[Improved Indophenol Titration Method for Ascorbic Acid Using a Dropper and Electronic Balance: Enhanced Convenience and Efficiency].

The analysis of ascorbic acid using the 2,6-dichloroindophenol (DCIP) titration method is a well-established technique, but requires the skilled handling of a burette for accurate measurements. In the present study, we propose a modified DCIP titrimetric method that replaces the burette with a dropper and employs an electronic balance to measure the titrated amount by weight. The dropper used can be flexibly selected, allowing for a wide range of drop sizes, from large to very small. This modification offers several advantages, including lower skill requirements, a 43% reduction in the analysis time, a 50% decrease in sample/reagent consumption, and the ability to prepare DCIP standard solutions tailored to the concentration of ascorbic acid in the sample being analyzed. Our analysis of several food samples using this improved method showed that inherent issues of the DCIP method, such as determining the titration end point, could not be resolved. Nevertheless, the improved titration method remains more convenient and adaptable than the original approach using a burette, enabling quick and accurate analysis, especially for unskilled analysts.

Differences in health literacy related to gestational weight gain and children's birth weight according to maternal nativity status in the Japan Environment and Children's Study (JECS): a longitudinal cohort study.

OBJECTIVES: We examined literacy related to healthy gestational weight gain (GWG) in immigrant and native Japanese mothers and determined whether it is associated with children's birth weight. DESIGN: Longitudinal cohort study. SETTING: As the baseline survey in the Japan Environment and Children's Study (JECS), mothers completed self-administered questionnaires distributed by hand during pregnancy. The self-administered questionnaires used in this study were distributed by mail 6 months after delivery. Children's birth weight, actual GWG and any complications during delivery were recorded by obstetricians collaborating with JECS. PARTICIPANTS: Of 97 452 mothers who consented to participate in the JECS during pregnancy between January 2011 and March 2014, 67 953 were included in this study after exclusions for multiple births, multiple instances of consent by the same pregnant woman, miscarriages/stillbirths or withdrawal from the study within 3 years after participating. In total, 324 immigrant mothers and 963 native Japanese mothers were selected by propensity score matching for analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Data were collected on maternal literacy related to healthy GWG at the baseline survey, and data on actual GWG and children's birth weight were collected by obstetricians. The associations of knowledge about healthy GWG and mothers' actual GWG with maternal nativity status were examined using a χ2 or Student's t-test. RESULTS: More native Japanese mothers than immigrant mothers knew the appropriate GWG and reason the for needing to know this. Actual GWG was significantly higher among the immigrant mothers, but was within the recommended range. The low birthweight (LBW) incidence was significantly higher among the native mothers. CONCLUSIONS: Immigrant mothers to Japan had less knowledge about appropriate GWG, but their actual GWG was appropriate and they delivered fewer LBW infants than native Japanese mothers. These findings may indicate the presence of other protective factors for pregnancy or delivery among immigrant mothers.

Enhanced Cochlear Transduction by AAV9 with High-Concentration Sucrose.

The inner ear is a primary lesion in sensorineural hearing loss and has been a target in gene therapy. The efficacy of gene therapy depends on achieving sufficient levels of transduction at a safe vector dose. Vectors derived from various adeno-associated viruses (AAVs) are predominantly used to deliver therapeutic genes to inner ear cells. AAV9 and its variants vector are attractive candidates for clinical applications since they can cross the mesothelial cell layer and transduce inner hair cells (IHCs), although this requires relatively high doses. In this study, we investigated the effects of sucrose on the transduction of a variant of the AAV9 vector for gene transfer in the inner ear. We found that high concentrations of sucrose increased gene transduction in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells in vitro. In addition, we demonstrated that simultaneous administration of sucrose enhanced the transduction of mouse IHCs and spiral ligament cells using an AAV9 variant vector. The procedure did not increase the thresholds in the auditory brainstem response, suggesting that sucrose had no adverse effect on auditory function. This versatile method may be valuable in the development of novel gene therapies for adult-onset sensorineural hearing loss.

Usefulness of measuring fast valley height rate using high-performance liquid chromatography for variant hemoglobin, Hb A2-Niigata.

