In-silico and in-vitro studies revealed alpha-amyrin as a potent pnhibitor of TLR2 for the therapeutics of bacterial infection and sepsis.

This study employed a multifaceted approach to investigate the inhibitory potential of alpha-amyrin against TLR2, a key player in bacterial infection and sepsis. A high-resolution TLR2 model was constructed using Swiss-MODEL, exhibiting excellent quality with 100% sequence identity and coverage. Cavity detection revealed five significant cavities on TLR2. Molecular docking identifies alpha-amyrin as a potent inhibitor, displaying a strong binding affinity of -8.6 kcal/mol. Comprehensive analyses, including ADMET predictions, PASS analysis, and SwissTargetPrediction, affirm alpha-amyrin's drug-like properties and diverse biological activities. Cytotoxicity assays on HEK-293 cells confirm its safety, and fluorescence-based inhibition assays provide empirical evidence of its inhibitory potency on TLR2 enzymatic activity. Further validations in HUVECs show a significant decrease in TLR2 mRNA expression (p<0.01) and activity (p<0.05) upon alpha-amyrin treatment. In conclusion, this integrative study positions alpha-amyrin as a promising therapeutic candidate for TLR2 inhibition, emphasizing its potential in combating bacterial infections with safety and efficacy.

Major placenta previa among patients with and without previous cesarean section: Maternal characteristics, outcomes and risk factors.

OBJECTIVES: To compare maternal characteristics and outcomes among patients having major placenta previa (PP) with and without previous cesarean section (CS). And to determine if previous CS alone is a risk factor for associated adverse maternal outcomes in these patients. MATERIALS AND METHODS: This is a retrospective analysis including two groups of major PP patients, with previous CS (n = 184) and without CS (n = 115); who were admitted to Abha Maternity and Children's Hospital over the last ten-years (January 2012-December 2021), Aseer region, Saudi Arabia. RESULTS: Compared to those without previous CS, major PP patients with previous CS had significantly advanced ages with higher mean numbers of gravidity and parity, but significantly less rates of previous uterine surgery and IVF pregnancies. Moreover, they were more likely to acquire higher rates of adverse maternal outcomes. In the same way, these patients had an increased Odds Ratios of cesarean hysterectomy (OR of 20.462), urinary tract injuries (OR of 12.361), associated PAS (OR of 4.375), moderate/ heavy intra-operative bleeding (OR of 2.153) and the need for transfusion of 3+ units of packed RBCs (OR of 1.849). CONCLUSION: (1) Patients with combined existence of major PP and previous CS had significantly higher rates of adverse maternal outcomes (2) Alone, prior CS in major PP patients increased the Odds Ratios of cesarean hysterectomy, urinary tract injuries, diagnosis of PAS, excessive intra-operative bleeding and repeated packed RBCs transfusions. (3) Among our PP patients with previous CS, the increased rate and OR of PAS diagnosis could in-part explain the adverse maternal outcomes.

Incidence, risk factors, and maternal outcomes of major degree placenta previa: A 10-year retrospective analysis.

OBJECTIVES: To determine the incidence, risk factors, and maternal outcomes of "major degree" placenta previa (PP)/placenta accreta spectrum (PAS) in Abha Maternity and Children's Hospital, Abha, Saudi Arabia. Secondly, to compare our findings to those of previous studies on PP/PAS in Saudi Arabia. METHODS: This is a retrospective study that included 299 patients diagnosed with major degree PP/PAS and admitted to Abha Maternity and Children's Hospital, Abha, Saudi Arabia, within 10 years (January 2012-December 2021). Also, we compared our results to the outcomes of PP/PAS patients in 6 previous Saudi studies. RESULTS: The total number of deliveries was 54,341; PP minor and major degrees were diagnosed in 376 (0.69%) patients. Of them, 299 patients had PP major degree (79.5%). The pattern of main risk factors for major PP/PAS included: elder age, high parity, and previous cesarean deliveries. Nearly 30.5% had evidence of PAS on antenatal MRI (n=91). Approximately 68.5% (n=205) of patients were delivered <37 weeks. Of 299 patients, 29 (9.7%)patients had emergency cesarean hysterectomy. The maternal mortality rate was 0.3% (n=1). Generally, in many aspects, our results are comparable to similar Saudi studies on PP/PAS. CONCLUSION: Major degree of PP/PAS is associated with high maternal morbidity but rare mortality. Over 30 years, our patients' obstetric characteristics did not change, including both elder age and high parity. A substantial increase in the rate of cesarean deliveries is a leading cause of major PP/PAS.

Comparison between invasive and non-invasive assessment of blood pressure in hypertensive disorders of pregnancy.

BACKGROUND: The management of hypertensive disorders of pregnancy (HDP) during hospitalization requires an accurate blood pressure (BP) measurement, mainly by invasive intra-arterial reading. Nevertheless, little is known about the precision of non-invasive (NI) central BP measurements in HDP. We aimed to assess the accuracy of NI central BP assessment in comparison to invasive BP measurement in HDP. This cross-sectional study included all patients with HDP that were admitted to university hospitals for high BP control, from December 2018 till December 2019, and 10 healthy matched non-hypertensive controls. Patients were compared for demographic, anthropometric, and echocardiographic data. In all subjects, invasive BP assessment was done by radial arterial cannulation and NI assessment of BP was performed by an oscillometric automated device (Mobil-O-Graph); the comparison was done after initial control of BP. RESULTS: One hundred patients were included and divided into 3 groups (pre-existing hypertension (HTN), gestational HTN, and pre-eclampsia). There was no statistically significant difference between NI central and invasive methods in measuring both systolic BP (SBP) (126.39 ± 14.5 vs 127.43 ± 15.3, p = 0.5) and diastolic BP (82.41 ± 9.0 vs 83.78 ± 8.9, p = 0.14) among the total studied population. A strong positive correlation was found between NI central and invasive SBP (r = 0.96, p < 0.001). HDP was associated with an increase in arterial stiffness, left ventricular diastolic dysfunction, and complications. CONCLUSION: Non-invasive measurement of BP using oscillometric automated devices is as accurate as the invasive method, and it is a practical safe method in pregnant women with hypertensive disorders (CTR no. = NCT04303871).

Clinical and Ultrasound Evaluation of Early Threatened Miscarriage to Predict Pregnancy Continuation up to 28 Weeks: A Prospective Cohort Study.

OBJECTIVES: (1) To study the predictors of pregnancy continuation up to 28 weeks in first-trimester threatened miscarriage after a single clinical and ultrasound (US) evaluation. (2) To assess the role of both clinical and US predictors in counseling and decreasing repeated emergency follow-up scans. METHODS: A prospective observational study that included a cohort of 241 patients with threatened miscarriage (≥6-12 weeks) was conducted. They had a single clinical and US evaluation, and then they were contacted by weekly phone calls until completing 28 weeks' gestation or reporting miscarriage. Independently, all patients were followed by the recommended routine US scanning with or without emergency visits. RESULTS: Two hundred thirty-three patients completed the study, of whom 193 patients continued up to 28 weeks' gestation, and 40 miscarried (17.1%). Only spotting/mild bleeding episodes and progesterone treatment were the clinical predictors of fetal viability. The embryonic/fetal heart rate (E/FHR) was the best single US predictor, with a specificity and positive predictive value of 95.3% and 97.2%, respectively. Combining 3 US parameters, at their best cutoff points (E/FHR >113 beats per minute, crown-rump length >19.9 mm, and gestational sac diameter >27.3 mm), had a specificity and positive predictive value of 98% and 99% (first-trimester US triad of fetal viability). CONCLUSIONS: [1] In first-trimester threatened miscarriage, clinical parameters that could predict fetal viability included spotting/ mild bleeding and progesterone treatment. [2] After a single US scan, the presence of at least an E/FHR of greater than 113 bpm or the suggested first-trimester US triad appeared as a simple, measurable, and effective predictor of pregnancy continuation up to 28 weeks. [3] These US predictors are not to replace the recommended scheduled scanning during pregnancy. [4] This can improve patients' counseling and decrease the need for repeated emergency follow-up scans. Otherwise, there is an indication for repeating US scans at a 1-week to 10-day interval.

Intramuscular 17α-hydroxyprogesterone caproate to decrease preterm delivery in women with placenta praevia: a randomised controlled trial.

We tested the hypothesis that 17α-hydroxyprogesterone caproate (17α-OHP-C) may decrease preterm delivery (PTD) in women with placenta praevia. This was a randomised controlled trial included 114 women with placenta praevia (between 24 and 28 weeks). They were randomly assigned to group I (17α-OHP-C) who received weekly injection of 17α-OHP-C (250 mg/IM) till completing 37 weeks' gestation or group II (Non 17α-OHP-C). The percentage of placenta praevia patients went into PTD in the 17α-OHP-C group was significantly less in comparison to the PTD in the Non 17α-OHP-C group (∼37% vs. 63.5%, p = .004). Furthermore, the mean gestational age was significantly longer (36.7 ± 0.7 vs. 34.9 ± 1.2 weeks, p < .000), the mean number of bleeding attacks was significantly less and the mean birth weight was significantly higher (2841 ± 159 vs. 2561 ± 168 g, p < .000). In conclusion, maintenance tocolysis with intramuscular 17α-OHP-C in placenta praevia women appears beneficial in decreasing the number of bleeding attacks, the percentage of PTD and the neonatal ICU admission.IMPACT STATEMENTWhat is already known on this subject? Over the last two decades, a large number of studies indicated that placenta praevia is a major risk factor for preterm labour and prematurity with its neonatal complications. Increasing caesarean section rates had proportionally increased the incidence of placenta praevia.What do the results of this study add? Up to now, the effective and safe tocolytic agent among these patients is not established. The results of this study (prospective, randomised and controlled with calculated sample size) added a considerable support for hydroxyprogesterone caproate as an effective, safe and cheap tocolytic agent with excellent patient compliance.What are the implications of these findings for clinical practice and/or further research? Our findings may prompt researchers to conduct a large multicentre study to evaluate the prophylactic use of hydroxyprogesterone caproate to decrease preterm labour due to placenta praevia.

Home-Based Extended Low-Dose Oral Misoprostol in Management of First-Trimester Pregnancy Loss in Low-Resource Communities: A Randomized Trial.

OBJECTIVE: To investigate the efficacy, safety and tolerability of a home-based extended low-dose oral misoprostol for management of first-trimester pregnancy loss. MATERIALS AND METHODS: A randomized trial that was conducted in the Woman's Health University Hospital and El-eman Maternity Hospital, Assiut, Egypt. One hundred and sixty patients were included. They were randomly assigned to receive four tablets of 200 µg misoprostol vaginally (max. 800 µg-hospital group) or 12 tablets orally, one every 3 h, over 2 consecutive days (max. 2400 µg-extended low-dose home group). For failed first dose, another similar second dose was given. Primary outcome measure was the percentage of patients with 'medically completed miscarriages' in each group (including complete miscarriages + incomplete miscarriages with successful post-miscarriage misoprostol). RESULTS: The total number of patients with 'medically completed miscarriages' in home group was 65/79 (82.3%), which was comparable to the hospital group (52/71 or 73.2%) (P = 0.182). However, the majority of patients in home group had significantly successful miscarriages after a single course of low-dose oral misoprostol, experienced much less heavy bleeding attacks and had less systemic side effects. CONCLUSION: In low-resource communities, the home-based extended low-dose oral misoprostol protocol proved high efficacy, safety and tolerability in management of first-trimester pregnancy loss.

A comparative study of the levonorgestrel-releasing intrauterine system Mirena versus the Copper T380A intrauterine device during lactation: breast-feeding performance, infant growth and infant development.

BACKGROUND: Mirena is a levonorgestrel-releasing intrauterine system (LNG-IUS) that provides highly effective and long-acting progestogen-only contraception. OBJECTIVE: The objective of this study was to analyze the possible effects of using LNG-20 microg IUS on breast-feeding performance, infant growth and infant development during the first postpartum year as compared with the Copper T380A intrauterine device (Cu T380A IUD). DESIGN: This study is a prospective, controlled and randomized trial. SETTING: The study was conducted at the Department of Obstetrics and Gynecology, Assiut University Hospital, Egypt. METHODS: Three hundred twenty lactating women asking for initiation of contraception during the early postpartum stage were assigned randomly into two groups, the LNG-20 microg IUS group (n=163) and the Cu T380A group (n=157). The insertions were done 6-8 weeks postpartum. Each participant was followed up at three monthly intervals after insertion and until the first birthday of her baby. During these visits, the breast-feeding pattern was assessed, certain infant physical growth parameters were measured and a set of infant development tests was performed. RESULTS: No pregnancy occurred in both groups. There were no significant differences in the net continuation rates between the two groups (89.3 for LNG-IUS vs. 90.9 for Cu T380A). The LNG-20 microg IUS group had comparable rates of breast-feeding continuation, complete weaning, full breast-feeding and partial breast-feeding, with the Cu-IUD group. No statistically significant differences were found between groups with regard to all infant physical growth parameters and various infant development tests. CONCLUSION: The findings of the current study confirm that the use of LNG-20 microg IUS during the first postpartum year in lactating women provides highly effective and acceptable contraception and does not negatively influence breast-feeding or the growth and development of breast-fed infants.

Prediction of successful menorrhagia treatment after thermal balloon endometrial ablation.

BACKGROUND: Thermal balloon endometrial ablation (TBEA) is a non-hysteroscopic technique, which relies on a combination of heat and pressure within the uterine cavity to destroy endometrium and superficial myometrium. It is a simple, easy and minimally invasive procedure with an equivalent effectiveness to hysteroscopic endometrial ablation. OBJECTIVES: To evaluate the effectiveness of TBEA in the treatment of menorrhagia and to identify the possible predictive factors for a successful outcome after 2-year follow-up. METHODS: A prospective study was conducted, including 45 patients suffering from serious menorrhagia. Under local anesthesia with i.v. sedation, the Therma-Choice trade mark (Gynecare, Somerville, NJ, USA) balloon was inserted transcervically and after inflation in the endometrial cavity with 5% dextrose, it was heated to 87 degrees C for an 8-minute treatment cycle. RESULTS: There were no intraoperative complications and postoperative morbidity was minimal. At 2-year follow-up the overall improvement of menstrual pattern was 85%; with reported 29% amenorrhea, 23.5% hypomenorrhea and 32.5% euomenorrhea. Menorrhagia persisted in 15% of patients. Multiple logistic regression analysis of the factors that could affect the outcome showed that the chance for a successful treatment increased significantly with increased age (P = 0.044), shorter uterine depth (P = 0.049) and adequate balloon pressure (P = 0.027). These were the predictive factors for successful outcome. However, parity, uterine volume and endometrial thickness were not predictive factors. CONCLUSION: At 2-year follow-up, thermal balloon endometrial ablation is effective in menorrhagia treatment. Increased age, shorter uterine depth and adequate balloon pressure can be predictive factors for successful treatment.