Neonatal Filaggrin Genetic Screening and Counseling to Prevent Atopic Dermatitis in High-Risk Infants.

Background: Mutations in filaggrin (FLG), the gene that codes for the skin barrier protein, have been shown to be associated with atopic dermatitis (AD). Objective: The objectives of this study were to determine the effects of genetic counseling and parental education on infants at a high risk of AD. Methods: We enrolled 7521 newborns in Taiwan from January 1, 2016, to March 30, 2020, and all of them received genetic testing encompassing 20 known FLG mutations. The genetic counseling and AD prevention and care team consisted of pediatricians, dermatologists, social workers, and genetic counselors. The counseling was arranged for at least 30 minutes within 45 days after delivery. Results: A total of 2963 high-risk infants (39.4%) were identified. Homozygous c.1432C>T was the most commonly identified mutation. A total of 418 neonates' parents were stratified into counseling and noncounseling groups, where the effect of parental education was evaluated. The genetically stratified parental education program was effective in preventing AD development by 63.3% in high-risk infants before 12 months of life (P < 0.0001). Conclusion: Genetic stratification and parental education are effective in preventing the development of AD in high-risk infants before 12 months of life.

Changing the standardised obstetric care by expanded carrier screening and counselling: a multicentre prospective cohort study.

BACKGROUND: Expanded genetic screening before conception or during prenatal care can provide a more comprehensive evaluation of heritable fetal diseases. This study aimed to provide a large cohort to evaluate the significance of expanded carrier screening and to consolidate the role of expanded genetic screening in prenatal care. METHODS: This multicentre, retrospective cohort study was conducted between 31 December 2019 and 21 July 2022. A screening panel containing 302 genes and next-generation sequencing were used for the evaluation. The patients were referred from obstetric clinics, infertility centres and medical centres. Genetic counsellors conducted consultation for at least 15 min before and after screening. RESULTS: A total of 1587 patients were screened, and 653 pairs were identified. Among the couples who underwent the screening, 62 (9.49%) had pathogenic variants detected on the same genes. In total, 212 pathogenic genes were identified in this study. A total of 1173 participants carried at least one mutated gene, with a positive screening rate of 73.91%. Among the pathogenic variants that were screened, the gene encoding gap junction beta-2 (GJB2) exhibited the highest prevalence, amounting to 19.85%. CONCLUSION: Next-generation sequencing carrier screening provided additional information that may alter prenatal obstetric care by 9.49%. Pan-ethnic genetic screening and counselling should be suggested for couples of fertile age.

The challenging presentation of gastric cancer during pregnancy with krukenberg tumor: a case report.

The incidence of ovarian tumors in pregnancy is around 0.05%. Primary ovarian cancer and metastatic malignancy are rare in pregnancy, and women often delayed in diagnosis. Importance: This is the first case ever reported on gastric cancer diagnosed during pregnancy presenting with a Krukenberg tumor and mimic ovarian tumor torsion, cholecystitis. By reporting this case, we could sensitize physicians to be more vigilance of abnormal abdominal pain in pregnant women. Case presentation: A 30-year-old female came to our hospital at the 30th week of gestational age due to preterm uterine contraction and worsening abdominal pain. A cesarean section was performed due to preterm uterine contraction and intolerable abdominal pain suspected to be ovarian torsion. Microscopic examination of the ovarian specimen showed signet-ring cells. The patient was diagnosed with gastric adenocarcinoma at stage IV after complete surveillance. Postpartum chemotherapy consisted of oxaliplatin and high-dose 5-fluorouracil. The patient died 4 months after delivery. Clinical discussion: Malignancies during pregnancy should be kept in mind while encountering atypical clinical presentations. Krukenburg tumor is rare in pregnancy and gastric cancer is the most common cause. Early diagnosis of the gastric cancer in the operable stage is the key to a better prognosis. Conclusion: Diagnostic examinations for gastric cancer in pregnancy could be performed after first trimester. Treatment should be introduced after balancing maternal-fetal risks. Early diagnosis and intervention are crucial to decrease the high mortality rate of gastric cancer in pregnancy.

Clinical outcomes of fetuses with chromosome 16 short arm copy number variants.

