Factors Defining Human Adipose Stem/Stromal Cell Immunomodulation in Vitro.

Human adipose tissue-derived stem/stromal cells (hASCs) are adult multipotent mesenchymal stem/stromal cells with immunomodulatory capacities. Here, we present up-to-date knowledge on the impact of different experimental and donor-related factors on hASC immunoregulatory functions in vitro. The experimental determinants include the immunological status of hASCs relative to target immune cells, contact vs. contactless interaction, and oxygen tension. Factors such as the ratio of hASCs to immune cells, the cellular context, the immune cell activation status, and coculture duration are also discussed. Conditioning of hASCs with different approaches before interaction with immune cells, hASC culture in xenogenic or xenofree culture medium, hASC culture in two-dimension vs. three-dimension with biomaterials, and the hASC passage number are among the experimental parameters that greatly may impact the hASC immunosuppressive potential in vitro, thus, they are also considered. Moreover, the influence of donor-related characteristics such as age, sex, and health status on hASC immunomodulation in vitro is reviewed. By analysis of the literature studies, most of the indicated determinants have been investigated in broad non-standardized ranges, so the results are not univocal. Clear conclusions cannot be drawn for the fine-tuned scenarios of many important factors to set a standard hASC immunopotency assay. Such variability needs to be carefully considered in further standardized research. Importantly, field experts' opinions may help to make it clearer.

Intravenous tranexamic acid vs. sublingual misoprostol in high-risk women for postpartum haemorrhage following cesarean delivery; a randomised clinical trial.

OBJECTIVE: This study compares the effectiveness of administering sublingual misoprostol combined with oxytocin to that of IV tranexamic acid combined with oxytocin to reduce intra and post-operative blood loss in high-risk women for postpartum haemorrhage (PPH) following cesarean section (CS). METHODS: About 315 high-risk pregnant women undergoing CS participated in this trial. They were randomly assigned into three groups; tranexamic group, misoprostol group, and control group, according to the medication given in the operative theatre. All patients received oxytocin intraoperatively. They were assessed regarding intraoperative blood loss, the incidence of PPH, and the reduction in haemoglobin and hematocrit values. RESULTS: Both tranexamic and misoprostol groups had similar results in reducing intra and post-operative blood loss. However, the reduction in haemoglobin and hematocrit were significantly lower in tranexamic and misoprostol groups compared to the control group (-0.78 ± 0.57 vs. -0.83 ± 0.52 vs. -1.32 ± 0.57 gm/dl, P < 0.001 and - 3.05 ± 1.28 vs. -3.06 ± 1.13 vs. -4.94 ± 1.82%, P < 0.001 respectively). In addition, the estimated blood loss was significantly lower in the tranexamic and misoprostol groups compared to the control group (641.6 ± 271.9 vs. 617.9 ± 207.4 vs. 1002.4 ± 340.7 ml, P < 0.001). CONCLUSION: Both tranexamic acid and misoprostol are equally capable of reducing blood loss, but the results were significantly better compared to using oxytocin alone in high-risk patients. CLINICAL TRIAL REGISTRATION: Registered at www. CLINICALTRIALS: govon07/10/2019 with registration number NCT04117243.

Influence of type 2 diabetes and obesity on adipose mesenchymal stem/stromal cell immunoregulation.

