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Arianna Giannetti,1 Giampaolo Ricci,1 Michela Procaccianti,2 Angelica Santoro,2 Carlo Caffarelli2 1Pediatric Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; 2Clinica Pediatrica, Department of Medicine and Surgery, University of Parma, Parma, ItalyCorrespondence: Carlo CaffarelliClinica Pediatrica, Dipartimento di Medicina e Chirurgia, Azienda Ospedaliera-Universitaria, University of Parma, Parma, ItalyTel +39 0521 702207Fax +39 0521 702807Email carlo.caffarelli@gmail.comAbstract: Allergen-specific immunotherapy is currently the only treatment with the potential to modify and prevent progression of allergic asthma in children. In clinical practice, it is available in two forms: subcutaneous immunotherapy and sublingual immunotherapy. Trials and meta-analyses showed both the safety and the short- and long-term benefits of allergen-specific immunotherapy in asthmatic children. However, its use and role in asthma remains controversial, since studies are largely heterogeneous. This is mainly due to the lack of consensus on the optimal primary outcome to be considered for clinical trials evaluating the efficacy of allergen-specific immunotherapy in asthma. Therefore, well-conducted researchis needed using standardized and validated tools to evaluate key outcomes in asthmatic children.Keywords: asthma, allergen-specific immunotherapy, children, allergy, grass, house dust mite

Barbara Bortot, 1 Maurizio Mongiat, 2 Erica Valencic, 3 Simeone Dal Monego, 4 Danilo Licastro, 4 Matteo Crosera, 5 Gianpiero Adami, 5 Enrico Rampazzo, 6 Giuseppe Ricci, 7, 8 Federico Romano, 7 Giovanni Maria Severini, 1 Stefania Biffi 7 1Department of Medical Genetics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 2Department of Research and Diagnosis, Division of Molecular Oncology, Centro Di Riferimento Oncologico Di Aviano (CRO) IRCCS, Aviano, Italy; 3Department of Pediatrics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 4ARGO Open Lab Platform for Genome Sequencing, AREA Science Park, Trieste, Italy; 5Department of Chemical and Pharmaceutical Sciences, University of Trieste, Trieste, Italy; 6Department of Chemistry “G. Ciamician”, University of Bologna, Bologna, Italy; 7Department of Obstetrics and Gynecology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 8Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, ItalyCorrespondence: Stefania Biffi Email stefania.biffi@burlo.trieste.itBackground: Platinum resistance is a major challenge in the management of ovarian cancer. Even low levels of acquired resistance at the cellular level lead to impaired response to cisplatin. In ovarian cancer intraperitoneal therapy, nanoparticle formulation can improve the cisplatin’s pharmacokinetics and safety profile.Purpose: This work aimed to investigate the chemo-sensitivity of ovarian cancer SKOV3 cells upon short-term (72h) single treatment of cisplatin and cisplatin-loaded biodegradable nanoparticles (Cis-NP). The aim was then to determine the therapeutic properties of Cis-NP in vivo using a SKOV3-luc cells’ xenograft model in mice.Methods: Cell cytotoxicity was assessed after the exposure of the cell culture to cisplatin or Cis-NP. The effect of treatments on EMT and CSC-like phenotype was studied by analyzing a panel of markers by flow cytometry. Intracellular platinum concentration was determined by inductively coupled plasma mass spectrometry (ICS-MS), and gene expression was evaluated by RNAseq analysis. The efficacy of intraperitoneal chemotherapy was evaluated in a SKOV3-luc cells’ xenograft model in mice, through a combination of bioluminescence imaging, histological, and immunohistochemical analyses.Results: We observed in vitro that short-term treatment of cisplatin has a critical role in determining the potential induction of chemoresistance, and a nanotechnology-based drug delivery system can modulate it. The RNAseq actg 3nalysis underlines a protective effect of nanoparticle system according to their ability to down-regulate several genes involved in chemoresistance, cell proliferation, and apoptosis. The highest intracellular platinum concentration obtained with Cis-NP treatment significantly improved the efficacy. Consistent with in vitro results, we found that Cis-NP treatment in vivo can significantly reduce tumor burden and aggressiveness compared to the free drug.Conclusion: Nanoparticle-mediated cisplatin delivery may serve as an intracellular depot impacting the cisplatin pharmacodynamic performance at cellular levels. These features may contribute to improving the drawbacks of conventional intraperitoneal therapy, and therefore will require further investigations in vivo.Keywords: cisplatin resistance, ovarian cancer, SKOV3, nanoparticle, epithelial-mesenchymal transition, Ca125, apoptosis

