The commitment problem of secured lending

The paper presents a new theory of trade credit in which firms buy inputs on credit from suppliers to restore the benefits of secured bank financing impaired by contract incompleteness. In a setting where investment is endogenous and unobservable to financiers, we show that a bank-secured credit contract is time-inconsistent. Upon being granted credit, the entrepreneur has an incentive to alter the original input combination, jeopardizing the bank’s revenues. Anticipating the entrepreneur’s opportunism, the bank offers an unsecured credit contract, reducing the surplus from the venture. One way for the entrepreneur to commit to the contract terms is to purchase inputs on credit from the supplier. The supplier observes the input investment and acts as a guarantor that inputs will be purchased as contracted, thus facilitating access to secured bank financing. The commitment role of trade credit still holds in a multi-period extension that investigates the impact of bank relationship lending on secured debt and trade credit. Our model provides novel testable predictions on optimal financial contracts in both one-period and repeated lending relationships

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

Stillbirth occurrence during COVID-19 pandemic: A population-based prospective study

Objectives: Data collected worldwide on stillbirth (SB) rates during the Covid-19 pandemic are contradictory. Variations may be due to methodological differences or population characteristics. The aim of the study is to assess the changes in SB rate, risk factors, causes of death and quality of antenatal care during the pandemic compared to the control periods. Methods: This prospective study is based on the information collected by the Emilia-Romagna Surveillance system database. We conducted a descriptive analysis of SB rate, risk factors, causes of death and quality of cares, comparing data of the pandemic (March 2020-June 2021) with the 16 months before. Results: During the pandemic, the SB rate was 3.45/1,000 births, a value in line with the rates of previous control periods. Neonatal weight >90th centile was the only risk factor for SB that significantly changed during the pandemic (2.2% vs. 8.0%; p-value: 0.024). No significant differences were found in the distribution of the causes of death groups. Concerning quality of antenatal cares, cases evaluated with suboptimal care (5.2%) did not change significantly compared to the control period (12.0%), as well as the cases with less than recommended obstetric (12.6% vs. 14%) and ultrasound evaluations (0% vs. 2.7%). Conclusions: During the COVID-19 pandemic, no significant differences in SB rates were found in an area that maintained an adequate level of antenatal care. Thus, eventual associations between SB rate and the COVID-19 infection are explained by an indirect impact of the virus, rather than its direct effect

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

Mode of Delivery in Women with Stillbirth: Results of an Area-Based Italian Prospective Cohort Study

Introduction: The choice of the mode of delivery, in case of stillbirth (SB) (fetus non-viable >22 weeks' gestation), should consider maternal preference, gestational age, bishop score, the clinical condition of the woman, and her previous obstetric history. However, despite these clear indications, data on the effective implementation of the latter are lacking. The aim of our study is to evaluate the different modes of delivery in an Italian population of SBs, according to gestational age, parity, causes of death, obstetric history, and maternal characteristics. Material and Methods: This is an area-based, prospective cohort study conducted in Emilia Romagna, Italy between January 2014 to December 2020. Data included all cases of SB (>22 weeks). Results: From 2014 to 2020, 783 SB occurred out of a total of 232.506 births, with a SB rate of 3.3 per 1000. Labor was spontaneous in 85 (11%). Of remnant, 567 (73.6%) were induced and 118 (15.3%) had no labor. The mode of delivery was vaginal in most of the cases (649/770, 84.3%) and by cesarean section in 121/770 (15.7%) of cases. Emergency CS was most frequent and performed in 89/121 (73.5%) of total CS, representing 11.5% of SB deliveries. Mode of induction did not differ in relation to gestational age at stillbirth, while vaginal delivery was significantly higher in women induced with prostaglandins (p = 0.000) respect to other methods. Nulliparous women had a significantly higher need for multiple methods of induction (p = 0.000) respect multiparous and obese women used more frequently prostaglandins (p = 0.03) than other methods. Women with a history of previous CS presented a significantly higher rate of repeated elective CS (p = 0.000). Moreover, emergency CS was performed more frequent in obese (p = 0.02), diabetic (p = 0.04) and hypertensive (p = 0.04) women and in SB caused by placenta disorders, namely in abruptio placentae (p = 0.000). In the case of chorioamnionitis and funisitis women significantly were induced with prostaglandin (p = 0.000) and delivered vaginally (p = 0.000). Conclusions: The method of induction of labor and the mode of delivery in case of SB did not depend on gestational age at the diagnosis of death, while they are related to placenta disorders representing a relevant condition leading to emergency CS also after diagnosis of fetal death. These data could help obstetric providers in managing the deliveries of stillborn infants

