Prevalence, Risk Factors, and Perinatal Outcomes of Velamentous Umbilical Cord Insertion in Twin Pregnancies: A Single-Center Retrospective Study.

BACKGROUND: The effect of velamentous cord insertion (VCI) on perinatal outcomes in twin pregnancies is unclear due to conflicting findings. This retrospective study aimed to examine VCI prevalence and related risk factors in twin pregnancies and its association with adverse perinatal outcomes. METHODS: Women with twin pregnancies who delivered between January 2012 and December 2021 in a single tertiary hospital were included. The participants were divided into dichorionic (DC) and monochorionic diamniotic (MCDA) groups, and their maternal and fetal characteristics and VCI rates were compared. Logistic regression models were used to identify risk factors for VCI and VCI-related perinatal outcomes. RESULTS: Among the 694 twin pregnancies included in this study, the VCI rate was significantly higher in MCDA than in DC twins. Body mass index and MCDA twins were significant risk factors for VCI, whereas assisted reproductive technology pregnancy was a significant protective factor against VCI. In DC twins, VCI did not affect perinatal outcomes. In MCDA twins, VCI was a significant risk factor for fetal growth restriction, twin-to-twin transfusion syndrome, and preterm birth at <36 weeks. CONCLUSIONS: VCI was a prominent risk factor for adverse perinatal outcomes only in MCDA twins. Antenatal sonographic assessment of the umbilical cord insertion site would be beneficial.

Analysis method for psychological and physiological responses to body massage "Using POMS and HRV".

This study aimed to compare and proposed an analytical method for evaluating the effectiveness of massage using various measurement parameters. The parameters were divided psychologically using the Profile of Mood States (POMS) and physiologically using heart rate variability. In the experiment, the psycho-physiological effects of the rest(a) and two massage techniques (b, c) were evaluated. The effect of each massage technique on the parameters was examined, and a statistical analysis approach for evaluating massage responses is given in the conclusion.Clinical Relevance- This case study compares and contrasts the differences and advantages of each statistical approach for analyzing on studying the effects of massage and presents the response results for two massage techniques.

Impact of the interpregnancy interval after cesarean delivery on subsequent perinatal risks: a retrospective study.

PURPOSE: To assess the impact of the interpregnancy interval (IPI) after cesarean delivery on the risks of adverse perinatal events during subsequent pregnancies. METHODS: We retrospectively examined perinatal outcomes of subsequent pregnancies of women whose most recent birth experience involved cesarean delivery at our hospital between January 2014 and December 2019. IPI was defined as the time between live birth and subsequent conception. Three IPI groups: < 18 months, 18-60 months, and > 60 months, were assessed. The risks of preterm birth, preeclampsia, placenta previa, placental abruption, fetal growth restriction, and successful vaginal birth were compared among the three IPI groups using uni- and multivariate analyses. RESULTS: We registered 592 births after cesarean delivery: 178, 288, and 126 in the IPI < 18 months, 18-60 months, and > 60 months groups, respectively. The groups did not differ significantly regarding perinatal outcomes. The multivariate analysis revealed no significant differences in the risks of adverse perinatal outcomes among all groups. The odds ratios (ORs) for preterm birth at < 37 weeks of gestation were 1.24 and 1.64 for those in the < 18 months and > 60 months groups, respectively (P = 0.362 and P = 0.055, respectively). The groups did not differ significantly regarding vaginal birth success rate (ORs 1.72 for the < 18 months group, 0.49 for the > 60 months group; P = 0.486 and P = 0.446, respectively). CONCLUSION: After cesarean delivery, IPIs shorter than 18 months and longer than 60 months do not significantly impact the risks of adverse perinatal outcomes or successful vaginal birth compared with IPIs of 18-60 months.

The efficacy of therapeutic cervical cerclage in singleton pregnancies: a retrospective study.

