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Designing small molecules able to break down G4 structures in mRNA (RG4s) offers an interesting approach to cancer therapy. Here, we have studied cationic porphyrins (CPs) bearing an alkyl chain up to 12 carbons, as they bind to RG4s while generating reactive oxygen species upon photoirradiation. Fluorescence-activated cell sorting (FACS) and confocal microscopy showed that the designed alkyl CPs strongly penetrate cell membranes, binding to KRAS and NRAS mRNAs under low-abundance cell conditions. In Panc-1 cells, alkyl CPs at nanomolar concentrations promote a dramatic downregulation of KRAS and NRAS expression, but only if photoactivated. Alkyl CPs also reduce the metabolic activity of pancreatic cancer cells and the growth of a Panc-1 xenograft in SCID mice. Propidium iodide/annexin assays and caspase 3, caspase 7, and PARP-1 analyses show that these compounds activate apoptosis. All these data demonstrate that the designed alkyl CPs are efficient photosensitizers for the photodynamic therapy of ras-driven cancers.

The aim of this systematic review with meta-analysis was to evaluate the effect on length of labor when patients receive IVF with or without dextrose. Searches were performed in electronic databases from inception of each database to May 2018. Trials comparing intrapartum IVF containing dextrose (i.e. intervention group) with no dextrose or placebo (i.e. control group) were included. Only trials examining low-risk pregnancies in labor at ≥36 weeks were included. Studies were included regardless of oral intake restriction. The primary outcome was the length of total labor from randomization to delivery. The meta-analysis was performed using the random effects model. Sixteen trials (n = 2503 participants) were included in the meta-analysis. Women randomized in the IVF dextrose group did not have a statistically significant different length of total labor from randomization to delivery compared to IVF without dextrose (MD −38.33 min, 95% CI −88.23 to 11.57). IVF with dextrose decreased the length of the first stage (MD −75.81 min, 95% CI −120.67 to −30.95), but there was no change in the second stage. In summary, use of IVF with dextrose during labor in low-risk women at term does not affect total length of labor, but it does shorten the first stage of labor.

Background. With the aim to inform potential SHE programs in Italian schools, we run a survey on 4,552 freshmen of four different Italian universities (Padua, Palermo, Bergamo and Milan) to investigate their level of SHK on STI prevention and associated factors. Methods. The survey was conducted with an anonymous self-reported paper questionnaire administered during teaching lectures to university freshmen of four Italian universities and different undergraduate courses. Results. The final number of freshmen surveyed was 4,552 (97.9% response rate), 1,842 (40.5%) from the university of Padua; 1,743 (38.3%) from the university of Palermo; 667 (14.7%) from the university of Bergamo and 300 (6.6%) from the university of Milan. The mean age of respondents was 21.4 2.2 years and most of them (70.3%) were females. An overall low STI knowledge among sample students was found. Only 28% respondents knew the most effective contraceptives to prevent STI (i.e. condom and sexual abstinence), with a slightly higher prevalence of correct answers among females (31.3%) than males (25.8%). Students with history of STIs reported referring mostly to their GP (38.1%), rather than discussing the problem with a family member (15.1%), booking an appointment with a consultant gynecologist (13.1%), discussing with their partner (13.1%) or with an experienced friend (12.5%). At multivariable analysis significantly lower levels of STI knowledge was found among males, students of the university of Palermo, those who completed a vocational secondary school education and non-Italian nationals. Categories with significantly less SHK on the most effective contraceptives to prevent STIs included males, students of the university of Palermo, students of educational sciences, students of economics/political sciences, those of foreign nationality, those with two siblings and those whose fathers had a lower educational level. Conclusions. The above findings provided indirect information on the standard of SHE delivered in Italian schools and call for the development of tailored multi-agency SHE programs involving several actors. In addition to school-based SHE programs, primary care services dedicated to sexual health should be strengthened in Italy.

Delayed cord clamping for at least 60 s in both term and preterm babies is a major recent change in clinical care. Delayed cord clamping has several effects on other possible interventions. One of these is the effect of delayed cord clamping on umbilical artery gas analysis. When indicated, umbilical artery gas analysis can safely be done either with early cord clamping or, probably most of the times it is necessary, during delayed cord clamping with the cord still unclamped. Paired blood samples (one from the umbilical artery and one from the umbilical vein) can be taken from the pulsating and unclamped cord, immediately after birth, during delayed cord clamping, without any effect on either the accuracy of umbilical artery gas analysis or the transfusion of blood through delayed cord clamping. Umbilical artery gas analysis should instead not be done after delayed cord clamping, since delayed cord clamping alters several acid-based parameters and lactate values.

The difficulty of asthmatic adolescents to take care of their own health through a regular intake of drugs and the adhesion to the physiotherapic treatments, it is very well documented. Curing asthma is not automatic, since it is an emotionally intense experience, where em-barrasment, sense of powerfulness and loss of control are perceived. All the above cannot be neglected particularly in an evolutive stage which is characterized by the relationships between peers together with a need for authonomy even on beliefs and values about health. This article follows the line marked by international literature, using the same theoretical and methodological setting (symbolic interactionism and narrative interview). 10 boys and 10 girls between 14 and 18 years old, admitted to Istituto Pio XII (Misurina, BL) were enrolled in the study. The interviews allowed the researchers to develop a theory based on the subjects’ self perceptions. The stories collected were about: 1) Identity building of an asthmatic person; 2) perception of the different daily lifestyle compared to persons of the same age; 3) Perception of friends and parents support; 4) Perception of the relationship with health professional; 5) Emotional impact (both happy and potentially traumatic experiences); 6) Therapy adherence. Having asthma is a stressful experience, particularly about the limitations on social life and the shame connected with it. Adolescents experience frustrations when they try to conquer their own authonomy by getting rid of what they perceive as an excessive parental control, so they carry out prejudicial behaviours (e.g. smoking) using their illness management as a favored battlefield. Health professionals are experienced as aloof and unsympathetic. The passage from therapeutic adherence to therapeutic agreement seems to be essential to promote rehabilitation projects in adolescents.

Information concerning the mechanisms underlying oxidative stress and low-grade inflammation in young healthy women predisposing eventually to future diseases is scarce. We investigated the relationship of oxidative stress and high-sensitivity C-reactive protein (hsCRP) in fertile-age women by oral combined contraceptive (OC) use. Caucasian Italian healthy non-obese women (n = 290, 100 OC-users, 190 non-OC-users, mean age 23.2 ± 4.7 years) were analyzed. Blood hydroperoxides, as oxidative stress biomarkers, were assessed by Free Oxygen Radical Test (FORT). Serum hsCRP was determined by an ultra-sensitive method (hsCRP). Markedly elevated oxidative stress (≥400 FORT Units) was found in 77.0% of OC-users and 1.6% of non-OC-users, odds ratio (OR) = 209, 95% CI = 60.9–715.4, p &lt, 0.001. Elevated hsCRP levels ≥ 2.0 mg/L, considered risky for cardiovascular diseases (CVDs), were found in 41.0% of OC-users and 9.5% of non-OC-users, OR = 6.6, 95%CI 3.5–12.4, p &lt, 0.001. Hydroperoxides were strongly positively correlated to hsCRP in all women (rs = 0.622, p &lt, 0.001), in OC-users (rs = 0.442, p &lt, 0.001), and in non-OC-users (rs = 0.426, p &lt, 0.001). Women with hydroperoxides ≥ 400 FORT Units were eight times as likely to have hsCRP ≥ 2 mg/L. In non-OC-users only, hydroperoxides values were positively correlated with weight and body mass index, but negatively correlated with red meat, fish and chocolate consumption. Our research is the first finding a strong positive correlation of serum hydroperoxides with hsCRP, a marker of low-grade chronic inflammation, in young healthy women. Further research is needed to elucidate the potential role of these two biomarkers in OC-use associated side-effects, like thromboembolism and other CVDs.

The herpes simplex virus 1 (HSV-1) genome is extremely rich in guanine tracts that fold into G-quadruplexes (G4s), nucleic acid secondary structures implicated in key biological functions. Viral G4s were visualized in HSV-1 infected cells, with massive virus cycle-dependent G4-formation peaking during viral DNA replication. Small molecules that specifically interact with G4s have been shown to inhibit HSV-1 DNA replication. We here investigated the antiviral activity of TMPyP4, a porphyrin known to interact with G4s. The analogue TMPyP2, with lower G4 affinity, was used as control. We showed by biophysical analysis that TMPyP4 interacts with HSV-1 G4s, and inhibits polymerase progression in vitro, in infected cells, it displayed good antiviral activity which, however, was independent of inhibition of virus DNA replication or entry. At low TMPyP4 concentration, the virus released by the cells was almost null, while inside the cell virus amounts were at control levels. TEM analysis showed that virus particles were trapped inside cytoplasmatic vesicles, which could not be ascribed to autophagy, as proven by RT-qPCR, western blot, and immunofluorescence analysis. Our data indicate a unique mechanism of action of TMPyP4 against HSV-1, and suggest the unprecedented involvement of currently unknown G4s in viral or antiviral cellular defense pathways.

The promoter of the Kirsten ras (KRAS) proto-oncogene contains, upstream of the transcription start site, a quadruplex-forming motif called 32R with regulatory functions. As guanine under oxidative stress can be oxidized to 8-oxoguanine (8OG), we investigated the capacity of glycosylases 8-oxoguanine glycosylase (OGG1) and endonuclease VIII-like 1 (Neil1) to excise 8OG from 32R, either in duplex or G-quadruplex (G4) conformation. We found that OGG1 efficiently excised 8OG from oxidized 32R in duplex but not in G4 conformation. By contrast, glycosylase Neil1 showed more activity on the G4 than the duplex conformation. We also found that the excising activity of Neil1 on folded 32R depended on G4 topology. Our data suggest that Neil1, besides being involved in base excision repair pathway (BER), could play a role on KRAS transcription.

