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Background Adverse cardiac remodeling is a major risk factor for the development of post myocardial infarction (MI) heart failure (HF). This study investigates the effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute ST-segment-elevation myocardial infarction (STEMI). Methods In this double-blind, randomized, placebo-controlled trial patients with first STEMI were eligible. To preferentially enrich patients at high risk of adverse remodeling, main inclusion criteria were a left-ventricular ejection fraction (LVEF) ≤45% and an infarct size >10% on day 5 to 9 post MI as measured by cardiac MRI. Patients were then randomized to 6 months treatment with either 25 mg fulacimstat (n = 54) or placebo (n = 53) twice daily on top of standard of care starting day 6 to 12 post MI. The changes in LVEF, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume index (LVESVI) from baseline to 6 months were analyzed by a central blinded cardiac MRI core laboratory. Results Fulacimstat was safe and well tolerated and achieved mean total trough concentrations that were approximately tenfold higher than those predicted to be required for minimal therapeutic activity. Comparable changes in LVEF (fulacimstat: 3.5% ± 5.4%, placebo: 4.0% ± 5.0%, P = .69), LVEDVI (fulacimstat: 7.3 ± 13.3 mL/m2, placebo: 5.1 ± 18.9 mL/m2, P = .54), and LVESVI (fulacimstat: 2.3 ± 11.2 mL/m2, placebo: 0.6 ± 14.8 mL/m2, P = .56) were observed in both treatment arms. Conclusion Fulacimstat was safe and well tolerated in patients with left-ventricular dysfunction (LVD) after first STEMI but had no effect on cardiac remodeling.

Purpose: To investigate age-related differences in outcomes of critically ill patients with sepsis around the world., Methods: We performed a secondary analysis of data from the prospective ICON audit, in which all adult ( >16 years ) patients admitted to participating ICUs between May 8 and 18, 2012, were included, except admissions for routine postoperative observation. For this sub-analysis, the 10,012 patients with completed age data were included. They were divided into five age groups - 80 years. Sepsis was defined as infection plus at least one organ failure., Results: A total of 2963 patients had sepsis, with similar proportions across the age groups (80 = 30.9%). Hospital mortality increased with age and in patients >80 years was almost twice that of patients 70 years was independently associated with increased risk of dying., Conclusions: The odds for death in ICU patients with sepsis increased with age with the maximal rate of increase occurring between the ages of 71 and 77 years. (C) 2019 Elsevier Inc. 