Synergistic association of valproate and resveratrol reduces brain injury in ischemic stroke

Histone deacetylation, together with altered acetylation of NF-κB/RelA, encompassing the K310 residue acetylation, occur during brain ischemia. By restoring the normal acetylation condition, we previously reported that sub-threshold doses of resveratrol and entinostat (MS-275), respectively, an activator of the AMP-activated kinase (AMPK)-sirtuin 1 pathway and an inhibitor of class I histone deacetylases (HDACs), synergistically elicited neuroprotection in a mouse model of ischemic stroke. To improve the translational power of this approach, we investigated the efficacy of MS-275 replacement with valproate, the antiepileptic drug also reported to be a class I HDAC blocker. In cortical neurons previously exposed to oxygen glucose deprivation (OGD), valproate elicited neuroprotection at 100 nmol/mL concentration when used alone and at 1 nmol/mL concentration when associated with resveratrol (3 nmol/mL). Resveratrol and valproate restored the acetylation of histone H3 (K9/18), and they reduced the RelA(K310) acetylation and the Bim level in neurons exposed to OGD. Chromatin immunoprecipitation analysis showed that the synergistic drug association impaired the RelA binding to the Bim promoter, as well as the promoter-specific H3 (K9/18) acetylation. In mice subjected to 60 min of middle cerebral artery occlusion (MCAO), the association of resveratrol 680 µg/kg and valproate 200 µg/kg significantly reduced the infarct volume as well as the neurological deficits. The present study suggests that valproate and resveratrol may represent a promising ready-to-use strategy to treat post-ischemic brain damage

Myomectomy in infertile women: More harm than good?

Adhesion formation following gynecological surgery remains a challenge. The adoption of minimally invasive surgical approaches, such as conventional or robotic-assisted laparoscopy combined with meticulous microsurgical principles and the application of adhesion–reducing substances, is able to reduce the risk of de novo adhesion formation but do not eliminate it entirely. Myomectomy is the most adhesiogenic surgical procedure and postoperative adhesions can have a significant impact on the ability to conceive. Therefore, when surgery is performed as infertility treatment, attention should be paid to whether the benefits outweigh the risks. Among several factors, the size and the location of fibroids are the most accountable factors in terms of adhesion development and post surgical infertility; therefore, the search for effective strategies against adhesion formation in this setting is of paramount importance. The purpose of this review is to evaluate the incidence and factors of adhesion formation and the best preventive measures current available