Objective To determine the optimal and safest proximal sealing length (PSL) during thoracic endovascular aortic repair (TEVAR), depending on anatomical aortic arch types and proximal landing zones (LZs). Methods This was a single centre retrospective observational study of consecutive TEVAR patients (2008–2020). All aortic pathologies requiring Ishimaru landing zone (LZ) 0 – 3 were included; results were stratified by aortic arch type. The PSL was measured as the length of complete aortic wall to endograft apposition at the level of the proximal neck. The primary endpoint was proximal failure (type 1A endoleak, endograft migration, or re-intervention requiring proximal graft extension). Freedom from proximal failure was estimated with Kaplan–Meier curves. An “optimal” sealing length (PSL cutoff maximising sensitivity + specificity for proximal failure) and “safest length” (PSL cutoff determining ≥ 90% sensitivity) were identified using receiver operating characteristic curve analysis. Results One hundred and forty patients received TEVAR; mean ± standard deviation PSL was 29 ± 9 mm. Freedom from proximal endograft failure at five years (median 31 months) was 82.4% (95% confidence interval [CI] 72 – 95); the shorter the PSL, the greater was the risk of failure (hazard ratio 0.90, 95% CI 0.84 – 0.97; p = .004). Overall optimal and safest PSL were 25 mm (sensitivity 78%, specificity 66%) and 30 mm (sensitivity 92%, specificity 30%), respectively. In type I arch, the optimal PSL was 22 mm (sensitivity 50%, specificity 87%). In type II, the optimal PSL was 25 mm (sensitivity 89%, specificity 59%) overall and 27 mm for type II/LZ 2 – 3 (sensitivity 31%, specificity 68%). For type III, the optimal PSL was 27 mm (sensitivity 80%, specificity 87%); the safest was 30 mm (sensitivity 100%, specificity 61%) In type III/LZ 2 – 3, the optimal PSL was 27 mm (sensitivity 31%, specificity 68%) and safest was 30 mm (sensitivity 100%, specificity 55%). Conclusion A 20 mm PSL may be acceptable only for type I arches. For types II/III, that represent the majority of cases, a 25 – 30 mm PSL may be required for a safe and durable TEVAR.

Objectives: To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods: This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results: In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251 (27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions: SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. © 2020 International Society of Ultrasound in Obstetrics and Gynecology

