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5. Nationwide SARS-CoV-2 Surveillance Study for Sewage and Sludges of Wastewater Treatment Plants in Turkey

Author

A. M. Saatçı, Bekir Pakdemirli, Halil Kurt, Sait A, Bilge Alpaslan Kocamemi, Hamza Kadi, Sarac F, and Ismail Aydin

Subjects
2019-20 coronavirus outbreak, Surveillance study, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Environmental science, Sewage, Sewage treatment, business, Virology
Abstract

1.AbstractSince the announcement of the pandemic of Covid-19 by WHO on March 11, 2020, the countries have started to monitor surveillance of SARS-CoV-2 through medical tests. However, people with no and very light symptoms are usually not medically tested or never hospitalized and they are missed. In the study of Wu et al. [1], it was realized that the urine and faeces of all infected people contain SARS-CoV-2. After that, sewage, and sludge-based SARS-CoV-2 surveillance studies have gained significant importance around the world (Fig.1). SARS-CoV-2 was detected in wastewaters in The Netherlands [2,3,4], USA [1,5,6,7, 8, 9, 10], Australia [11], France [12, 13, 14], China [15], Spain [16,17,18,19,20], Italy [21, 22,23], Israel [24], Turkey[25], Germany[26], Japan [27,28], India [29,30], Pakistan [31], Brazil [32,33], Chile [34], Denmark, France, Belgium[35], Equator [36] and Sweden [37] using different virus concentration techniques. Published data show that high concentrations of the SARS-CoV-2 RNA reaches to wastewater treatment plants (WWTPs). On 7th of May 2020, Turkey took its place among a few country which have been started wastewater based surveillance studies at the early stages of pandemic by reporting SARS-CoV-2 RT-qPCR levels of major WWTPs of Istanbul [25]. Turkey [38] first detected SARS-CoV-2 in both primary and waste activated sludges of Istanbul WWTPs. Later, USA [39] and Spain [40] were also studied on sludge samples. There are also studies evaluating the SARS-CoV-2 in WWTPs effluents [10,13,14, 28, 29,30, 34, 36].This study aimed to scan distribution of Covid-19 through Turkey by SARS-CoV-2 measurements in influent, effluent and sludge samples of WWTPs. The influent, effluent and sludge samples were collected from main WWTPs located in 81 cities of Turkey through May 2020-July 2020. Among those 81 cities, Istanbul metropole with 15.5 million inhabitants was chosen as the pilot city since 65% of all cases in Turkey were present here. Hence, all treatment plants in Istanbul were scanned through the study. The viral activity tests were also conducted for the influent, effluent and sludge samples resulting high qPCR.

Published
2020

6. SARS-CoV-2 Detection in Istanbul Wastewater Treatment Plant Sludges

Author

Halil Kurt, Sait A, Bekir Pakdemirli, Sarac F, A. M. Saatçı, and Alpaslan Kocamemi B

Subjects
Secondary treatment, Activated sludge, Wastewater, Aerobic treatment system, Biomass, Environmental science, Sewage treatment, Pulp and paper industry, Anoxic waters, Mixed liquor suspended solids
Abstract

Following the announcement of SARS-CoV-2 worldwide pandemic spread by WHO on March 11, 2020, wastewater based epidemiology received great attention in several countries: The Netherlands [Medama et al., 2020; K-Lodder et al., 2020], USA [Wu et al., 2020; Memudryi et al., 2020], Australia [Ahmed et al., 2020], France [Wurtzer et al., 2020], China [Wang et al., 2020], Spain [Randazzo et al., 2020; Walter et al., 2020], Italy (La Rosa et al., 2020; Rimoldi et al., 2020) and Israel [Or et al., 2020], performed analysis in wastewaters by using different virus concentration techniques. Turkey took its place among these countries on 7th of May, 2020 by reporting SARS-CoV-2 RT-qPCR levels at the inlet of seven (7) major municipal wastewater treatment plants (WWTPs) of Istanbul [Alpaslan Kocamemi et al., 2020], which is a metropole with 15.5 million inhabitants and a very high population density (2987 persons/km2) and having about 65 % of Covid-19 cases in Turkey. Sludges that are produced in WWTPs should be expected to contain SARS-CoV-2 virus as well. There has not yet been any study for the fate of SAR-CoV-2 in sludges generated from WWTPs. Knowledge about the existing of SARS-CoV-2 in sludge may be useful for handling the sludge during its dewatering, stabilizing and disposal processes. This information will also be valuable in case of sludges that are used as soil conditioners in agriculture or sent to landfill disposal.In wastewater treatment plants, generally two different types of sludges are generated; primary sludge (PS) and waste activated sludge (WAS). PS forms during the settling of wastewater by gravity in the primary settling tanks. Little decomposition occurs during primary sludge formation. Since most of the inorganic part of the wastewater is removed in the earlier grit removal process, the PS consists of mainly organic material that settles. The PS is about 1-2 % solids by weight. In the biological treatment part of the WWTPs, the biomass that forms in the anaerobic, anoxic and oxic zones of the process is settled in final clarifiers by gravity and returned to the beginning of the biological process so that it is not washed off. The waste activated sludge (WAS) is the excess part of the biomass that grows in this secondary treatment process. It has to be removed from the process not to increase the mixed liquor suspended solids concentration (bacteria concentration) in the secondary process more than a fixed value. The WAS is about 0.6 - 0.9 % solids by weight.This work aims to find whether SARS-CoV-19 is present in the PS and WAS before it is dewatered and sent to anaerobic or aerobic digester processes or to thermal drying operations.For this purpose, on the 7th of May 2020, two (2) PS samples were collected from Ambarliı and Tuzla WWTPs, seven (7) WAS samples were collected from Terkos, Ambarliı, Atakoy I & II, Pasakoy II, Buyukcekmece and Tuzla I WWTPs. Polyethylene glycol 8000 (PEG 8000) adsorption [Wu et al., 2020] SARS-Cov-2 concentration method was used for SARS-CoV-2 concentration after optimization. [Alpaslan Kocamemi et al., 2020]. Real time RT-PCR diagnostic panel validated by US was used to quantify SARS-CoV-2 RNA in primary and waste activated sludge samples taken from WWTPs in Istanbul. All samples were tested positive. Titers of SARS-CoV-2 have been detected ranging copies between 1.17×104 to 4.02×104 per liter.Value of the DataThe dataset provides information about SARS-CoV-19 in primary and waste activated sludges generated in WWTPs.As being the first study in the world, the dataset presented is expected to be beneficial in handling the sludge during its dewatering, stabilizing and disposal processesData DescriptionSARS-CoV-2 copy numbers per liter measured for sludge samples from WWTPs were summarized in Table 1 and shown in Figure 1 together with SARS-CoV-2 copy numbers observed in an earlier study [Alpaslan Kocamemi et al., 2020] in the influent of the WWTPs from which the sludge samples were taken.To the best of our knowledge, no study has yet been reported the presence of SARS-CoV-2 in primary sludge (PS) and waste activated sludge (WAS) samples. Herein we report the results of SARS-CoV-2 presence in two (2) PS and seven (7) WAS samples from WWTPs in Istanbul. A total of nine (9) sludge samples were collected on the 7th May of 2020 and investigated for presence of SARS-CoV-2 with RT-qPCR methodology. SARS-CoV-2 genome was detected quantitatively from all samples. Sludge samples presented CT ranging from 33.5 to 35.8. Titers of SARS-CoV-2 have been detected ranging from 1.17×104 to 4.02×104 per liter.The detected numbers of SARS-CoV-2 in PS samples were found similar to those observed for WAS samples. SARS-CoV-2 copy numbers detected in PS and WAS on 7th of May, 2020 are greater than the copy numbers observed in the influent of these WWTPs on 21st April, 2020 [Alpaslan Kocamemi, 2020]. By considering the fact that the number of cases reported for Istanbul on the 7th of May, 2020 is less than the cases reported for the 21st April, 2020, it may be concluded that SARS-CoV-2 concentrations are more in both primary and waste activated sludge.