EPMA-World Congress 2015: Bonn, Germany. 3-5 September 2015

Table of contents A1 Predictive and prognostic biomarker panel for targeted application of radioembolisation improving individual outcomes in hepatocellular carcinoma Jella-Andrea Abraham, Olga Golubnitschaja A2 Integrated market access approach amplifying value of “Rx-CDx” Ildar Akhmetov A3 Disaster response: an opportunity to improve global healthcare Russell J. Andrews, Leonidas Quintana A4 USA PPPM: proscriptive, profligate, profiteering medicine-good for 1 % wealthy, not for 99 % unhealthy Russell J. Andrews A5 The role of IDO in a murine model of gingivitis: predictive and therapeutic potentials Babak Baban, Jun Yao Liu, Xu Qin, Tailing Wang, Mahmood S. Mozaffari A6 Specific diets for personalised treatment of diabetes type 2 Viktoriia V. Bati, Tamara V. Meleshko, Olga B. Levchuk, Nadiya V. Boyko A7 Towards personalized physiotherapeutic approach Joanna Bauer, Ewa Boerner, Halina Podbielska A8 Cells, animal, SHIME and in silico models for detection and verification of specific biomarkers of non-communicable chronic diseases Alojz Bomba, Viktor O. Petrov, Volodymyr G. Drobnych, Rostyslav V. Bubnov, Oksana M. Bykova, Nadiya V. Boyko A9 INTERACT-chronic care model: Self-treatment by patients with decision support e-Health solution Hans-Peter Brunner-La Rocca, Lutz Fleischhacker, Olga Golubnitschaja, Frank Heemskerk, Thomas Helms, Tiny Jaarsma, Judita Kinkorova, Jan Ramaekers, Peter Ruff, Ivana Schnur, Emilio Vanoli, Jose Verdu A10 PPPM in cardiovascular medicine in 2015 Hans-Peter Brunner-La Rocca A11 Magnetic resonance imaging of nanoparticles in mice, potential for theranostic and contrast media development – pilot results Rostyslav V. Bubnov, Sergiy A. Grabovetskyi, Olena M. Mykhalchenko, Natalia O. Tymoshok, Oleksandr B. Shcherbakov, Igor P. Semeniv, Mykola Y. Spivak A12 Ultrasound diagnosis for diabetic neuropathy - comparative study Rostyslav V. Bubnov, Tetyana V. Ostapenko A13 Ultrasound for stratification patients with diabetic foot ulcers for prevention and personalized treatment - pilot results Rostyslav V. Bubnov, Nazarii M. Kobyliak, Nadiya M. Zholobak, Mykola Ya. Spivak A14 Project ImaGenX – designing and executing a questionnaire on environment and lifestyle risk of breast cancer John Paul Cauchi A15 Genomics – a new structural brand of predictive, preventive and personalized medicine or the new driver as well? Dmitrii Cherepakhin, Marina Bakay, Artem Borovikov, Sergey Suchkov A16 Survey of questionnaires for evaluation of the quality of life in various medical fields Barbara Cieślik, Agnieszka Migasiewicz, Maria-Luiza Podbielska, Markus Pelleter, Agnieszka Giemza, Halina Podbielska A17 Personalized molecular treatment for muscular dystrophies Sebahattin Cirak A18 Secondary mutations in circulating tumour DNA for acquired drug resistance in patients with advanced ALK + NSCLC Marzia Del Re, Paola Bordi, Valentina Citi, Marta Palombi, Carmine Pinto, Marcello Tiseo, Romano Danesi A19 Recombinant species-specific FcεRI alpha proteins for diagnosis of IgE-mediated allergies in dogs, cats and horses Lukas Einhorn, Judit Fazekas, Martina Muhr, Alexandra Schoos, Lucia Panakova, Ina Herrmann, Krisztina Manzano-Szalai, Kumiko Oida, Edda Fiebiger, Josef Singer, Erika Jensen-Jarolim A20 Global methodology for developmental neurotoxicity testing in humans and animals early and chronically exposed to chemical contaminants Arpiné A. Elnar, Nadia Ouamara, Nadiya Boyko, Xavier Coumoul, Jean-Philippe Antignac, Bruno Le Bizec, Gauthier Eppe, Jenny Renaut, Torsten Bonn, Cédric Guignard, Margherita Ferrante, Maria Liusa Chiusano, Salvatore Cuzzocrea, Gerard O'Keeffe, John Cryan, Michelle Bisson, Amina Barakat, Ihsane Hmamouchi, Nasser Zawia, Anumantha Kanthasamy, Glen E. Kisby, Rui Alves, Oscar Villacañas Pérez, Kim Burgard, Peter Spencer, Norbert Bomba, Martin Haranta, Nina Zaitseva, Irina May, Stéphanie Grojean, Mathilde Body-Malapel, Florencia Harari, Raul Harari, Kristina Yeghiazaryan, Olga Golubnitschaja, Vittorio Calabrese, Christophe Nemos, Rachid Soulimani