Due to a technical error, the author list at the end of this article is unfortunately incorrect. Elif Gül Yapar Eyi is not a co-author, and therefore, his name and affiliation should not appear in the list. The correct author list and affiliations read as follows: Daniele Di Mascio, Cihat Sen, Gabriele Saccone, Alberto Galindo, Amos Grünebaum, Jun Yoshimatsu, Milan Stanojevic, AsimKurjak, Frank Chervenak, María Jos´e Rodríguez Suárez, Zita Maria Gambacorti-Passerini, María de los Angeles Anaya Baz, Esther Vanessa Aguilar Galán, Yolanda Cuñarro López, Juan Antonio De León Luis, Ignacio Cueto Hernández, Ignacio Herraiz, Cecilia Villalain, Roberta Venturella, Giuseppe Rizzo, Ilenia Mappa, Giovanni Gerosolima, Lars Hellmeyer, Josefine Königbauer, Giada Ameli, Tiziana Frusca, Nicola Volpe, Giovanni Battista Luca Schera, Stefania Fieni, Eutalia Esposito, Giuliana Simonazzi, Gaetana Di Donna, Aly Youssef, Anna Nunzia Della Gatta, Mariano Catello Di Donna, Vito Chiantera, Natalina Buono, Giulio Sozzi, Pantaleo Greco, Danila Morano, Beatrice Bianchi, Maria Giulia Lombana Marino, Federica Laraud, Arianna Ramone, Angelo Cagnacci, Fabio Barra, Claudio Gustavino, Simone Ferrero, Fabio Ghezzi, Antonella Cromi, Antonio Simone Laganá, Valentina Laurita Longo, Francesca Stollagli, Angelo Sirico, Antonio Lanzone, Lorenza Driul, Fabiana Cecchini D, Serena Xodo, Brian Rodriguez, Felipe Mercado-Olivares, Deena Elkafrawi, Giovanni Sisti, Rosanna Esposito, Antonio Coviello, Marco Cerbone, Maddalena Morlando, Antonio Schiattarella, Nicola Colacurci, Pasquale De Franciscis, Ilaria Cataneo, Marinella Lenzi, Fabrizio Sandri, Riccardo Buscemi, Giorgia Gattei, Francesca della Sala, Eleonora Valori, Maria Cristina Rovellotti, Elisa Done, Gilles Faron, Leonardo Gucciardo, Valentina Esposito, Flaminia Vena, Antonella Giancotti, Roberto Brunelli, Ludovico Muzii, Luigi Nappi, Felice Sorrentino, Lorenzo Vasciaveo, Marco Liberati, Danilo Buca, Martina Leombroni, Francesca Di Sebastiano, Luciano Di Tizio, Diego Gazzolo, Massimo Franchi, Quintino Cesare Ianniciello, Simone Garzon, Giuliano Petriglia, Leonardo Borrello, Albaro Jos´e Nieto-Calvache, Juan Manuel Burgos-Luna, Caroline Kadji, Andrew Carlin, Elisa Bevilacqua, Marina Moucho, Pedro Viana Pinto, Rita Figueiredo, Jos´e Morales Roselló, Gabriela Loscalzo, Alicia Martinez-Varea, Vincente Diago, Jesús S Jimenez Lopez, Alicia Yeliz Aykanat, Stefano Cosma, Andrea Carosso, Chiara Benedetto, Amanda Bermejo, Otto Henrique May Feuerschuette, Ozlem Uyaniklar, Sakine Rahimli Ocakouglu, Zeliha Atak, Reyhan Gündüz, Esra Tustas Haberal, Bernd Froessler, Anupam Parange, Peter Palm, Igor Samardjiski, Chiara Taccaliti, Erhan Okuyan, George Daskalakis, Renato Augusto Moreira de Sa, Alejandro Pittaro, Maria Luisa Gonzalez-Duran, Ana Concheiro Guisan, Serife Özlem Genç, Blanka Zlatohlávková, Anna Luengo Piqueras, Dolores Esteban Oliva, Aylin Pelin Cil, Olus Api, Panos Antsaklis, Liana Ples, Ioannis Kyvernitakis, Holger Maul, Marcel Malan, Albert Lila, Roberta Granese, Alfredo Ercoli, Giuseppe Zoccali, Andrea Villasco, Nicoletta Biglia, Ciuhodaru Madalina, Elena Costa, Caroline Daelemans, Axelle Pintiaux, Elisa Cueto, Eran Hadar, Sarah Dollinger, Noa A. Brzezinski Sinai, Erasmo Huertas, Pedro Arango, Amadeo Sanchez, Javier Alfonso Schvartzman, Liviu Cojocaru, Sifa Turan, Ozhan Turan, Maria Carmela Di Dedda, Rebeca Garrote Molpeceres, Snezana Zdjelar, Tanja Premru-Srsen, Lilijana Kornhauser Cerar, Mirjam Druškovic, Valentina De Robertis, Vedran Stefanovic, Irmeli Nupponen, Kaisa Nelskylä, Zulfiya Khodjaeva, Ksenia A. Gorina, Gennady T. Sukhikh, Giuseppe Maria Maruotti, Silvia Visentin, Erich Cosmi, Jacopo Ferrari, Alessandra Gatti, Daniela Luvero, Roberto Angioli, Ludovica Puri, Marco Palumbo, Giusella D’Urso, Francesco Colaleo, Agnese Maria Chiara Rapisarda, Ilma Floriana Carbone, Antonio Mollo, Giovanni Nazzaro, Mariavittoria Locci, Maurizio Guida, Attilio Di Spiezio Sardo, Pierluigi Benedetti Panici, Vincenzo Berghella, Maria Elena Flacco, Lamberto Manzoli, Giuseppe Bifulco, Giovanni Scambia, Fulvio Zullo and Francesco D’Antonio Flaminia Vena, Antonella Giancotti, Roberto Brunelli, Ludovico Muzii and Pierluigi Benedetti Panici, Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy Rosanna Esposito, Antonio Coviello, Marco Cerbone, Giuseppe Maria Maruotti, Giovanni Nazzaro, Mariavittoria Locci, Maurizio Guida, Attilio Di Spiezio Sardo, Giuseppe Bifulco and Fulvio Zullo, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy Ignacio Herraiz and Cecilia Villalain, Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Maternal and Child Health and Development Network, University Hospital 12 de Octubre, Complutense University of Madrid, Madrid, Spain María Jos´e Rodríguez Suárez, Hospital Universitario Central de Asturias, Asturias, Spain Zita Maria Gambacorti-Passerini, Department of Obstetrics and Gynaecology, Ciudad Real University General Hospital, Ciudad Real, Spain María de los Angeles Anaya Baz and Esther Vanessa Aguilar Galán, Department of Obstetrics and Gynaecology, Ciudad Real University General Hospital, Ciudad Real, Spain; University of Castilla-La Mancha, Ciudad Real, Spain Yolanda Cuñarro López, Juan Antonio De León Luis and Ignacio Cueto Hernández, Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Maternal and Child Health and Development Network, Gregorio Marañón Hospital, Complutense University of Madrid, Madrid, Spain Roberta Venturella, Department of Obstetrics and Gynaecology, School of Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy Giuseppe Rizzo, University of Roma Tor Vergata, Division of Maternal Fetal Medicine, Ospedale Cristo Re Roma, Rome, Italy; Department of Obstetrics and Gynaecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia Ilenia Mappa, University of Roma Tor Vergata, Division of Maternal Fetal Medicine, Ospedale Cristo Re Roma, Rome, Italy Giovanni Gerosolima, Department of Obstetrics and Gynaecology, Ospedale AOSG Moscati, Avellino, Italy Lars Hellmeyer, Josefine Königbauer and Giada Ameli, Department of Gynaecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany Tiziana Frusca, Nicola Volpe, Giovanni Battista Luca Schera and Stefania Fieni, Department of Obstetrics and Gynaecology, University of Parma, Parma, Italy Eutalia Esposito, Department of Obstetrics and Gynaecology, Ospedale di San Leonardo, Castellammare di Stabia, Italy Giuliana Simonazzi, Gaetana Di Donna, Aly Youssef and Anna Nunzia Della Gatta, Department of Obstetrics and Gynaecology, University of Bologna, Sant’Orsola- Malpighi University Hospital, Bologna, Italy Mariano Catello Di Donna, Vito Chiantera, Natalina Buono and Giulio Sozzi, Department of Gynaecologic Oncology, University of Palermo, Palermo, Sicilia, Italy Pantaleo Greco, Danila Morano, Beatrice Bianchi and Maria Giulia Lombana Marino, Department ofMedical Sciences, Section of Obstetrics and Gynaecology, Azienda Ospedaliera-Universitaria Sant’Anna, University of Ferrara, Ferrara, Italy Federica Laraud, Arianna Ramone, Angelo Cagnacci, Fabio Barra, Claudio Gustavino and Simone Ferrero, Academic Unit of Obstetrics and Gynaecology, IRCCS Ospedale Policlinico, San Martino, Genova, Italy Fabio Ghezzi, Antonella Cromi and Antonio Simone Laganà, Department of Obstetrics and Gynaecology, “Filippo Del Ponte” Hospita University of Insubria, Varese, Italy Valentina Laurita Longo, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy; and Queen Margaret University, Institute for Global Health and Development, Edinburgh, UK Francesca Stollagli and Ludovica Puri, Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy Angelo Sirico and Giovanni Scambia, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy Antonio Lanzone, Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario A Gemelli IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy; Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy Lorenza Driul, Fabiana Cecchini D and Serena Xodo, Clinic of Obstetrics and Gynaecology, University of Udine, Udine, Italy Brian Rodriguez, Felipe Mercado-Olivares, Deena Elkafrawi and Giovanni Sisti, Department of Obstetrics and Gynaecology, New York Health and Hospitals/Lincoln Bronx, The Bronx, NY, USA Maddalena Morlando, Antonio Schiattarella, Nicola Colacurci and Pasquale De Franciscis, Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy Ilaria Cataneo, Marinella Lenzi and Fabrizio Sandri, Unit of Obstetrics and Gynaecology, Ospedale Maggiore, Bologna, Italy Riccardo Buscemi, Giorgia Gattei, Francesca della Sala and Maria Cristina Rovellotti, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy Eleonora Valori, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy; Hospital Castelli, Verbania, Italy Elisa Done, Gilles Faron and Leonardo Gucciardo, UZ Brussel, Universitair Ziekenhuis, Brussel, Belgium Valentina Esposito, University of Milan, Milan, Italy Luigi Nappi, Felice Sorrentino and Lorenzo Vasciaveo, Department of Obstetrics and Gynaecology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. © 2021 De Gruyter. All rights reserved.

