Effects of an animated educational video on knowledge of cell-free DNA screening among Thai pregnant women: a randomized control trial.

BACKGROUND: In developing countries, pregnant women have insufficient knowledge about cell-free DNA screening. Reports from developed countries have found that various tools in prenatal genetic counseling can improve the knowledge of pregnant women who undergo cell-free DNA screening. Data are limited from developing countries where women have different baseline socio-educational backgrounds. The objective of this study was to compare the effects of an animated educational video combined with traditional counseling versus traditional counseling alone in changing pregnant women's knowledge of cell-free DNA screening. METHODS: This study was a randomized control trial at an antenatal clinic. Eligible subjects who were Thai pregnant women, were randomized to either view or not view the 4-minute animated educational video explaining cell-free DNA screening. Both groups received traditional counseling. The women were asked to complete a Thai questionnaire assessing knowledge of the screening before and after intervention. The questionnaire consisted of three sections: demographic data of the research participants and their existing awareness about cell-free DNA testing; performance and limitations of cell-free DNA screening; and participants' attitudes toward the positive screening. Primary outcome was the change in knowledge scores. Secondary outcomes were attitudes toward positive screening test, levels of satisfaction with counseling, and screening acceptance rates. RESULTS: Data from 83 women in the video group and 82 in the non-video group were analyzed. The knowledge score (range 0-18) change after counseling was significantly higher in the video group than the non-video group (+ 7.1 ± 3.3 vs + 4.2 ± 2.5; p = 0.03). There were no significant differences in attitudes toward positive screening test (p = 0.83), levels of satisfaction (p = 0.24), or screening acceptance rates (p = 0.15) between the groups. CONCLUSIONS: Adding the video to traditional counseling was better than traditional counseling alone in improving pregnant women's knowledge about cell-free DNA screening. TRIAL REGISTRATION: The study was retrospectively registered with the Thai Clinical Trials Registry (TCTR20210917001, 17/09/2021).

Neurosonographic Measurements of the Fetal Anterior Complex in Singleton Pregnancies.

OBJECTIVE: To construct reference ranges of the fetal cerebral anterior complex, including ventricular index (VI), anterior horn of lateral ventricle width (AW), and cavum septi pellucidi (CSP) width, as a function of gestational age (GA), in Thai fetuses. METHODS: Low-risk pregnancies were recruited to measure fetal anterior complex on axial transventricular and coronal transcaudate planes using transabdominal ultrasound. The downside and upside hemisphere were defined as cerebral hemisphere located distal and proximal to the transducer, respectively. The five variables, downside/upside VI, downside/upside AW and CSP width, were measured from each fetus. Best-fit models in predicting mean and standard deviation for each value as a function of GA were constructed, using regression analysis. Distributions of Z-scores of all values based on GA were created to evaluate the fitness of models. Intraclass correlation coefficients were used to assess inter-/intraobserver variability. RESULTS: A total of 395 fetuses were measured for anterior complex. All parameters changed with GA with quadratic function. The models for predicting means and standard deviation of the five parameters as well as percentile charts were created. All models were proven well-fitted. The intra-/interobserver reliability coefficients of all values showed excellent agreement. CONCLUSION: The reference ranges of the fetal anterior complex, including VI, AW, and CSP, in axial transventricular and coronal transcaudate planes have been established and available for clinical use.

Parental Awareness, Knowledge, and Attitudes Regarding Current and Future Newborn Bloodspot Screening: The First Report from Thailand.

Newborn screening (NBS) is a public health service that is used to screen for treatable conditions in many countries, including Thailand. Several reports have revealed low levels of parental awareness and knowledge about NBS. Because of limited data on parental perspectives toward NBS in Asia and the differences in socio-cultural and economic contexts between Western and Asian countries, we conducted a study to explore parental perspectives on NBS in Thailand. A Thai questionnaire to assess awareness, knowledge, and attitudes regarding NBS was constructed. The final questionnaire was distributed to pregnant women, with or without their spouses, and to parents of children aged up to one year who visited the study sites in 2022. A total of 717 participants were enrolled. Up to 60% of parents were identified as having good awareness, which was significantly associated with gender, age, and occupation. Only 10% of parents were classified as having good knowledge relative to their education level and occupation. Providing appropriate NBS education should be initiated during antenatal care, focusing on both parents. This study noted a positive attitude toward expanded NBS for treatable inborn metabolic diseases, incurable disorders, and adult-onset diseases. However, modernized NBS should be holistically evaluated by multiple stakeholders in each country because of different socio-cultural and economic contexts.

