Induction of Labor According to Medical Indications: A Critical Evaluation through a Prospective Study

Background: The induction of labor (IOL) is a common obstetric intervention, steadily increasing (one out four pregnancies) in the last years. This procedure should be considered only when there is a medical indication, and when the benefits outweigh the maternal and/or fetal risks of waiting for spontaneous onset of labor. Therefore, this study aims to compare the efficacy of the IOL in terms of induction to delivery time, mode of delivery, and neonatal well-being among different evidence-based and non-evidence-based indications. Methods: This prospective study was conducted at the University Hospital of Modena, between January and December 2020. We included singleton pregnant women undergoing IOL, at the term. Intrauterine deaths, small for gestational age fetuses <5th centile as well women with hypertensive disorders were excluded. Women have been subdivided into 3 groups based on the indication to IOL: premature rupture of membranes (PROM), post-date pregnancy (>41 weeks + 3 days), and non-evidence-based indications (NEBI). The primary outcome is the time occurring between IOL and delivery (TIME), analyzing separately by parity. Moreover, mode of delivery and neonatal wellbeing were evaluated. Results: A total of 585 women underwent IOL in the study period. Overall, the median TIME between IOL and delivery was 19 hours, and the mean cesarean section CS rate was 15.5% (91/585). Pregnancies induced for postdate and non-evidencebased indications registered respectively a significantly higher mean time (p < 0.001), compared with women induced for PROM. This occurred both in nulliparous and multiparous women. Moreover, at multivariate analysis, the IOL TIME ≥24 hours was significantly influenced by Bishop score (p = 0.000) and NEBI (p = 0.02) in nulliparous and by gestational age (p = 0.000) and NEBI (p = 0.02) in multiparous. Moreover, CS rate was significantly influenced by Bishop score (p = 0.003) in nulliparous and by gestational age (p = 0.01) in multiparous. Finally, neonatal intensive care unit (NICU) admission resulted significantly influenced only by gestational age (p = 0.002) in multiparous. Conclusions: Our study confirms that IOL in non-evidence-based indications, leads to an increase in induction to delivery time comparing with women induced for PROM, both in nulliparous and multiparous women, thus it should be justified and carefully evaluated. Further randomized controlled trials (RCT) conducted in European/Italian settings are needed to determine the perinatal outcomes of IOL in non-evidence-based indications

PRIMA-1 induces autophagy in cancer cells carrying mutant or wild type p53.

PRIMA-1 is a chemical compound identified as a growth suppressor of tumor cells expressing mutant p53. We previously found that in the MDA-MB-231 cell line expressing high level of the mutant p53-R280K protein, PRIMA-1 induced p53 ubiquitination and degradation associated to cell death. In this study, we investigated the ability of PRIMA-1 to induce autophagy in cancer cells. In MDA-MB-231 and HCT116 cells, expressing mutant or wild type p53, respectively, autophagy occurred following exposure to PRIMA-1, as shown by acridine orange staining, anti-LC3 immunofluorescence and immunoblots, as well as by electron microscopy. Autophagy was triggered also in the derivative cell lines knocked-down for p53, although to a different extent than in the parental cells expressing mutant or wild type p53. In particular, while wild type p53 limited PRIMA-1 induced autophagy, mutant p53 conversely promoted autophagy, thus sustaining cell viability following PRIMA-1 treatment. Therefore, the autophagic potential of PRIMA-1, besides being cell context dependent, could be modulated in a different way by the presence of wild type or mutant p53. Furthermore, since both cell lines lacking p53 were more sensitive to the cytotoxic effect of PRIMA-1 than the parental ones, our findings suggest that a deregulated autophagy may favor cell death induced by this drug

Pyrrolizidine alkaloid profiles of the Senecio cineraria group (Asteraceae).

Alkaloid profiles of five Senecio species (Asteraceae), including S. ambiguus subsp. ambiguus, S. ambiguus subsp. nebrodensis, S. gibbosus subsp. bicolor, S. gibbosus subsp. gibbosus, and S. gibbosus subsp. cineraria, were studied. Eleven pyrrolizidine alkaloids were identified and their content was evaluated by GLC-MS and GLC analysis. Otosenine and florosenine were found to be the major alkaloids in all studied species. It is interesting that only S. ambiguus subsp. nebrodensis was characterized by a high content of the alkaloids jacobine, jacoline, jaconine, and jacozin