We investigated the effect of the length and tortuosity of directional branches on the mid-term outcomes of branched endovascular aneurysm repair (BEVAR) for thoracoabdominal aortic aneurysms (TAAA).We retrospectively reviewed single-center data of consecutive patients who had undergone BEVAR for TAAA from 2015 to 2019. Three-dimensional computed tomography angiogram reconstructions (Aquarius iNtuition software; TeraRecon, Durham, NC) of the first postoperative imaging studies were used to measure the branch total length (TL), branch vertical length (VL), and branch tortuosity index (TI). The branch TL was measured as the centerline distance between the branch proximal radiopaque marker and the distal edge of the bridging stent. The VL was measured as the centerline distance between the branch distal radiopaque marker and the origin of the target artery. The TI was measured in accordance with the Society for Vascular Surgery reporting standard. The primary end point was freedom from branch instability, defined as any branch-related death, occlusion, or rupture and any reintervention for stenosis, endoleak, or disconnection. Cox proportional hazards were used to identify predictors of branch instability. A penalized spline function was used to identify the relationship between branch instability and the branch TL and VL.Postimplantation analysis was conducted on 32 TAAAs (extent I-III, n = 18 [56%]; extent IV, n = 14 [44%]), with 123 arteries included through a directional branch. A covered self-expanding bridging stent was used in all cases. Intraoperative reinforcement with an additional bare metal stent was performed in 85 cases (69%). The overall freedom from branch instability at 3 years was 88% (95% confidence interval [CI], 81%-94%). Five cases of occlusion and eight cases of branch-related endoleak occurred. A concomitant endoleak and severe stenosis requiring intervention developed in three cases. The Cox model with splines showed that the minimal risk of branch instability was achieved with a branch TL of 60 to 100 mm (P = .002) and a branch VL of 25 to 50 mm (P = .038). A TI of1.15 was a predictor of branch complications (hazard ratio [HR], 8.6; 95% CI, 2.4-31.4; P .001). After multivariate analysis, aneurysm diameter (HR, 1.08; 95% CI, 0.03-1.15; P = .003), TI1.15 (HR, 6.81; 95% CI, 2.17-27.33; P .001), and TL 60 or100 mm (P = .002) were significantly associated with branch instability.The branch length and TI seemed to play an important role in BEVAR outcomes. The lowest branch instability rates were obtained with a branch TL of 60 to 100 mm, and this should be considered during planning and implantation. A branch TI1.15 might require a more strict monitoring to prevent mid- and long-term complications.

Background The purpose of this study was to evaluate how a multidisciplinary approach, including patients and familiar genetic counseling, preoperative succinate-dehydrogenase (SDH) gene mutation analysis, preoperative adjunctive endovascular procedures (PAEPs) and postoperative rehabilitative team may affect the outcomes in patients who underwent surgery for carotid body tumors (CBTs). Methods Fifty-seven consecutive CBT resections were performed from January 1995 to December 2019 in a single center institution. Two groups of patients were compared: group A (1995–2003; n = 10) and group B (2004–2019; n = 47), treated before and after the establishment of a multidisciplinary approach to CBTs. Group A and group B were evaluated retrospectively and prospectively for SDH mutations, respectively. PAEPs (external carotid artery stenting, percutaneous transfemoral embolization or direct percutaneous puncture of the tumor with simultaneous embolization) were performed only in patients of group B, when the size of the tumor exceeded the 45 mm. Primary endpoints were blood loss (BL) and cranial nerve injuries. Secondary endpoint was the number of new silent masses (NSMs) discovered after genetic evaluation. Results SDH mutations were found in 2 patients of group A and in 11 patients of group B. There were no significant differences in mass diameter between the groups. A significant difference regarding the surgical procedure time was observed in the 2 groups, with a higher time in the group A (Group A: 180 ± 77.3; Group B: 138 ± 54.5, P= 0.04). BL was significantly lower in group B (203 ± 69.5 mL vs. 356 ± 102 mL; P = 0.0001), as well as for patients underwent PAEPs vs. those underwent direct surgery (n = 15, 149 ± 53 mL vs. n = 42, 273 ± 88 mL; P = 0.0001). No differences between transient and persistent cranial nerve injuries were observed between the 2 groups. Carotid reconstruction was necessary for 2 patients of group A (n = 2 vs. n = 0; P = 0.02). Unilateral tumor recurrence was detected in 7 patients, with a significantly higher rate (P ≤ 0.002) in patients carrying SDH mutations compared to those without SDH mutation (wild-type). SDH mutations detected in the groups lead to discover 7 NSMs (group A n = 1 vs. group B n = 6; P = 1.00). Conclusion The impact of the multidisciplinary team suggests that surgical resection still remains the gold standard for the treatment of CBTs, but the use of PAEPs in selected cases may reduce surgical procedure time, BL and the need for reconstructive carotid surgery. Genetic counseling and SDH gene analysis allow to diagnose NSMs in asymptomatic patients. Larger studies should be considered to evaluate the effectiveness of postoperative rehabilitative program.

