength wastewater.

Low energy consumption treatment of high-strength wastewater is crucial in controlling groundwater pollution and eutrophication in closed waterbodies. In this study, the sulfate reduction, denitrification/anammox, and partial nitrification (SRDAPN) process, which is an effective organic carbon and nitrogen removal process with low energy consumption for low strength wastewater, was applied to treat livestock wastewater with high COD and sulfate concentration, and microbial reaction and community were examined using an anaerobic-anoxic biological filter reactor that simulates circulation from an aerobic reactor. At a total organic carbon loading rate of 2.7-5.8 kgC/m3·day, sulfate reduction and methane production occurred simultaneously in the anaerobic column of the reactor. Specifically, sulfate reduction resulted in organic matter removal rates of 38 and 26% at ambient temperature and 25 °C, respectively. Furthermore, both heterotrophic and autotrophic denitrification occurred in the anoxic column, and when the organic loading rate in the anoxic reactor was below 0.2 kgC/m3·day, 33%-37% of ammonium and 33%-34% of nitrite were removed by the anammox reaction. Heterotrophic denitrification bacteria (Thauera, Comamonas, and Denitratisoma) and sulfur denitrification bacteria (Sulfurimonas denitrificans) grew in the lower and middle parts of the anoxic column, whereas anammox bacteria (2.5% of Candidatus Brocadia at ambient temperature and 9.4% of Candidatus Kuenenia at 25 °C) grew in the upper part of the anoxic column. These results indicate that the SRDAPN process based on sulfur cycle and anammox is useful for treatment of high strength wastewater with low energy consumption.

Amino acid residue at position 188 determines the UV-sensitive bistable property of vertebrate non-visual opsin Opn5.

Opsins are G protein-coupled receptors specialized for photoreception in animals. Opn5 is categorized in an independent opsin group and functions for various non-visual photoreceptions. Among vertebrate Opn5 subgroups (Opn5m, Opn5L1 and Opn5L2), Opn5m and Opn5L2 bind 11-cis retinal to form a UV-sensitive resting state, which is inter-convertible with the all-trans retinal bound active state by photoreception. Thus, these opsins are characterized as bistable opsins. To assess the molecular basis of the UV-sensitive bistable property, we introduced comprehensive mutations at Thr188, which is well conserved among these opsins. The mutations in Opn5m drastically hampered 11-cis retinal incorporation and the bistable photoreaction. Moreover, T188C mutant Opn5m exclusively bound all-trans retinal and thermally self-regenerated to the original form after photoreception, which is similar to the photocyclic property of Opn5L1 bearing Cys188. Therefore, the residue at position 188 underlies the UV-sensitive bistable property of Opn5m and contributes to the diversification of vertebrate Opn5 subgroups.

Evaluating folic acid supplementation among Japanese pregnant women with dietary intake of folic acid lower than 480 µg per day: results from TMM BirThree Cohort Study.

OBJECTIVE: In Japan, supplementation with 400 µg of folic acid per day is recommended for women who are planning to get pregnant to decrease the risk of their babies getting neural tube defects (NTD). However, the proportion of women who have taken folic acid supplements before conception is low among Japanese pregnant women. In addition, the dietary intake of folic acid has not yet reached the government recommended dietary intake levels (480 µg per day). This study aimed to clarify the prevalence and determinants of adequate folic acid supplements among Japanese pregnant women with dietary folic acid intake lower than 480 µg per day. METHODS: This cross-sectional study was a part of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. We collected information on folic acid supplements before conception, sociological/lifestyle characteristics, and food consumption. The primary outcome was the use of folic acid supplements (adequate or inadequate, based on the timing of initiation of folic acid supplements). Multiple logistic regression analysis was used to examine the association between sociological/lifestyle characteristics and the adequate intake of folic acid supplements. RESULTS: Among the 11,562 pregnant women who took lower than 480 µg per day of folic acid from food, the prevalence of adequate users was 18.0%. Pregnant women who reported adequate use of folic acid supplements were more likely to be older and educated; and reported higher household income, and history of fertility treatment. Conversely, they were less likely to be ever or current smokers and multipara. CONCLUSION: This study found that the prevalence of folic acid supplements use for the prevention of NTD among Japanese pregnant women was still low.