A Comprehensive Overview of NF1 Mutations in Iranian Patients.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in the NF1 gene. This disorder shows nearly complete penetrance and high phenotypic variability. We used the whole-exome sequencing technique to identify mutations in 32 NF1 cases from 22 Iranian families. A total of 31 variants, including 30 point mutations and one large deletion, were detected. In eight cases, variants were inherited, while they were sporadic in the remaining. Seven novel variants, including c.5576 T > G, c.6658_6659insC, c.2322dupT, c.92_93insAA, c.4360C > T, c.3814C > T, and c.4565_4566delinsC, were identified. The current study is the largest in terms of the sample size of Iranian NF1 cases with identified mutations. The results can broaden the spectrum of NF1 mutations and facilitate the process of genetic counseling in the affected families.

The duration of spinal anaesthesia in elective caesarean section in Trendelenburg and reverse Trendelenburg positions: a randomized clinical trial.

Objective: One of the common methods of anaesthesia for caesarean sections (CSs) involves the use of spinal anaesthesia in mothers. Various positions are utilized in this method. This study aims to compare the evaluation of two positions, Trendelenburg and reverse Trendelenburg, in candidates for CS to assess the duration of anaesthesia and changes in vital signs in women. Methods: This study was a randomized clinical trial in which 60 pregnant mothers who met the inclusion criteria entered the study. These mothers were randomly allocated into two equal groups using block randomization. One group of patients received spinal anaesthesia in the Trendelenburg position, while the other group received it in the Reverse Trendelenburg position. Vital signs (systolic and diastolic blood pressure, heart rate, Apgar score, and SPO2) of participants from both groups were evaluated for 1 h after the induction of anaesthesia. Additionally, sensory level and duration of anaesthesia were measured. Finally, the data from both groups were subjected to statistical analysis using SPSS version 26 software. Results: The mean (SD) age of participating mothers in the Reverse Trendelenburg and Trendelenburg groups was 28.93 (5.82) and 30.97 (4.94), respectively. The two study groups did not significantly differ in baseline characteristics such as age, BMI, which could potentially impact vital sign outcomes or anaesthesia duration, and education (P>0.05). The mean (SD) duration of anaesthesia in the Trendelenburg position was significantly higher than in the Reverse Trendelenburg position [221.57(min) vs. 159.00(min)] (P<0.0001). There was no significant difference between the two positions, Trendelenburg and Reverse Trendelenburg, in terms of sensory level and its extent (P=0.08). The two study groups did not significantly differ in hemodynamic changes measured 13 times, including heart rate, systolic and diastolic blood pressure, and Apgar score (P>0.05). Conclusion: In spinal anaesthesia with the Trendelenburg position compared to the Reverse Trendelenburg position, there is a longer duration of anaesthesia. This is while the two positions did not differ in terms of hemodynamic changes and sensory level.

Correlation of Fetal Heart Rate, Uterine Artery Pulsatility Index, Pregnancy Associated Plasma Protein-A and Crown-Rump Length in Pre-eclampsia - a Prospective Cohort Study.

BackgroundThe prevalence of pre-eclampsia (PE) as a systemic disease in pregnancy is about 3-5%, but it is still one of the most important causes of maternal and infant mortality worldwide. This study aimed to investigate the association between fetal heart rate (FHR) and uterine artery pulsatility index (UtA-PI) in Doppler. Methods:The current cohort study was carried out on 317 pregnant women with a gestational age of 11 to 13 weeks and six days. Mothers were followed up from the first trimester until the delivery between March 2019 and March 2020. Uterine artery pulsatility index, FHR and ductus venosus pulsatility index (DVPI) were recorded. Finally, the Doppler index of ductus venosus, FHR and other design variables were compared between the two groups with and without preeclampsia. Results: Subjects' mean body mass index (BMI) was 25.31±3.98 kg/m2. The UtA-PI was correlated with Crown rump length (CRL) (r=-0.207, p=0.001), pregnancy associated plasma protein-A (PAPP-A) (r=-0.167, p=0.003), FHR (r=0.14, p=0.011) and uterine artery multiples of the median (UA MoM) (r=0.990, p=0.001), with the last one showing a strong positive correlation with CRL; PAPP-A had a reverse correlation with UA MoM (r=-0.171, p=0.002) and UtA-PI (r=-0.167, p=0.003), while FHR had a poor correlation with UA MoM (r=0.118, p=0.035) and UtA-PI (r=0.142, p=0.011). Conclusions:Uterine artery multiples of the median (UA MoM) was found to have a strong correlation with UtA-PI and, but a reverse correlation with PAPP-A. Intrauterine growth restriction (IUGR) had a significant association with FHR and UtA-PI. These findings imply the necessity of further future follow-up of offspring with a history of increased UtA-PI or maternal PE for cardiac alteration.