Published
2020
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8. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes

Author

Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR, Josse RG, Califf RM, Goldstein BJ, Shapiro DR, Silverman R, Bethel A, Green J, Hayden S, Hannan K, Quintero K, Rorick T, Berdan L, Leloudis D, Califf S, Wilson M, McFarron D, Trollinger K, Pesarchick J, Eskenazi L, Campbell C, Townes O, Tolsma D, Keenan J, Milton J, Athwal R, Darbyshire J, Doran Z, Kennedy I, Gregory V, Lokhnygina Y, Prather K, Wolfley A, Usman M, Tajjar A, Gray R, Pfeffer MA, Gerstein HC, Groop L, McMurray JJ, Pocock SJ, Clayton T, Sinay I, Brieger D, Stranks S, Scheen A, Lopes R, Tankova T, Hramiak I, Grado CR, Wenying Y, Ge J, Aschner P, Skrha J, Ambos A, Strandberg T, Travert F, Hanefeld M, Riefflin A, Chan JC, Ofner P, Reddy NK, Christopher J, Mathur A, Arambam P, Mittal S, Manchanda M, Wainstein J, Ambrosio G, Pirags V, Jakuboniene N, Mohamed M, Scott R, White H, Cornel J, Halvorsen S, Tykarski A, Veresiu IA, Dreval AV, Misinkova I, Tai E, Krahulec B, Distiller L, Park Y, Rovira A, Alversson M, Chuang LM, Delibasi T, Adler A, Rodbard HW, Marre M, Goff D, Chacra A, DeVore A, Beaven A, Shah B, Hirsch B, Batch B, Bushnell C, Patel C, Melloni C, Henshaw C, Kong D, Bernecki G, Tillman H, Kang HJ, Hawes J, Strickler J, Piccini J, Wilder J, Alexander K, Mahaffey K, Patel K, Hyland K, Newby K, Jackson L, Cooper L, Armaganijan L, Szczeh L, Koshizaka M, Roe M, Morse M, Guimaraes P, Hess P, Tricoci P, Mehta R, Mathews R, Kociol R, Harrison R, Mentz R, Pokorney S, Leblanc T, Lazzarini V, Eapen Z, Truffa A, Fosbol E, Brito F, Katz M, Bahit M, Santos M, Barros P, Bernardez S, Alvarisqueta AF, Arias P, Cagide AL, Calella PR, Cantero MC, Canella JP, Cipullo MA, de Loredo L, Gelersztein ES, Gorban de Lapertosa SB, Klyver MI, Maffei LE, Maldonado N, Oviedo AI, Piskorz DL, Ridruejo MC, Saavedra SS, Sessa HA, Sinay IR, Sposetti GD, Ulla MR, Vico ML, Waitman JN, Binnekamp M, Carroll P, Cheung W, Colman P, Davis T, De Looze F, dEmden M, Fulcher G, Gerstman M, Hamilton A, Lehman S, Moses R, Proietto J, Roberts A, Shaw J, Simpson R, Sinha A, Tan Y, Topliss D, Vora P, Waites J, Crenier L, Descamps O, Keymeulen B, Mathieu C, Nobels F, Van den Bruel A, Van Gaal L, Borges JL, Costa e Forti A, Eliaschewitz FG, Felício JS, Griz LH, Hissa MN, Leite S, Panarotto D, Pimentel Filho P, Rassi N, Saraiva JK, Sgarbi JA, Silva RP, Tambascia M, Weber Silva DM, Bobeva R, Bostandzhieva R, Cinlikov I, Georgieva M, Iliev D, Ilieva E, Kovacheva S, Liubenova L, Nikitov Z, SHeinikova G, Slavcheva A, Spasova V, Temelkova-Kurktschiev T, Velichka D, Yakov A, Carpentier A, Chiasson JL, Constance C, Dumas R, Filteau P, Garceau C, Huynh T, Kaiser S, Kornder J, Leiter L, Mereu L, Miller D, Pandey S, Punthakee Z, Rabasa-Lhoret R, Robitaille Y, Saunders K, Sigal R, Sigalas J, Vizel S, Weisnagel S, Woo V, Yale JF, Yared K, Zinman B, Bunster Balocchi LB, Escobar Cerda EE, Garces Flores EE, Lanas Zanetti FT, Larrazabal Miranda Adel P, Morales Alvarado JM, Olivares Cañon CM, Potthoff Cárdenas SH, Raffo Grado CA, Rodriguez Venegas ME, Saavedra Gajardo VA, Westerberg Maldonado BH, Chen LL, Dong J, Guo X, Li QM, Shi B, Tang XL, Yang T, Yang WY, Zheng SX, Aschner Montoya P, Botero Lopez R, Coronel Arroyo JA, Cure CA, Gómez Medina AM, Molina DI, Perez Amador GA, Reyes Rincon A, Urina Triana MA, Valenzuela Rincon A, Vélez Pelaez S, Yupanqui Lozno H, Brabec T, Brychta T, Hasalova Zapletalova J, Havelkova J, Hejnicova K, Hola O, Hornackova M, Hrdina T, Kafkova D, Kellnerova I, Krystl T, Kutejova V, Mikulkova I, Nevrla J, Pantlikova C, Petr M, Racicka E, Sarbochova R, Smolenakova K, Turcinek R, Urbancova K, Vejvodova