BACKGROUND: The short arm of chromosome 16 consists of several copy number variants (CNVs) that are crucial in neurodevelopmental disorders; however, incomplete penetrance and diverse phenotypes after birth aggravate the difficulty of prenatal genetic counseling. METHODS: We screened 15,051 pregnant women who underwent prenatal chromosomal microarray analysis between July 2012 and December 2017. Patients with positive array results were divided into four subgroups based on the type of mutation identified on screening (16p13.3, 16p13.11, 16p12.2, and 16p11.2), and the maternal characteristics, prenatal examinations, and postnatal outcomes of different cases were reviewed. RESULTS: Chromosome 16 CNVs were identified in 34 fetuses, including four with 16p13.3 CNVs, 22 with 16p13.11 CNVs, two with 16p12.2 microdeletions, and six with 16p11.2 CNVs. Of the 34 fetuses, 17 delivered without early childhood neurodevelopmental disorders, three developed neurodevelopmental disorders during childhood, and 10 were terminated. CONCLUSION: Incomplete penetrance and variable expressivity make prenatal counseling challenging. Most cases with inherited 16p13.11 microduplication were reported to have normal development in early childhood, and we also report a few cases of de novo 16p CNVs without further neurodevelopmental disorders.

Propess versus prostin for induction of labour in term primiparous women.

BACKGROUND: The rate of induction of labour has increased over the decades and numerous medications are available in the market. This study compares the efficacy and safety between dinoprostone slow-release pessary (Propess) and dinoprostone tablet (Prostin) for labour induction at term in nulliparous women. METHODS: This was a prospective single-blind randomized controlled trial conducted in a tertiary medical centre in Taiwan from September 1, 2020 to February 28, 2021. We recruited nulliparous women at term with a singleton pregnancy, fetus in cephalic presentation, an unfavourable cervix, and the cervical length had been measured by transvaginal sonography three times during labour induction. The main outcomes are duration from induction of labour to vaginal delivery, vaginal delivery rate, maternal and neonatal complication rates. RESULTS: In both groups, Prostin and Propess, 30 pregnant women were enrolled. The Propess group had higher vaginal delivery rate but it did not meet statistically significant difference. The Prostin group had significantly higher rate of adding oxytocin for augmentation (p = 0.0002). No significant difference was observed in either labouring course, maternal or neonatal outcomes. The probability of vaginal delivery was independently related to the cervical length measured by transvaginal sonography 8 h after Prostin or Propess administration as well as neonatal birth weight. CONCLUSION: Both Prostin and Propess can be used as cervical ripening agents with similar efficacy and without significant morbidity. Propess administration was associated with higher vaginal delivery rate and less need to add oxytocin. Intrapartum measurement of cervical length is helpful in predicting successful vaginal delivery.

The correlation of forkhead box protein M1 (FOXM1) with gestational diabetes mellitus in maternal peripheral blood and neonatal umbilical cord blood.

OBJECTIVE: The transcription activator FOXM1 was found to be essential for beta cell expansion and glucose homeostasis during pregnancy in a mouse model. We assumed that the mechanism would be similar in humans. Thus, we aimed to determine the correlation, if any, between FOXM1 and gestational diabetes mellitus in pregnant women. MATERIALS AND METHODS: Participants were recruited and collected from a single tertiary medical center in Taiwan. Participants' maternal peripheral blood was retrieved upon their admission for labor. The postpartum cord blood was harvested within 5 min after delivery of the fetus to test the FOXM1 mRNA expression level, as well as glucose, insulin, and C-peptide protein concentrations. RESULT: We recruited 83 pregnant women, 63 without GDM and 20 with GDM. The non-GDM maternal samples had a FOXM1ΔCt of 9.2 ± 1.53, whereas it was 8.92 ± 1.48 in the GDM group (p = 0.504). In the cord blood group, the GDM and non-GDM FOXM1ΔCt were 7.7 ± 1.02 and 7.95 ± 1.56, respectively (p = 0.416). CONCLUSION: This is the first study to prove a relationship between FOXM1 and GDM in humans. Although the exact linear correlation is still unknown, our results may provide an impetus for further research.

Antibiotic choice for the management of preterm premature rupture of membranes in Taiwanese women.