Human Vitreous Collagen Fragments Dimension As a Function of Vitrectomy Cut Rate

Purpose: To study the dimensions and distribution of human vitreous collagen type II fragments collected after vitrectomy performed at varying cut rates and to evaluate if increasing the cut rate produces smaller collagen fragments, thus reducing retinal traction and/or viscosity. Methods: Fluid was collected during core vitrectomies performed for macular surgery at cut rates from 1000 to 16,000 cuts per minute (CPM) and immediately refrigerated. Protein fractions were separated by molecular weight (MW; >100 kDa, 50–100 kDa, 50– 30 kDa, 30–10 kDa, and <10 kDa) through centrifugal filters. The Human Collagen II ELISA Kit colorimetric assay was then used to measure the COL2A1 in unfiltered and filtered samples. Results: Vitreous samples collected after vitrectomy performed at 16,000 CPM contained a higher concentration of protein with MW over 100 kDa than at any other cutting frequency (P < 0.01). No significant differences were found in fractions collected with a MW between 50 and 100 kDa. Collagen type II fragments over 100 kDa were significantly more represented than smaller fragments at each cut rate. The proportion of smaller (50–100 kDa) collagen fragments compared with those over 100 kDa was higher at 2000 CPM than at higher cut rates. Conclusions: Vitreous samples collected at different cut rates do not contain a significantly different proportion of collagen type II fragments of the tested MW. The extreme variability of vitreous flowthrough the cutter port may explain the uncertain predictability of collagen fragment MWs. Translational Relevance: Increasing the cut rate does not produce vitreous fragments of proportionally smaller dimension. It is necessary to achieve an invariant instantaneous flow through the cutter port in order to decrease retinal traction during vitrectomy

06N-P63\u3b1 and TA-P63\u3b1 exhibit intrinsic differences in transactivation specificities that depend on distinct features of DNA target sites.

TP63 is a member of the TP53 gene family that encodes for up to ten different TA and 06N isoforms through alternative promoter usage and alternative splicing. Besides being a master regulator of gene expression for squamous epithelial proliferation, differentiation and maintenance, P63, through differential expression of its isoforms, plays important roles in tumorigenesis. All P63 isoforms share an immunoglobulin-like folded DNA binding domain responsible for binding to sequence-specific response elements (REs), whose overall consensus sequence is similar to that of the canonical p53 RE. Using a defined assay in yeast, where P63 isoforms and RE sequences are the only variables, and gene expression assays in human cell lines, we demonstrated that human TA- and 06N-P63\u3b1 proteins exhibited differences in transactivation specificity not observed with the corresponding P73 or P53 protein isoforms. These differences 1) were dependent on specific features of the RE sequence, 2) could be related to intrinsic differences in their oligomeric state and cooperative DNA binding, and 3) appeared to be conserved in evolution. Since genotoxic stress can change relative ratio of TA- and 06N-P63\u3b1 protein levels, the different transactivation specificity of each P63 isoform could potentially influence cellular responses to specific stresses

Prunus persica var. platycarpa (Tabacchiera Peach): bioactive compounds and antioxidant activity of pulp, peel and seed ethanolic extracts

A comparative analysis of ethanol extracts from peel, pulp and seed of Prunus persica var. platycarpa (Tabacchiera peach) was done. The total phenols, flavonoids and carotenoids content as well as the antioxidant properties were evaluated. Peach pulp extract was characterized by the highest total phytonutrients content and exhibited the highest antioxidant activity in all in vitro assays. Interestingly, pulp extract showed IC50 values of 2.7 and 2.2 g/mL at 30 and 60 minutes of incubation, respectively using -carotene bleaching test. A remarkable result was also obtained by using Fe-chelating assay (IC50 of 2.9 g/mL vs 1.3 g/mL for positive control BHT). Pulp extract was subjected to liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS). Six main compounds, namely gallic acid, protocatechuic acid, protocatechualdehyde, chlorogenic acid, p-coumaric acid, and ferulic acid, were identified. Overall, the results suggest that Prunus persica var. platycarpa displays a good antioxidant activity and its consumption could be promote

Perinatal outcomes in twin late preterm pregnancies: results from an Italian area-based, prospective cohort study

Background: Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16–50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. Methods: Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013–2015. The primary outcome was a composite of adverse perinatal outcomes. Results: Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p < 0.01), higher gestational age at delivery (p < 0.01), Caucasian race (p 0.04), ART use (p < 0.01), gestational diabetes (p < 0.01), vaginal bleeding (p < 0.01), antenatal corticosteroids (p < 0.01), diagnosis of fetal growth restriction (FGR) (p < 0.01), and monochorionic (p < 0.01). Two hundred twenty-six pregnancies (65.3%) had at least one fetus experiencing one composite of adverse perinatal outcome. Multivariate analysis confirmed that delivery indication did not affect the composite of adverse perinatal outcomes; the only characteristic that affect the outcome after controlling for confounding was gestational age at delivery (p < 0.01). Moreover, there was at least one adverse neonatal outcome for 94% of babies born at 34 weeks, for 73% of those born at 35 weeks and for 46% of those born at 36 weeks (p < 0.01). Conclusion: Our study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants’ prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications