Relationship between sensory saltiness intensity and added oil in low-viscosity and high-viscosity polymer solutions.

Generally, the foods we usually eat are not only aqueous solutions, but also viscous solutions and solids. Therefore, it is interesting for us to explore how taste components are perceived in a viscous polymer solution. The relationship between the sensory evaluation of saltiness intensity, amount of added oil, and apparent viscosity was clarified in low-viscosity and high-viscosity polymer solutions. The study was conducted using samples containing corn oil, sodium chloride, and [xanthan gum] or [xanthan gum + locust bean gum] as a thickener. Oil was added to the viscous polymer solutions regardless of whether they were low- or high-viscosity, and saltiness intensity was evaluated as compared with a reference solution. The low-viscous polymer solutions with [xanthan gum] were perceived to be saltier than the high-viscous polymer solutions with [xanthan gum + LBG] as the amount of oil increased. The shear stress value gradually increased as the amount of oil increased in both the low-viscosity and the high-viscosity polymer solutions, as derived from the fluid constitutive equation. There was a correlation between saltiness intensity and apparent viscosity in both high- and low-viscosity polymer solutions. A coefficient of determination (R2 ) of 0.918 was obtained between saltiness intensity and "apparent viscosity" for the samples using [xanthan gum] and that of 0.683 between saltiness intensity and "apparent viscosity" for the samples using [xanthan gum+LBG]. The low-viscosity polymer solutions showed a saltier intensity as the amount of oil increased and a greater correlation with apparent viscosity, as compared with the high-viscosity polymer solutions.

Efficacy of discontinuing the use of low-dose aspirin at 28 weeks of gestation for preventing preeclampsia.

AIM: Low-dose aspirin (LDA) has been shown to reduce the incidence of preeclampsia (PE). Previous studies have focused on the timing of LDA initiation, but no study to date has assessed the timing of LDA discontinuation. This study aimed to evaluate the effect of LDA when LDA is initiated between 12 and 16 weeks of gestation and continued until 28 weeks of gestation. METHODS: This prospective cohort study with historical controls investigated singleton pregnancies that were at a high risk for PE. High-risk factors were defined as a history of hypertensive disorders of pregnancy, chronic hypertension, diabetes mellitus, autoimmune disease, obesity, and high normal blood pressure in the first trimester. We performed adjustments using propensity score matching (PSM) for each indication of LDA, maternal age, primiparity, and assisted reproductive technology. The primary outcome was the incidence of PE. Secondary outcomes were the incidence of preterm PE, fetal growth restriction (FGR), preterm birth, fetal malformation, and maternal postpartum hemorrhage (PPH). RESULTS: A total of 203 and 543 participants were assigned to the LDA and control group, respectively. After PSM, there was no significant difference in the incidence of PE (22.0% vs. 16.8%; p = 0.20), preterm PE (12.0% vs. 13.1%; p = 0.76), FGR (7.9% vs. 12.0%; p = 0.17), or preterm birth (17.3% vs. 15.7%; p = 0.68). There was also no significant increase in maternal PPH or in the incidence of fetal malformations. CONCLUSION: Discontinuing the use of LDA at 28 weeks of gestation did not result in a lower incidence of PE and FGR.

Changes in the deep vasculature assessed using anterior segment OCT angiography following trabecular meshwork targeted minimally invasive glaucoma surgery.

The effect of trabecular meshwork (TM)-targeted minimally invasive glaucoma surgery (MIGS) on the vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) has not been established. In this prospective, longitudinal study, we investigated changes in the deep vasculature following TM-targeted MIGS using AS-OCTA for open-angle glaucoma in 31 patients. AS-OCTA images of the sclera and conjunctiva at the nasal corneal limbus were acquired preoperatively and 3 months postoperatively, and the vessel densities (VDs) of the superficial (conjunctival) and deep (intrascleral) layers were calculated. The VDs before and after MIGS were compared, and the factors associated with the change in VD following MIGS were analyzed. The mean deep VD decreased from 11.98 ± 6.80% at baseline to 10.42 ± 5.02% postoperatively (P = 0.044), but superficial VD did not change (P = 0.73). The multivariate stepwise regression analysis revealed that deep VD reduction was directly associated with IOP reduction (P < 0.001) and preoperative IOP (P = 0.007) and inversely associated with preoperative deep VD (P < 0.001). The deep VD reduction following MIGS was significant in the successful group (21 eyes) (P = 0.032) but not in the unsuccessful group (10 eyes) (P = 0.49). The deep VDs assessed using AS-OCTA decreased following TM-targeted MIGS, especially in the eyes with good surgical outcomes.