Type 2 diabetes (T2D), associated with obesity, represents a state of metabolic inflammation and oxidative stress leading to insulin resistance and progressive insulin deficiency. Adipose-derived stem cells (ASCs) are adult mesenchymal stem/stromal cells identified within the stromal vascular fraction of adipose tissue. These cells can regulate the immune system and possess anti-inflammatory properties. ASCs are a potential therapeutic modality for inflammatory diseases including T2D. Patient-derived (autologous) rather than allogeneic ASCs may be a relatively safer approach in clinical perspectives, to avoid occasional anti-donor immune responses. However, patient characteristics such as body mass index (BMI), inflammatory status, and disease duration and severity may limit the therapeutic utility of ASCs. The current review presents human ASC (hASC) immunoregulatory mechanisms with special emphasis on those related to T lymphocytes, hASC implications in T2D treatment, and the impact of T2D and obesity on hASC immunoregulatory potential. hASCs can modulate the proliferation, activation, and functions of diverse innate and adaptive immune cells via direct cell-to-cell contact and secretion of paracrine mediators and extracellular vesicles. Preclinical studies recommend the therapeutic potential of hASCs to improve inflammation and metabolic indices in a high-fat diet (HFD)-induced T2D disease model. Discordant data have been reported to unravel intact or detrimentally affected immunomodulatory functions of ASCs, isolated from patients with obesity and/or T2D patients, in vitro and in vivo. Numerous preconditioning strategies have been introduced to potentiate hASC immunomodulation; they are also discussed here as possible options to potentiate the immunoregulatory functions of hASCs isolated from patients with obesity and T2D.

Zinc Oxide Nanoparticles Promise Anticancer and Antibacterial Activity in Ovarian Cancer.

BACKGROUND: Ovarian cancer is the most lethal cancer in gynaecology. Surgery, chemotherapy, and radiotherapy are the most often used cancer-fighting strategies. Post-surgery infection is fairly prevalent, especially among people with insufficient immunity. Zinc oxide nanoparticles (ZnOnps) have amazing biomedical features as anticancer and antibacterial agents. METHODS: We investigated the behaviour of ZnOnps synthesized by green methods on ovarian cancers using established human ovarian cancer cell lines, besides the antibacterial action toward models of gram + ve and gram -ve bacteria. The cytotoxic effect of ZnOnps was calculated using a Sulforhodamine B (SRB) trial. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were tested as models for gram + ve and gram -ve bacteria. The selected bacteria were subjected to concentrations of 20, 40, 80, and 100 µg/ml. RESULTS: The synthesized ZnOnps induced 50% inhibitory concentration (IC50) at a concentration of 27.45 µg/ml. The diameter of inhibition ranged between 20.16 ± 0.16 and 27 ± 0.57 mm for S. aureus and 25.66 ± 0.33 to 31 ± 0.33 mm for E. coli. ZnOnps antagonistic effect statistically differed with neomycin, cefaclor, and cefadroxil. CONCLUSIONS: Green synthesis of ZnOnps is easily prepared, low cost, non-toxic, and eco-friendly. Their cytotoxic action on SKOV3 cells and their antibacterial characteristics pave the way to be an alternative therapy for ovarian cancer and S. aureus and E. coli infection.

Effect of topical oxytocin gel on vaginal mucosa in postmenopausal Egyptian women: a clinical randomized trial.

BACKGROUND: Vaginal atrophy is common after menopause and is often linked to sexual dysfunction, particularly dyspareunia. AIM: The study aimed to investigate the effect of intravaginally applied oxytocin on expressions of vaginal atrophy. METHODS: Fifty postmenopausal women aged 47 to 66 years with vaginal atrophy participated in this double-blinded placebo-controlled study. The women were randomized to intravaginal treatment with either gel with 600 IU/mL of oxytocin (oxytocin group) or gel alone (control group) once daily for 2 weeks. The gel consisted of hypromellose, pH 3.8 (Vagovital). OUTCOMES: The color of the vaginal mucosa, the vaginal pH, and the cytology of vaginal epithelial cells were investigated before and after treatment. RESULTS: The color of the vaginal mucosa shifted from pale to red in all 25 patients treated with oxytocin but only in 4 patients in the control group (P < .001). There was a significant decrease in intravaginal pH in the oxytocin group and the control group, with the delta value being significantly greater in the oxytocin group than in the control group (P < .001). The vaginal maturation index increased significantly (P < .001) in the oxytocin group but not in the control group. CLINICAL IMPLICATIONS: Topical oxytocin gel offers an effective solution to the sexual dysfunction that is related to vaginal atrophy after menopause. STRENGTHS AND LIMITATIONS: Strengths include studying different outcomes of applying the oxytocin gel for vaginal atrophy. Limitations include the small-scale population with a relatively short duration of treatment (2 weeks). CONCLUSION: Intravaginal treatment with a gel containing 600 IU/mL of oxytocin effectively counteracts physical expressions of vaginal atrophy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05275270; https://clinicaltrials.gov/ct2/show/NCT05275270).