A21 Mental indicators at young people with attributes hypertension and pre-hypertension Maria E. Evsevyeva, Elena A. Mishenko, Zurida V. Kumukova, Evgeniy V. Chudnovsky, Tatyana A. Smirnova A22 On the approaches to the early diagnosis of stress-induced hypertension in young employees of State law enforcement agencies Maria E. Evsevyeva, Ludmila V. Ivanova, Michail V. Eremin, Maria V. Rostovtseva A23 Сentral aortic pressure and indexes of augmentation in young persons in view of risk factors Maria E. Evsevyeva, Michail V. Eremin, Vladimir I. Koshel, Oksana V. Sergeeva, Nadesgda M. Konovalova A24 Breast cancer prediction and prevention: Are reliable biomarkers in horizon? Shantanu Girotra, Olga Golubnitschaja A25 Flammer Syndrome and potential formation of pre-metastatic niches: A multi-centred study on phenotyping, patient stratification, prediction and potential prevention of aggressive breast cancer and metastatic disease Olga Golubnitschaja, Manuel Debald, Walther Kuhn, Kristina Yeghiazaryan, Rostyslav V. Bubnov, Vadym M. Goncharenko, Ulyana Lushchyk, Godfrey Grech, Katarzyna Konieczka A26 Innovative tools for prenatal diagnostics and monitoring: improving individual pregnancy outcomes and health-economy in EU Olga Golubnitschaja, Jan Jaap Erwich, Vincenzo Costigliola, Kristina Yeghiazaryan, Ulrich Gembruch A27 Immunohistochemical assessment of APUD cells in endometriosis Vadym M. Goncharenko, Vasyl O. Beniuk, Olga V. Kalenska, Rostyslav V. Bubnov A28 Updating personalized management algorithm of endometrial hyperplasia in pre-menopause women Vadym M. Goncharenko, Vasyl O. Beniuk, Rostyslav V. Bubnov, Olga Melnychuk A29 The personified treatment approach of polimorbid patients with periodontal inflammatory diseases Irina A. Gorbacheva, Lyudmila Y. Orekhova, Vadim V. Tachalov A30 Ukrainian experience in hybrid war – the challenge to update algorithms for personalized care and early prevention of different military injuries Olena I. Grechanyk, Rizvan Ya. Abdullaiev, Rostyslav V. Bubnov A31 Tear fluid biomarkers: a comparison of tear fluid sampling and storage protocols Suzanne Hagan, Eilidh Martin, Ian Pearce, Katherine Oliver A32 The correlation of dietary habits with gingival problems during menstruation Cenk Haytac, Fariz Salimov, Servin Yoksul, Anatoly A. Kunin, Natalia S. Moiseeva A33 Genomic medicine in a contemporary Spanish population of prostate cancer: our experience Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara, Antonia Angulo, Francisco Javier Machuca Santa-Cruz A34 Challenges, opportunities and collaborations for personalized medicine applicability in uro-oncological disease Bernardo Herrera-Imbroda, Sergio del Río-González, Maria Fernanda Lara A35 Metabolic hallmarks of cancer as targets for a personalized therapy John Ionescu A36 Influence of genetic polymorphism as a predictor of the development of periodontal disease in patients with gastric ulcer and 12 duodenal ulcer Alfiya Z. Isamulaeva, Anatoly A. Kunin, Shamil Sh. Magomedov, Aida I. Isamulaeva A37 Challenges in diabetic macular edema Tatjana Josifova A38 Overview of the EPMA strategies in laboratory medicine relevant for PPPM Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja, Vincenzo Costigliola A39 EPMA initiative for effective organization of medical travel: European concepts and criteria Vincenzo Costigliola, Marko Kapalla, Juraj Kubáň, Olga Golubnitschaja A40 Design and innovation in e-textiles: implications for PPPM Anthony Kent, Tom Fisher, Tilak Dias A41 Biobank in Pilsen as a member of national node BBMRI_CZ Judita Kinkorová, Ondřej Topolčan A42 Big data in personalized medicine: hype and hope Matthias Kohl A43 The 3P approach as the platform of the European Dentistry Department (DPPPD) Anatoly A. Kunin, Natalia S. Moiseeva A44 The endometrium cytokine patterns for predictive diagnosis of proliferation severity and cancer prevention Andrii I. Kurchenko, Vasyl A. Beniuk, Vadym M. Goncharenko, Rostyslav V. Bubnov, Nadiya V. Boyko, Andriy M. Strokan A45 A monocyte-based in-vitro system for testing individual responses