BACKGROUND: Preterm premature rupture of membranes (PPROM) is one of the most common causes of preterm birth. Antibiotic treatment is recommended to prolong the pregnancy course and reduce fetal morbidity in women with PPROM. However, the guidelines for antibiotic selection are based on studies done years ago, mostly in Western countries, which may not reflect the geographic, temporal, and ethnic variation in microbial colonization and infection in other parts of the world. We aimed to understand whether the antibiotics recommended by the current guidelines were sufficient to eradicate the majority of pathogens involved. METHODS: This is a single-center retrospective study at a tertiary medical center in Taiwan with patients recruited from January 1, 2017, to December 31, 2019. All patient included had a confirmed diagnosis of PPROM. In this study, we aimed to investigate which broad-spectrum antibiotic was most suitable for PPROM cases in Taiwan. RESULTS: 133 women were included, and 121 women had positive culture results. Most of the pregnant women had one positive result (35.5%). The most common pathogen was Lactobacillus species (27.8%), followed by Streptococcus species (12.9%) and Staphylococcus species (12.09%). CONCLUSION: The most appropriate antibiotic therapy for PPROM was a combination of 1 g azithromycin given orally on admission plus a third-generation cephalosporin administered intravenously in the first 48 hours and followed by amoxicillin 500 mg per os for another five days. This recommended antibiotic regimen for women with PPROM needs further study under a randomized clinical trial with a larger study population to evaluate its efficacy.

Uncontrolled before-after study adding carbetocin in addition to oxytocin decreases blood loss for cesarean section in twin pregnancies.

PURPOSE: To evaluate the effectiveness of adding carbetocin to regular uterotonic agents for prevention of postpartum hemorrhage (PPH) after cesarean section for twin pregnancies. METHODS: This is a retrospective uncontrolled before-after study done in a tertiary center in Taiwan, 2010-2017. Women with twin pregnancies that underwent cesarean section were enrolled. The control group (n = 114) received oxytocin infusion and direct uterine injection. In addition to these, the study group (n = 127) received 100ug of intravenous carbetocin. Primary endpoint was the change in hemoglobin. Secondary endpoints included risk of PPH and undiagnosed PPH (Hb dropped more than 2 g/dL), blood loss, the need for additional uterotonic maneuvers, and blood transfusion. Hemodynamic changes were also investigated. RESULTS: After adjusting for confounding factors, the change in Hb (0.35 g/dL, 95% CI: -0.03∼0.74) and incidence of PPH (OR 0.30, 95% CI: 0.03∼3.28) were comparable in both groups. However, women with undiagnosed PPH decreased (OR 0.43, 95% CI:0.22∼0.85). Total blood loss in 24 h after delivery also decreased (-40.33 mL, 95%CI: -80.32∼ -0.34). The use of extra uterotonic medications and the need for blood transfusion did not differ. The systolic blood pressure 4 h after childbirth was higher in the carbetocin group (6.71, 95% CI: 2.27∼11.15). CONCLUSION: The use of carbetocin in addition to regular uterotonic agents decreased total blood loss and undiagnosed PPH. Also, systolic blood pressure 4 h after childbirth is higher in the carbetocin group. There was no significant difference in hemoglobin change and risk of PPH.

Prolapsed epiploica of bowel after robotic hysterectomy: A case report.

PURPOSE: Vaginal cuff dehiscence with evisceration was defined as expulsion of intraperitoneal organs through the separated incision. Prolapsed epiploica of the colon is a rare complication after hysterectomy. The most common organ to prolapsed out from the dehiscence vaginal cuff is terminal ileum. We reported the first known case of prolapsed epiploica of the colon after robotic hysterectomy. CASE: This is a case who had prolapse of a vaginal tumor after sexual intercourse 5 months after robotic hysterectomy. Vaginal tumor resection and primary closure were performed successfully without complications. The final pathology revealed fat prolapse with foreign body reaction and confirmed prolapse of epiploica of the colon. Being aware of the risk factors and patients who are more likely to develop this complication is essential in making the correct diagnosis in time. MAJOR CONCLUSION: Patients with a higher risk of vaginal cuff dehiscence are advised to avoid sexual activity for a longer period of time. Surgical intervention is the primary treatment. Prolapsed epiploica of the colon should be kept in mind for those who have undergone hysterectomy in order to provide appropriate treatment in time.

The Alexipharmic Mechanisms of Five Licorice Ingredients Involved in CYP450 and Nrf2 Pathways in Paraquat-Induced Mice Acute Lung Injury.