Delayed versus early umbilical cord clamping for near-term infants born to preeclamptic mothers; a randomized controlled trial.

OBJECTIVE: This study aims to assess delayed versus early umbilical cord clamping in preeclamptic mothers undergoing scheduled caesarean delivery regarding the maternal intra-operative blood loss and neonatal outcomes. METHODS: A clinical trial was conducted on 62 near-term preeclamptic mothers (36-38+6 weeks) who were planned for caesarean delivery. They were randomly assigned into two groups. The first group was the early cord clamping (ECC) group (n= 31), in which clamping the umbilical cord was within 15 seconds, while the second group was the delayed cord clamping (DCC) group (n= 31), in which clamping the umbilical cord was at 60 seconds. All patients were assessed for intra-operative blood loss and incidence of primary postpartum haemorrhage (PPH). Otherwise, all neonates were assessed for APGAR scores, the need for the neonatal intensive care unit (NICU) admission due to jaundice, and blood tests (haemoglobin, haematocrit. and serum bilirubin). RESULTS: There was not any significant difference between the two groups regarding the maternal estimated blood loss (P=0.673), the rates of PPH (P=0.1), post-delivery haemoglobin (P=0.154), and haematocrit values (P=0.092). Neonatal outcomes also were showing no significant difference regarding APGAR scores at the first minute (P=1) and after 5 minutes (P=0.114), day 1 serum bilirubin (P=0.561), day 3 serum bilirubin (P=0.676), and the rate of NICU admission (P=0.671). However, haemoglobin and haematocrit values were significantly higher in the DCC group than in the ECC group (P<0.001). CONCLUSION: There is no significant difference between DCC and ECC regarding maternal blood loss. However, DCC has the advantage of significantly higher neonatal haemoglobin. TRIAL REGISTRATION: It was first registered at ClinicalTrials.gov on 10/12/2019 with registration number NCT04193345.

Hysteroscopic management versus ultrasound-guided evacuation for women with first-trimester pregnancy loss, a randomised controlled trial.

OBJECTIVE: We aimed to evaluate the hysteroscopic management of first-trimester pregnancy loss compared to surgical evacuation either blind or under ultrasonographic guidance . METHODS: This clinical trial included 315 women with first-trimester pregnancy loss, divided equally into three groups. Group 1 underwent traditional blind surgical evacuation, group 2 underwent ultrasound-guided evacuation, and group 3 underwent hysteroscopic management. All women were assessed for retained products, surgical complications, the need for further management, and pregnancy occurrence after evacuation within 2 years of follow up. RESULTS: The rate of presence of conception remnants and the need for further treatment was significantly higher in group 1 compared to groups 2 and 3 (4.8% vs. 0% vs. 0%, P = 0.012). The conception rate within 2 years was significantly lower in group 1 compared to groups 2 and 3 (57.4% vs. 73.2% vs. 82.7%, P = 0.002), and the duration needed to conceive was significantly prolonged in group 1 compared to groups 2 and 3 (9.8 vs. 8.3 vs. 6.9 months, P < 0.001). Interestingly, women who underwent hysteroscopic management needed a significantly shorter time to conceive than those who underwent ultrasound-guided evacuation (6.9 vs. 8.3 months, P = 0.006). CONCLUSIONS: Hysteroscopic management of first-trimester pregnancy loss was superior to ultrasound-guided surgical evacuation regarding the time interval to conceive. Both techniques were superior to the blind evacuation technique regarding removal of the whole conception remnants, need for further treatment and fertility outcomes. Clinical trial registration: It was first registered at ClinicalTrials.gov on 16/03/2017 with registration number NCT03081104.

Lidocaine vs. tramadol vs. placebo wound infiltration for post-cesarean section pain relief: a randomized controlled trial.