We have reported cases of hemoglobin (Hb) A2-Niigata (δ1Val → Ala) with δ chain variant Hb and falsely high HbA1c levels. In subjects with Hb A2-Niigata, shoulder-shaped anomalous peak was detected immediately before the HbA1c peaks using high-performance liquid chromatography (HPLC; HLC-723 G9). The phenomenon where the valley between peaks of LA1c+ , a fraction containing labile HbA1c, and HbA1c fraction [fast valley (FV)] became shallow owing to the anomalous peak was observed. In this study, we attempted to quantify the height index of the FV. We assumed that the index FV height rate (FVHR) was useful for screening Hb A2-Niigata. Five subjects with Hb A2-Niigata were compared with the control group of 50 subjects without diabetes and 50 with diabetes. Various indices were measured using HPLC chromatograms, and FVHR was calculated based on these indices. FVHR in subjects with Hb A2-Niigata was significantly higher than that in subjects without and with diabetes (all P < 0.001). Furthermore, when the cutoff value of FVHR was set at 23-30%, Hb A2-Niigata could be diagnosed with high sensitivity and specificity (both 100%). Hb A2-Niigata can be screened using FVHR with high sensitivity and specificity. FVHR might be also useful for screening other variant hemoglobins with abnormal HPLC chromatograph.

Early distribution of18 F-labeled AAV9 vectors in the cerebrospinal fluid after intracerebroventricular or intracisternal magna infusion in non-human primates.

BACKGROUND: The delivery of adeno-associated virus (AAV) vectors via the cerebrospinal fluid (CSF) has emerged as a valuable method for widespread transduction in the central nervous system. Although infusion into the cerebral ventricles is a common protocol in preclinical studies of small animals, the cisterna magna has been recognized as an alternative target for clinical studies because it can be reached in a less invasive manner using an intrathecal catheter via the subarachnoid space from a lumbar puncture. METHODS: We evaluated the early distribution of fluorine-18-labeled AAV9 vectors infused into the lateral ventricle or cisterna magna of four non-human primates using positron emission tomography. The expression of the green fluorescent protein was immunohistochemically determined. RESULTS: In both approaches, the labeled vectors diffused into the broad arachnoid space around the brain stem and cervical spinal cord within 30 min. Both infusion routes efficiently transduced neurons in the cervical spinal cord. CONCLUSIONS: For gene therapy that primarily targets the cervical spinal cord and brainstem, such as amyotrophic lateral sclerosis, cisterna magna infusion would be a feasible and effective administration method.

Repeated Lineage Switches in an Elderly Case of Refractory B-Cell Acute Lymphoblastic Leukemia With MLL Gene Amplification: A Case Report and Literature Review.

Lineage switches in acute leukemia occur rarely, and the underlying mechanisms are poorly understood. Herein, we report the case of an elderly patient with leukemia in which the leukemia started as B-cell acute lymphoblastic leukemia (B-ALL) and later changed to B- and T-cell mixed phenotype acute leukemia (MPAL) and acute myeloid leukemia (AML) during consecutive induction chemotherapy treatments. A 65-year-old woman was initially diagnosed with Philadelphia chromosome-negative B-ALL primarily expressing TdT/CD34/HLA-DR; more than 20% of the blasts were positive for CD19/CD20/cytoplasmic CD79a/cytoplasmic CD22/CD13/CD71.The blasts were negative for T-lineage markers and myeloperoxidase (MPO). Induction chemotherapy with the standard regimen for B-ALL resulted in primary induction failure. After the second induction chemotherapy regimen, the blasts were found to be B/T bi-phenotypic with additional expression of cytoplasmic CD3. A single course of clofarabine (the fourth induction chemotherapy regimen) dramatically reduced lymphoid marker levels. However, the myeloid markers (e.g., MPO) eventually showed positivity and the leukemia completely changed its lineage to AML. Despite subsequent intensive chemotherapy regimens designed for AML, the patient's leukemia was uncontrollable and a new monoblastic population emerged. The patient died approximately 8 months after the initial diagnosis without experiencing stable remission. Several cytogenetic and genetic features were commonly identified in the initial diagnostic B-ALL and in the following AML, suggesting that this case should be classified as lineage switching leukemia rather than multiple simultaneous cancers (i.e., de novo B-ALL and de novo AML, or primary B-ALL and therapy-related myeloid neoplasm). A complex karyotype was persistently observed with a hemi-allelic loss of chromosome 17 (the location of the TP53 tumor suppressor gene). As the leukemia progressed, the karyotype became more complex, with the additional abnormalities. Sequential target sequencing revealed an increased variant allele frequency of TP53 mutation. Fluorescent in situ hybridization (FISH) revealed an increased number of mixed-lineage leukemia (MLL) genes, both before and after lineage conversion. In contrast, FISH revealed negativity for MLL rearrangements, which are well-known abnormalities associated with lineage switching leukemia and MPAL. To our best knowledge, this is the first reported case of acute leukemia presenting with lineage ambiguity and MLL gene amplification.

Genomic diversity and intragenic recombination of species C rotaviruses.

Rotavirus C (RVC) is a major cause of diarrhoea in swine, cattle, and humans worldwide. RVC exhibits sequence diversity in all 11 genes, especially in VP4 and VP7, and all segment-based genotyping has been performed similar to rotavirus A. To date, recombination events have been reported in rotavirus A and B. However, there are no reports describing gene recombination of RVC, except for recombination in NSP3 between RVC and rotavirus H. In this study, nine porcine RVC strains identified in Japanese pigs were completely sequenced and analysed together with RVC sequences from the GenBank database. The analyses showed that sequences of the VP4, VP2, and NSP1 of several porcine RVC strains did not branch with any of those of the RVC strains in the GenBank database, suggesting new genotypes. Several homologous recombination events, between or within genotypes, were identified in the VP4, VP7, VP2, NSP1, and NSP3 genes. Of these, nine, one, and one intergenotypic recombination events in the VP4, VP2, and NSP3 genes, respectively, were supported with sufficient statistical values. Although these findings suggest occurrences of the intragenic recombination events in the RVC genome, potential sequence errors and poor sequence assemblies in the databases should be watched with care. The results in this study present data about the important recombination events of the RVCs, which influence evolution of the virus by aiding them to gain genetic diversity and plasticity, although further sequence data will be necessary to obtain more comprehensive understanding of such mechanisms.

Probiotics including Clostridium butyricum, Enterococcus faecium, and Bacillus subtilis may prevent recurrent spontaneous preterm delivery.

AIM: A large cohort study of Japanese women reported that the rate of recurrent spontaneous preterm delivery (sPTD) in the next pregnancy was 22.3%; therefore, it is important to prevent recurrent sPTD. The present study investigated the rate of recurrent sPTD in pregnant women treated with probiotics. METHODS: This was a retrospective study. Fifty-one pregnant women with a history of sPTD and who had been taking probiotics before 14 weeks of gestation were selected. The rate of sPTD in the next pregnancy among 255 pregnant women with a history of sPTD who had not taken probiotics was compared with that in the probiotics group. RESULTS: The rate of recurrent sPTD was 9.8% (5/51), which was lower than previously reported values. Furthermore, the rate of recurrent sPTD was significantly lower in the probiotics group (9.8%) than in the nonprobiotics group (31.0% [79/255]; p = 0.002). CONCLUSIONS: Probiotics may reduce the rate of recurrent sPTD.

Provision of educational events and subsequent questionnaire response rates in a large-scale birth cohort study from Japan.

OBJECTIVES: We examined whether providing educational events for participants in a birth cohort study would increase the response rates of study questionnaires. DESIGN: Birth cohort study. SETTING: Questionnaires were distributed and returned by post twice in 1 year. We developed and implemented two educational sessions; a Baby Food lecture for mothers with children around 8 months old (analysis 1) and a Eurythmic session for mothers with children around 1 year and 8 months old (analysis 2). Mothers with children over the target ages were not invited (not-invited group). The invited participants were divided into three groups: those who did not apply to attend (not-applied group), those who applied but did not attend (applied group), and those who applied and attended (attended group). PARTICIPANTS: The participants were 5379 mother-child pairs registered with the Toyama Regional Center of the Japan Environment and Children's Study (JECS). OUTCOME MEASURE: The outcome measure was return of the JECS questionnaire for 1 year old sent out after the Baby Food lecture and the JECS questionnaire for 2 years old sent out after the Eurythmic session. The questionnaires were returned to us by post. RESULTS: The response rate for the attended group of the Baby Food lecture was 99.7%, and the odds ratio (OR) was significantly higher for this group than for the not-invited group (crude OR 24.54; 95% confidence interval (CI) 3.42 to 176.13; analysis 1). After the exclusion of participants who had previously attended the Baby Food lecture, the response rate for the attended group of the Eurythmic session was 97.8%, and the OR was significantly higher for this group than for the not-invited group (adjusted OR 5.66; 95% CI 1.93 to 16.54; analysis 2). CONCLUSION: Providing educational events that are appropriate to the age and needs of the participants may increase questionnaire response rates in birth cohort studies. TRIAL REGISTRATION NUMBER: UMIN 000030786.

Oral Gonadotropin-Releasing Hormone Antagonist Relugolix Has the Same Effect as Gonadotropin-Releasing Hormone Agonist Injections in Terms of Preparation for Transcervical Resection Myomectomy.

For preparing the optimal condition in transcervical resection (TCR) surgery, gonadotropin-releasing hormone (GnRH) agonist has been utilized. Recently, an oral GnRH antagonist (relugolix) is available and acts directly on GnRH receptor, avoiding flare up and reducing blood E2 levels rapidly. We retrospectively compared the oral GnRH antagonist (n = 14) effect to that of subcutaneous GnRH agonist (n = 19) for the pretreatment of endometrium in TCR myomectomy. Endometrial thickening was determined by intraoperative videos. The color tone of the endometrium in the normal part was assessed by digital image processing. The median duration of the first GnRH agonist injection and the surgery was 67 days (21-136 days), which is significantly longer than that of the oral GnRH antagonist group, 18.5 days (7-157 days P < 0.01). Both the GnRH agonist and antagonist groups did not exhibit prominence in the endometrium. The GnRH antagonist group showed the same degree of whiteness in the normal endometrium as the GnRH agonist group. The oral GnRH antagonist administration could rapidly atrophy the endometrium and create an optimal surgical field for TCR in a short period.

Pre-eclampsia Complicated With Maternal Renal Dysfunction Is Associated With Poor Neurological Development at 3 Years Old in Children Born Before 34 Weeks of Gestation.

Objective: The purpose of this study was to investigate perinatal factors associated with a poor neurodevelopmental outcome in preterm infants. Methods: A retrospective study was conducted by searching our clinical database between January 2006 and December 2016. A total of 165 singleton children who were born between 23 and 33 weeks of gestation were included. We defined poor neurological development outcomes as follows: cerebral palsy; intellectual disability; developmental disorder including autism and attention-deficit/hyperactivity disorder; low score (<85 points) on Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III); or low score of Kyoto Scale of Psychological Development corrected at 3 years old. We diagnosed maternal renal dysfunction according to the Clinical Practice Guideline for chronic kidney disease 2018 and the Best Practice Guide 2015 for Care and Treatment of Hypertension in Pregnancy. Results: The rate of poor neurological development was 25/165 (15.2%): cerebral palsy (n = 1), intellectual disability (n = 1), developmental disorder (n = 2), low score of Bayley-III (n = 20), and low score of Kyoto Scale of Psychological Development (n = 1). Preeclampsia complicated with maternal renal dysfunction (P = 0.045) and delivery at <30 weeks of gestation (P = 0.007) were independent risk factors for poor neurological development. Conclusions: In addition to previous risk factors such as delivery at <30 weeks of gestation, preeclampsia complicated with renal dysfunction was also associated with poor neurodevelopmental outcomes corrected at 3 years old.

Association between maternal smoking history and congenital anomalies in children: Results from the Japan Environment and Children's Study.

We investigated the relationship between maternal smoking history and congenital anomalies in children. Drawing on data from the Japan Environment and Children's Study collected between January 2011 and March 2014, the smoking habits of pregnant women were categorized as "never smoked," "quit before pregnancy, "quit after pregnancy," and "full smoking." Of the 91 626 participants examined, a total of 2199 (2.4%) infants were born with any congenital anomalies. Logistic regression analysis was used to determine the odds ratio for congenital anomalies in each group based on maternal smoking history. No significant difference was seen between the full-smoking and never smoked groups in the odds ratios for congenital anomalies of the nervous system; the eyes, ears, face, and neck; the cardiovascular system; or the musculoskeletal system. However, in the full-smoking group, the odds ratios for trisomy (adjusted odds ratio, 2.14; 95% confidence interval, 1.15-3.97) and any congenital anomalies (adjusted odds ratio, 1.35; 95% confidence interval, 1.09-1.67) were significantly higher compared with the never smoked group. Our results indicate that continuing to smoke during pregnancy is associated with increased risk of trisomy and any congenital anomalies in the general Japanese population.

Engineered adeno-associated virus 3 vector with reduced reactivity to serum antibodies.

The natural serotypes of adeno-associated virus (AAV) or their variants, such as AAV8 and AAV5, are commonly used as vectors in the clinical programs for liver-targeted gene therapy. While AAV8 vectors are not highly efficient at targeting primary human hepatocytes, AAV3 vectors have recently demonstrated remarkable efficiency at targeting both human and non-human primate hepatocytes. However, the presence of high levels of neutralizing antibodies (NAbs) impedes transduction into hepatocytes, representing a major obstacle to the clinical application of AAV3 vectors. Herein, we engineered the viral capsid to reduce its reactivity with pre-existing NAbs, thereby enhancing the transduction efficiency. By introducing three substitutions (S472A, S587A, and N706A) on the surface loop of AAV3B capsid protein, we generated a triple mutant AAV3 (AAV.GT5) vector with less reactivity to anti-AAV capsid NAbs. While the transduction efficiency of AAV.GT5 into human hepatocellular cell lines was similar to those of parental AAV3B, it was 50-fold higher for hepatocytes derived from humanized mice compared to AAV8 vectors. Moreover, the AAV.GT5 vector yield was similar to those of the AAV2 and AAV3B vectors. Thus, high resistance to pre-existing NAbs makes AAV.GT5 a promising candidate for future liver-targeted gene therapy clinical trials.

Intra-cisterna magna delivery of an AAV vector with the GLUT1 promoter in a pig recapitulates the physiological expression of SLC2A1.

Glucose transporter 1 deficiency syndrome (GLUT1DS) is caused by haplo-insufficiency of SLC2A1, which encodes GLUT1, resulting in impaired hexose transport into the brain. Previously, we generated a tyrosine-mutant AAV9/3 vector in which SLC2A1 was expressed under the control of the endogenous GLUT1 promoter (AAV-GLUT1), and confirmed the improved motor function and cerebrospinal fluid glucose levels of Glut1-deficient mice after cerebroventricular injection of AAV-GLUT1. In preparation for clinical application, we examined the expression of transgenes after intra-cisterna magna injection of AAV-GFP (tyrosine-mutant AAV9/3-GFP with the CMV promoter) and AAV-GLUT1. We injected AAV-GFP or AAV-GLUT1 (1.63 × 1012 vector genomes/kg) into the cisterna magna of pigs to compare differential promoter activity. After AAV-GFP injection, exogenous GFP was expressed in broad areas of the brain and peripheral organs. After AAV-GLUT1 injection, exogenous GLUT1 was expressed predominantly in the brain. At the cellular level, exogenous GLUT1 was mainly expressed in the endothelium, followed by glia and neurons, which was contrasted with the neuronal-predominant expression of GFP by the CMV promotor. We consider intra-cisterna magna injection of AAV-GLUT1 to be a feasible approach for gene therapy of GLUT1DS.

3 cases of variant hemoglobin Hb A2-Niigata detected by falsely high HbA1c values.