J, Vondrakova M, Zachoval R, Alt I, Kaasik Ü, Kiiroja K, Lanno R, Märtsin K, Past M, Vides H, Viitas L, Kantola I, Nieminen S, Perhonen M, Strand J, Valle T, Clergeot A, Couffinhal T, Courreges JP, Gouet D, Moulin P, Ziegler O, Badenhoop K, Behnke T, Bender G, Braun M, Dshabrailov J, Hamann A, Himpel-Boenninghoff A, Kamke W, Kasperk C, Luedemann J, Mayr P, Merkel M, Oerter EM, Ohlow MA, Ott P, Overhoff U, Paschen B, Remppis R, Rose L, Schumm-Draeger PM, Segiet T, Strotmann HJ, Stuchlik G, Stürmer W, Thinesse-Mallwitz M, Tytko A, Wendisch U, Wurziger J, Ho AY, Kam G, Kong AP, Lam YY, Lau EY, Lee S, Siu SC, Tomlinson B, Tsang CC, Yeung VT, Dezső E, Dudás M, Földesi I, Fülöp T, Késmárki N, Koranyi L, Nagy K, Oroszlán T, Pécsvárady Z, Ples Z, Taller A, Agarwal P, Ambulkar S, Aravind S, Balaji V, Kalra S, Kesavadev J, Kudalkar H, Kumar A, Misra A, Mithal A, Mohan V, Pitale S, Ramu M, Reddy N, Shah S, Shamanna P, Sharda A, Sharma A, Shunmugavelu M, Srikanta S, Suryaprakash G, Abramov G, Adawi F, Bashkin A, Darawsha M, Fuchs S, Harman-Boehm I, Hayek T, Jaffe A, Knobler H, Minuchin O, Mosseri M, Shechter M, Shimon I, Stern N, Tsur A, Vishlitzky V, Alfonsi F, Cavalot F, Del Vecchio L, Frisinghelli A, Gambardella S, Lauro D, Lembo G, Leotta S, Mondillo S, Novo S, Pedrinelli R, Piatti P, Salvioni A, Tritto I, Zavaroni DZ, Ahn KJ, Choi KM, Chung C, Han SJ, Kim DM, Kim IJ, Kim MH, Lee IK, Nam M, Park IeB, Park KS, Park TS, Rhee EJ, Yoo SJ, Andersone I, Balode A, Eglite R, Gersamija A, Kakurina N, Jegere B, Leitane I, Pastare S, Stalte V, Teterovska D, Baltramonaitiene K, Barsiene L, Ceponis J, Lasiene J, Levinger A, Sirutaviciene A, Sulskiene M, Urbanaviciene L, Valius L, Varanauskiene E, Velickiene D, Mahendran KA, Abu Hassan MR, Aziz NA, Hussein Z, Ismail IS, Kamaruddin NA, Nordin Z, Nayar SK, Ramanathan GR, Sothiratnam R, Beijerbacht H, Breedveld R, Cornel JH, Den Hartog F, Hermans W, Kietselaer B, Kooy A, Lenderink T, Nierop P, Remmen J, Rojas Lingan G, Ronner E, Van der Heijden R, Van Hessen M, van Kempen W, Voors-Pette C, Westendorp I, Baker J, Benatar J, Cutfield R, Krebs J, Leikis R, Lunt H, Manning P, Williams M, Birkeland K, Claudi T, Istad H, Karlsson T, Ossum Gronert J, Arciszewska M, Artemiuk E, Blach E, Blicharski T, Cypryk K, Dabrowska M, Górny G, Górska M, Jakubowska I, Jazwinska-Tarnawska E, Karczmarczyk A, Kitowska-Koterla J, Koltowski L, Krzyzagorska E, Pasternak D, Pentela-Nowicka J, Piesiewicz W, Przekwas-Jaruchowska M, Rajzer M, Salamon-Ferenc A, Sawicki A, Skowron T, Śmiałowski A, Albota A, Alexandru C, Crisan C, Dumitrescu A, Ferariu IE, Lupusoru DA, Munteanu M, Negru D, Nicolau A, Pintiliei E, Popescu A, Serban G, Voitec M, Babenko A, Barbarash O, Bondar I, Chizhov P, Demin A, Dora S, Dreval A, Ershova O, Gratsiansky N, Ketova G, Kotelnikov M, Levashov S, Morugova T, Mustafina S, Pekarskiy S, Raskina T, Rechkova E, Samoylova Y, Sazonova O, Sherenkov A, Shilkina N, Stetsyuk O, Tretyakova T, Turova E, Valeeva F, Zadionchenko V, Dalan R, Tan RS, Tay L, Buganova I, Fabry J, Jan C, Toserova E, Zak R, Zimanova J, Badat A, Bester F, Burgess L, De Jong D, Ellis G, Fouche L, Govender P, Govind U, Naidoo V, Nieuwoudt G, Nortje H, Rheeder P, Robertson L, Siddique N, Stapelberg AM, Trinder Y, Van Der Merwe A, Van Zyl L, Viljoen M, Wilhase A, Botella M, Civeira Murillo F, de Teresa L, Del Cañizo FJ, Extremera BG, Gimeno EJ, Martin-Hidalgo A, Morales C, Nubiola A, Tinahones Madueño F, Tranche S, Trescolí Serrano C, Alvarsson M, Eizyk E, Gillblad A, Johansson P, Löndahl M, Ohlsson-Önerud Å, Rautio A, Sundström U, Torstensson I, Chen JF, Chou CW, Ho LT, Hsieh IC, Huang BH, Huang CL, Huang CN, Lai WT, Lo PH, Pei D, Sheu WH, Wang SY, Araz M, Bakiner O, Comlekci