Clinicopathological and prognostic value of lncRNA TPT1-AS1 in cancer: A systematic review study and meta-analysis.

INTRODUCTION: Aberrant expression of lncRNAs in cancer cells can impact their key phenotypes. We aimed to summarize available evidence on clinicopathological and prognostic value of lncRNA TPT1-AS1 in cancer. METHODS: A systematic search was performed on Medline and Embase databases using relevant key terms covering lncRNA TPT1-AS1, cancer, and clinical outcomes. The effect size estimates and their 95 % confidence interval (CI) were pooled using random-effects models. Meta- analyses were conducted using STATA 16.0 software. RESULTS: Seventeen articles met our eligibility criteria. Tumor tissue compared to normal tissue showed increased level of lncRNA TPT1-AS1 expression (pooled standardized mean difference (95 % CI): 0.65 (0.52-0.79)). Overexpression of this lncRNA was a significant predictor for poor prognosis (Pooled log-rank test P-value < 0.001); in patients with high-level of lncRNA TPT1-AS1, the risk of death at five years was 1.40 times greater than their counterparts. The pooled Odds ratios for association lncRNA TPT1-AS1 with tumor stage, tumor size, and lymph node metastasis were 1.94 (95 % CI: 0.90-4.19, 8 studies, I2 = 79.6 %), 2.33 (95 % CI: 1.31-4.14, 5 studies, I2 = 40.0 %), and 1.89 (95 % CI: 1.08-3.36, 5 studies, I2 = 61.7 %), respectively. Regarding the identified potential mechanisms, lncRNA TPT1-AS1 plays a role in cancer growth mainly by sponging miRNAs and regulating their downstream targets or controlling the expression of key cell cycle regulators. CONCLUSION: In cancer patients, elevated expression of lncRNA TPT1-AS1 might be associated with a shorter Overall Survival, advanced stages, larger tumor size, and lymph node metastasis.

The Effect of Using Dexamethasone Tablets Vaginally for Improving Cervical Bishop Score in Nulliparous Pregnant Women: A Randomized Clinical Trial.

Background: Cervix ripening and labor induction are common interventions in obstetrics. For optimal maternal health, labor may be induced under certain situations to improve fetal survival outcomes. Labor induction of an unripe cervix can lead to complications; therefore, several approaches can facilitate the ripening process. Methods: This randomized clinical trial was a triple-blind study that involved 84 pregnant nulliparous women enrolled between October 2019 and June 2021 in the labor ward of Kamali Hospital, Karaj, Iran. The pregnant women in the study underwent labor induction and were randomized into 2 groups: 1 group received vaginal dexamethasone and the other group was given a placebo. Results: There was no significant difference between the groups regarding maternal age, demographic characteristics, and initial Bishop score. The median second Bishop score (6 hours after intervention) was 3.5 in dexamethasone recipients and 3 in placebo recipients (P = 0.48). The median labor latent phase duration was 4 hours in dexamethasone recipients and 5 hours in placebo recipients (P = 0.57). Conclusions: This randomized clinical trial demonstrated that administering dexamethasone tablets vaginally did not significantly improve cervical Bishop scores. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX). ClinicalTrials.gov identifier: NCT05070468.

Cancer Is Associated with the Emergence of Placenta-Reactive Autoantibodies.

Placenta-specific antigens are minimally expressed or unexpressed in normal adult tissues, while they are widely expressed in cancer. In the course of carcinogenesis, a vast array of autoantibodies (AAbs) is produced. Here, we used a quantitative approach to determine the reactivity of AAbs in the sera of patients with breast (BrC: N = 100, 100% female, median age: 51 years), gastric (GC: N = 30, 46.6% female, median age: 57 years), bladder (BC: N = 29, 34.4% female, median age: 57 years), and colorectal (CRC: N = 34, 41.1% female, median age: 51 years) cancers against first-trimester (FTP) and full-term placental proteome (TP) in comparison with age- and sex-matched non-cancer individuals. Human-on-human immunohistochemistry was used to determine reactive target cells in FTP. The effect of pregnancy on the emergence of placenta-reactive autoantibodies was tested using sera from pregnant women at different trimesters of pregnancy. Except for BC, patients with BrC (p < 0.0284), GC (p < 0.0002), and CRC (p < 0.0007) had significantly higher levels of placenta-reactive AAbs. BrC (p < 0.0001) and BC (p < 0.0409) in the early stages triggered higher autoantibody reactivity against FTP. The reactivities of BrC sera with FTP did not show an association with ER, PR, or HER2 expression. Pregnancy in the third trimester was associated with the induction of TP- and not FTP-reactive autoantibodies (=0.018). The reactivity of BrC sera with placental proteins was found to be independent of gravidity or abortion. BrC sera showed a very strong and specific pattern of reactivity with scattered cells beneath the syncytiotrophoblast layer. Our results reinforce the concept of the coevolution of placentation and cancer and shed light on the future clinical application of the placental proteome for the non-invasive early detection and treatment of cancer.