BACKGROUND: HbA1c measurements in blood are used to monitor diabetes status. METHODS: We detected 3 cases (1 diabetic case, 1 borderline diabetic case, and 1 case with normal glucose tolerance) of variant hemoglobin Hb A2-Niigata based on falsely high HbA1c values measured by high-performance liquid chromatography (HPLC). RESULTS: In all 3 cases, HbA1c values measured by the HPLC method were higher than the reference range whereas the HbA1c values measured by immunoassay, plasma glucose and glycated albumin were within the reference range. The results of the genetic test revealed heterozygous mutation GTG (Val) → GCG (Ala) in codon 1 of the δ-globin gene in all 3 cases, based on which Hb A2-Niigata was found. Although until now Hb A2-Niigata has been reported in 3 cases, this is the first report on Hb A2-Niigata with falsely high HbA1c values. CONCLUSIONS: In this report, 3 cases of Hb A2-Niigata were found in a single institution in a short period; therefore, Hb A2-Niigata would exist frequently in a certain area. As a pathology causing falsely high HbA1c values, Hb A2-Niigata should be kept in mind.

Maternal dietary intake of fish and PUFAs and child neurodevelopment at 6 months and 1 year of age: a nationwide birth cohort-the Japan Environment and Children's Study (JECS).

BACKGROUND: Although emerging evidence indicates a relation between maternal intake of fish and improved child neurodevelopment, the results are inconsistent. OBJECTIVES: This study investigated whether dietary consumption of fish during pregnancy is associated with offspring neurodevelopment at age 6 mo and 1 y. As exploratory research, we also examined the association between consumption of PUFAs and neurodevelopment at the same time points. METHODS: After exclusion and multiple imputation from a dataset comprising 104,065 records from the Japan Environment and Children's Study, we evaluated 81,697 and 77,751 mother-child pairs at age 6 mo and 1 y, respectively. RESULTS: Maternal fish intake during pregnancy was independently associated with reduced risk of delay in problem-solving at age 6 mo (lowest compared with highest quintile OR = 0.88; 95% CI: 0.79, 0.99; P-trend = 0.01) and in fine motor skills (highest quintile OR = 0.90; 95% CI: 0.81, 0.99; P-trend = 0.02) and problem-solving (fourth quintile OR = 0.89; 95% CI: 0.81, 0.98; and highest quintile OR = 0.90; 95% CI: 0.81, 0.99; P-trend = 0.005) at age 1 y. Dietary intake of total n-3 PUFAs was associated with reduced risk of delay in fine motor skills at 6 mo, and in fine motor skills and problem-solving at 1 y. Dietary intake of total n-6 PUFAs was associated with reduced risk of delay in communication and fine motor skills at 6 mo, and in gross motor skills, fine motor skills, and problem-solving at 1 y. In contrast, the dietary n-6/n-3 ratio was positively associated with increased risk of delay in problem-solving at 1 y. CONCLUSIONS: The results of this study suggest there might be beneficial effects of fish intake during pregnancy on some domains of child psychomotor development and this effect might be partially explained by PUFA intake from fish. Trial registration: UMIN000030786.

Association of blood cadmium levels in pregnant women with infant birth size and small for gestational age infants: The Japan Environment and Children's study.

BACKGROUND: There is growing evidence of an association between cadmium (Cd) and unfavorable birth outcomes. The effect of Cd exposure on anthropometric measures at birth or small for gestational age (SGA) infants in a large, nationwide Japanese cohort remains to be clarified. OBJECTIVES: To analyze the association between maternal blood Cd levels at different sampling times and sex-dependent infant birth size, weight, body length, chest, and head circumferences, in addition to SGA. METHODS: Data of 17,584 pregnant women in the Japan Environment and Children's Study were analyzed for anthropometric measurements. For SGA determination, 13,969 cases of vaginal delivery were analyzed after excluding infants born by cesarean section. Maternal blood Cd levels were categorized into quartiles (Q1-Q4), and the Q1 was used as a reference. Multiple linear regression analysis was performed for anthropometric measurements, and multiple logistic regression analysis was used to investigate the association of maternal blood Cd levels with the risk of SGA. RESULTS: Birth weight tended to decrease according to the increase in quartiles of blood Cd levels (15.63 g decrease [95% confidence level (CI): -33.26, 2.01] for Q4). The overall analysis revealed no decreases in body length and head and chest circumference, but subgroup analysis revealed that chest circumference tended to decrease according to the increase in quartiles in the female sex/third-trimester stratification (0.16 cm decrease [95% CI: -0.32, 0.00] for Q4). SGA risk was also higher and paralleled the increase in blood Cd levels associated with the female sex/third-trimester group (Odds Ratio 1.90 [95% CI: 1.23, 2.94] for Q4). CONCLUSION: Our results provide further evidence of sex-specific health risks associated with Cd exposure in early life in a large Japanese pregnancy cohort.

Effects of combining exercise with long-chain polyunsaturated fatty acid supplementation on cognitive function in the elderly: a randomised controlled trial.

Multifactorial lifestyle intervention is known to be more effective for ameliorating cognitive decline than single factor intervention; however, the effects of combining exercise with long-chain polyunsaturated fatty acids (LCPUFA) on the elderlies' cognitive function remain unclear. We conducted a randomised, single-masked placebo-controlled trial in non-demented elderly Japanese individuals. Participants were randomly allocated to the exercise with LCPUFA, placebo, or no exercise with placebo (control) groups. Participants in the exercise groups performed 150 min of exercise per week, comprised resistance and aerobic training, for 24 weeks with supplements of either LCPUFA (docosahexaenoic acid, 300 mg/day; eicosapentaenoic acid, 100 mg/day; arachidonic acid, 120 mg/day) or placebo. Cognitive functions were evaluated by neuropsychological tests prior to and following the intervention. The per-protocol set analysis (n = 76) revealed no significant differences between the exercise and the control groups in changes of neuropsychological tests. Subgroup analysis for participants with low skeletal muscle mass index (SMI) corresponding to sarcopenia cut-off value showed changes in selective attention, while working memory in the exercise with LCPUFA group was better than in the control group. These findings suggest that exercise with LCPUFA supplementation potentially improves attention and working memory in the elderly with low SMI.

Dietary intake of fish and n-3 polyunsaturated fatty acids and risk of postpartum depression: a nationwide longitudinal study - the Japan Environment and Children's Study (JECS).

BACKGROUND: Pregnant women require increased levels of n-3 polyunsaturated fatty acids (PUFAs) due to the demands of the growing fetus. Although some evidence indicates that maternal intake of fish and n-3 PUFAs is associated with reduced risk of postpartum depression, the results are inconsistent. METHODS: We investigated whether dietary consumption of fish and/or n-3 PUFAs during pregnancy is associated with a reduced risk of maternal postpartum depression at 6 months after delivery and of serious mental illness at 1 year in a Japanese population. After exclusion and multiple imputation from a dataset comprising 103 062 pregnancies obtained in the Japan Environment and Children's Study, we evaluated 84 181 and 81 924 women at 6 months and 1 year after delivery, respectively. RESULTS: Multivariable logistic regression showed a reduced risk of postpartum depression at 6 months in the second to fifth quintiles v. the lowest quintile for fish and n-3 PUFA intake, with trend tests also revealing a significant linear association. At 1 year after delivery, fish intake was associated with a reduced risk of serious mental illness in the second to fifth quintiles v. the lowest quintile for fish and in the third to fifth quintiles v. the lowest quintile for n-3 PUFA intake, with trend tests also revealing a significant linear association. CONCLUSIONS: Women with higher fish and/or n-3 PUFA intake showed reduced risk of postpartum depression at 6 months after delivery and of serious mental illness at 1 year after delivery.

Intracellular build-up RNAi with single-strand circular RNAs as siRNA precursors.

We herein report a new approach for RNA interference, so-called "build-up RNAi" approach, where single-strand circular RNAs with a photocleavable unit or disulfide moiety were used as siRNA precursors. The advantages of using these circular RNA formats for RNAi were presented in aspects of immunogenicity and cellular uptake.