Oxidative stress is an important mechanism in acute lung injury (ALI) induced by paraquat (PQ), one of the most widely used herbicides in developing countries. In clinical prophylaxis and treatment, licorice is a widely used herbal medicine in China due to its strong alexipharmic characteristics. However, the corresponding biochemical mechanism of antioxidation and detoxification enzymes induced by licorice's ingredients is still not fully demonstrated. In this study, the detoxification effect of licorice was evaluated in vivo and in vitro. The detoxification and antioxidation effect of its active ingredients involved in the treatment was screened systematically according to Absorption, Distribution, Metabolism, and Excretion (ADME): predictions and evidence-based literature mining methods in silico approach. Data shows that licorice alleviate pulmonary edema and fibrosis, decrease Malondialdehyde (MDA) contents and increase Superoxide Dismutase (SOD) activity in PQ-induced ALI mice, protect the morphologic appearance of lung tissues, induce cytochrome 3A4 (CYA3A4) and Nuclear factor erythroid 2-related factor 2 (Nrf2) expression to active detoxification pathways, reduce the accumulation of PQ in vivo, protect or improve the liver and renal function of mice, and increase the survival rate. The 104 genes of PPI network contained all targets of licorice ingredients and PQ, which displayed the two redox regulatory enzymatic group modules cytochrome P450 (CYP450) and Nrf2 via a score-related graphic theoretic clustering algorithm in silico. According to ADME properties, glycyrol, isolicoflavonol, licochalcone A, 18beta-glycyrrhetinic acid, and licoisoflavone A were employed due to their oral bioavailability (OB) ≥ 30%, drug-likeness (DL) ≥ 0.1, and being highly associated with CYP450 and Nrf2 pathways, as potential activators to halt PQ-induced cells death in vitro. Both 3A4 inhibitor and silenced Nrf2 gene decreased the alexipharmic effects of those ingredients significantly. All these disclosed the detoxification and antioxidation effects of licorice on acute lung injury induced by PQ, and glycyrol, isolicoflavonol, licochalcone A, 18beta-glycyrrhetinic acid, and licoisoflavone A upregulated CYP450 and Nrf2 pathways underlying the alexipharmic mechanisms of licorice.

Network pharmacological mechanisms of Vernonia anthelmintica (L.) in the treatment of vitiligo: Isorhamnetin induction of melanogenesis via up-regulation of melanin-biosynthetic genes.

BACKGROUND: Vitiligo is a long-term skin disease characterized by the loss of pigment in the skin. The current therapeutic approaches are limited. Although the anti-vitiligo mechanisms of Vernonia anthelmintica (L.) remain ambiguous, the herb has been broadly used in Uyghur hospitals to treat vitiligo. The overall objective of the present study aims to identify the potential lead compounds from Vernonia anthelmintica (L.) in the treatment of vitiligo via an oral route as well as the melanogenic mechanisms in the systematic approaches in silico of admetSAR and substructure-drug-target network-based inference (SDTNBI). RESULTS: The results showed that the top 5 active compounds with a relatively higher bioavailability that interacted with 23 therapeutic targets were identified in Vernonia anthelmintica (L.) using admetSAR and SDTNBI methods. Among these compounds, Isorhamnetin and Kaempferide, which are methyl-flavonoids, performed 1st and 2nd. Isorhamnetin and Kaempferide significantly increased the expression of melanin-biosynthetic genes (MC1R, MITF, TYR, TYRP1 and DCT) and the tyrosinase activity in B16F10 cells. Isorhamnetin and Kaempferide significantly increased the mRNA-expression of melanin-biosynthetic genes (MC1R, MITF, TYR, TYRP1 and DCT), the protein level of MITF and the tyrosinase activity. Based on the SDTNBI method and experimental verification, Isorhamnetin and Kaempferide effectively increased melanogenesis by targeting the MC1R-MITF signaling pathway, MAPK signaling pathway, PPAR signaling pathway (PPARA, PPARD, PPARG), arachidonic acid metabolism pathway (ALOX12, ALOX15, CBR1) and serotonergic synapses (ALOX12, ALOX15) in the treatment of vitiligo from a network perspective. CONCLUSION: We identified the melanogenic activity of the methyl-flavonoids Isorhamnetin and Kaempferide, which were successfully predicted in a network pharmacological analysis of Vernonia anthelmintica (L.) by admetSAR and SDTNBI methods.