A, Guler S, Sahin I, Sarac F, Tarkun I, Ukinc K, Yilmaz M, Abdulhakim E, Abraham P, Adamson K, Blagden M, Bundy C, Daly M, Davies M, Deshpande M, Gillings S, Harvey P, Horvathova V, Hristova D, Jaap A, Johnson A, Jones H, Kerrane J, Kilvert A, Ko T, Kumar J, Lindsay R, Litchfield J, McCrimmon R, McKnight J, Millward B, Oyesile B, Purewal T, Ravikumar C, Robinson A, Sathyapalan T, Simpson H, Thomas H, Turner W, Weaver J, Wilding J, Wiles P, Adkins K, Akpunonu B, Albu J, Anagnostis G, Anastasi L, Argoud G, Aroda V, Azizad M, Banerji MA, Bartkowiak A Jr, Bays H, Behn P, Bergenstal R, Bhargava A, Bias D, Bolster E, Buchanan P, Busch R, Chadha C, Chang M, Cheng C, Cohen A, Cohen J, Cole B, Connery L, Cooperman M, Cushman W, DAgostino R, Dayamani P, De Lemos J, De Meireles M, Dean J, DeHart D, Detweiler R, Donovan D, Dugano-Daphnis P, Dulin M, Dunn F, Eaton C, Erickson B, Estevez R, Feinglos M, Fonseca V, Force R, Forker A, Fox D, Gabriel J, Garcia R, Garvey T, Gaudiani L, Getaneh A, Goldberg A, Goldman S, Hairston K, Harris R, Haught W, Hidalgo H Jr, Higgins A, Houchin V, Ison R, Jacobs G, Jaffrani N, Jafry B, Kapsner P, Kaye W, Labroo A, Levinson L, Lewis S, Lillestol M, Luttrell L, Madu I, McNeill R, Merrick B, Metzger F, Nadar V, Nagelberg S, Nash S, Oparil S, Osei K, Papademetriou V, Patel N, Pedley C, Prentiss A, Radbill M, Raisinghani A, Rassouli N, Reddy R, Rees P, Rendell M, Robbins D, Rodbard H, Rohlf J, Roseman H, Rudolph L, Sadler L, Schnall A, Schramm R, Schubart U, Seneviratne T, Shanik M, Snyder H, Sorli C, Stich M, Sweeney ME, Tsao J, Ukwade P, Viswanath D, Vo A, Vogel C, Voyce S, Weintraub H, White J, Wood M, Wu P, Wysham C, Zimmerman R, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR, Holman RR, Peterson ED, Holman RR, Peterson ED, Armstrong PW, Buse JB, Josse RG, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Engel SS, Califf RM, Goldstein BJ, Shapiro DR, Silverman R, Bethel A, Green J, Hayden S, Hannan K, Quintero K, Rorick T, Berdan L, Leloudis D, Califf S, Wilson M, McFarron D, Trollinger K, Pesarchick J, Eskenazi L, Campbell C, Townes O, Tolsma D, Keenan J, Milton J, Athwal R, Darbyshire J, Doran Z, Kennedy I, Gregory V, Garg J, Lokhnygina Y, Prather K, Wolfley A, Usman M, Tajjar A, Gray R, Pfeffer MA, Gerstein HC, Groop L, McMurray JJ, Pocock SJ, Clayton T, Sinay I, Brieger D, Stranks S, Scheen A, Lopes R, Tankova T, Hramiak I, Grado CR, Wenying Y, Ge J, Aschner P, Skrha J, Ambos A, Strandberg T, Travert F, Hanefeld M, Riefflin A, Chan JC, Ofner P, Reddy NK, Christopher J, Mathur A, Arambam P, Mittal S, Manchanda M, Wainstein J, Ambrosio G, Pirags V, Jakuboniene N, Mohamed M, Scott R, White H, Cornel J, Halvorsen S, Tykarski A, Veresiu IA, Dreval AV, Misinkova I, Tai E, Krahulec B, Distiller L, Park Y, Rovira A, Alversson M, Chuang LM, Delibasi T, Adler A, Rodbard HW, Marre M, Goff D, Chacra A, DeVore A, Beaven A, Shah B, Hirsch B, Batch B, Bushnell C, Patel C, Melloni C, Henshaw C, Kong D, McFarron D, Bernecki G, Tillman H, Kang HJ, Green J, Hawes J, Strickler J, Piccini J, Wilder J, Alexander K, Mahaffey K, Patel K, Hyland K, Newby K, Jackson L, Cooper L, Armaganijan L, Szczeh L, Koshizaka M, Roe M, Morse M, Guimaraes P, Hess P, Tricoci P, Mehta R, Lopes R, Mathews R, Kociol R, Harrison R, Mentz R, Pokorney S, Leblanc T, Lazzarini V, Eapen Z, Truffa A, Fosbol E, Brito F, Katz M, Bahit M, Santos M, Barros P, Bernardez S, Alvarisqueta AF, Arias P, Cagide AL, Calella PR, Cantero MC, Canella JP, Cipullo MA, de Loredo L, Gelersztein ES, Gorban de Lapertosa SB, Klyver MI, Maffei LE, Maldonado N, Oviedo AI, Piskorz DL, Ridruejo MC, Saavedra SS, Sessa HA, Sinay IR, Sposetti GD, Ulla MR, Vico ML, Waitman JN, Binnekamp M, Carroll P, Cheung W, Colman P, Davis T, De Looze F, dEmden M, Fulcher G, Gerstman M, Hamilton A, Lehman S, Moses R, Proietto J, Roberts A, Shaw J, Simpson R, Sinha A, Stranks S, Tan Y, Topliss D, Vora P, Waites J, Crenier L, Descamps O, Keymeulen B, Mathieu C, Nobels F, Scheen A, Van den Bruel A, Van Gaal L, Borges JL, Costa e Forti A, Eliaschewitz FG, Felício JS, Griz LH, Hissa MN, Leite S, Panarotto D, Pimentel Filho P, Rassi N, Saraiva JK, Sgarbi JA, Silva RP, Tambascia M, Weber Silva DM, Bobeva R, Bostandzhieva R, Cinlikov I, Georgieva M, Iliev D, Ilieva E, Kovacheva S, Liubenova L, Nikitov Z, SHeinikova G, Slavcheva A, Spasova V, Tankova T, Temelkova-Kurktschiev T, Velichka D, Yakov A, Carpentier A, Chiasson JL, Constance C, Dumas R, Filteau P, Garceau C, Hramiak I, Huynh T, Kaiser S, Kornder J, Leiter L, Mereu L, Miller D, Pandey S, Punthakee Z, Rabasa-Lhoret R, Robitaille Y, Saunders K, Sigal R, Sigalas J, Vizel S, Weisnagel S, Woo V, Yale JF, Yared K, Zinman B, Bunster Balocchi LB, Escobar Cerda EE, Garces Flores EE, Lanas Zanetti FT, Larrazabal Miranda Adel P, Morales Alvarado JM, Olivares Cañon CM, Potthoff Cárdenas SH, Raffo Grado CA, Rodriguez Venegas ME, Saavedra Gajardo VA, Westerberg Maldonado BH, Chen LL, Dong J, Guo X, Li QM, Shi B, Tang XL, Yang T, Yang WY, Zheng SX, Aschner Montoya P, Botero Lopez R, Coronel Arroyo JA, Cure CA, Gómez Medina AM, Molina DI, Perez Amador GA, Reyes Rincon A, Urina Triana MA, Valenzuela Rincon A, Vélez Pelaez S, Yupanqui Lozno H, Brabec T, Brychta T, Hasalova Zapletalova J, Havelkova J, Hejnicova K, Hola O, Hornackova M, Hrdina T, Kafkova D, Kellnerova I, Krystl T, Kutejova V, Mikulkova I, Nevrla J, Pantlikova C, Petr M, Racicka E, Sarbochova R, Skrha J, Smolenakova K, Turcinek R, Urbancova K, Vejvodova J, Vondrakova M, Zachoval R, Alt I, Ambos A, Kaasik Ü, Kiiroja K, Lanno R, Märtsin K, Past M, Vides H, Viitas L, Kantola I, Nieminen S, Perhonen M, Strand J, Strandberg T, Valle T, Clergeot A, Couffinhal T, Courreges JP, Gouet D, Moulin P, Travert F, Ziegler O, Badenhoop K, Behnke T, Bender G, Braun M, Dshabrailov J, Hamann A, Hanefeld M, Himpel-Boenninghoff A, Kamke W, Kasperk C, Luedemann J, Mayr P, Merkel M, Oerter EM, Ohlow MA, Ott P, Overhoff U, Paschen B, Remppis R, Riefflin A, Rose L, Schumm-Draeger PM, Segiet T, Strotmann HJ, Stuchlik G, Stürmer W, Thinesse-Mallwitz M, Tytko A, Wendisch U, Wurziger J, Ho AY, Kam G, Kong AP, Lam YY, Lau EY, Lee S, Siu SC, Tomlinson B, Tsang CC, Yeung VT, Dezső E, Dudás M, Földesi I, Fülöp T, Késmárki N, Koranyi L, Nagy K, Ofner P, Oroszlán T, Pécsvárady Z, Ples Z, Taller A, Agarwal P, Ambulkar S, Aravind S, Balaji V, Christopher J, Kalra S, Kesavadev J, Kudalkar H, Kumar A, Misra A, Mithal A, Mohan V, Pitale S, Ramu M, Reddy N, Shah S, Shamanna P, Sharda A, Sharma A, Shunmugavelu M, Srikanta S, Suryaprakash G, Abramov G, Adawi F, Bashkin A, Darawsha M, Fuchs S, Harman-Boehm I, Hayek T, Jaffe A, Knobler H, Minuchin O, Mosseri M, Shechter M, Shimon I, Stern N, Tsur A, Vishlitzky V, Wainstein J, Alfonsi F, Cavalot F, Del Vecchio L, Frisinghelli A, Gambardella S, Lauro D, Lembo G, Leotta S, Mondillo S, Novo S, Pedrinelli R, Piatti P, Salvioni A, Tritto I, Zavaroni DZ, Ahn KJ, Choi KM, Chung C, Han SJ, Kim DM, Kim IJ, Kim MH, Lee IK, Nam M, Park IeB, Park KS, Park TS, Park Y, Rhee EJ, Yoo SJ, Andersone I, Balode A, Eglite R, Gersamija A, Kakurina N, Jegere B, Leitane I, Pastare S, Pirags V, Stalte V, Teterovska D, Baltramonaitiene K, Barsiene L, Ceponis J, Jakuboniene N, Lasiene J, Levinger A, Sirutaviciene A, Sulskiene M, Urbanaviciene L, Valius L, Varanauskiene E, Velickiene D, Mahendran KA, Abu Hassan MR, Aziz NA, Hussein Z, Ismail IS, Kamaruddin NA, Mohamed M, Nordin Z, Nayar SK, Ramanathan GR, Sothiratnam R, Beijerbacht H, Breedveld R, Cornel JH, Den Hartog F, Hermans W, Kietselaer B, Kooy A, Lenderink T, Nierop P, Remmen J, Rojas Lingan G, Ronner E, Van der Heijden R, Van Hessen M, van Kempen W, Voors-Pette C, Westendorp I, Baker J, Benatar J, Cutfield R, Krebs J, Leikis R, Lunt H, Manning P, Scott R, Williams M, Birkeland K, Claudi T, Halvorsen S, Istad H, Karlsson T, Ossum Gronert J, Arciszewska M, Artemiuk E, Blach E, Blicharski T, Cypryk K, Dabrowska M, Górny G, Górska M, Jakubowska I, Jazwinska-Tarnawska E, Karczmarczyk A, Kitowska-Koterla J, Koltowski L, Krzyzagorska E, Pasternak D, Pentela-Nowicka J, Piesiewicz W, Przekwas-Jaruchowska M, Rajzer M, Salamon-Ferenc A, Sawicki A, Skowron T, Śmiałowski A, Tykarski A, Albota A, Alexandru C, Crisan C, Dumitrescu A, Ferariu IE, Lupusoru DA, Munteanu M, Negru D, Nicolau A, Pintiliei E, Popescu A, Serban G, Veresiu IA, Voitec M, Babenko A, Barbarash O, Bondar I, Chizhov P, Demin A, Dora S, Dreval A, Ershova O, Gratsiansky N, Ketova G, Kotelnikov M, Levashov S, Morugova T, Mustafina S, Pekarskiy S, Raskina T, Rechkova E, Samoylova Y, Sazonova O, Sherenkov A, Shilkina N, Stetsyuk O, Tretyakova T, Turova E, Valeeva F, Zadionchenko V, Dalan R, Tan RS, Tay L, Buganova I, Fabry J, Jan C, Krahulec B, Toserova E, Zak R, Zimanova J, Badat A, Bester F, Burgess L, De Jong D, Distiller L, Ellis G, Fouche L, Govender P, Govind U, Naidoo V, Nieuwoudt G, Nortje H, Rheeder P, Robertson L, Siddique N, Stapelberg AM, Trinder Y, Van Der Merwe A, Van Zyl L, Viljoen M, Wilhase A, Botella M, Civeira Murillo F, de Teresa L, Del Cañizo FJ, Extremera BG, Gimeno EJ, Martin-Hidalgo A, Morales C, Nubiola A, Rovira A, Tinahones Madueño F, Tranche S, Trescolí Serrano C, Alvarsson M, Eizyk E, Gillblad A, Johansson P, Löndahl M, Ohlsson-Önerud Å, Rautio A, Sundström U, Torstensson I, Chen JF, Chou CW, Chuang LM, Ho LT, Hsieh IC, Huang BH, Huang CL, Huang CN, Lai WT, Lo PH, Pei D, Sheu WH, Wang SY, Araz M, Bakiner O, Comlekci A, Delibasi T, Guler S, Sahin I, Sarac F, Tarkun I, Ukinc K, Yilmaz M, Abdulhakim E, Abraham P, Adamson K, Adler A, Blagden M, Bundy C, Daly M, Davies M, Deshpande M, Gillings S, Harvey P, Horvathova V, Horvathova V, Hristova D, Jaap A, Johnson A, Jones H, Kerrane J, Kilvert A, Ko T, Kumar J, Lindsay R, Litchfield J, McCrimmon R, McKnight J, Millward B, Oyesile B, Purewal T, Ravikumar C, Robinson A, Sathyapalan T, Simpson H, Thomas H, Turner W, Weaver J, Wilding J, Wiles P, Adkins K, Akpunonu B, Albu J, Anagnostis G, Anastasi L, Argoud G, Aroda V, Azizad M, Banerji MA, Bartkowiak A Jr, Bays H, Behn P, Bergenstal R, Bhargava A, Bias D, Bolster E, Buchanan P, Busch R, Chadha C, Chang M, Cheng C, Cohen A, Cohen J, Cole B, Connery L, Cooperman M, Cushman W, DAgostino R, Davies M, Dayamani P, De Lemos J, De Meireles M, Dean J, DeHart D, Detweiler R, Donovan D, Dugano-Daphnis P, Dulin M, Dunn F, Eaton C, Erickson B, Estevez R, Feinglos M, Fonseca V, Force R, Forker A, Fox D, Gabriel J, Garcia R, Garvey T, Gaudiani L, Getaneh A, Goff D, Goldberg A, Goldman S, Hairston K, Harris R, Haught W, Hidalgo H Jr, Higgins A, Houchin V, Ison R, Jacobs G, Jaffrani N, Jafry B, Kapsner P, Kaye W, Labroo A, Levinson L, Lewis S, Lillestol M, Luttrell L, Madu I, McNeill R, Merrick B, Metzger F, Nadar V, Nagelberg S, Nash S, Oparil S, Osei K, Papademetriou V, Patel N, Pedley C, Prentiss A, Radbill M, Raisinghani A, Rassouli N, Reddy R, Rees P, Rendell M, Robbins D, Rodbard H, Rohlf J, Roseman H, Rudolph L, Sadler L, Schnall A, Schramm R, Schubart U, Seneviratne T, Shanik M, Snyder H, Sorli C, Stich M, Sweeney ME, Tsao J, Ukwade P, Viswanath D, Vo A, Vogel C, Voyce S, Weintraub H, White J, Wood M, Wu P, Wysham C, Zimmerman R