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Moradi] Tehran Med Sci Univ, Tehran, Iran., [Cohen, J.] Rabin Med Ctr, Petah Tiqwa, Israel., [Sold, O.] Sourasky Tel Aviv Med Ctr, Tel Aviv, Israel., [Sfeir, T.] Ctr Hosp Nord, Ettelbruck, Luxembourg., [Hasan, A.] Sohar Hosp, Sohar, Oman., [Abugaber, D.] Specialized Arab Hosp, Nablus, Palestine., [Ahmad, H.] Almana Gen Hosp, Khobar, Saudi Arabia., [Tantawy, T.] KFSHRC, Riyadh, Saudi Arabia., [Baharoom, S.] King Abdulaziz Med City Riyadh, Riyadh, Saudi Arabia., [Algethamy, H.] King Abdulaziz Univ, Jeddah, Saudi Arabia., [Amr, A.] King Saud Med City, Riyadh, Saudi Arabia., [Almekhlafi, G.] Riyadh Mil Hosp, Riyadh, Saudi Arabia., [Coskun, R.] Erciyes Univ, Med Fac, Kayseri, Turkey., [Sungur, M.] Erciyes Univ, Med Sch, Kayseri, Turkey., [Cosar, A.] Gulhane Mil Med Acad, Ankara, Turkey., [Gucyetmez, B.] Int Hosp, Istanbul, Turkey., [Demirkiran, O.] Istanbul Univ, Cerrahpasa Med Sch Hosp, Istanbul, Turkey., [Senturk, E.] Istanbul Univ, Istanbul Med Fac, Istanbul, Turkey., [Ulusoy, H.] Karadeniz Tech Univ, Med Fac, Trabzon, Turkey., [Atalan, H.] Mem Atasehir Hosp, Istanbul, Turkey., [Serin, S.] Pamukkale Univ, Denizli, Turkey., [Kati, I] Yuzuncu Yil Univ, Med Fac, Van, Turkey., [Alnassrawi, Z.] Dubai Hosp, Dubai, U Arab Emirates., [Almemari, A.] Mafraq Hosp, Abu Dhabi, U Arab Emirates., [Krishnareddy, K.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates., [Kashef, S.] Tawam Hosp, Al Ain, U Arab Emirates., [Alsabbah, A.] City Hosp, Dubai, U Arab Emirates., [Poirier, G.] Hop Charles Lemoyne, Longueuil, PQ, Canada., [Marshall, J.] St Michaels Hosp, Toronto, ON, Canada., [Herridge, M.] Toronto Gen Hosp, Toronto, ON, Canada., [Herridge, M.] Toronto Western Hosp, Toronto, ON, Canada., [Fernandez-Medero, R.] San Juan Hosp, San Juan, PR USA., [Fulda, G.] Christiana Care Hlth Syst, Newark, DE USA., [Banschbach, S.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA., [Quintero, J.] El Camino Hosp, Mountain View, CA USA., [Schroeder, E.] George Washington Hosp, Washington, DC USA., [Sicoutris, C.] Hosp Univ Penn, Philadelphia, PA 19104 USA., [Gueret, R.] John H Stroger Hosp Cook Cty, Chicago, IL USA., [Kashyap, R.] Mayo Clin, CCM, Rochester, MN USA., [Bauer, P.] Mayo Clin, PCC, Rochester, MN USA., [Nanchal, R.] Med Coll Wisconsin, Milwaukee, WI 53226 USA., [Wunderink, R.] Northwestern Mem Hosp, Chicago, IL 60611 USA., [Jimenez, E.] Orlando Reg Med Ctr Inc, Orlando, FL USA., [Ryan, A.] Washington Hosp Ctr, Washington, DC 20010 USA., [Ryan, A.] Washington Hosp Ctr, 2H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 2G, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 3H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 3G, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, 4H, Washington, DC USA., [Ryan, A.] Washington Hosp Ctr, CVRR, Washington, DC USA., [Prince, D.] Armadale Hlth Serv, Mount Nasura, WA, Australia., [Edington, J.] Bendigo Hosp, Bendigo, Vic, Australia., [Van Haren, F.] Canberra Hosp, Canberra, ACT, Australia., [Bersten, A.] Flinders Med Ctr, Bedford Pk, SA, Australia., [Hawkins, D. 