Objectives The Padova Hospital Vascular Surgery Division is located in Veneto, one of the area of the Northern Italy most hit by the Coronavirus disease 2019 outbreak. The aim of this paper is to describe the protocols adopted and to evaluate their impact during the acute phase of Coronavirus spread, focusing on the management of elective and urgent/emergent surgery, outpatients activity, and also health staff preservation from intra-hospital Coronavirus disease 2019 infection. Methods Several measures were progressively adopted in the Padova University Hospital to front the Coronavirus disease 2019 outbreak, with a clear strong asset established by 9 March 2020, after the Northern Italy lockdown. Since this date, the Vascular Surgery Unit started a “scaled-down” activity, both for elective surgical procedures and for the outpatient Clinical activities; different protocols were developed for health preservation of staff and patients. We compared a two months period, 30 days before and 30 days after this time point. In particular, emergent vascular surgery was regularly guaranteed as well as urgent surgery (to be performed within 24 h). Elective cases were scheduled for “non-deferrable” pathology. A swab test protocol for COVID-19 was applied to health-care professionals and hospitalized patients. Results The number of urgent or emergent aortic cases remained stable during the two months period, while the number of Hospital admissions via Emergency Room related to critical limb ischemia decreased after national lockdown by about 20%. Elective vascular surgery was scaled down by 50% starting from 9 March; 35% of scheduled elective cases refused hospitalization during the lockdown period and 20% of those contacted for hospitalization where postponed due to fever, respiratory symptoms, or close contacts with Coronavirus disease 2019 suspected cases. Elective surgery reduction did not negatively influence overall carotid or aortic outcomes, while we reported a higher major limb amputation rate for critical limb ischemia (about 10%, compared to 4% for the standard practice period). We found that 4 out of 98 (4%) health-care providers on the floor had an asymptomatic positive swab test. Among 22 vascular doctors, 3 had a confirmed Coronavirus disease 2019 infection (asymptomatic); a total of 72 swab were performed (mean = 3.4 swab/person/month) during this period; no cases of severe Coronavirus disease 2019 (deaths or requiring intensive care treatment) infection were reported within this period for the staff or hospitalized patients. Conclusions Elective vascular surgery needs to be guaranteed as possible during Coronavirus disease 2019 outbreak. The number of truly emergent cases did not reduce, on the other side, Emergency Room accesses for non-emergent cases decreased. Our preliminary results seem to describe a scenario where, if the curve of the outbreak in the regional population is flattened, in association with appropriate hospitals containment rules, it may be possible to continue the activity of the Vascular Surgery Units and guarantee the minimal standard of care.

OBJECTIVE: To evaluate whether intrapartum cardiotocography with computer analysis decreases the incidence of newborn metabolic acidosis or obstetric intervention when compared with visual analysis through a systematic review with meta-analysis of randomized controlled trials. METHODS: The research was conducted using Medline, Embase, Web of Science, Scopus, ClinicalTrial.gov, Ovid and Cochrane Library as electronic databases from the inception of each database to May 2018. Selection criteria included randomized trial evaluating women with cephalic presentation at term or late preterm term during labor who were randomized to electronic fetal heart rate monitoring with either computer analysis (i.e. intervention group) or standard visual analysis (i.e. control group). Trials evaluating antenatal fetal heart rate monitoring in women not in labor were excluded. The primary outcome was incidence of newborn metabolic acidosis, defined as pH less than 7.05 and base deficit greater than 12 mmol/L. Secondary outcomes were mode of delivery, admission to neonatal intensive care unit, hypoxic-ischemic encephalopathy, and perinatal death. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI). RESULTS: Three randomized controlled trials (RCTs), including 54,492 participants, which met inclusion criteria for this meta-analysis, were analyzed. All the included trials enrolled women with cephalic presentation at term or late preterm. Women were randomized in the active first stage of labor and all of them received continuous cardiotocography (CTG) from randomization until delivery. Women who received continuous CTG during labor with computerized analysis had similar risk of newborn metabolic acidosis. No between group differences were found in the secondary outcomes. CONCLUSIONS: Compared with visual analysis, use of computer analysis of fetal monitoring signals during labor did not significantly reduce the rate of metabolic acidosis or obstetric intervention.