to the implanted material: future for personalized implant construction Julia Kzhyshkowska, Alexandru Gudima, Ksenia S. Stankevich, Victor D. Filimonov4, Harald Klüter, Evgeniya M. Mamontova, Sergei I. Tverdokhlebov A46 Prediction and prevention of adverse health effects by meteorological factors: Biomarker patterns and creation of a device for self-monitoring and integrated care Ulyana B. Lushchyk, Viktor V. Novytskyy, Igor P. Babii, Nadiya G. Lushchyk, Lyudmyla S. Riabets, Ivanna I. Legka A47 Targeting "disease signatures" towards personalized healthcare Mira Marcus-Kalish, Alexis Mitelpunkt, Tal Galili, Neta Shachar, Yoav Benjamini A48 Influence of the skin imperfection on the personal quality of life and possible tools for objective diagnosis Agnieszka Migasiewicz, Markus Pelleter, Joanna Bauer, Ewelina Dereń, Halina Podbielska A49 The new direction in caries prevention based on the ultrastructure of dental hard tissues and filling materials Natalia S. Moiseeva, Anatoly A. Kunin, Dmitry A. Kunin A50 The use of LED radiation in prevention of dental diseases Natalia S. Moiseeva, Yury A. Ippolitov, Dmitry A. Kunin, Alexei N. Morozov, Natalia V. Chirkova, Nakhid T. Aliev A51 Status of endothelial progenitor cells in diabetic nephropathy: predictive and preventive potentials Mahmood S. Mozaffari, Jun Yao Liu, Babak Baban A52 The status of glucocorticoid-induced leucine zipper protein in salivary gland in Sjögren’s syndrome: predictive and personalized treatment potentials Mahmood S. Mozaffari, Jun Yao Liu, Rafik Abdelsayed, Xing-Ming Shi, Babak Baban A53 Maximal aerobic capacity - important quality marker of health Jaroslav Novák, Milan Štork, Václav Zeman A54 The EMPOWER project: laboratory medicine and Horizon 2020 Wytze P. Oosterhuis, Elvar Theodorsson A55 Personality profile manifestations in patient’s attitude to oral care and adherence to doctor’s prescriptions Lyudmila Y. Orekhova, Tatyana V. Kudryavtseva, Elena R. Isaeva, Vadim V. Tachalov, Ekaterina S. Loboda A56 Results of an European survey on personalized medicine addressed to directions of laboratory medicine Mario Pazzagli, Francesca Malentacchi, Irene Mancini, Ivan Brandslund, Pieter Vermeersch, Matthias Schwab, Janja Marc, Ron H.N. van Schaik, Gerard Siest, Elvar Theodorsson, Chiara Di Resta A57 MCI or early dementia predictive speech based diagnosis techniques Matus Pleva, Jozef Juhar A58 Personalized speech based mobile application for eHealth Matus Pleva, Jozef Juhar A59 Circulating tumor cell-free DNA as the biomarker in the management of cancer patients Jiří Polívka jr., Filip Janků, Martin Pešta, Jan Doležal, Milena Králíčková, Jiří Polívka A60 Complex stroke care – educational programme in Stroke Centre University Hospital Plzen Jiří Polívka, Alena Lukešová, Nina Müllerová, Petr Ševčík, Vladimír Rohan A61 Sleep apnea and sleep fragmentation contribute to brain aging Kneginja Richter, Lence Miloseva, Günter Niklewski A62 Personalised approach for sleep disturbances in shift workers Kneginja Richter, Jens Acker, Guenter Niklewski A63 Medical travel and innovative PPPM clusters: new concept of integration Olga Safonicheva, Vincenzo Costigliola A64 Medical travel and women health Olga Safonicheva A65 Continuity of generations in the training of specialists in the field of reconstructive microsurgery Maxim Sautin, Janna Sinelnikova, Sergey Suchkov A66 Telemonitoring of stroke patients – empirical evidence of individual risk management results from an observational study in Germany Songül Secer, Stephan von Bandemer A67 Women’s increasing breast cancer risk with n-6 fatty acid intake explained by estrogen-fatty acid interactive effect on DNA damage: implications for gender-specific nutrition within personalized medicine Niva Shapira A68 Cytobacterioscopy of the gingival crevicular fluid as a method for preventive diagnosis of periodontal diseases Aleksandr Shcherbakov, Anatoly A. Kunin, Natalia S. Moiseeva A69 Use of specially treated composites in dentistry to avoid violations of aesthetics Bogdan R. Shumilovich, Zhanna Lipkind, Yulia Vorobieva, Dmitry