Subjects
Oral, medicine.medical_specialty, Heart diseases, Glycosylated, Administration, Oral, heart failure, Type 2 diabetes, Dipeptidyl peptidase-4 inhibitor, Kaplan-Meier Estimate, Placebo, Sitagliptin Phosphate, Sitagliptin, Cardiovascular Outcomes, chemistry.chemical_compound, Drug Therapy, Double-Blind Method, Internal medicine, Diabetes Mellitus, medicine, Humans, Hypoglycemic Agents, Glycated Hemoglobin, Hemoglobin A, Glycosylated, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Follow-Up Studies, Heart Diseases, Heart Failure, Hospitalization, Pyrazines, Triazoles, Medicine (all), business.industry, Semaglutide, Hemoglobin A, General Medicine, ta3121, medicine.disease, Surgery, Cardiovascular diseases, chemistry, Sitagliptin, Administration, Combination, Glycated hemoglobin, business, Type 2, Alogliptin, medicine.drug
Abstract

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to-0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P

Published
2015

32. Cardiovascular risk factors in obese women and their first-degree relatives.

Author

Sarac F, Ozgen AG, Yilmaz C, and Tuzun M

Abstract

OBJECTIVE: Evidence for a connection between obesity and cardiovascular disease is derived from epidemiological studies. The aim of this study was to evaluate the cardiovascular risk factors in obese women and their first-degree relatives. METHODS: Fifty-five obese women and their 154 first-degree relatives (daughter, son, sister, brother), 60 non-obese women and their 100 first-degree relatives were enrolled in this cross-sectional controlled study. Blood pressure, heart rate, body mass index (BMI), waist-to-hip ratio (WHpR), waist circumference (WC) and lipid levels were measured in all participants. Serum concentrations of insulin were measured by chemiluminescence method, plasma levels of high sensitive C-reactive protein (hs CRP) by immunoturbimetric assay and fibrinogen by coagulation method. Measurement of insulin resistance (IR) was calculated using homeostasis model assessment (HOMA). Statistical analysis was preformed using Chi-square, Student's t and Mann-Whitney U tests. The relationship between obesity indices and cardiovascular risk factors were studied using linear regression analysis. RESULTS: Mean values of BMI in female and male relatives were found as 25.10+/-2.5 kg/m2 and 23.5+/-4.98 kg/m2, respectively. In relatives, the frequencies of obesity, overweight and normal weight were found to be 8.9%, 25.8% and 65.1%, respectively. Central obesity was found higher in males than in females in the first-degree relatives, using WC (28.5% vs. 14.3%, p=0.001) or WHpR (30.9% vs. 24.5%, p=0.002). Elevated blood pressure (>or=140/90 mmHg) was recorded in 23.6% of obese women and in 8.4% of their relatives. Mean HOMA-IR levels of obese women and their relatives were found as 3.26+/-0.7 and 2.07+/-1.1, respectively. Mean hs CRP levels of obese women and their relatives were 0.98+/-0.08 mg/dl and 0.23+/-0.03 mg/dl, respectively (p=0.002). Mean fibrinogen levels of obese women and their relatives were 443.21+/-45.9 mg/dl and 321.10+/-38.23 mg/dl, respectively. CONCLUSION: In obese women and their relatives, body mass index and waist circumferences are related with blood pressure, total cholesterol, fibrinogen and insulin resistance. If there are obese women in family, first-degree relatives have 1.8 fold increased obesity frequency. Body mass index increases together with cardiovascular risk factors. In early term, prevention of obesity may decrease developing of cardiovascular risk. [ABSTRACT FROM AUTHOR]

Published
2007

33. Metabolic syndrome, insulin resistance, fibrinogen, homocysteine, leptin, and C-reactive protein in obese patients with obstructive sleep apnea syndrome

Author

Basoglu Ozen, Sarac Fulden, Sarac Sefa, Uluer Hatice, and Yilmaz Candeger

Subjects
C-reactive protein, fibrinogen, homocysteine, insulin resistance, leptin, metabolic syndrome, obesity, obstructive sleep apnea syndrome, Diseases of the circulatory (Cardiovascular) system, RC666-701, Diseases of the respiratory system, RC705-779
Abstract