Endoplasmic reticulum stress promotes nuclear translocation of calmodulin, which activates phenotypic switching of vascular smooth muscle cells.

BACKGROUND AND AIMS: Increased endoplasmic reticulum (ER) stress is strongly associated with the phenotypic switching of vascular smooth muscle cells (VSMCs) in atherosclerosis. Depletion of the ER Ca2+ content is one of the leading causes of increased ER stress in VSMCs. The ryanodine receptor (RyR) is a major Ca2+ release channel in the sarcoplasmic reticulum membrane. Calmodulin (CaM), which binds to RyR (CaM-RyR), stabilizes the closed state of RyR in the resting state in normal cells. Defective CaM-RyR interactions can cause abnormal Ca2+ leakage through RyR, resulting in decreased Ca2+ content, indicating that defective CaM-RyR interactions may be a cause of increased ER stress. Herein, we used a mouse VSMCs to assess whether CaM-RyR plays a pivotal role in VSMCs phenotypic switching, which is caused by ER stress, and whether dantrolene, which enhances the binding affinity of CaM to RyR, affects VSMCs phenotypic switching. METHODS AND RESULTS: Tunicamycin was used to mimic ER stress in vitro. Tunicamycin-induced ER stress caused CaM to dissociate from the RyR and translocate to the nucleus, which stimulated phenotypic switching through the activation of MEF2 and KLF5. Dantrolene suppressed tunicamycin-induced apoptosis, ER stress (restoring ER Ca2+ content), and phenotypic switching of VSMCs. Suramin, which directly unbinds CaM from RyR, promoted nuclear CaM accumulation with parallel VSMCs phenotypic switching, and dantrolene prevented these effects. CONCLUSIONS: We observed that ER stress causes CaM translocation to the nucleus and drives the phenotypic switching of VSMCs. Thus, restoration of the binding affinity of CaM to RyR may be a therapeutic target for atherosclerosis.

Benefits of group compassion-focused therapy for treatment-resistant depression: A pilot randomized controlled trial.

Major depression is one of the most common mental health problems worldwide. More than one-third of patients suffer from treatment-resistant depression (TRD). In this study, we explored the feasibility of group compassion-focused therapy (CFT) for TRD using a randomized controlled trial with two parallel groups. Eighteen participants were randomly allocated to the intervention group (CFT and usual care) and control group (usual care alone) and a participant in each group withdrew. Participants in the intervention group received a 1.5-h session every week for 12 weeks. The effects of the intervention on the participants' scores were calculated using a linear mixed model. There was a larger reduction in their depressive symptoms and fears of compassion for self and a greater increase in their compassion for self compared to the control group participants. The reliable clinical indices showed that in the CFT (intervention) group, three of nine participants recovered (33%), two improved (22%), two recovered but non-reliably (22%), and the condition of two remained unchanged (22%). These findings indicate adequate feasibility of group CFT for TRD in Japanese clinical settings. Clinical trial registration: [https://clinicaltrials.gov/], identifier [UMIN 000028698].

Development of Social Life Impact for Mother (SLIM) scale at first trimester to identify mothers who need social support postpartum: a hospital-based prospective study in Japan.

OBJECTIVE: To develop and validate the Social Life Impact for Mother (SLIM) scale to identify mothers in Japan who need social support postpartum. METHODS: Hospital-based prospective study was implemented nationwide in Japan. A total of 7462 pregnant women completed the SLIM scale in their first trimester, and postpartum social problems (postpartum depression and bonding disorders) were assessed at 1 month after delivery (N = 5768, follow-up rate 77.3%). Multivariate logistic regression was applied to investigate the association between SLIM scale and postpartum social problems. RESULTS: The SLIM scale is made up of nine risk factors for postpartum social problems, including relationship problems, lower financial status, and lack of social support. The SLIM scale predicted postpartum social problems with moderate accuracy (area under the curve 0.63, 95% confidence interval 0.60-0.65). Further stratification by local clinic and tertiary hospital did not affect the estimates. CONCLUSION: The SLIM scale at prenatal check-up may be useful for obstetricians to detect mothers with postpartum social problems. Further intervention studies using the SLIM score are warranted.

Improvement in social anxiety following a return-to-work intervention for patients with depression.

PURPOSE: To retrospectively examine depression and social anxiety improvement in patients on sick leave due to depression who participated in a return-to-work intervention (RTW-I) program. METHODS: Patients visited a psychiatric outpatient clinic simulating workplaces to learn recurrence prevention skills through RTW-Is, including group cognitive behavioral therapy, from April 1, 2013, to September 30, 2017. The Beck Depression Inventory-Second Edition (BDI-II), Social Adaptation Self-Evaluation Scale (SASS), and Liebowitz Social Anxiety Scale (LSAS) scores of 112 patients were analyzed before and after the intervention program. Missing postprogram data were substituted using the last observation carried forward scores. Next, 45 patients who responded to the work continuity survey 1 year after RTW-I were categorized into Group A (patients who continued working: 37) and Group B (those who did not continue: 8). RESULTS: The mean BDI-II scores significantly decreased from preintervention 19.4 to postintervention 7.9 (t = 13.303, P < .001). The mean SASS scores significantly increased from preintervention 31.9 to postintervention 36.0 (t = -5.953, P < .001). The mean LSAS scores significantly decreased from preintervention 54.7 to postintervention 37.0 (t = 8.682, P < .001), and all scores demonstrated an improvement. Patients who continued working showed improved depressive and social anxiety symptoms. The BDI-II and SASS scores showed no significant differences between the groups, but the postintervention LSAS scores were significantly different (P = .041). LSAS score changes: Group A = -26.2; Group B = -9.8; estimated difference: -17.920, 95% CI: -32.181 to -3.659, P = .015. CONCLUSIONS: The RTW-I program improved depressive and social anxiety symptoms. Patients with improved scores continued working for 1 year after the intervention.Trial registration: This trial was retrospectively registered with the UMIN Clinical Trial Registry (UMIN-CTR) (ID: UMIN000037662) on August 10, 2019.

Prevalence of common aneuploidy in twin pregnancies.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Prediction of trabecular meshwork-targeted micro-invasive glaucoma surgery outcomes using anterior segment OCT angiography.

We performed a prospective, longitudinal study to investigate the association between the preoperative intrascleral vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) and surgical outcomes of trabecular meshwork-targeted micro- or minimally invasive glaucoma surgery (MIGS). We included 37 patients with primary open-angle glaucoma. Preoperative AS-OCTA images of the sclero-conjunctiva of the nasal corneal limbus were acquired in the superficial (conjunctival) and deep (intrascleral) layers. The vessel densities (VDs) of each layer were measured separately in the entire area, limbal side, and fornix area. Surgical success was determined by postoperative intraocular pressure (IOP) and IOP reduction. Twenty-three and 14 eyes were classified as having successful and unsuccessful outcomes, respectively. The deep VDs of the entire area and fornix area were significantly lower in the successful group (P = 0.031 and P = 0.009). The success rate was significantly higher for eyes with a lower deep VD than for eyes with a higher deep VD. A greater IOP reduction was significantly associated with lower deep VD in the fornix area (P = 0.022) and higher preoperative IOP (P < 0.001). These results indicate that intrascleral vasculature assessed using preoperative AS-OCTA was negatively correlated with surgical success and IOP reduction resulting from trabecular meshwork-targeted MIGS. AS-OCTA images might help predict MIGS outcomes.

Evaluation of the clinical performance of noninvasive prenatal testing at a Japanese laboratory.

AIM: We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high-risk pregnant women. METHODS: Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age-specific PPV and NPV were estimated. RESULTS: Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78-99.96), 99.12% (95% CI: 96.83-99.76), and 100% (95% CI: 88.30-100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age-specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. CONCLUSION: The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high-risk pregnant women, and maternal age-specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan.

Involvement of acid ceramidase in the degradation of bioactive N-acylethanolamines.

Bioactive N-acylethanolamines (NAEs) include palmitoylethanolamide, oleoylethanolamide, and anandamide, which exert anti-inflammatory, anorexic, and cannabimimetic actions, respectively. The degradation of NAEs has been attributed to two hydrolases, fatty acid amide hydrolase and NAE acid amidase (NAAA). Acid ceramidase (AC) is a lysosomal enzyme that hydrolyzes ceramide (N-acylsphingosine), which resembles NAAA in structure and function. In the present study, we examined the role of AC in the degradation of NAEs. First, we demonstrated that purified recombinant human AC can hydrolyze various NAEs with lauroylethanolamide (C12:0-NAE) as the most reactive NAE substrate. We then used HEK293 cells metabolically labeled with [14C]ethanolamine, and revealed that overexpressed AC lowered the levels of 14C-labeled NAE. As analyzed with liquid chromatography-tandem mass spectrometry, AC overexpression decreased the amounts of different NAE species. Furthermore, suppression of endogenous AC in LNCaP prostate cells by siRNA increased the levels of various NAEs. Lastly, tissue homogenates from mice genetically lacking saposin D, a presumable activator protein of AC, showed much lower hydrolyzing activity for NAE as well as ceramide than the homogenates from wild-type mice. These results demonstrate the ability of AC to hydrolyze NAEs and suggest its physiological role as a third NAE hydrolase.

Pregnancy Outcomes in 2 Women Born with Complex Anorectal Malformations: Challenges and Considerations.

BACKGROUND: Complex anorectal malformations (ARMs) are a group of rare congenital malformations involving numerous anomalies that require reconstruction and can affect sexuality, fertility, and pregnancy outcomes. Few cases of pregnancy in complex ARM patients have been reported. CASES: We report on 2 patients with ARMs who delivered 3 term infants, all by cesarean section with successful collaboration between pediatric urologists and obstetricians. Both patients fully recovered with no long-term consequences after experiencing maternal morbidities including urinary infections, clitoral abscesses, vaginal lacerations, extensive adhesive disease, bladder injury, and maternal hemorrhage. SUMMARY AND CONCLUSION: In managing pregnancies and deliveries in women with complex ARMs, coordination between obstetricians, pediatric urologists, and pediatric surgeons is crucial.

Retrospective details of false-positive and false-negative results in non-invasive prenatal testing for fetal trisomies 21, 18 and 13.

OBJECTIVE: Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT). STUDY DESIGN: A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth. RESULTS: Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21. CONCLUSION: These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT.

Short-Term Effects of Different Types of Anti-Glaucoma Eyedrop on the Sclero-Conjunctival Vasculature Assessed Using Anterior Segment OCTA in Normal Human Eyes: A Pilot Study.

BACKGROUND: To investigate the short-term effects of different types of anti-glaucoma eyedrop on sclero-conjunctival vasculatures and their associations with intraocular pressure (IOP) reduction. METHODS: This was a prospective study including 20 healthy subjects. A single instillation of ripasudil or bimatoprost was introduced into the right eyes of the participants. The superficial (conjunctival) and deep (intrascleral) vasculatures of the corneal limbus using anterior-segment optical coherence tomography angiography (OCTA) and IOP were examined in both eyes at baseline and 15 min and 2 h after instillation. RESULTS: In the ripasudil group, the vessel density (VD) (median) at baseline (deep, 13.1%; superficial, 28.5%) significantly increased in both layers at 15 min (deep, 19.9%; superficial, 37.3%) and the deep layer at 2 h (deep, 14.8%; superficial, 31.6%). In the bimatoprost group, the superficial VD significantly changed over time, but the deep VD did not. The greater effect of ripasudil on IOP reduction was significantly associated with a lower baseline VD in the deep layer (at 15 min, p = 0.004; at 2 h, p = 0.018). CONCLUSIONS: Differences in the timing, depth, and extent of the effects on vasculature after instillations, could be detected using OCTA. The IOP-lowering effects of ripasudil might be associated with the deep vasculature.

Longitudinal changes in superficial microvasculature in glaucomatous retinal nerve fiber layer defects after disc hemorrhage.