Differential gene expression in ovaries of Qira black sheep and Hetian sheep using RNA-Seq technique.

The Qira black sheep and the Hetian sheep are two local breeds in the Northwest of China, which are characterized by high-fecundity and low-fecundity breed respectively. The elucidation of mRNA expression profiles in the ovaries among different sheep breeds representing fecundity extremes will helpful for identification and utilization of major prolificacy genes in sheep. In the present study, we performed RNA-seq technology to compare the difference in ovarian mRNA expression profiles between Qira black sheep and Hetian sheep. From the Qira black sheep and the Hetian sheep libraries, we obtained a total of 11,747,582 and 11,879,968 sequencing reads, respectively. After aligning to the reference sequences, the two libraries included 16,763 and 16,814 genes respectively. A total of 1,252 genes were significantly differentially expressed at Hetian sheep compared with Qira black sheep. Eight differentially expressed genes were randomly selected for validation by real-time RT-PCR. This study provides a basic data for future research of the sheep reproduction.

[Functional analysis of cancer-derived immunoglobulin G whole molecule-interacting proteins identified by LC-MS/MS].

OBJECTIVE: To identify cancer-derived immunoglobulin G (IgG) whole molecule-interacting proteins to provide important clues for studying IgG biological functions. METHOS: HeLa cell lysate was immunoprecipitated with rabbit antihuman IgG whole molecule antibody and normal rabbit IgG. The immunocomplex underwent sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and was detected with silver staining. Three prominently enhanced bands were subjected to protein identification with liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the MS data were analyzed with Swiss-Prot database. Cancer-derived IgG whole molecule-interacting proteins were screened and functionally annotated. RESULTS AND CONCLUSION: We identified 6 potential cancer-derived IgG whole molecule-interacting proteins with co-immunoprecipitation combined with LC-MS/MS, which provides valuable clues for studying the function of cancer-derived IgG.

Identification of SNPs within the sheep PROP1 gene and their effects on wool traits.

Regarding mutations of PROP1 (Prophet of POU1F1) gene significantly associating with combined pituitary hormone deficiency (CPHD) in human patients and animals, PROP1 gene is a novel important candidate gene for detecting genetic variation and growth, reproduction, metabolism traits selection and breeding. The aim of this study was to detect PROP1 gene mutation of the exon 1-3 and its association with wool traits in 345 Chinese Merino sheep. In this study, on the basis of PCR-SSCP and DNA sequencing methods, ten novel SNPs within the sheep PROP1 gene, namely, AY533708: g.45A>G resulting in Glu15Glu, g.1198A>G, g.1341G>C resulting in Arg63Ser, g.1389G>A resulting in Ala79Ala, g.1402C>T resulting in Leu84Leu, g.1424A>G resulting in Asn91Ser, g.1522C>T, g.1556A>T, g.1574T>C, g.2430C>G were reported. In addition, association analysis showed that three genotypes of P4 fragment were significantly associated with fiber diameter in the analyzed population (P=0.044). These results strongly suggested that polymorphisms of the PROP1 gene could be a useful molecular marker for sheep breeding and genetics through marker-assisted selection (MAS).

Betel nut chewing behavior among adolescents in eastern Taiwan: a cluster analysis.

The prevalence of betel nut chewing among junior high school students is highest in the eastern region of Taiwan (Lin, 1990). Although there is some research on the prevalence rate, little effort has been paid to developing a classification of betel nut chewing behavior applicable to adolescents. Eight-hundred and forty-three students, including 435 males (51.6%) and 408 females (48.4%), 552 non-aborigines (65.5%) and 291 aborigines (34.5%), completed a questionnaire concerning betel nut chewing behavior, beliefs (perceptions) toward betel nut chewing, self-esteem, and locus of control. Using a cluster analysis, this study identified 3 sub-types ofbetel nut chewing behaviors. They were identified as "Self-regulation oriented" (Internally controlled-oriented), "Indigenously oriented" (Taiwan culture-oriented), and "Symbolically oriented" (Externally controlled-oriented). The validity of clusters was explored in terms of gender and ethnicity. This study describes the implications for reducing betel nut chewing behaviors among adolescents.