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Dalcomune, D.] Hosp Meridional, Cariacica, ES, Brazil., [Teixeira, C.] Hosp Moinhos Vento, Porto Alegre, RS, Brazil., [Kaefer, K.] Hosp Municipal Ruth Cardoso, Balneario, Brazil., [Maia, I] Hosp Nereu Ramos, Florianopolis, SC, Brazil., [Souza Dantas, V] Hosp Pasteur, Rio De Janeiro, Brazil., [Costa Filho, R.] Hosp Pro Cardiaco, Rio De Janeiro, Brazil., [Amorim, F.] Hosp Reg Samambaia, Brasilia, DF, Brazil., [Assef, M.] Hosp Reg Hans Dieter Schmidt, Joinville, Brazil., [Schiavetto, P.] Hosp Santa Casa Campo Mourao, Campo Mourao, PR, Brazil., [Houly, J.] Hosp Santa Paula, Sao Paulo, SP, Brazil., [Houly, J.] Hosp Santapaula, Sao Paulo, Brazil., [Bianchi, F.] Hosp Sao Jose Avai, Itaperuna, RJ, Brazil., [Dias, F.] Hosp Sao Lucas Pucrs, Porto Alegre, RS, Brazil., [Avila, C.] Hosp Sao Vicente Paula, Rio De Janeiro, RJ, Brazil., [Gomez, J.] Hosp Sao Vicente Paulo, Rio De Janeiro, Brazil., [Rego, L.] Hosp Saude Mulher, Belem, Para, Brazil., [Castro, P.] Hosp Tacchini, Bento Goncalves, RS, Brazil., [Passos, J.] Hosp Unimed Costa Do Sol Macae Rj, Macae, RJ, Brazil., [Mendes, C.] Hosp Univ Ufpb Joao Pessoa, Joao Pessoa, Paraiba, Brazil., [Grion, C.] Hosp Univ Londrina, Londrina, Brazil., [Colozza Mecatti, G.] Hosp Univ Sao Francisco, Braganca Paulista, SP, Brazil., [Ferrreira, M.] Santa Casa Caridade Diamantina, Diamantina, MG, Brazil., [Irineu, V] Santa Casa Misericordia Tatui, Tatui, Brazil., [Guerreiro, M.] Sao Francisco de Paula Hosp, Sao Francisco De Paula, RS, Brazil., [Ugarte, S.] Clin Indisa, Providencia, Chile., [Tomicic, V] Clin Las Lilas, Providencia, Chile., [Godoy, C.] Hosp Carlos Van Buren, Valparaiso, Chile., [Samaniego, W.] Hosp Trabajador Santiago, Santiago, Chile., [Escamilla, I] Hosp El Pino, San Bernardo, Chile., [Escamilla, I] Hosp Mutual De Seguridad, Santiago, Chile., [Castro Castro, L.] Ctr Med Imbanaco, Valle Del Cauca, Colombia., [Libreros Duque, G.] Clin Colombia Cali, Cali, Colombia., [Diaz-Guio, D.] Clin Del Cafe, Armenia, Colombia., [Benitez, F.] Clin La Estancia SA, Popayan, Colombia., [Guerra Urrego, A.] Clin Medellin, Medellin, Colombia., [Buitrago, R.] Fdn Clin Shaio, Bogota, Colombia., [Ortiz, G.] Hosp Santa Clara, Bogota, Colombia., [Villalba Gaviria, M.] Hosp Univ Fdn Santa Fe De Bogota, Bogota, Colombia., [Salas, D.] Calderon Guardia Hosp, San Jose, Costa Rica., [Ramirez-Arce, J.] Hosp Dr Rafael Angel Varlderon Guardia Ccss, San Jose, Costa Rica., [Salgado, E.] Clin La Merced, Quito, Ecuador., [Morocho, D.] Hosp Eugenio Espejo, Quito, Ecuador., [Vergara, J.] Hosp Luis Vernaza, Quito, Ecuador., [Chung Sang, M.] Shdug Sistema Hosp Docente De La Univ Guayaquil, Quito, Ecuador., [Orellana-Jimenez, C.] Gen Hosp, San Salvador, El Salvador., [Garrido, L.] Hosp Ctr Med, Guatemala City, Guatemala., [Diaz, O.] Inst Hondureno Seguro Social, La Ceiba, Honduras., [Resiere, D.] Ctr Hosp Univ Ft De France, Fort De France, Martinique, France., [Osorio, C.] Ctr Estatal Cuidados Crit, Salamanca, Mexico., [De La Vega, A.] Ctr Med Nacl 20 Noviembre Issste, Mexico City, DF, Mexico., [Carrillo, R.] Fdn Clin Med Sur, Mexico City, DF, Mexico., [Sanchez, V] Hosp San Jose TEC Monterrey, Monterrey, Mexico., [Villagomez, A.] Hosp 