Notch signaling regulates vasculogenic mimicry and promotes cell morphogenesis and the epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma.

Vasculogenic mimicry (VM) is the process where cancer cells adopt endothelial characteristics by forming tube-like structures and perfusing channels. This phenomenon has been demonstrated in several types of solid tumors and associated with the growth and survival of tumor cells. In this study, we investigated the presence of VM formation in human pancreatic ductal adenocarcinoma (PDAC) and elucidated the molecular mechanisms underlying the VM process. In human PDAC tissues, CD31-negative, periodic acid-Schiff (PAS)-positive channels were predominantly found in desmoplastic areas, which are generally also hypovascularized. We found a positive correlation of VM capacity to tumor size and NOTCH1 expression and nuclear localization with statistical significance, implicating that Notch activity is involved with VM formation. Additionally, our data showed that the presence of growth or angiogenic factors significantly increased Notch activity in PDAC cell lines and upregulated several mesenchymal marker genes, such as TWIST1 and SNAI1, which can be inhibited by a gamma-secretase inhibitor. Our data showed that Notch signaling plays an important role in inducing VM formation in PDAC by promoting the epithelial-to-mesenchymal transition process.

Factors influencing parental decisions to terminate pregnancies following prenatal diagnoses of major fetal anomalies at Ramathibodi Hospital, Bangkok, Thailand.

BACKGROUND: The rate of termination of pregnancy (TOP) for fetal anomalies and the factors affecting TOP vary among different populations. Optimisation of prenatal care and counselling requires understanding the factors influencing parental decisions in the relevant population. This study aimed to evaluate the rate of TOP after diagnoses of major fetal anomalies and assess factors associated with TOP-related decisions at a university hospital in Thailand. METHODS: A retrospective chart review was conducted at the Fetal Anomaly Clinic of Ramathibodi Hospital, Bangkok, Thailand. Medical records of all women with singleton pregnancies prenatally diagnosed with major fetal anomalies before 24 gestational weeks between 2010 and 2020 were reviewed. RESULTS: During the study period, 461 cases of major fetal anomalies were diagnosed, and 264 (57.3%) of these pregnancies were terminated. Three factors influencing parental TOP decisions were lethal anomalies (odds ratio [OR], 197.39; 95% confidence interval [CI], 49.95-779.95; p < 0.001), presence of genetic abnormalities (OR, 10.19; 95% CI, 4.17-24.87; p < 0.001) and gestational age at diagnosis (OR, 0.74; 95% CI, 0.65-0.84; p < 0.001). CONCLUSIONS: Over half of the pregnant women whose records were reviewed and who were prenatally diagnosed with major fetal anomalies terminated their pregnancies. Fetal factors, particularly lethality, genetic abnormalities and early gestational age at diagnosis, showed the most powerful associations with parental TOP decisions. Other maternal background factors were not key considerations.

Feasibility and learning curve of performing first trimester fetal anatomy screening among operators with varying experience using the protocol of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG).

OBJECTIVE: To compare the feasibility of performing a complete first trimester fetal anatomy screening between two operators with different levels of experience using the protocol of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), and to compare the duration of scan and learning curve of each operator as secondary outcomes. METHODS: A prospective study was conducted on singleton pregnancies at 11+0-13+6 weeks of gestation. Transabdominal ultrasound anatomy screening was performed by a maternal fetal medicine (MFM) staff (operator 1) or a first year MFM fellow (operator 2) following ISUOG guidelines. The visibility of fetal structures and time taken by each operator were recorded and analyzed. RESULTS: Data from 98 participants in operator 1 group and 96 participants in operator 2 group were analyzed. The success rate of visualizing all structures was feasible in 87.8% and 91.7% (p = .370) of cases in operator 1 and operator 2, respectively. The significant improvement in visualization success rate was observed between the first 50 and the last 50 scans in both groups (p = .004 vs. p = .006). Average time spent on the exam by operator 1 was significantly shorter than the time spent by operator 2 (11.3 ± 4.8 min vs. 15.0 ± 6.2 min; p < .001). CONCLUSION: Completeness of first trimester fetal anatomy screening following ISUOG protocol were feasible with no statistical difference between the two different levels of experienced operators. Moreover, time allocatable with a brief learning curve were demonstrated in both groups.

A synonymous variant in MYO15A enriched in the Ashkenazi Jewish population causes autosomal recessive hearing loss due to abnormal splicing.