In pancreatic Panc-1 cancer cells, an increase of oxidative stress enhances the level of 7,8-dihydro-8-oxoguanine (8OG) more in the KRAS promoter region containing G4 motifs than in non-G4 motif G-rich genomic regions. We found that H2O2 stimulates the recruitment to the KRAS promoter of poly [ADP-ribose] polymerase 1 (PARP-1), which efficiently binds to local G4 structures. Upon binding to G4 DNA, PARP-1 undergoes auto PARylation and thus becomes negatively charged. In our view this should favor the recruitment to the KRAS promoter of MAZ and hnRNP A1, as these two nuclear factors, because of their isoelectric points &gt, 7, are cationic in nature under physiological conditions. This is indeed supported by pulldown assays which showed that PARP-1, MAZ, and hnRNP A1 form a multiprotein complex with an oligonucleotide mimicking the KRAS G4 structure. Our data suggest that an increase of oxidative stress in Panc-1 cells activates a ROS-G4-PARP-1 axis that stimulates the transcription of KRAS. This mechanism is confirmed by the finding that when PARP-1 is silenced by siRNA or auto PARylation is inhibited by Veliparib, the expression of KRAS is downregulated. When Panc-1 cells are treated with H2O2 instead, a strong up-regulation of KRAS transcription is observed.

A continuous state of oxidative stress during inflammation contributes to the development of 25% of human cancers. Epithelial and inflammatory cells release reactive oxygen species (ROS) and reactive nitrogen species (RNS) that can damage DNA. ROS/RNS have biological implications in both chemoresistance and tumor recurrence. As several clinically employed anticancer drugs can generate ROS/RNS, we have addressed herein how inducible nitric oxide synthase and nitric oxide (iNOS/•NO) affect the molecular pathways implicated in the tumor response to oxidative stress. To mimic the oxidative stress associated with chemotherapy, we used a photosensitizer (pheophorbide a) that can generate ROS/RNS in a controlled manner. We investigated how iNOS/•NO modulates the tumor response to oxidative stress by involving the NF-κB and Nrf2 molecular pathways. We found that low levels of iNOS induce the development of a more aggressive tumor population, leading to survival, recurrence and resistance. By contrast, high levels of iNOS/•NO sensitize tumor cells to oxidative treatment, causing cell growth arrest. Our analysis showed that NF-κB and Nrf2, which are activated in response to oxidative stress, communicate with each other through RKIP. For this critical role, RKIP could be an interesting target for anticancer drugs. Our study provides insight into the complex signaling response of cancer cells to oxidative treatments as well as new possibilities for the rational design of new therapeutic strategies.

Background Information concerning oxidative stress and low-grade inflammation in oral contraception users is scarce. We investigated relationships of oxidative stress and high-sensitivity C-reactive protein (hsCRP) in women by oral combined contraceptive (OC) use. Methods Caucasian Italian healthy non-obese women (n = 290; 100 OC-users; 190 non-OC-users; mean age 23.2 ± 4.7 years) were analyzed. Blood hydroperoxides, as oxidative stress biomarkers, were assessed by Free Oxygen Radical Test (FORT), and serum hsCRP was determined by routine methods. Results Oxidative stress levels were elevated (≥ 400 FORT Units) in 77.0% and 15.8% of OC-users and non-OC-users, respectively (odds ratio (OR) = 209, 95%CI = 60.9-715.4, p s=0.622, p s=0.442, p s=0.426, p

Background The aim of this study was to retrospectively analyze the prevalence of severe preeclampsia and low sodium (PALS) among the pregnant population admitted at the University Hospital of Udine in the past 4 years and to compare these data with the current literature. Methods Only women with a diagnosis of preeclampsia were included. According to the lowest sodium level measured either 5 days before or 5 days after delivery, patients were divided in two groups: women with hyponatremia ( 135 mmol/L). Moreover, a search literature was performed. Results Of 59 patients with preeclampsia, 20 (34%) had hyponatremia. Only one case (1.6%) of severe maternal hyponatremia (sodium level 117 mmol/L) in the setting of preeclampsia was identified. After literature search, a total of 22 manuscripts including 60 case reports of PALS were identified. The lowest sodium level was 113 mmol/L, at 25 weeks of gestation. In most cases hyponatremia was treated with fluid restriction. In only 5 cases hyponatremia was treated with a saline hypertonic solution. Hyponatremia resolution, when reported, occurred in about 48 h. Sodium level in neonates ranged from 118 and 128 mmol/L. Conclusions PALS may occur in about a third of women with severe preeclampsia. Severe maternal hyponatremia should be treated with fluid restriction and with hypertonic saline solution. Moreover neonatologists should be alerted in order to treat the neonate for the best outcome.

The aim is to report a case of spontaneous uterine rupture in the first trimester of pregnancy and to review the literature on the topic. Methods: A literature search was performed using PubMed and Scopus. Relevant English articles were identified without any time or study limitations. The data were aggregated, and a summary statistic was calculated. Results: A 35-year-old gravida 5, para 2 was admitted at our department because of fainting and abdominal pain. The woman had a first-trimester twin pregnancy and a history of two previous cesarean sections (CSs). Suspecting a uterine rupture, an emergency laparotomy was performed. The two sacs were completely removed, and the uterine rupture site was closed with a double-layer suture. The patient was discharged from hospital four days later in good condition. On the basis of this experience, a total of 76 case reports were extracted from PubMed and included in the review. Fifty-three patients out of 76 (69.74%) underwent previous surgery on the uterus. Most women (67.92%) had a CS, and in this group a cesarean scar pregnancy (CSP) or a placenta accreta spectrum (PAS) disorder was found to be the etiology in 77.78% of cases. Furthermore, 35.85% of the women had hysterectomy after uterine rupture. Twenty-three patients out of 76 (30.26%) had an unscarred uterus. Of this group, most women presented a uterine anomaly (43.48%). Moreover, 17.39% of these women had a hysterectomy. Conclusion: According to the literature, the current pandemic use of CS explains most cases of first-trimester uterine rupture.