A. Kunin, Anastasiia V. Sudareva A70 National eHealth system – platform for preventive, predictive and personalized diabetes care Ivica Smokovski, Tatjana Milenkovic A72 The common energy levels of Prof. Szent-Györgyi, the intrinsic chemistry of melanin, and the muscle physiopathology. Implications in the context of Preventive, Predictive, and Personalized Medicine Arturo Solís-Herrera, María del Carmen Arias-Esparza, Sergey Suchkov A73 Plurality and individuality of hepatocellular carcinoma: PPPM perspectives Krishna Chander Sridhar, Olga Golubnitschaja A74 Strategic aspects of higher medical education reforms to secure newer educational platforms for getting biopharma professionals matures Maria Studneva, Sihong Song, James Creeden, Мark Мandrik, Sergey Suchkov A75 Overview of the strategies and activities of the European Federation of Clinical Chemistry and Laboratory Medicine, (EFLM) Elvar Theodorsson, EFLM A76 New spectroscopic techniques for point of care label free diagnostics Syed A. M. Tofail A77 Tumor markers for personalized medicine and oncology - the role of Laboratory Medicine Ondřej Topolčan, Judita Kinkorová, Ondřej Fiala, Marie Karlíková, Šárka Svobodová, Radek Kučera, Radka Fuchsová, Vladislav Třeška, Václav Šimánek, Ladislav Pecen, Jan Šoupal, Štěpán Svačina2 A78 Modern medical terminology (MMT) as a driver of the global educational reforms Evgeniya Tretyak, Maria Studneva, Sergey Suchkov A79 Juvenile hypertension; the relevance of novel predictive, preventive and personalized assessment of its determinants Francesca M. Trovato, G. Fabio Martines, Daniela Brischetto, Daniela Catalano, Giuseppe Musumeci, Guglielmo M. Trovato A80 Proteomarkers Biotech George Th. Tsangaris, Athanasios K. Anagnostopoulos A81 Proteomics and mass spectrometry based non-invasive prenatal testing of fetal health and pregnancy complications George Th. Tsangaris, Athanasios K. Anagnostopoulos A82 Integrated Ecosystem for an Integrated Care model for Heart Failure (HF) patients including related comorbidities (ZENITH) José Verdú, German Gutiérrez, Jordi Rovira, Marta Martinez, Lutz Fleischhacker, Donna Green, Arthur Garson, Elena Tamburini, Stefano Cuomo, Juan Martinez-Leon, Teresa Abrisqueta, Hans-Peter Brunner-La Rocca, Tiny Jaarsma, Teresa Arredondo, Cecilia Vera, Giuseppe Fico, Olga Golubnitschaja, Fernando Arribas, Martina Onderco, Isabel Vara, on behalf of ZENITH consortium A83 Predictive, preventive and personalized medicine in diabetes onset and complication (MOSAIC project) José Verdú, Francesco Sambo, Barbara Di Camillo, Claudio Cobelli, Andrea Facchinetti, Giuseppe Fico, Riccardo Bellazzi, Lucia Sacchi, Arianna Dagliati, Daniele Segnani, Valentina Tibollo, Manuel Ottaviano, Rafael Gabriel, Leif Groop, Jacqueline Postma, Antonio Martinez, Liisa Hakaste, Tiinamaija Tuomi, Konstantia Zarkogianni, on behalf of MOSAIC consortium A84 Possibilities for personalized therapy of diabetes using in vitro screening of insulin and oral hypoglycemic agents Igor Volchek, Nina Pototskaya, Andrey Petrov A85 The innovative technology for personalized therapy of human diseases based on in vitro drug screening Igor Volchek, Nadezhda Pototskaya, Andrey Petrov A86 Bone destruction and temporomandibular joint: predictive markers, pathogenetic aspects and quality of life Ülle Voog-Oras, Oksana Jagur, Edvitar Leibur, Priit Niibo, Triin Jagomägi, Minh Son Nguyen, Chris Pruunsild, Dagmar Piikov, Mare Saag A87 Sub-optimal health management – global vision for concepts in medical travel Wei Wang A88 Sub-optimal health management: synergic PPPM-TCAM approach Wei Wang A89 Innovative technologies for minimal invasive diagnostics Andreas Weinhäusel, Walter Pulverer, Matthias Wielscher, Manuela Hofner, Christa Noehammer, Regina Soldo, Peter Hettegger, Istvan Gyurjan, Ronald Kulovics, Silvia Schönthaler, Gabriel Beikircher, Albert Kriegner, Stephan Pabinger, Klemens Vierlinger A90 Rare disease diobanks for personalized medicine Ayşe Yüzbaşıoğlu, Meral Özgüç, Member of EuroBioBank - European Network of DNA, Cell and Tissue Banks for Rare Disease