Nonsyndromic hearing loss is genetically heterogeneous. Despite comprehensive genetic testing, many cases remain unsolved because the clinical significance of identified variants is uncertain or because biallelic pathogenic variants are not identified for presumed autosomal recessive cases. Common synonymous variants are often disregarded. Determining the pathogenicity of synonymous variants may improve genetic diagnosis. We report a synonymous variant c.9861 C > T/p.(Gly3287=) in MYO15A in homozygosity or compound heterozygosity with another pathogenic or likely pathogenic MYO15A variant in 10 unrelated families with nonsyndromic sensorineural hearing loss. Biallelic variants in MYO15A were identified in 21 affected and were absent in 22 unaffected siblings. A mini-gene assay confirms that the synonymous variant leads to abnormal splicing. The variant is enriched in the Ashkenazi Jewish population. Individuals carrying biallelic variants involving c.9861 C > T often exhibit progressive post-lingual hearing loss distinct from the congenital profound deafness typically associated with biallelic loss-of-function MYO15A variants. This study establishes the pathogenicity of the c.9861 C > T variant in MYO15A and expands the phenotypic spectrum of MYO15A-related hearing loss. Our work also highlights the importance of multicenter collaboration and data sharing to establish the pathogenicity of a relatively common synonymous variant for improved diagnosis and management of hearing loss.

Successful pregnancy outcome in Herlyn-Werner-Wunderlich syndrome with pyocolpos: A case report and literature review.

The presence of pelvic pain, a pelvic/paravaginal mass, and purulent vaginal discharge in primigravida should raise the possibility of obstructed hemivagina and uterine didelphys. Though conservative management could result in successful pregnancy outcomes, early excision of vaginal septum and adequate drainage offer a shorter course of management and complication avoidance.

Klinefelter Syndrome Mosaicism 46,XX/47,XXY: A New Case and Literature Review.

Most cases of Klinefelter syndrome (KS) have 47,XXY karyotype. We reported the first case of 46,XX/47,XXY KS whose genital ambiguity was detected prenatally with postnatal confirmation of the mosaicism and ovotesticular disorder of sex development (OT-DSD). The paternal origin of the extra X chromosome was identified using trio cytogenomic single-nucleotide polymorphism array. Additional 18 cases were also reviewed. The clinical presentation of 46,XX/47,XXY is age-dependent with two age peaks, including ambiguous genitalia during infancy and gynecomastia with or without cyclical hematuria and left scrotal pain and mass in adolescence. The 46,XX is the predominant karyotype both in peripheral blood and gonadal tissue. The risk of germ cell tumor is very high throughout life in these individuals. Individuals with 46,XX/47,XXY mosaicism should be treated more as OT-DSD other than a simple mosaic KS. A multidisciplinary approach and long-term monitoring are necessary.

Effects of probiotic supplements on insulin resistance in gestational diabetes mellitus: A double-blind randomized controlled trial.

AIMS/INTRODUCTION: To evaluate the effect of probiotic supplements on insulin resistance in pregnant women with diet-controlled gestational diabetes mellitus. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was carried out between June 2016 and February 2017. Pregnant women with diet-controlled gestational diabetes mellitus were enrolled in the study at 24-28 weeks-of-gestation and randomized to receive either probiotic supplements containing Bifidobacterium and Lactobacillus or a placebo daily for four consecutive weeks. Primary outcomes were mean differences in insulin resistance (homeostatic model assessment for insulin resistance), fasting insulin and fasting plasma glucose between the two groups. Secondary outcomes were changes in maternal weight after the intervention. RESULTS: Data from 28 patients in the probiotic group and 29 in the placebo group were analyzed. The changes in metabolic parameters after randomization showed significant improvement in glucose metabolism in the probiotic group compared with the placebo group, including fasting plasma glucose (0.68 ± 5.88 vs 4.620 ± 7.78 mg/dL, mean difference -3.94 mg/dL, 95% confidence interval -7.62, -0.27, P = 0.034), fasting plasma insulin (1.11 ± 1.71 vs 3.77 ± 1.70 mIU/L, mean difference -2.67 mIU/L, 95% confidence interval -3.57, -1.76, P = 0.001) and homeostatic model assessment for insulin resistance (0.25 ± 0.37 vs 0.89 ± 0.46, mean difference -0.63, 95% confidence interval -0.86, -0.41, P = 0.001). Weight gain during randomization was similar between the two groups. CONCLUSIONS: Four weeks of probiotic supplements in women with diet-controlled gestational diabetes in the late second and early third trimester lowered fasting glucose and increased insulin sensitivity. Probiotic supplements may be considered as an adjunct treatment for glycemic control in these patients.