OBJECTIVES: In low-income settings, postoperative pain relief could be challenging as a high patient/nurse ratio limits pain assessment and adequate analgesics administration. The multi-center prospective double-blinded parallel randomized controlled trial was done to compare lidocaine, tramadol, and placebo (saline) intraoperative wound infiltration to relieve post-cesarean section wound pain during the first 24 h. METHODS: Ninety-nine cases were equally randomized into three groups, each containing 33 pregnant women undergoing cesarean section under general anesthesia. During operation, the wound was infiltrated subcutaneously with 20 mL of 2% lidocaine solution in the first group, 2 mg/kg tramadol in the second group, and saline in the third group. The primary outcome was to assess the postoperative pain at 2, 4, 6, 12, and 24 h by the Yes-No-Don't Know (YNDK) Scale, while the secondary outcome was to assess the need for further postoperative analgesia. RESULTS: Wound infiltration with lidocaine or tramadol was effective in pain relief, and both were superior to placebo. Wound infiltration with tramadol was superior to lidocaine in pain relief at 2 h and up to 24 h. CONCLUSIONS: Wound infiltration with tramadol has a more prolonged pain relief effect than lidocaine in post-cesarean section pain relief in patients performing cesarean section under general anesthesia lasting up to 24 h, and both are superior to placebo in pain relief.

Intrapartum versus postpartum insertion of intrauterine device in women delivering by cesarean section.

BACKGROUND: The intrauterine device (IUD), being a reversible and effective contraception method, is the most widely used worldwide. This study aims to demonstrate the efficacy of IUD insertion during elective lower segment cesarean section (LSCS) versus its insertion six weeks postpartum. METHODS: A cohort study was conducted on 200 women planned for elective cesarean delivery and desired IUD as a contraceptive method. They were allocated into two groups; group I, in which IUD was inserted during LSCS, and group II, in which IUD was inserted six weeks or more after LSCS. Both groups were compared regarding failed insertion, post-insertion pain, and uterine perforation. They were followed for one year for the incidence of menorrhagia, vaginal infection, IUD displacement/expulsion, missed threads, or unintended pregnancy. RESULTS: Women in the second group showed a significantly higher incidence of failed insertion and uterine perforation than women in the first group. On the contrary, women in the first group showed a significantly higher incidence of missed threads than women in the second group. Regarding other consequences, there were no significant differences between both groups concerning menorrhagia, vaginal infection, IUD displacement/expulsion, or unintended pregnancy. CONCLUSION: IUD insertion during elective LSCS showed a significantly lower incidence of failed insertion and uterine perforation than its insertion six weeks postoperative.

Relation between Maternal and Neonatal Serum Lipid Profile and Their Impact on Birth Weight.

OBJECTIVE: Maternal malnutrition with disturbed lipid metabolism during pregnancy may affect the fetal lipid profile. We aimed to detect the relation between maternal and neonatal serum lipid profile, as well as to detect the serum lipid profile difference between small for gestational age (SGA) infants and appropriate for gestational age (AGA) infants to disclose the impact of maternal malnutrition on birth weight. STUDY DESIGN: A cross-sectional study was conducted on 150 pregnant women coming to the labor room. Before delivery, maternal serum levels of high-density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TGs), and total cholesterol were assessed, then after delivery, cord blood samples were taken for assessment of the neonatal lipid profile. Birth weights were measured, then the neonates were divided into SGA and AGA groups. RESULTS: Serum levels of LDL, TGs, and total cholesterol in the SGA infants were lower than that in the AGA infants. A positive correlation between maternal and neonatal serum TGs levels was found. Besides, there was a positive correlation between birth weight and maternal serum levels of LDL, TGs, and total cholesterol. CONCLUSION: Maternal serum lipid profile could be an indicator of the neonatal serum lipid profile and birth weight. KEY POINTS: · SGA neonates have lower levels of serum lipids compared to AGA neonates.. · There is a positive correlation between maternal and neonatal triglycerides.. · There is a positive correlation between birth weight and maternal serum lipids..

Effect of maternal BMI on labor outcomes in primigravida pregnant women.