OBJECTIVES: We compared the pregnancy prolongation effect attributable to cervical cerclage to that achieved by conservative management, and determined the cervical length for which cervical cerclage is effective. METHODS: We retrospectively examined medical records of 281 women admitted to our hospital between January 2013 and December 2017 for management of threatened preterm birth at 22-28 weeks of gestation. Obstetricians determined suitability for cervical cerclage, which was performed using the McDonald procedure in all cases. Of the 281 subjects, 71 underwent cervical cerclage (cerclage group); the other 210 received conservative therapy (non-cerclage group). We recorded maternal and neonatal characteristics of all patients. The two groups were compared in terms of length of extension of pregnancy and weeks of gestation at delivery. Multivariate analysis was performed to identify factors associated with extension of time to delivery. RESULTS: Our analyses revealed that the cerclage group was hospitalized earlier in pregnancy than the non-cerclage group (23.7 ± 1.5 weeks vs. 26.4 ± 1.9 weeks, p < .001) and had shorter cervixes (6.0 ± 9.4 mm vs. 16.9 ± 13.0 mm, p < .001). The two groups did not differ significantly in terms of gestational weeks at delivery. Multivariate analysis regarding extension of pregnancy revealed significant differences in extension of pregnancy related with cervical cerclage (26.65 days, 95% CI 17.0 - 36.3, p < .001) and cervical length <10 mm (-27.4 days, 95% CI -36.0--18.8, p < .001). While the time to delivery was extended by cervical cerclage in women with short cervixes (<25 mm), the two groups did not differ when cervical length was ≥15 mm. CONCLUSIONS: Cervical cerclage was a significant positive factor and short cervix was a significant negative factor for elongating pregnancy. In primigravida and multigravida women with no history of preterm birth, when the cervix is short (<10 mm), cervical cerclage should be recommended.

Maternal Renal Dysfunction in Late Pregnancy in Twin and Singleton Pregnancies: Retrospective Study.

This study aimed to evaluate the differences in the impact on maternal renal function between singleton and twin pregnancies in the second half of pregnancy. It retrospectively enrolled 1711 pregnant women consisting of 1547 singleton pregnancies and 164 twin pregnancies from Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital from January 2019 to June 2021. Patients underwent renal function tests (serum blood urea nitrogen, creatinine, and estimated glomerular filtration rate (eGFR)) at least one month before delivery. The main outcome measure was maternal renal dysfunction, defined as a serum creatinine level above 0.8 mg/dL. The serum creatinine level was significantly higher and the eGFR was significantly lower in twin than in singleton pregnancies (p < 0.001). In addition, the rate of renal dysfunction was significantly higher in twin than in singleton pregnancies (7.9% vs. 2.6%; p < 0.01). Multivariate analysis revealed that twin pregnancy (odds ratio (OR) 3.38), nulliparity (OR 2.31), and preeclampsia (OR 3.64) were significant risk factors for maternal renal dysfunction. Maternal renal dysfunction was observed in 13 twin pregnancies, all of which recovered to within normal limits during the early months of the postpartum period. Twin pregnancy is a significant risk factor for maternal renal dysfunction; renal function should be carefully monitored in twin pregnancies.

Evaluation of the risk factors for antepartum hemorrhage in cases of placenta previa: a retrospective cohort study.

OBJECTIVE: The aim of this study was to examine the risk factors for antepartum hemorrhage (APH) in women with placenta previa. METHODS: In this retrospective cohort study, we analyzed the medical records of 233 women with singleton pregnancies presenting with placenta previa whose deliveries were performed at our hospital between January 2009 and July 2018. RESULTS: Of the 233 women included in this study, 130 (55.8%) had APH. In the APH group, the gestational age and neonatal birth weight were significantly lower compared with the no hemorrhage group. Maternal age <30 years and multiparity were identified as significant risk factors for APH in both the univariate and multivariate analyses. Focusing on the previous route of delivery in multiparous women, the risk of APH was significantly higher in multiparous women who had experienced at least one vaginal delivery compared with nulliparous women (adjusted odds ratio (OR): 3.42 [95% confidence interval: 1.83-6.38]). CONCLUSION: We showed that women with placenta previa who were under 30 years old and who had a history of vaginal delivery may be at significant risk of experiencing APH.