1 Octubre, Issste, Mexico., [Martinez Zubieta, R.] Hosp Espanol Mexico, Mexico City, DF, Mexico., [Sandia, M.] Hosp Gen Ajusco Medio, Mexico City, DF, Mexico., [Zalatiel, M.] Hosp Gen Guadalupe Victoria, Texcoco, Mexico., [Poblano, M.] Hosp Juarez Mexico, Mexico City, DF, Mexico., [Rodriguez Gonzalez, D.] Hosp Civil Guadalajara, Hspitaljuan I Menchaca, Guadalajara, Jalisco, Mexico., [Arrazola, F.; Juan Francisco, L.] Inst Mexicano Seguro Social, Mexico City, DF, Mexico., [Liamendys-Silva, S. A.] Inst Nacl Cancerol, Mexico City, DF, Mexico., [Hernandez, M.] ISSSTE Guerra Moya, Mexico City, DF, Mexico., [Hernandez, M.] Med Ctr ISSEMYM Toluca, Mexico City, DF, Mexico., [Rodriguez Cadena, D.] Mixta, Mexico City, DF, Mexico., [Lopez Islas, I.] Secretaria Salud Dist Fed, Mexico City, DF, Mexico., [Ballesteros Zarzavilla, C.] Hosp Santo Comas, Panama City, Panama., [Matos, A.] Social Secur Hosp, La Chorrera, Panama., [Oyanguren, I] Clin Anglo Amer, Lima, Peru., [Cerna, J.] Essalud, Lima, Peru., [Quispe Sierra, R.] Hosp Nacl Dos De Mayo, Lima, Peru., [Jimenez, R.] Hosp Rebagliati, Lince Dist, Peru., [Castillo, L.] Inst Nacl Enfermedades Neoplas, Surquillo, Peru., [Ocal, R.] Gulhane Med Fac, Istanbul, Turkey., [Sencan, A.] Izmir Ataturk Educ & Res Hosp, Izmir, Turkey., [Gianoni, S. Mareque] CAMS, Montevideo, Uruguay., [Deicas, A.] CASMU, Montevideo, Uruguay., [Hurtado, J.] Hosp Espanol Asse, Montevideo, Uruguay., [Burghi, G.] Hosp Maciel, Montevideo, Uruguay., [Martinelli, A.] Ctr Med Caracas, Caracas, Venezuela., [Von der Osten, I] Hosp Miguel Perez Carreno, Caracas, Venezuela., [Du Maine, C.] MSF Trauma Hosp Kunduz, Kunduz, Afghanistan., [Bhattacharyya, M.] Amri Hosp, Kolkata, India., [Bandyopadhyay, S.] Amri Hosp Salt Lake, Kolkata, W Bengal, India., [Yanamala, S.] Apollo Hosp, Hyderabad, India., [Gopal, P.] Apollo Hosp, Bangalore, Karnataka, India., [Sahu, S.] Apollo Hosp, Bhubaneswar, India., [Ibrahim, M.] Apollo Special Hosp, Chennai, Tamil Nadu, India., [Rathod, D.] Asian Heart Inst, Mumbai, Maharashtra, India., [Mukundan, N.] Baby Mem Hosp Ltd, Calicut, Kerala, India., [Dewan, A.] Batra Hosp & Mrc, New Delhi 110062, India., [Amin, P.] Bombay Hosp Inst Med Sci, Mumbai, Maharashtra, India., [Samavedam, S.] Care Hosp, Hyderabad, India., [Shah, B.] Cims Hosp, Ahmadabad, Gujarat, India., [Gurupal, D.] Columbiaasia Hosp, Mysore, Karnataka, India., [Lahkar, B.] Dispur Hosp, Gauhati, India., [Mandal, A.] Fortis Hosp, Bangalore, Karnataka, India., [Sircar, M.] Fortis Hosp, Noida, India., [Ghosh, S.] Fortis Escorts Hosp, Faridabad, India., [Balasubramani, V] Ganga Med Ctr & Hosp P Ltd, Coimbatore, Tamil Nadu, India., [Kapadia, F.] Hinduja Hosp, Mumbai, Maharashtra, India., [Vadi, S.] KDAH, Mumbai, Maharashtra, India., [Nair, K.] Kerala Inst Med Sci, RMCC, Thiruvananthapuram, Kerala, India., [Tripathy, S.] Kalinga Inst Med Sci, DTEM, Bhubaneswar, Odisha, India., [Nandakumar, S.] Kovai Med Ctr & Hosp, Coimbatore, Tamil Nadu, India., [Sharma, J.] Medanta Medic, Gurgaon, India., [Kar, A.] Med Superspecialty Hosp, Kolkata, W Bengal, India., [Jha, S.] Metro Heart Inst Multispecial, Faridabad, India., [Gurav, K. Zirpe] Ruby Hall Pune, Pune, Maharashtra, India., [Patel, M.] Saifee Hosp, Mumbai, Maharashtra, India., [Bhaysar, A.] Spandan Multispecial Hosp, Vadodara, India., [Samaddar, D.] Tata Main Hosp, Jamshedpur, Jharkhand, India., [Kulkarni, A.] Tata Mem Hosp, Mumbai, Maharashtra, India., [Hashmi, M.] Aga Khan Univ, Karachi, Pakistan., [Ali, W.] Hearts Int Hosp, Rawalpindi, Pakistan., [Nadeem, S.] Liaquat Natl Hosp, Karachi, Pakistan., [Indraratna, K.] Sri Jayewardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka., [Margarit, A.] Hosp Nostra Senyora Meritxell, Les Escaldes, Andorra., [Urbanek, P.] Akh Wien, Vienna, Austria., [Schlieber, J.] Allgemeines & Orthopad Landeskrankenhaus Stolzalp, Stolzalpe, Austria., [Reisinger, J.] Barmherzige Schwestern Linz, Linz, Austria., [Auer, U.] Gen Hosp Braunau, Braunau, Austria., [Hartjes, A.] Krankenhaus D Barmherzigen Schwestern Ried II, Ried Im Innkreis, Austria., [Lerche, A.] Krankenhaus Floridsdorf, Vienna, Austria., [Janous, T.] LK Gmund Waidhofen Thaya Zwettl, Standort Zwettl, Austria., [Kink, E.] LKH Horgas Enzenbach, Gratwein, Austria., [Krahulec, W.] LKH West, Graz, Austria., [Smolle, K.] Univ Hosp, Graz, Austria., [Van der Schueren, M.] AZ Groeninge Kortrijk, Kortrijk, Belgium., [Thibo, P.] AZ Jan Palfijn Gent, Ghent, Belgium., [Vanhoof, M.] AZ Turnhout, Turnhout, Belgium., [Ahmet, I] Bracops Anderlecht, Anderlecht, Belgium., [Gadisseux, P.] Ctr Hosp Mouscron, Mouscron, Belgium., [Dufaye, P.] CH Peltzer La Tourelle, Verviers, Belgium., [Jacobs, O.] Chirec Edith Cavell, Auderghem, Belgium., [Fraipont, V] CHR Citadelle, Liege, Belgium., [Biston, P.] CHU Charleroi, Charleroi, Belgium., [Dive, A.] CHU Mt Godinne, Yvoir, Belgium., [Bouckaert, Y.] CHU Tivoli, La Louviere, Belgium., [Gilbert, E.] CHwapi, Tournai, Belgium., [Gressens, B.] Clin St Pierre Ottignies, Ottignies, Belgium., [Pinck, E.] Clin Maternite St Elisabeth, Namur, Belgium., [Collin, V] Clin Europe St Michel, Etterbeek, Belgium., [Vincent, J. L.] Erasme Univ Hosp, Anderlecht, Belgium., [De Waele, J.] Ghent Univ Hosp, Ghent, Belgium., [Rimachi, R.] Moliere Hosp, Forest, Belgium., [Gusu, D.] Notre Dame, Brussels, Belgium., [De Decker, K.] Onze Lieve Vrouw Hosp, Aalst, Belgium., [Mandianga, K.] Ixelles Hosp, Ixelles, Belgium., [Heytens, L.] Sint Augustinus, Antwerp, Belgium., [Wittebole, X.] St Luc Univ Hosp UCL, Brussels, Belgium., [Spapen, H.] UZ Brussel, Brussels, Belgium., [Olivier, V] Vivalia Site Libramt, Libramont, Belgium., [Vandenheede, W.] VZW Gezondheidszorg Oostkust Knokke Heist, Knokke Heist, Belgium., [Rogiers, P.] ZNA Middelheim, Antwerp, Belgium., [Kolodzeike, P.] Herning Hosp, Herning, Denmark., [Kruse, M.] Hjoerring Hosp, Hjorring, Denmark., [Andersen, T.] Vejle Hosp, Vejle, Denmark., [Harjola, V] Helsinki Univ Cent Hosp, Helsinki, Finland., [Saarinen, K.] Seinajoki Cent Hosp, Seinajoki, Finland., [Leone, M.] Aix