Lupeol and stigmasterol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor-α.

Lupeol and stigmasterol, major phytosterols in various herbal plants, possess anti-inflammatory activities and have been proposed as candidates for anti-cancer agents, but their molecular mechanisms are still unclear. Here, we investigated the effects of lupeol and stigmasterol on tumor and endothelial cells in vitro and their anti-cancer activities in vivo. Our results demonstrated that lupeol and stigmasterol suppressed cell viability, migration, and morphogenesis of human umbilical vein endothelial cells (HUVECs) but not cholangiocarcinoma (CCA) cells. Expression analyses showed that the treatment of both compounds significantly reduced the transcript level of tumor necrosis factor-α (TNF-α), and Western blot analyses further revealed a decrease in downstream effector levels of VEGFR-2 signaling, including phosphorylated forms of Src, Akt, PCL, and FAK, which were rescued by TNF-α treatment. In vivo, lupeol and stigmasterol disrupted tumor angiogenesis and reduced the growth of CCA tumor xenografts. Immunohistochemical analyses confirmed a decrease in CD31-positive vessel content and macrophage recruitment upon treatment. These findings indicate that lupeol and stigmasterol effectively target tumor endothelial cells and suppress CCA tumor growth by their anti-inflammatory activities and are attractive candidates for anti-cancer treatment of CCA tumors.

Sonographic measurement of fetal thymus size in uncomplicated singleton pregnancies.

PURPOSE: To establish sonographic reference ranges of the normal fetal thymus size between 17 and 38 weeks of gestational age (GA). METHODS: The study was conducted between April 1 and December 31, 2013. Low-risk singleton pregnancies without obstetrical and medical complications at the GAs between 17 and 38 weeks were recruited for thymus measurement. The fetal thymus was identified on transabdominal sonography at the three-vessel view. Maximal transverse diameter, perimeter, and thymus/thoracic ratio were measured. The best-fit models in predicting thymic dimensions as a function of GA and biparietal diameter (BPD) were determined using regression analysis, and percentile charts for predicting thymic dimensions were constructed. RESULTS: A total of 296 singleton pregnancies were recruited in this study. Maximal transverse diameter, perimeter, and thymus/thoracic ratio increased throughout pregnancy. The regression equation for maximal transverse diameter of the thymus as a function of GA was as follows: Predicted mean thymus diameter (mm) = -25.904 + 2.476 × GA - 0.019 × GA2 (r = 0.915; p < 0.001) with predicted standard deviations of thymus diameter (mm) = 1.428 + 0.044 × GA (r = 0.017; p < 0.001). CONCLUSIONS: Sonographic reference ranges of the normal fetal thymic dimensions between 17 and 38 weeks of GA have been established. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:150-159, 2017.

Effect of cord puncture site in cordocentesis at mid-pregnancy on pregnancy outcomes.

OBJECTIVES: To compare the procedure and pregnancy outcomes of pregnancies undergoing cordocentesis between a group of cord insertion puncture and that of free loop puncture. MATERIALS AND METHODS: Pregnancies undergoing cordocenteses meeting the following inclusion criteria were recruited: (1) singleton pregnancies at gestational ages of 18-22 weeks; (2) no fetal abnormalities; (3) the procedures performed by experienced operators; and (4) the procedures of no placenta penetration. The recruited cases were classified into two groups: a group of cordocenteses with puncture site at placental cord insertion (Group 1) and those with puncture site at cord free loop (Group 2). The primary outcomes to be compared were rates of fetal loss, newborns with low birth weight and preterm birth. The secondary outcomes included a rate of successful procedures, umbilical cord bleeding, fetal bradycardia, maternal blood contamination, and duration of the procedure time. RESULTS: Of 6147 cordocenteses recruited, 2214 met inclusion criteria. The mean duration to complete the procedure in Group 1 was significantly shorter than that in Group 2 (4.5 ± 5.4 vs. 6.7 ± 8.5 min, Student's t-test; p = 0.001). The mean birth weight and gestational age at delivery were comparable between the two groups. No significant differences between the two groups were seen in rates of fetal loss, low birth weight, preterm birth, successful procedures, umbilical cord bleeding, or fetal bradycardia. However, the rate of maternal blood contamination was significantly higher in the group of puncture at the cord insertion site. CONCLUSION: Of cordocenteses performed based on accessibility and quality of visualization, cord insertion puncture may cause more maternal blood contamination but free loop puncture may be associated with more difficult procedures, while the safety was comparable.