Comparison of the frequencies of ENU-induced point mutations in male germ cells and inherited germline mutations in their offspring.

BACKGROUND: Gene mutations induced in germ cells may be transmitted to the next generation and cause adverse effects such as genetic diseases. Certain mutations may result in infertility or death in early development. Thus, the mutations may not be inheritable. However, the extent to which point mutations in male germ cells are transmitted to the next generation or eliminated during transmission is largely unknown. This study compared mutation frequencies (MFs) in sperm of N-ethyl-N-nitrosourea (ENU)-treated gpt delta mice and de novo MFs in the whole exome/genome of their offspring. RESULTS: Male gpt delta mice were treated with 10, 30, and 85 mg/kg of ENU (i.p., weekly × 2) and mated with untreated females to generate offspring. We previously reported a dose-dependent increase in de novo MFs in the offspring estimated by whole exome sequencing (WES) (Mutat. Res., 810, 30-39, 2016). In this study, gpt MFs in the sperm of ENU-treated mice were estimated, and the MFs per reporter gene were converted to MFs per base pair. The inherited de novo MFs in the offspring (9, 26 and 133 × 10- 8/bp for 10, 30, and 85 mg/kg ENU-treated groups, respectively) were comparable to those of the converted gpt MFs in the sperm of ENU-treated fathers (6, 16, and 69 × 10- 8/bp). It indicated that the gpt MFs in the ENU-treated father's sperm were comparable to the inherited de novo MFs in the offspring as estimated by WES. In addition, de novo MFs in the offspring of 10 mg/kg ENU-treated and control fathers were estimated by whole genome sequencing (WGS), because WES was not sufficiently sensitive to detect low background MF. The de novo MF in the offspring of the ENU-treated fathers was 6 × 10- 8/bp and significantly higher than that of the control (2 × 10- 8/bp). There were no significant differences in de novo MFs between gene-coding and non-coding regions. WGS analysis was able to detect ENU-induced characteristic de novo base substitutions at a low dose group. CONCLUSIONS: Despite a difference between exome/genome and exogenous reporter genes, the results indicated that ENU-induced point mutations in male germ cells could be transmitted to the next generation without severe selection.

Evaluation of the risk of umbilical cord prolapse in the second twin during vaginal delivery: a retrospective cohort study.

OBJECTIVE: This study aimed to evaluate the success rate of vaginal delivery, the reasons for unplanned caesarean delivery, the rate of umbilical cord prolapse and the risk of umbilical cord prolapse in twin deliveries. DESIGN: Retrospective cohort study. SETTING: Single institution. PARTICIPANTS: This study included 455 women pregnant with twins (307 dichorionic and 148 monochorionic) who attempted vaginal delivery from January 2009 to August 2018. The following criteria were considered for vaginal delivery: diamniotic twins, cephalic presentation of the first twin, no history of uterine scar, no other indications for caesarean delivery, no major structural abnormality in either twin and no fetal aneuploidy. RESULTS: The rate of vaginal delivery of both twins was 89.5% (407 of 455), caesarean delivery of both twins was 7.7% (35 of 455) and caesarean delivery of only the second twin was 2.9% (13 of 455). The major reasons for unplanned caesarean delivery were arrest of labour and non-reassuring fetal heart rate pattern. The rate of umbilical cord prolapse in the second twin was 1.8% (8 of 455). Multivariate analysis revealed that abnormal umbilical cord insertion in the second twin (velamentous or marginal) was the only significant factor for umbilical cord prolapse in the second twin (OR, 5.05, 95% CI 1.139 to 22.472, p=0.033). CONCLUSIONS: Abnormal umbilical cord insertion in the second twin (velamentous or marginal) was a significant factor for umbilical cord prolapse during delivery. Antenatal assessment of the second twin's umbilical cord insertion using ultrasonography would be beneficial.

New homozygous gpt delta transgenic rat strain improves an efficiency of the in vivo mutagenicity assay.

BACKGROUND: Gene mutation assays in transgenic rodents are useful tools to investigate in vivo mutagenicity in a target tissue. Using a lambda EG10 transgene containing reporter genes, gpt delta transgenic mice and rats have been developed to detect point mutations and deletions. The transgene is integrated in the genome and can be rescued through an in vitro packaging reaction. However, the packaging efficiency is lower in gpt delta rats than in mice, because of the transgene in gpt delta rats being heterozygous and in low copy number. To improve the packaging efficiency, we herein describe a newly developed homozygous gpt delta rat strain. RESULTS: The new gpt delta rat has a Wistar Hannover background and has been successfully maintained as homozygous for the transgene. The packaging efficiency in the liver was 4 to 8 times higher than that of existing heterozygous F344 gpt delta rats. The frequency of gpt point mutations significantly increased in the liver and bone marrow of N-nitroso-N-ethylurea (ENU)- and benzo[a]pyrene (BaP)-treated rats. Spi- deletion frequencies significantly increased in the liver and bone marrow of BaP-treated rats but not in ENU-treated rats. Whole genome sequencing analysis identified ≥ 30 copies of lambda EG10 transgenes integrated in rat chromosome 1. CONCLUSIONS: The new homozygous gpt delta rat strain showed a higher packaging efficiency, and could be useful for in vivo gene mutation assays in rats.

Intraocular penetration of liposomal amphotericin B after intravenous injection in inflamed human eyes.

PURPOSE: To determine the intraocular penetration of amphotericin B (AMPH-B) after an intravenously injection of liposomal amphotericin B (L-AMB) in inflamed human eyes. METHODS: Seven eyes of 5 patients with fungal eye diseases (endophthalmitis in 6 eyes and keratitis in 1 eye) were treated with intravenous injections of 100-250 mg/day of L-AMB. Samples of blood, corneal button, aqueous humor, and vitreous humor were collected and assessed for AMPH-B. RESULTS: The AMPH-B level in the cornea (604.0 µg/g) of the case with fungal keratitis exceeded the minimum inhibitory concentration. However, the levels in the aqueous and vitreous humors of the cases with fungal endophthalmitis were lower, e.g., 0.02 ± 0.01 µg/ml (0.09% of serum level) in the aqueous humor and 0.05 ± 0.08 µg/ml (0.17% of serum level) in the vitreous humor. CONCLUSIONS: The AMPH-B levels administered intravenously were very low in the aqueous and vitreous humors. Our findings indicate that intravenous L-AMB can be considered only for patients with mild endogenous fungal endophthalmitis, e.g., isolated chorioretinitis without vitreous extensions.

Successful outcome of a pregnancy derived from premature ovulation in a gonadotropin-releasing hormone antagonist protocol: A case report.

In the gonadotropin-releasing hormone (GnRH) antagonist protocol, it is necessary to reinforce contraceptive guidance assuming that luteinizing hormone surge is not detected by measurement of serum level and ovulation is not suppressed by GnRH antagonist.

Benchmark dose analysis of multiple genotoxicity endpoints in gpt delta mice exposed to aristolochic acid I.

As the carcinogenic risk of herbs containing aristolochic acids (AAs) is a global health issue, quantitative evaluation of toxicity is needed for the regulatory decision-making and risk assessment of AAs. In this study, we selected AA I (AAI), the most abundant and representative compound in AAs, to treat transgenic gpt delta mice at six gradient doses ranging from 0.125 to 4 mg/kg/day for 28 days. AAI-DNA adduct frequencies and gpt gene mutation frequencies (MFs) in the kidney, as well as Pig-a gene MFs and micronucleated reticulocytes (MN-RETs) frequencies in peripheral blood, were monitored. The dose-response (DR) relationship data for these in vivo genotoxicity endpoints were quantitatively evaluated using an advanced benchmark dose (BMD) approach with different critical effect sizes (CESs; i.e., BMD5, BMD10, BMD50 and BMD100). The results showed that the AAI-DNA adduct frequencies, gpt MFs and the MN-RETs presented good DR relationship to the administrated doses, and the corresponding BMDL100 (the lower 90% confidence interval of the BMD100) values were 0.017, 0.509 and 3.9 mg/kg/day, respectively. No positive responses were observed in the Pig-a MFs due to bone marrow suppression caused by AAI. Overall, we quantitatively evaluated the genotoxicity of AAI at low doses for multiple endpoints for the first time. Comparisons of BMD100 values across different endpoints provide a basis for the risk assessment and regulatory decision-making of AAs and are also valuable for understanding the genotoxicity mechanism of AAs.

The impact of the abruption severity and the onset-to-delivery time on the maternal and neonatal outcomes of placental abruption.

Objective: We examined the impact of the abruption severity and the onset-to-delivery time on the maternal and neonatal outcomes of cases of clinically diagnosed placental abruption (PA).Material and methods: We investigated 84 patients who were diagnosed with PA at our hospital from January 2009 to September 2017. We classified the patients with PA into three groups based on the extent of the abruption: (1) mild abruption, <20%; (2) moderate abruption, 20-49%; (3) severe abruption, ≥50%, which was defined by the attending obstetricians at the time of delivery. The neonatal outcome was measured by the umbilical artery pH and the maternal outcome was measured by the obstetric disseminated intravascular coagulation score (DIC score).Results: The rate of hypertensive disorders of pregnancy in the moderate abruption group was significantly lower than that in other groups (p = .010). The umbilical artery pH was below 7.00 in 29 cases. The umbilical artery pH of the severe abruption group (6.92) was the lowest and was significantly lower in comparison to other groups (mild group [7.24], p < .001; moderate group [7.11], p < .05). There was a significant correlation between the onset-to-delivery time and the umbilical artery pH in the moderate group (R = -0.43). The maternal DIC scores in the three groups did not differ to a statistically significant extent.Conclusions: The severity of placental separation is significantly correlated with poor neonatal outcomes and there was a significant negative correlation between the onset-to-delivery time and the umbilical artery pH in moderate abruption.

Systematic expression analysis of genes related to generation of action potentials in human iPS cell-derived cardiomyocytes.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable tool to characterize the pharmacology and toxic effects of drugs on heart cells. In particular, hiPSC-CMs can be used to identify drugs that generate arrhythmias. However, it is unclear whether the expression of genes related to generation of CM action potentials differs between hiPSC-CM cell lines and the mature human heart. To address this, we obtained accurate gene expression profiles of commercially available hiPSC-CM cell lines with quantitative real time RT-PCR analysis. Expression analysis of ten cardiac proteins important for generation of action potentials and three cardiac proteins important for muscle contractility was performed using GAPDH for normalization. Comparison revealed large variations in expression levels among hiPSC-CM cell lines and between hiPSC-CMs and normal human heart. In general, gene expression in hiPSC-CM cell lines was more similar to an immature, stem-like cell than a mature cardiomyocyte from human heart samples. These results provide quantitative information about differences in gene expression between hiPSC-CM cell lines, essential for interpreting pharmacology experiments. Our approach can be used as an experimental guideline for future research on gene expression in hiPSC-CMs.

Gene mutation and micronucleus assays in gpt delta mice treated with 2,2',4,4'-tetrabromodiphenyl ether.

Flame retardant polybrominated diphenyl ethers (PBDEs) are a class of persistent organic pollutants (POPs). 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is a representative PBDE congener with widespread distribution and relatively high toxicity potential. Although it has been reported that BDE-47 can cause DNA damage in various in vitro systems, few studies have provided in vivo genotoxicity information. The aim of the present study was to investigate the genotoxicity of BDE-47 in mice. Male gpt delta mice were administered BDE-47 by gavage at 0, 0.0015, 1.5, 10 and 30 mg/kg/day, and 6 days per week for six consecutive weeks. Before the first treatment, and at 2.5 and 5 weeks after the first treatment, peripheral blood was collected from tails and the micronucleus assay and the Pig-a gene mutation assay were performed. After the last treatment, the mutant frequencies of the gpt gene in the liver and the germ cells from seminiferous tubules were determined. All these assays failed to produce positive results, suggesting that BDE-47 was neither clastogenic nor mutagenic in both target and non-target tissues in gpt delta mice.