Marseille Univ, Hop Nord, Marseille, France., [Durocher, A.] Calmette Hosp, Lille, France., [Moulront, S.] Ctr Hosp Dunkerque, Dunkerque, France., [Lepape, A.] Ctr Hosp Lyon Sud, Lyon, France., [Losser, M.] CHU Nancy Brabois, Nancy, France., [Cabaret, P.] CH St Philibert, GHICL, Lille, France., [Kalaitzis, E.] CHR Dax, Dax, France., [Zogheib, E.] CHU Amiens, Amiens, France., [Charve, P.] CHU Dijon, Dijon, France., [Francois, B.] CHU Dupuytren, Limoges, France., [Lefrant, J. Y.] CHU Nimes, Nimes, France., [Beilouny, B.] Ctr Hosp Troyes, Troyes, France., [Forceville, X.] Ctr Hosp Meaux, Grp Hosp Est Francilien, Meaux, France., [Misset, B.] Grp Hosp Paris St Joseph, Paris, France., [Jacobs, F.] Hop Antoine Beclere, Clamart, France., [Floccard, B.] Hop Edouard Herriot, Lyon, France., [Payen, D.] Hop Lariboisere, AP HP, Paris, France., [Wynckel, A.] Hop Maison Blanche, Reims, France., [Castelain, V] Hop Univ Strasbourg, Strasbourg, France., [Faure, A.] Hosp Civils Lyon, Lyon, France., [Lavagne, P.] CHU Grenoble, Grenoble, France., [Thierry, I] CHU Nantes, Nantes, France., [Moussa, M.] CHRU Lille, Reanimat Chirurg Cardiovasc, Lille, France., [Vieillard-Baron, A.] Univ Hosp Ambroise Pare, Boulogne, France., [Durand, M.] Univ Hosp Grenoble, La Tronche, France., [Gainnier, M.] Univ Hosp Marseille, Marseille, France., [Ichai, C.] Univ Nice, Nice, France., [Arens, S.] Alexianer Krefeld Gmbh, Krefeld, Germany., [Hoffmann, C.] Charite Hochschulmed Berlin, Berlin, Germany., [Kaffarnik, M.] Charite, Berlin, Germany., [Scharnofske, C.] Diakoniekrankenhaus Henriettenstiftung Gmbh, Hannover, Germany., [Voigt, I] Elisabeth Krankenhaus Essen, Essen, Germany., [Peckelsen, C.] Munich Municipal Hosp Grp, Harlaching Hosp, Munich, Germany., [Weber, M.] Helios St Johannes Klin, Duisburg, Germany., [Gille, J.] Hosp St Georg Leipzig, Leipzig, Germany., [Lange, A.] Klin Hennigsdorf Oberhavel Kliniken Gmbh, Hennigsdorf, Germany., [Schoser, G.] Klin Tettnang, Tettnang, Germany., [Sablotzki, A.] Klinikum St Georg Leipzig, Leipzig, Germany., [Jaschinski, U.; Bluethgen, A.] Klinikum Augsburg, Augsburg, Germany., [Vogel, F.] Klinikum Bremen Mitte, Bremen, Germany., [Tscheu, A.] Klinikum Bremen Ost, Bremen, Germany., [Fuchs, T.] Klinikum Heidenheim, Heidenheim, Germany., [Wattenberg, M.] Klinikum Links Weser Gmbh, Bremen, Germany., [Helmes, T.] Klinikum Luedenscheid, Luedenscheid, Germany., [Scieszka, S.] Krankenhaus Neuwerk, Monchengladbach, Germany., [Heintz, M.] Marienkrankenhaus Schwerte, Schwerte, Germany., [Sakka, S.] Med Ctr Cologne Merheim, Cologne, Germany., [Kohler, J.] Schwarzwald Baar Klinikum Villingen Schwenningen, Villingen Schwenningen, Germany., [Fiedler, F.] St Elisabeth Krankenhaus Koln Hohenlind, Cologne, Germany., [Danz, M.] St Martinus Hosp Olpe, Olpe, Germany., [Sakr, Y.] Uniklinikum Jena, Jena, Germany., [Riessen, R.] Univ Klinikum Tubingen, Tubingen, Germany., [Kerz, T.] Univ Med Mainz, Mainz, Germany., [Kersten, A.] Univ Hosp Aachen, CPACC, Aachen, Germany., [Tacke, F.] Univ Hosp Aachen, DMIII, Aachen, Germany., [Marx, G.] Univ Hosp Aachen, OIC, Aachen, Germany., [Volkert, T.] Univ Hosp Muenster, Munster, Germany., [Schmutz, A.] Univ Med Ctr Freiburg, Fr