The role of lncRNA CERS6-AS1 in cancer and its molecular mechanisms: A systematic review and meta-analysis.

BACKGROUND: LncRNAs have the potential to play a regulatory role in different processes of cancer development and progression. We conducted a systematic review and meta-analysis of evidence on the clinical significance and prognostic value of lncRNA CERS6-AS1 in cancer. METHODS: This systematic review was conducted following PRISMA guidelines. Medline and Embase databases were searched using the relevant key terms covering lncRNA CERS6-AS1 and cancer. We pooled the estimated effect sizes and their 95 % confidence interval (CI) using random-effects models in STATA 16.0 (StataCorp, College Station, TX, USA). RESULTS: Eleven articles on pancreatic, colorectal, gastric, papillary thyroid, breast, and hepatocellular cancers fulfilled our eligibility criteria. Studies consistently found that lncRNA CERS6-AS1 expression is upregulated in all assessed cancers. Based on our meta-analysis, its aberrant expression was directly associated with unfavorable clinical outcomes, including higher stage (pooled Odds ratios (95 % CI): 3.15 (2.01-4.93; I2 = 0.0 %), tumor size (1.97 (1.27-3.05; I2 = 37.8 %), lymph node metastasis (6.48 (4.01-10.45; I2 = 0.40 %), and poor survival (Pooled log-rank test P-value < 0.001) in patients. Regarding potential mechanisms, functional studies revealed that LncRNA CERS6-AS1 is involved in cancer growth mainly by sponging miRNAs and regulating their downstream targets. CONCLUSION: Available evidence suggests that LncRNA CERS6-AS1 is upregulated in different cancers and has an oncogenic role. LncRNA CERS6-AS1 expression level might predict cancer prognosis, highlighting its potential application as a prognostic biomarker for cancer.

The prevalence of high-risk human papillomavirus genotypes and related risk factors among Iranian women.

Human papillomavirus (HPV) infection, which often includes high-risk genotype infection, is one of the leading causes of cervical cancer. This cross-sectional research included 503 Iranian women referred to the gynecology clinic of Kamali Hospital in Karaj, Iran, for routine cervical cancer screening between 2020 and 2021. Cervical specimens were collected from all participants with a special brush and transported to the laboratory for cervical cytology diagnosis. Overall HPV incidence among Iranian women was 39.96%, of which 23.06% had high-risk HPV genotypes and 9.7% had low-risk HPV types. The risk associated with HR-HPV types was considerably associated with employment and marital status.

Prophylactic effect of rectal and sublingual misoprostol on postpartum hemorrhage in mothers with preeclampsia following cesarean section surgery; a double-blind randomized controlled trial.

Background: Postpartum hemorrhage is one of the three major causes of maternal morbidity and mortality, so delay in the diagnosis and proper management of postpartum hemorrhage is of great importance. The present study aimed to determine the prophylactic effect of misoprostol on postpartum hemorrhage in patients with preeclampsia. Methods: This was a double-blind randomized controlled clinical trial performed on 128 pregnant women with preeclampsia undergoing cesarean section in Kamali hospital in Karaj. After cesarean delivery, immediately after clamping the umbilicus, the first group was administered 400 µg of rectal misoprostol and the second group was given 400 µg of sublingual misoprostol. The third group (control) was given 30 units of oxytocin during surgery and within 12 h after surgery, respectively. Hemoglobin and hematocrit were measured 24 h later. The estimated bleeding rate by the physician, the need for additional medication to control bleeding, and the amounts of hemoglobin and hematocrit in the first 24 h were compared in the three groups. Finally, the obtained information was entered into SPSS version 21 and analyzed using statistical tests. Results: The mean hemoglobin and hematocrit levels 6 and 12 h after cesarean section were significantly lower in the oxytocin group than in the sublingual and rectal misoprostol groups (Hemoglobin level (mg/dl) for oxytocin group 10.39 ± 0.73 and 9.53 ± 1.09 vs. sublingual misoprostol 11.05 ± 0.71 and 10.39 ± 0.84 vs. rectal misoprostol 10.92 ± 0.85 and 10 ± 1.01; hematocrit level for Hemoglobin level (%) for oxytocin group 31.27 ± 2.29 and 28.64 ± 2.93 vs. sublingual misoprostol 33.09 ± 2.20 and 31.05 ± 2.37 vs. rectal misoprostol 32.54 ± 2.7 and 29.92 ± 2.86) (p < 0.005). The mean estimation of visual bleeding in the oxytocin group was higher than the other three groups, followed by the rectal and the sublingual groups, respectively. However, there was no significant difference between the three groups regarding visual bleeding. There was no significant difference in hemoglobin and hematocrit between the two groups of sublingual and rectal misoprostol before and 6 and 12 h after the surgery (P > 0.05). Conclusion: It seems that sublingual or rectal misoprostol administration along with oxytocin is associated with a reduction in postpartum cesarean section bleeding compared to oxytocin administration alone.