Carlo Bouchè,1 Uri Wiesenfeld,1 Luca Ronfani,1 Roberto Simeone,2 Paolo Bogatti,1 Kristina Skerk,1 Giuseppe Ricci1,2 1Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 2Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy Background/aim: Clinical data with respect to the impact of meconium on the risk of maternal hemorrhage are scarce. Therefore, in this study, we aimed to determine whether meconium-stained amniotic fluid (MSAF) represents a risk factor for postpartum hemorrhage (PPH) after vaginal delivery in a large unselected population. Patients and methods: A retrospective cohort study evaluated 78,542 consecutive women who had a vaginal delivery between 24th and 44th weeks of gestation. The women who had undergone cesarean section were excluded to avoid possible bias. Postpartum blood loss was measured with graduated blood sack. Postpartum blood loss between 1,000 and 2,000 mL and >2,000 mL were classified as moderate and severe PPH, respectively. Results: A total of 74,144 patients were available for analysis. According to the color of amniotic fluid (AF), two groups of patients were identified: MSAF (n=10,997) and clear AF (n=63,147). The rates of severe and massive PPH were found to be significantly higher in the MSAF group than that of clear AF group (OR=1.3, 95% CI: 1.2–1.5, p

The energy difference (ΔEST) between the lowest singlet (S1) state and the triplet (T1) excited state of a set of azaphenalene compounds, which is theoretically and experimentally known to violate Hund's rule, giving rise to the inversion of the order of those states, is calculated here with a family of double-hybrid density functionals. That excited-state inversion is known to be very challenging to reproduce for time-dependent density functional theory employing common functionals, e.g., hybrid or range-separated expressions, but not for wavefunction methods due to the inclusion of higher-than-single excitations. Therefore, we explore here if the last developed family of density functional expressions (i.e., double-hybrid models) is able to provide not only the right excited-state energy order but also accurate ΔEST values, thanks to the approximate inclusion of double excitations within these models. We herein employ standard double-hybrid (B2-PLYP, PBE-QIDH, and PBE0-2), range-separated (ωB2-PLYP and RSX-QIDH), spin-scaled (SCS/SOS-B2PLYP21, SCS-PBE-QIDH, and SOS-PBE-QIDH), and range-separated spin-scaled (SCS/SOS-ωB2-PLYP, SCS-RSX-QIDH, and SOS-RSX-QIDH) expressions to systematically assess the influence of the ingredients entering into the formulation while concomitantly providing insights for their accuracy. [ABSTRACT FROM AUTHOR]

Serena Logrippo,1,2 Giovanna Ricci,3 Matteo Sestili,4 Marco Cespi,2 Letizia Ferrara,4 Giovanni F Palmieri,2 Roberta Ganzetti,4 Giulia Bonacucina,2 Paolo Blasi2 1School of Advanced Studies, 2School of Pharmacy, 3School of Law, University of Camerino, Camerino, 4Italian National Research Centers on Ageing (INRCA), Ancona, Italy Abstract: Demographic indicators forecast that by 2050, the elderly will account for about one-third of the global population. Geriatric patients require a large number of medicines, and in most cases, these products are administered as solid oral solid dosage forms, as they are by far the most common formulations on the market. However, this population tends to suffer difficulties with swallowing. Caregivers in hospital geriatric units routinely compound in solid oral dosage forms for dysphagic patients by crushing the tablets or opening the capsules to facilitate administration. The manipulation of a tablet or a capsule, if not clearly indicated in the product labeling, is an off-label use of the medicine, and must be supported by documented scientific evidence and requires the patient’s informed consent. Compounding of marketed products has been recognized as being responsible for an increased number of adverse events and medical errors. Since extemporaneous compounding is the rule and not the exception in geriatrics departments, the seriousness and scope of issues caused by this daily practice are probably underestimated. In this article, the potential problems associated with the manipulation of authorized solid oral dosage forms are discussed. Keywords: geriatric medicine, dysphagia, compounding, modified-release formulations, gastrointestinal tract toxicity

In this work, we focus on the understanding of the driving force behind the S1–T1 excited-state energy inversion (which would thus violate Hund's rule, making the S1 state lower in energy than the T1 state) of two non-benzenoid non-alternant hydrocarbons, composed of odd-membered rings. The molecules considered here have identical chemical composition but different atomic configuration in space. The delicate interplay between structural and electronic factors that might induce inversion and its energy extension, only by a few meV, is systematically investigated here by state-of-the-art calculations. Qualitative and quantitative accurate predictions are obtained employing post-HF methods, thanks to the balanced and careful inclusion of electron correlation effects. The obtained results might guide and rationalize new searches for molecules violating Hund's rule, concomitantly demonstrating the importance of key contributions from the theoretical method of choice. [ABSTRACT FROM AUTHOR]

Giuseppe Ricci,1,2 Stefano Restaino,2 Giovanni Di Lorenzo,1 Francesco Fanfani,1 Federica Scrimin,1 Francesco P Mangino1 1Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste, Italy; 2Department of Medical Sciences, University of Trieste, Trieste, Italy Purpose: To report a case of Essure microinsert abdominal migration and literature review.Methods: A 41-year-old woman was counseled to undergo Essure sterilization. The procedure was hampered by the presence of endometrial cavity adhesions, obscuring left tubal ostium. By using microscissors the adhesions were progressively lysed. Since the procedure had become very painful, the patient required general anesthesia. Once adhesion lysis was completed, the tubal ostium was well visible. Both devices were then easily introduced into the fallopian tubes. At the end of the procedure, five coils were visible on the right side and five coils on the left side, as recommended.Results: The 3-month hysterosalpingogram follow-up suspected abdominal migration of the left device. Laparoscopy confirmed the device displacement in the left lower abdominal quadrant. Both fallopian tubes and the uterus appeared normal. No signs of perforation were detected. The device was embedded into the omentum, but it was easily removed. Bilateral tubal sterilization was performed by bipolar coagulation.Conclusion: There are only 13 cases, including the present, of Essure abdominal migration in the literature. In most cases, abdominal displacement of the microinsert is asymptomatic and does not induce tissue damage. However, in some cases, it may cause a severe adverse event, requiring major surgery. Therefore, removal of the migrated device should be performed as soon as possible. Moreover, during presterilization counseling, the patient should also be correctly informed about the risk of this rare but relevant complication, as well as about the surgical interventions that could be required to solve it. Keywords: abdominal migration, Essure, hysteroscopic sterilization, hysteroscopy, tubal sterilization

Pietro Scicchitano,1 Francesca Cortese,1 Gabriella Ricci,1 Santa Carbonara,1 Michele Moncelli,1 Massimo Iacoviello,1 Annagrazia Cecere,1 Michele Gesualdo,1 Annapaola Zito,1 Pasquale Caldarola,2 Domenico Scrutinio,3 Rocco Lagioia,3 Graziano Riccioni,4 Marco Matteo Ciccone1 1Section of Cardiovascular Diseases, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Policlinico, Bari, Italy; 2Section of Cardiovascular Diseases, Policlinic, San Paolo Hospital, Bari, Italy; 3Section of Cardiovascular Diseases, Fondazione Maugeri, Cassano Murge, Italy; 4Intensive Cardiology Care Unit, San Camillo de Lellis Hospital, Manfredonia, Foggia, Italy Abstract: Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies. Keywords: chronic heart failure, heart rate reduction, cardiac ischemic disease, heart-rate lowering drugs, funny current