Medical and Surgical Strategies in Vulvar Paget Disease: Let’s Throw Some Light!

Background: Vulvar Paget’s disease (VPD) is defined as a neoplasm of epithelial origin, mostly in postmenopausal women. Due to the extreme rarity of VPD, limited data about recommended treatment options are available. Surgical excision has been the treatment of choice although in the recent decade medical treatments have been proposed. Methods: A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science, PubMed, and Cochrane Library), from 2003 to September 2022, in order to analyze all medical and surgical strategies used for the treatment of VPD. Results: Thirty-four articles were included in this review with findings as follows: 390 patients were treated with medical or other conservative treatment while 2802 patients were treated surgically; 235/434 (54%) patients had a complete response, 67/434 (15%) a partial response, 10/434 (2.3%) a stable disease, 3/434 (0.7%) disease progress, 3/434 (0.7%) died of the disease, 55/434 (13%) died of other causes during follow up while 7/434 (1.6%) had to stop topical treatments with 5% imiquimod cream because of side effects; 239/434 patients (55%) had a recurrence and 11/434 (2.5%) were lost to follow-up. The length of follow-up was variable, according to the different studies analyzed. Conclusion: VPD is a chronic disease with a high recurrence rate and low mortality. There are no significant differences in recurrence rates in patients who undergo surgery and those who do not and the margin status at the time of primary surgery and recurrence. Several surgical and medical approaches providing both local control of the disease and minimal tissue damage have been developed. Clock mapping, a recent preoperative vulvo-vaginal workup tool, can predict the invasiveness and the extension of VPD. However, to date, due to the different treatment options available and in the absence of a global consensus, it is critical to tailor treatments to individual patient characteristics and biopsy histopathologic findings, to ensure the best type of therapy

Successful management of a third-trimester pregnancy complicated by pheochromocytoma: case report

Pheochromocytoma (PH) is a tumor that arises from chromaffin cells of the adrenal medulla. Though being this benign neoplasm very rare in pregnancies, lack of treatment nevertheless causes high mortality rates for both the mother and the fetus. Classic symptoms related to PH are hypertension, abdominal pain, diaphoresis, and headache; but it can be easily misdiagnosed as gestational hypertension or preeclampsia. Its appearance is sporadic, but there are some genetic disorders that favor its onset (e.g. MEN 2A and 2B). Individual management is needed, because no single protocol is suitable in such a complex and rare condition. In this paper we describe our experience in the clinical and surgical management of a young pregnant patient affected by PH, and in particular the specific and unique pharmacological treatment with doxazosin, the use of corticosteroids and a close monitoring of fetal well-being, which proved being an effective approach

Activity restriction for women with arrested preterm labor: a randomized controlled trial

Objective: This study aimed to test the hypothesis that in women with singleton pregnancy and arrested preterm labor, activity restriction would reduce the rate of preterm birth at <37 weeks of gestation. Study design: This was a parallel-group nonblinded randomized trial conducted at a single center in Italy. Eligible patients were those with a diagnosis of arrested preterm labor, defined as not delivering after 48 hours of hospitalization for threatened preterm labor, with transvaginal ultrasound cervical length ≤25 mm, no other symptoms of possible uterine contractions, and cervical dilatation <3 cm at pelvic examination. Inclusion criteria were singleton pregnancies between 24 0/7 and 33 6/7 weeks of gestation. Participants were randomized in a 1:1 ratio to either activity restriction at the time of discharge or no activity restriction. Women in the intervention group were recommended activity restriction, defined as the following: pelvic rest, prohibition of sexual activity, and reduction of work and/or nonwork activity. The primary endpoint was preterm birth at <37 weeks of gestation. Results: A total of 120 participants were included in the trial; 60 patients were enrolled in the activity restriction group and 60 in the control group. Preterm birth at <37 weeks of gestation occurred in 15 of 60 women (25.0%) in the activity restriction group and 23 of 60 women (38.3%) in the control group (relative risk, 0.65; 95% confidence interval, 0.38-1.12). There was no significant between-group difference in the incidence of preterm birth at <32 weeks and in neonatal outcomes, but the trial was not powered for these outcomes. Conclusion: In singleton gestations with arrested preterm labor, activity restriction, including pelvic rest, prohibition of sexual activity, and reduction of work and/or nonwork activity, does not result in a lower rate of preterm birth at <37 weeks. Given the evidence on the lack of benefits, use of activity restriction in this population should be discouraged

FAM46C Is an Interferon-Stimulated Gene That Inhibits Lentiviral Particle Production by Modulating Autophagy

ABSTRACT FAM46C is a multiple myeloma (MM) tumor suppressor whose function is only starting to be elucidated. We recently showed that in MM cells FAM46C triggers apoptosis by inhibiting autophagy and altering intracellular trafficking and protein secretion. To date, both a physiological characterization of FAM46C role and an assessment of FAM46C-induced phenotypes outside of MM are lacking. Preliminary reports suggested an involvement of FAM46C with regulation of viral replication, but this was never confirmed. Here, we show that FAM46C is an interferon-stimulated gene and that the expression of wild-type FAM46C in HEK-293T cells, but not of its most frequently found mutant variants, inhibits the production of both HIV-1-derived and HIV-1 lentiviruses. We demonstrate that this effect does not require transcriptional regulation and does not depend on inhibition of either global or virus-specific translation but rather mostly relies on FAM46C-induced deregulation of autophagy, a pathway that we show to be required for efficient lentiviral particle production. These studies not only provide new insights on the physiological role of the FAM46C protein but also could help in implementing more efficient antiviral strategies on one side and lentiviral particle production approaches on the other. IMPORTANCE FAM46C role has been thoroughly investigated in MM, but studies characterizing its role outside of the tumoral environment are still lacking. Despite the success of antiretroviral therapy in suppressing HIV load to undetectable levels, there is currently no HIV cure, and treatment is lifelong. Indeed, HIV continues to be a major global public health issue. Here, we show that FAM46C expression in HEK-293T cells inhibits the production of both HIV and HIV-derived lentiviruses. We also demonstrate that such inhibitory effect relies, at least in part, on the well-established regulatory role that FAM46C exerts on autophagy. Deciphering the molecular mechanism underlying this regulation will not only facilitate the understanding of FAM46C physiological role but also give new insights on the interplay between HIV and the cellular environment

Pregnant women perspectives on SARS-COV-2 vaccine

Background: Since COVID-19 vaccines have been distributed, a debate has raised on whether pregnant women should get the vaccine. No available data exist so far regarding safety, efficacy and toxicology of these vaccines when administered during pregnancy. Most of the Obstetrics and Gynecology societies suggested that pregnant could agree to be vaccinated, after a thorough counseling of risks and benefits with their gynecologists, thus leading to an autonomous decision. Objective: The aim of this study was to evaluate the attitude to COVID-19 vaccination in pregnant and breastfeeding women in Italy. Study design: A survey was made at University of Naples Federico II and University of Rome Tor Vergata Ospedale Cristo Re on pregnant and breastfeeding women asking their perspectives on the available vaccines after reading the recommendations issued by our national Obstetrics, Gynecology and Neonatology societies. The questionnaire included 12 items finalized to evaluate general features of the women and 6 items specifically correlated to their attitudes towards the SARS-COV-2 vaccination. Chi square (χ2) or Fisher exact tests were used to compare group differences of categorical variables and Wilcoxon signed rank or Mann Whitney U test for continuous variables. The study was approved by the Institutional Review Boards of the University of Naples Federico II (ref. no. 409/2020), and University of Rome Tor Vergata Ospedale Cristo Re (ref. #Ost4-2020). Results: Most of the included women did not agree to eventually receive SARS-COV-2 vaccine during pregnancy (40, 28.2% vs 102, 71.8%). Being pregnant was considered a determinant factor to refuse the vaccine prophylaxis (99, 69.7% vs 43, 30.3%; χ2= 24.187, p<0.001), even if a very large percentage declared to be generally in favor of vaccines (128, 90.1% vs 14, 9.9%; χ2= 6.091, p=0.014) and most of them confirmed they received or would receive other recommended vaccines during pregnancy (75, 52.8% vs 67, 47.2%; χ2= 10.996, p=0.001). Conclusion: Urgent data are needed on safety, efficacy and toxicology of SARS-COV-2 vaccines during pregnancy to modify this trend and to help obstetricians during the counselling. Furthermore, pregnant women should be included in future vaccine development trials to not incur again in such uncertainty

Synergistic association of valproate and resveratrol reduces brain injury in ischemic stroke.

Different studies demonstrated that histone deacetylation and modification of NF-kB/RelA acetylation occur during brain ischemia. We previously demonstrated that, sub-threshold doses of resveratrol, a sirtuin 1 activator, and MS-275, a class I HDAC inhibitor, elicited neuroprotection in a mouse model of MCAO. In the present work, we replace MS-275 with valproate, an antiepileptic drug also reported as a class I HDACs inhibitor. In cortical neurons exposed to 3h of OGD, 24h of treatment with 100 µM valproate resulted neuroprotective per se, while in association with resveratrol it was active at 1µM. In mice subjected to 60 minutes of MCAO the association of resveratrol 680 µg/kg and valproate 200 µg/kg significantly reduced the infarct volume as well as the neurological deficits. Single treatments at the same doses had no effects, while at the higher doses, resveratrol 6,8 mg/kg or valproate 20 mg/kg limited the infarct volume but did not reduce the neurological deficits. In accordance with the effect observed by combining resveratrol and MS-275, the association of resveratrol and VPA restored the acetylation levels of histone H3 (K9/18) reduced after OGD exposure. Moreover, the application of resveratrol and VPA reversed the OGD-mediated increase in the RelA(K310) acetylation. Finally, ChIP assays in cortical neurons exposed to OGD demonstrated that the addition of resveratrol (3 μM) and valproate (1 μM), totally impaired the RelA binding at the Bim promoter as well as the promoter–specific H3 (K9/18) acetylation. We can conclude that valproate and resveratrol may represent a promising ready-to-use strategy for the therapy of post-ischemic brain damage