The effect of magnesium sulfate on maternal serum electrolytes and parathyroid hormone in pre-eclampsia.

OBJECTIVE: To evaluate possible interactions of magnesium sulfate-the drug of choice in the management of pre-eclampsia/eclampsia-in response to a few case reports that revealed maternal electrolyte disturbances, especially symptomatic changes, following magnesium sulfate administration in pre-eclampsia. METHODS: Prospectively, women with pre-eclampsia were given 4 g of intravenous magnesium sulfate followed by a 2 g/h infusion up to 24 h after delivery. Sequential blood samples were drawn from each patient and used to measure the serum levels of sodium, potassium, calcium, phosphorus, magnesium, and parathyroid hormone. RESULTS: A total of 30 pregnant women with pre-eclampsia were evaluated. They were aged between 20 and 41 years with median gestational age of 37.6 (interquartile range 35.4-38.9) weeks. Only five patients reached the therapeutic window of magnesium in at least one of our measuring intervals during magnesium sulfate infusion. Plasma magnesium concentrations increased significantly during magnesium sulfate administration and dropped during the next 12 and 24 h after infusion discontinuation (P < 0.05). Fifteen of 30 (50%) patients developed asymptomatic hypocalcemia, mainly at hour 24 of infusion. Negative moderate correlations were detected between the calcium and magnesium concentrations at 12 and 24 hours of infusion (ρ = -0.390, P = 0.044 and ρ = 0.315, P = 0.096, respectively). None of the patients with hypocalcemia reached the therapeutic level of magnesium or experienced parallel hyperphosphatemia. Eleven of 30 (36.6%) patients developed hyperphosphatemia mainly at 2 and 12 h of magnesium sulfate infusion. CONCLUSIONS: Our study implies that magnesium sulfate could cause hypermagnesemia-induced hypocalcemia in women with pre-eclampsia, independent from parathyroid hormone. The negative correlations between calcium and magnesium concentrations could be indicative of dose-dependent associations between serum magnesium level and degree of hypocalcemia in our study.

Ruled out of preeclampsia-like syndrome due to COVID-19: A case study.

Coronavirus disease (COVID-19) is an infectious disease. In this study, we report a 28-year-old pregnant woman who had a postpartum seizure with a background of HELLP syndrome and a proven COVID-19 infection. Her child survived, and at 12-week postpartum, all maternal COVID-19-related symptoms vanished, and she was cured.

Atypical presentation of cardiomyopathy in a case of maternal mortality that was demonstrated as hypovolemic shock.

Periconceptional and prenatal care should be continued even during COVID-19 pandemics. Indeed, prevention and intervention programs for managing heart failure with aggressive resuscitation and invasive monitoring help to provide the best outcomes in cardiomyopathies. PPH may be associated with cardiac diseases and the resuscitation measures need modification to prevent maternal mortality.

Gestational diabetes mellitus: the correlation between umbilical coiling index, and intrapartum as well as neonatal outcomes.

OBJECTIVES: The objective of this study was to investigate the relationship between the postnatal umbilical coiling index (pUCI), and intrapartum and neonatal outcomes in parturients with gestational diabetes mellitus (GDM) and non-GDM. METHODS: An evaluation of the umbilical cords and pUCI of 117 neonates of GDM and 105 of non-GDM parturients were prospectively studied within 24 h after delivery. Furthermore, obstetric history, intrapartum and neonatal data were recorded. RESULTS: Premature rupture of membrane (PROM) (p = 0.001), emergency cesarean delivery (p = 0.01), spontaneous preterm delivery (p = 0.006), duration of hospital admission (p < 0.001), and congenital malformations (p = 0.03) were significantly higher in the GDM group. Moreover, pUCI had a significant association with large for gestational age (LGA) (p = 0.009), and meconium-stained amniotic fluid (p = 0.04) in the GDM group. In addition, increment of pUCI had significant association with spontaneous preterm delivery in both groups (p = 0.002) (OR = 1.23). CONCLUSIONS: GDM is associated with spontaneous preterm delivery, PROM, emergency cesarean delivery, duration of hospital admission, and congenital malformations. Increase in pUCI could increase the rate of spontaneous preterm delivery in normal pregnancy and pregnancy complicated by GDM, as well as, the rate of LGA and meconium-stained amniotic fluid in GDM.