Background: Pregnancy in Parkinson's disease is a rare occurrence, and to date, clinical experience with its management is rather limited. In clinical practice, doubts concern mainly the impact of PD on gestation, labor, and delivery as well as the safety of dopaminergic drugs. Case and review of the literature: We report the case of a 40-year-old woman with an 8-year history of PD. In the first trimester of her pregnancy, her motor status was similar to the pre-conceptional period. In gestation week 16, her motor status dramatically worsened and she complained of predictable "off" periods in the afternoon. For this reason, her dose of L-DOPA/carbidopa was increased up to 500/125 mg per day. At 39 gestational weeks, she gave birth to a healthy girl with an Apgar score of 9 by an uncomplicated cesarean delivery. The child was not breast fed to avoid exposure to antiparkinsonian drugs. The L-DOPA/carbidopa dosage remained constant during the postpartum period. We performed a systematic review of the literature using Ovid Medline, Scopus, and PubMed (including Cochrane database). We used the search terms "Parkinson disease" AND "pregnancy." We identified 20 studies of PD in pregnancy with a total of 37 pregnant women with PD. The most important available data concern the safety of L-DOPA therapy during pregnancy. There seems to be some risk of worsening of the condition or upcoming of new PD symptoms during or shortly after pregnancy. Conclusion: More data concerning the safety of antiparkinsonian drugs in PD treatment, as well as the effect of pregnancy on parkinsonian symptoms are needed. According to the current state of the art, L-DOPA therapy should be considered preferable to other drugs during pregnancy.

Designing small molecules able to break down G4 structures in mRNA (RG4s) offers an interesting approach to cancer therapy. Here, we have studied cationic porphyrins (CPs) bearing an alkyl chain up to 12 carbons, as they bind to RG4s while generating reactive oxygen species upon photoirradiation. Fluorescence-activated cell sorting (FACS) and confocal microscopy showed that the designed alkyl CPs strongly penetrate cell membranes, binding to

Pancreatic ductal adenocarcinoma is a lethal disease for which no effective therapeutic options are available. Current therapies are based on different combinations of chemotherapeutics including fluorouracil and gemcitabine, but the prognosis is still poor. There is therefore a great need for novel therapeutic approaches. Among the new strategies, the inhibition of mutant KRAS, which is the causative agent of the disease, is an attractive one. To explore this strategy, some researchers have focused on two new targets for small effector molecules: (i) the KRAS promoter, with its critical nuclease hypersensitive element (NHE) forming a non-canonical G-quadruplex (G4) structure with regulatory functions; (ii) KRAS mRNA with its G-rich 5′-untranslated region that forms three contiguous RNA G4(RG4) structures flanking the 5′-cap. A number of G4 ligands have been proposed as therapeutic agents. For instance, alkyl porphyrins strongly penetrate the cell membrane and efficiently bind to and break down RG4 structures upon photoactivation. Alternatively, KRAS can be suppressed by treating the cells with oligonucleotides mimicking the G4 structure of NHE (G4-decoys). The G4-decoys delivered to the cells sequester the transcription factors that normally bind to the KRAS promoter and suppress gene expression. This chapter gives an overview of the current knowledge on G4 formation by DNA and RNA sequences of the KRAS oncogene, and also describes the molecular strategies employing KRAS G4/RG4 either as targets for anticancer agents or as G4 decoys.

OBJECTIVES Our goal was to assess the value of the Modified Arch Landing Areas Nomenclature (MALAN) for thoracic endovascular aortic repair (TEVAR), in which each landing area (LA) is identified by a proximal landing zone and the type of arch (e.g. 0/I), as predictors of postoperative proximal endograft performance. METHODS A multicentre retrospective analysis was performed of patients treated with arch TEVAR (i.e. proximal landing zone 0–3) for various indications between 2007 and 2017. Patients were stratified by the MALAN classification into hostile LAs (i.e. 2/III and 3/III) and favourable LAs (i.e. 0/I–III, 1/I–III, 2/I–II and 3/I–II). Outcome criteria included composite proximal endograft failure (including type Ia endoleak, persistent false lumen perfusion at the level of the most proximal communication between the lumina in aortic dissections, endograft migration and retrograde dissection) and deaths from all causes. Competing risk analyses were performed. RESULTS A total of 359 patients (hostile LAs 133; favourable LAs 226) were identified. The median age was 71.0 (62.0–77.0); 78.3% were men. Proximal endograft failure occurred in 28/133 patients (21.1%) in the hostile LA group and in 12/226 (5.3%) in the favourable LA group. On multivariate analysis, hostile LAs were independently associated with proximal endograft failure (P CONCLUSIONS The MALAN classification identifies hostile proximal landing zones for TEVAR, namely 2/III and 3/III LAs, which are associated with dismal proximal endograft performance. The MALAN appears to be an intuitive and valuable tool to improve the preoperative decision-making process.