Southern Italy was characterised by a complex prehistory that started with different Palaeolithic cultures, later followed by the Neolithization and the demic dispersal from the Pontic-Caspian Steppe during the Bronze Age. Archaeological and historical evidences point to a link between Southern Italians and the Balkans still present in modern times. To shed light on these dynamics, we analysed around 700 South Mediterranean genomes combined with informative ancient DNAs. Our findings revealed high affinities of South-Eastern Italians with modern Eastern Peloponnesians, and a closer affinity of ancient Greek genomes with those from specific regions of South Italy than modern Greek genomes. The higher similarity could be associated with a Bronze Age component ultimately originating from the Caucasus with high Iranian and Anatolian Neolithic ancestries. Furthermore, extremely differentiated allele frequencies among Northern and Southern Italy revealed putatively adapted SNPs in genes involved in alcohol metabolism, nevi features and immunological traits.

Nanomedicines are studied for application in the diagnosis and treatment of cancer, especially as nanoparticles (NPs). Inorganic NPs open new alternatives based on the properties of high atomic weight elements at the nanoscale as potential theranostic tools. However, NPs are rapidly coated with serum proteins in a biological environment called the Corona effect. This effect affects NPs transport through biological medium and cellular uptake and response, having significant consequences in therapeutic efficiency. Also, NP decoration with specific ligands to recognize cell surface receptors of tumor cells, is not enough to overcome this problem. This is currently the most critical issue to overcome for in vivo application of NPs. The extraordinary 3D arrangement of atoms in the protein structure is far from the current human ability to prepare nanomaterials. Therefore, we propose to use albumin, the natural carrier of the blood, as a building block to prepare ‘stealth’ NPs with the ability to avoid non-specific interactions with the biological media. Biohybrid NPs (bioHNPs) are prepared by coating AuNPs with a multilayer of albumin by dynamic aggregation and radiation-induced crosslinking method. Experimental data of NPs/biological media interaction, measured by changes in the hydrodynamic radii, shows a substantial reduction of the Corona effect of bioHNPs under in vitro biological conditions. In addition, Bombesin-decorated bioHNPs offer an enhanced NP uptake to PC-3 cell cultures, containing specific membrane receptors for Bombesin, using near-physiological conditions. This novel preparation method of crosslinked multilayer coating and decoration can be extended to other inorganic nanoparticles to improve biocompatibility.