Glaucoma is a multifactorial optic neuropathy, possibly involving vascular dysfunction, leading to the death of retinal ganglion cells and their axons. Disc hemorrhage (DH) is known to be closely associated with the widening of retinal nerve fiber layer defect (NFLD); however, it has not been well elucidated how DH affects retinal microvasculature. We aimed to investigate the association between DH history and longitudinal changes in superficial retinal microvasculature in NFLD. We enrolled 15 glaucoma patients with DH history (32 glaucomatous NFLD locations, with or without DH history). NFLD-angle, superficial retinal vessel density (VD), and decreased superficial retinal microvasculature (deMv)-angle were assessed using optical coherence tomography angiography for at least three times over time. The mean follow-up period and OCT/OCTA scan interval were 21.3 ± 5.4 months (range, 12-28) and 6.8 ± 0.4 months (range, 2-18), respectively. Linear mixed-effects models showed that the presence of DH history was significantly associated with an additional NFLD-angle widening of 2.19 degree/year (P = 0.030), VD decrease of 1.88%/year (P = 0.015), and deMv-angle widening of 3.78 degree/year (P < 0.001). These changes were significantly correlated with each other (P < 0.001). Thus, the widening of NFLD was closely associated with deMv, and DH was associated with a subsequent decrease in superficial retinal microvasculature in NFLD.

Perinatal Determinants of Child Maltreatment in Japan.

Background: Child maltreatment induces significant health problems, both during childhood and into adulthood. To prevent child maltreatment, it is important to detect perinatal risk factors for earlier intervention. The aim of this study was to evaluate the perinatal risk factors associated with child maltreatment during pregnancy. Methods: A case-control study was conducted to compare perinatal data from the Maternal and Child Health Handbook between the case and control groups. Cases were collected from children registered in two Child Guidance Centers in Japan. The control group consisted of 3.5-year-old children in a city in Osaka Prefecture whose mothers responded to questionnaires containing information from the Maternal and Child Health Handbook. The association between perinatal factors and child maltreatment was assessed using multiple logistic regression analysis. Results: The data of 70 cases and 345 controls were collected. The following were found to be perinatal factors related to child maltreatment: teenage pregnancy (OR: 257.3, 95% CI: 17.3-3832.7), a mother aged 20-24 years (OR: 22.8, 95% CI: 4.4-117.8), a father who is older than the mother by 10 years or more (OR: 14.1, 95% CI: 2.1-94.8), an unmarried mother (OR: 15.7, 95% CI: 2.6-93.6), maternal mental disorder (OR: 48.9, 95% CI: 9.3-258.3), the first maternal prenatal visit being later than 20 weeks (OR: 132, 95% CI: 12.7-1384.7), little prenatal care (<10 visits) (OR: 21.4, 95% CI: 2.9-157.1), a low-birth-weight baby (OR: 5.1, 95% CI: 1.1-24.1), and congenital disease (OR: 7.9, 95% CI: 1.1-56.4). Conclusions: This study revealed that young mothers, fathers much older than mothers, unmarried mothers, and maternal mental disorder, mothers with late first visit or little perinatal care, and low-birth-weight babies and babies with congenital disease were associated with child maltreatment. These findings can be used to detect high-risk families for child maltreatment during or after pregnancy.

Qualitative investigation of the factors that generate ambivalent feelings in women who give birth after receiving negative results from non-invasive prenatal testing.

BACKGROUND: Women who receive negative results from non-invasive prenatal genetic testing (NIPT) may find that they later have mixed or ambivalent feelings, for example, feelings of accepting NIPT and regretting undergoing the test. This study aimed to investigate the factors generating ambivalent feelings among women who gave birth after having received negative results from NIPT. METHODS: A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted focusing on ambivalent expressions for those 1562 women who responded the questionnaire. The qualitative data gathered from the questionnaire were analyzed using the N-Vivo software package. RESULTS: Environmental factors, genetic counseling-related factors, and increased anticipatory anxiety, affected the feeling of ambivalence among pregnant women. Furthermore, pregnant women desired more information regarding the detailed prognosis for individuals with Down syndrome and living with them and/or termination, assuming the possibility that they were positive. CONCLUSIONS: Three major interrelated factors affected the feeling of ambivalence in women. Highlighting and discussing such factors during genetic counseling may resolve some of these ambivalences, thereby enhancing the quality of decisions made by pregnant women.