Roles of Us8A and Its Phosphorylation Mediated by Us3 in Herpes Simplex Virus 1 Pathogenesis.

UNLABELLED: The herpes simplex virus 1 (HSV-1) Us8A gene overlaps the gene that encodes glycoprotein E (gE). Previous studies have investigated the roles of Us8A in HSV-1 infection using null mutations in Us8A and gE; therefore, the role of Us8A remains to be elucidated. In this study, we investigated the function of Us8A and its phosphorylation at serine 61 (Ser-61), which we recently identified as a phosphorylation site by mass spectrometry-based phosphoproteomic analysis of HSV-1-infected cells, in HSV-1 pathogenesis. We observed that (i) the phosphorylation of Us8A Ser-61 in infected cells was dependent on the activity of the virus-encoded Us3 protein kinase; (ii) the Us8A null mutant virus exhibited a 10-fold increase in the 50% lethal dose for virulence in the central nervous system (CNS) of mice following intracranial infection compared with a repaired virus; (iii) replacement of Ser-61 with alanine (S61A) in Us8A had little effect on virulence in the CNS of mice following intracranial infection, whereas it significantly reduced the mortality of mice following ocular infection to levels similar to the Us8A null mutant virus; (iv) the Us8A S61A mutation also significantly reduced viral yields in mice following ocular infection, mainly in the trigeminal ganglia and brains; and (v) a phosphomimetic mutation at Us8A Ser-61 restored wild-type viral yields and virulence. Collectively, these results indicate that Us8A is a novel HSV-1 virulence factor and suggest that the Us3-mediated phosphorylation of Us8A Ser-61 regulates Us8A function for viral invasion into the CNS from peripheral sites. IMPORTANCE: The DNA genomes of viruses within the subfamily Alphaherpesvirinae are divided into unique long (UL) and unique short (Us) regions. Us regions contain alphaherpesvirus-specific genes. Recently, high-throughput sequencing of ocular isolates of HSV-1 showed that Us8A was the most highly conserved of 13 herpes simplex virus 1 (HSV-1) genes mapped to the Us region, suggesting Us8A may have an important role in the HSV-1 life cycle. However, the specific role of Us8A in HSV-1 infection remains to be elucidated. Here, we show that Us8A is a virulence factor for HSV-1 infection in mice, and the function of Us8A for viral invasion into the central nervous system from peripheral sites is regulated by Us3-mediated phosphorylation of the protein at Ser-61. This is the first study to report the significance of Us8A and its regulation in HSV-1 infection.

Gender determines cortisol and alpha-amylase responses to acute physical and psychosocial stress in patients with borderline personality disorder.

Borderline personality disorder (BPD) is characterized by affective instability, unstable relationships, and identity disturbance. We measured salivary alpha-amylase (sAA) and salivary cortisol levels in all participants during exposure to the Trier Social Stress Test (TSST) and an electric stimulation stress. Seventy-two BPD patients were compared with 377 age- and gender- matched controls. The State and Trait versions of the Spielberger Anxiety Inventory test (STAI-S and STAI-T, respectively), the Profile of Mood State (POMS) tests, and the Beck Depression Inventory (BDI), the Depression and Anxiety Cognition Scale (DACS) were administered to participants before electrical stimulation. Following TSST exposure, salivary cortisol levels significantly decreased in female patients and significantly increased in male patients compared with controls. POMS tension-anxiety, depression-dejection, anger-hostility, fatigue, and confusion scores were significantly increased in BPD patients compared with controls. In contrast, vigor scores were significantly decreased in BPD patients relative to controls. Furthermore, STAI-T and STAI-S anxiety scores and BDI scores were significantly increased in BPD patient compared with controls. DACS scores were significantly increased in BPD patient compared with controls. Different stressors (e.g., psychological or physical) induced different responses in the HPA and SAM systems in female or male BPD patients.

Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress.

BACKGROUND: Decreased expression of brain-derived neurotrophic factor (BDNF) is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder. METHODS: To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men) using a social stress procedure (Trier Social Stress Test [TSST]) and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A). RESULTS: A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; P<0.05) was demonstrated that revealed different salivary cortisol responses in the TSST but not in electrical stimulation. Met/Met women had stronger cortisol responses than Val/Met and Val/Val individuals in the TSST. Met/Met men exhibited stronger salivary cortisol responses than Val/Met and Val/Val individuals in the TSST. CONCLUSION: These results indicate that a common, functionally significant polymorphism in BDNF had different effects on hypothalamic-pituitary-adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests.

Image-based evaluation of contraction-relaxation kinetics of human-induced pluripotent stem cell-derived cardiomyocytes: Correlation and complementarity with extracellular electrophysiology.

In this study, we used high-speed video microscopy with motion vector analysis to investigate the contractile characteristics of hiPS-CM monolayer, in addition to further characterizing the motion with extracellular field potential (FP), traction force and the Ca(2+) transient. Results of our traction force microscopy demonstrated that the force development of hiPS-CMs correlated well with the cellular deformation detected by the video microscopy with motion vector analysis. In the presence of verapamil and isoproterenol, contractile motion of hiPS-CMs showed alteration in accordance with the changes in fluorescence peak of the Ca(2+) transient, i.e., upstroke, decay, amplitude and full-width at half-maximum. Simultaneously recorded hiPS-CM motion and FP showed that there was a linear correlation between changes in the motion and field potential duration in response to verapamil (30-150nM), isoproterenol (0.1-10µM) and E-4031 (10-50nM). In addition, tetrodotoxin (3-30µM)-induced delay of sodium current was corresponded with the delay of the contraction onset of hiPS-CMs. These results indicate that the electrophysiological and functional behaviors of hiPS-CMs are quantitatively reflected in the contractile motion detected by this image-based technique. In the presence of 100nM E-4031, the occurrence of early after-depolarization-like negative deflection in FP was also detected in the hiPS-CM motion as a characteristic two-step relaxation pattern. These findings offer insights into the interpretation of the motion kinetics of the hiPS-CMs, and are relevant for understanding electrical and mechanical relationship in hiPS-CMs.

Association of microcephalin 1, syntrophin-beta 1, and other genes with automatic thoughts in the Japanese population.

Automatic thoughts may be risk factors for depression and anxiety, and should be detected early. However, the genetic basis of automatic thoughts remains unclear. This study aims to investigate the genetic association of automatic thoughts with SNPs (single nucleotide polymorphisms) involved in cognition, neurogenesis, neuronal cell structure, neurotransmitters, hypothalamus-pituitary adrenal axis and psychiatric illness. The study included 610 healthy participants. We used the Depression and Anxiety Cognition Scale (DACS), a Japanese psychological questionnaire, to assess automatic thoughts. Twenty-five SNPs including COMT, BDNF, FKBP5, SNTB1 (syntrophin-beta 1, rs4512418), and MCPH1 (microcephalin 1, rs2911968) were selected according to their minor allele frequency. Linear regression models were used to test association of mean DACS scores with each allele (major-allele homozygote, heterozygote, and minor-allele homozygote). The significant α-value was set at α < 0.002. Statistical analysis was conducted using SNPStats. Call rates for all genotypes were >98%. Eighteen SNPs did not deviate from Hardy-Weinberg equilibrium, and 7 were excluded from statistical analysis. Significant associations of SNTB1 with interpersonal threat and MCPH1 with future denial were observed only in females. SNTB1 and MCPH1 are located on chromosome 8, which may be involved in neuroticism, avoidant personality and depression. Our results demonstrated that DACS scores showing significant interaction with the 2 SNPs may be regarded as appropriate traits to detect the diathesis of automatic thoughts. The 2 SNPs may be important loci in research on cognitive vulnerability to depression and anxiety.