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

Minimal clinically important difference for asthma endpoints: an expert consensus report

Minimal clinically important difference (MCID) can be defined as the smallest change or difference in an outcome measure that is perceived as beneficial and would lead to a change in the patient's medical management.The aim of the current expert consensus report is to provide a "state-of-the-art" review of the currently available literature evidence about MCID for end-points to monitor asthma control, in order to facilitate optimal disease management and identify unmet needs in the field to guide future research.A series of MCID cut-offs are currently available in literature and validated among populations of asthmatic patients, with most of the evidence focusing on outcomes as patient reported outcomes, lung function and exercise tolerance. On the contrary, only scant and partial data are available for inflammatory biomarkers. These clearly represent the most interesting target for future development in diagnosis and clinical management of asthma, particularly in view of the several biologic drugs in the pipeline, for which regulatory agencies will soon require personalised proof of efficacy and treatment response predictors

Mudanças nos compostos bioativos e atividade antioxidante de pimentas da região amazônica.

A Embrapa Amazônia Oriental possui um Banco Ativo de Pimenteira com diferentes genótipos do gênero Capsicum, os quais ainda não foram analisados, quanto às suas características funcionais e capacidade antioxidante. Este estudo objetivou determinar os teores de ácido ascórbico, compostos fenólicos, carotenoides totais e a atividade antioxidante total, em frutos imaturos e maduros de genótipos de pimentas Capsicum spp. As concentrações de vitamina C (100,76-361,65 mg 100 g-1 nos frutos imaturos e 36,70-157,76 mg 100 g-1 nos maduros) decresceram com a maturação dos frutos. Carotenoides totais não foram detectados nos frutos imaturos, porém, nos frutos maduros, observaram-se valores de 73,80-1349,97 mg g-1, em função do genótipo. Os teores de compostos fenólicos aumentaram nos frutos maduros (147,40-718,64 mg GAE 100 g-1), para oito dos nove genótipos avaliados. Os frutos de pimenteira apresentaram significativa atividade antioxidante (55,02-92,03 mM trolox g-1 nos frutos imaturos e 39,60-113,08 mM trolox g- 1 nos maduros). Concluiu-se que o grau de maturação dos frutos influenciou nos teores de compostos bioativos dos genótipos estudados. Destacaram-se, como genótipos promissores com potencial para serem utilizados em programas de melhoramento genético, IAN-186301 e IAN-186324, pelos altos teores de carotenoides totais; IAN-186301, IAN-186311, IAN-186312 e IAN-186313, com relação às altas concentrações de ácido ascórbico; IAN-186304 e IAN-186311, pelos altos teores de compostos fenólicos; e IAN-186311, para atividade antioxidante

p53 Transactivation and the Impact of Mutations, Cofactors and Small Molecules Using a Simplified Yeast-Based Screening System

The p53 tumor suppressor, which is altered in most cancers, is a sequence-specific transcription factor that is able to modulate the expression of many target genes and influence a variety of cellular pathways. Inactivation of the p53 pathway in cancer frequently occurs through the expression of mutant p53 protein. In tumors that retain wild type p53, the pathway can be altered by upstream modulators, particularly the p53 negative regulators MDM2 and MDM4. promoter, ii) single copy, chromosomally located p53-responsive and control luminescence reporters, iii) enhanced chemical uptake using modified ABC-transporters, iv) small-volume formats for treatment and dual-luciferase assays, and v) opportunities to co-express p53 with other cofactor proteins. This robust system can distinguish different levels of expression of WT and mutant p53 as well as interactions with MDM2 or 53BP1.We found that the small molecules Nutlin and RITA could both relieve the MDM2-dependent inhibition of WT p53 transactivation function, while only RITA could impact p53/53BP1 functional interactions. PRIMA-1 was ineffective in modifying the transactivation capacity of WT p53 and missense p53 mutations. This dual-luciferase assay can, therefore, provide a high-throughput assessment tool for investigating a matrix of factors that can influence the p53 network, including the effectiveness of newly developed small molecules, on WT and tumor-associated p53 mutants as well as interacting proteins