BACKGROUND: This study aims to detect the effects of increased BMI on labor outcomes in primigravida pregnant women. METHODS: A cross-sectional study involved 600 full-term singleton primigravida pregnant women who presented in the active phase of labor to the labor ward. They were divided according to BMI into three equals groups; women with normal BMI (group I), overweight women (group II), and women with class I obesity (group III). RESULTS: We found that high BMI was associated with a significantly increased risk of Caesarean section (C.S.) (13% in group I, 18% in group II and 40% in group III). Women with higher BMI and delivered vaginally had a significantly prolonged first and second stage of labor, consequently increased the need for oxytocin augmentation as well as the oxytocin dose. Regarding the maternal and fetal outcomes, there are significantly increased risks of postpartum sepsis, perineal tears, wound infection, as well as significantly increased birth weight and longer neonatal stay in the neonatal unit (NNU). CONCLUSION: Obese primigravida pregnant women were at higher risk of suboptimal outcomes. Besides, prolonged first and second stages of labor and the incidence of C.S. have also been increased.

Assessment of fetal growth and anomalies in the era of COVID-19 pandemic: an Egyptian pilot study.

BACKGROUND: Many issues need to be studied regarding pregnant women during the SARS-CoV-2 (COVID-19) infection pandemic. The aim of this study was to assess fetal growth, fetal well-being, and any observed gross anomalies that may follow SARS-CoV-2 infection in Egyptian pregnant women. During fetal anomaly scan at 22 weeks, we compared 30 pregnant women with a history of SARS-CoV-2 infection at 6­12 weeks of gestation (group A) with 60 pregnant women (group B) who had no history of SARS-CoV-2. Then, we followed them on 28 and 34 weeks of gestation with fetal biometry and Doppler study. RESULTS: Our results revealed no significant difference between both groups regarding fetal biometry, estimated fetal weight, amniotic fluid index, Doppler scan, and gross anomaly scan throughout all visits. CONCLUSION: According to the results of our pilot study, SARS-CoV-2 infection in pregnancy was not found to increase the risk of fetal growth restriction or possible fetal gross anomalies. Nevertheless, larger-scale studies are needed to confirm those findings. Perhaps, post-SARS-CoV-2 infection pregnancies may run an uncomplicated course regarding fetal parameters.

Transverse versus longitudinal blunt extension of the uterine incision during cesarean section in women with a uterine scar of previous cesarean delivery: A randomized controlled trial.

OBJECTIVE: To compare two different blunt extension techniques of the lower segment transverse uterine incision at cesarean delivery in women with a uterine scar of previous cesarean delivery. METHODS: Study design: Prospective single-blinded parallel multi-center randomized controlled trial involving 392 cases equally divided into two groups. Group one had their incision extended transversely, while group two had their incision extended longitudinally. OUTCOME MEASURES: The primary outcome was the unintended extension of the uterine incision, while the secondary outcomes included the need for additional stitches to achieve hemostasis, the drop in hemoglobin level, uterine vessels injury, and the need for blood transfusion. RESULTS: No significant difference between the transverse and longitudinal extension of the uterine incision during cesarean section as regards unintended uterine extension (P = 0.860), uterine vessel injury (P = 0.501), and cases requiring blood transfusion (P = 0.814). Significantly lower drop in hemoglobin level (P ≤ 0.001) and significantly less need for additional stitches (P ≤ 0.001) in cases with the longitudinal extension of uterine incision. CONCLUSION: In women with a uterine scar of previous cesarean delivery, the blunt longitudinal extension of the uterine incision in the lower segment cesarean section didn't differ from the blunt transverse extension as regards unintended uterine extension but is associated with less hemoglobin drop and less need for additional stitches as compared to transverse extension of the incision. Further studies are needed to assess the long-term complications of both techniques.

Prevalence and determinants of anemia during the third trimester of pregnancy.

BACKGROUND: Anemia during pregnancy is a significant health problem. We aim to measure the prevalence of anemia in the third trimester of pregnancy in a specific geographical area and identify its risk factors. METHODS: A cross-section study was conducted in the antenatal clinic at Beni-Suef University Hospital on 383 pregnant women in the third trimester of pregnancy. All enrolled women were interviewed about age, education, occupation, family income, vitamin intake, medical history, and nutritional history. A blood sample was examined for hemoglobin concentration from each enrolled woman. RESULTS: The prevalence of anemia was 72%. Multiparity, infrequent antenatal visits, irregular intake of iron supplements, low weekly intake of meat and fruits, and frequent daily tea consumption were identified as risk factors for anemia. About 23.6% of the anemic women had small-for-gestational-age fetuses (RR = 25.2). CONCLUSION: Anemia by the third trimester of pregnancy represents a major health problem in Beni-Suef, Egypt.

Role of suppression of endometriosis with progestins before IVF-ET: a non-inferiority randomized controlled trial.

BACKGROUND: Endometriosis affects the responsiveness to ovarian stimulation. This study aimed to assess the role of Dienogest pretreatment for endometriosis suppression as compared to Gonadotropin-releasing hormone agonist (GnRHa) in patients with endometriosis pursuing IVF treatment. METHODS: In this randomized controlled trial, 134 women with endometriosis-related infertility were randomly allocated to group A (n = 67) who had monthly depot GnRHa for 3 months before ovarian stimulation in IVF treatment (Ultra-long protocol), and Group B (n = 67) who had daily oral Dienogest 2 mg/d for 3 months before starting standard long protocol for IVF. The primary outcome measure was the number of oocytes retrieved. The secondary outcome measures included the number of mature oocytes, fertilization rate, quality of life assessed by FertiQoL scores, cost of treatment, and pregnancy outcomes. RESULTS: Although there was no statistically significant difference between both groups regarding ovarian stimulation, response parameters, and pregnancy outcomes, the Dienogest group had a lower cost of treatment (2773 vs. 3664 EGP, P < 0.001), lower side effects (29.9% vs. 59.7%, P < 0.001), higher FertiQoL treatment scores (33.2 vs. 25.1, P < 0.001) and higher tolerability scores (14.1 vs. 9.4, P < 0.001 < 0.001). CONCLUSION: Our study indicates that Dienogest is a suitable and safe substitute for GnRHa pretreatment in endometriosis patients. TRIAL REGISTRATION: NCT04500743 "Retrospectively registered on August 5, 2020".

Role of first-trimester three-dimensional (3D) power Doppler of placental blood flow and 3D placental volume in early prediction of pre-eclampsia.

OBJECTIVE: To assess the efficacy of first-trimester three-dimensional (3D) placental volume as well as 3D power Doppler of placental vascular indices for early prediction of pre-eclampsia. METHODS: The prospective cohort study included over 2019 women with a singleton pregnancy in their first trimester at 11-13+ weeks of pregnancy. All women were examined by 3D abdominal ultrasound, including Doppler techniques for the placental volume and placental vascular indices. Uterine artery Doppler indices were also assessed. All participants were cared for until delivery for assessment of pregnancy outcomes. RESULTS: In all, 163 women developed pre-eclampsia while 1856 women remained normotensive. The women with pre-eclampsia had significantly lower placental volume (77.09 ml vs. 99.8 ml, p < 0.001), and placental vascular indices (vascularization index, flow index, and vascularization flow index were 7.41 vs. 9.89, 39.03 vs. 46.63, and 2.77 vs. 4.4, respectively, p < 0.001). In contrast, women with pre-eclampsia had significantly high mean uterine pulsatility index and resistance index (2.02 vs. 1.11, 0.83 vs. 0.64, respectively, p < 0.001) compared with the normotensive women. The placental vascular indices were highly sensitive, whereas the placental volume and the mean uterine pulsatility index and resistance index had higher specificity for the prediction of pre-eclampsia. CONCLUSION: First-trimester assessment through 3D placental volume and power Doppler of placental vascular indices, especially in combination with uterine artery Doppler assessment, revealed an increase in the accuracy of early detection of women at risk for developing pre-eclampsia.