Objective: The prevalence of obstructive sleep apnea syndrome (OSAS) and metabolic syndrome is increasing worldwide, in part linked to epidemic of obesity. The purposes of this study were to establish the rate of metabolic syndrome and to compare fibrinogen, homocysteine, high-sensitivity C-reactive protein (hsCRP), leptin levels, and homeostasis model assessment insulin resistance (HOMA-IR) in the obese patients with and without OSAS. Methods: The study population included 36 consecutive obese patients with OSAS (23 males; mean age, 50.0 ±19.7 years), and 34 obese patients without OSAS (17 males; mean age, 49.7±11.1 years) were enrolled as control group. Metabolic syndrome was investigated; fibrinogen, homocysteine, CRP, and leptin levels were measured, and IR was assessed. Results: Metabolic syndrome was found in 17 (47.2%) obese OSAS patients, whereas only 29.4% of obese subjects had metabolic syndrome (P > 0.05). Obese patients with OSAS had significantly higher mean levels of triglyceride (P< 0.001), total-cholesterol ( P = 0.003), low-density lipoprotein-cholesterol ( P = 0.001), fasting glucose ( P = 0.01), HOMA-IR ( PP = 0.03), fibrinogen ( P < 0.003), hsCRP ( P P = 0.03) than control group . Besides, leptin level was positively correlated with waist ( r = 0.512, P = 0.03) and neck circumferences ( r = 0.547, P = 0.03), and fasting glucose (r = 0.471, P = 0.04) in OSAS patients, but not in obese subjects. Conclusion: This study demonstrated that obese OSAS patients may have an increased rate of metabolic syndrome and higher levels of serum lipids, fasting glucose, IR, leptin, fibrinogen, and hsCRP than obese subjects without sleep apnea. Thus, clinicians should be encouraged to systematically evaluate the presence of metabolic abnormalities in OSAS and vice versa.

Published
2011

37. A Rare Case of a Child with Bended Scarf-Pin in Left Bronchus: Case Report with Systematic Review And Meta-Analysis.

Author

Kayrancioglu B, Azizoglu M, and Sarac F

Abstract

Background: In this report, we present the case of a 19-month-old female diagnosed with hijab pin aspiration after a week of persistent coughing, along with a meta analysis and systematic review of the relevant literature., Materials and Methods: A comprehensive search was conducted across multiple databases, including Ovid Medline, Cochrane, PubMed, Web of Science, and SCOPUS, yielding 182 records until August 2024. A total of 7 published study and our case included to final analysis. The complication, morbidity, and mortality analysis has been performed using Jamovi software v2.4 MAJOR proportion analysis section., Case Description: A 19-month-old female was admitted to another hospital with a persistent cough complaint. In X-ray left hijab pin has been detected. The patient underwent a succesfull removal with rigid broncoscopy (RB). A total of 71 patients included this meta analysis. The thoracotomy rate was 8%. The bleeding rate was reported as 1.4%. The reoperation rate was reported as 9.8%. The postoperative intubation rate was reported as 1.4%. The calculated complication rate was found to be 5.6% based on the existing literature. The postoperative hemoptysis incidence was calculated as 0%. Mortality was not reported across any included studies. However, the mortality incidence was calculated as 0% based on included studies., Conclusion: Effective and timely intervention is crucial for managing pediatric hijab pin aspiration. Multidisciplinary approaches ensure successful outcomes and prevent serious complications., Competing Interests: None, (Copyright© 2024, Galen Medical Journal.)

Published
2024
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38. Approach to primary spontaneous pneumothorax: Experiences of a new pediatric surgery clinic.

Author

Sarac F, Yazici M, and Kuzdan MÖ

Abstract

Background: The prevalence of spontaneous pneumothorax in children during adolescence is low, but not negligible. Treatment involves conservative management and surgery. The aim of this study was to review our patients treated with diagnoses of primary spontaneous pneumothorax and to describe our therapeutic approach, outcomes, and deficiencies., Methods: Ninety (90) patients diagnosed with primary spontaneous pneumothorax and treated and followed-up in our clinic between June 2020 and December 2023 were included in the study. The research was performed as a retrospective file review. Trauma, secondary pneumothorax, and newborn pneumothorax were excluded., Results: Seventy six (76) patients were boys and 14 were girls, with a mean age of 16,23 years. Right pneumothorax was present in 44 patients, left pneumothorax in 41, and bilateral pneumothorax in 5. The 90 patients' initial treatment involved tube thoracostomy, and 36 individuals with prolonged and recurrent pneumothorax underwent video-assisted thoracoscopic surgery (VATS)., Conclusion: The success rate of apical wedge resection and mechanical pleurodesis with direct VATS in the treatment of prolonged and recurrent primary spontaneous pneumothorax in children is greater than 90 %. We think that, VATS is a successful, effective and safe treatment for spontaneous pneumothorax due to a significantly lower recurrence rate compared to chest tube insertion., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Published
2024
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39. Humoral immune response profile of a cattle herd vaccinated with 5- and 10-times Bakirköy strain sheep pox vaccine under field conditions.

Author

Enul H, Uzar S, Satir E, Sarac F, Adiay C, Parmaksiz A, Colak G, and Asar E

Subjects
Female, Pregnancy, Animals, Cattle, Sheep, Immunity, Humoral, Antibodies, Viral, Vaccination veterinary, Viral Vaccines, Lumpy Skin Disease, Poxviridae Infections, Cattle Diseases prevention & control
Abstract

Vaccination is the most effective control measure for Lumpy Skin Disease (LSD). The Bakırköy strain-derived sheep pox vaccine (SPPV) has been used against LSD in Türkiye since 2013. In this study, a cattle herd was vaccinated with SPPV and 35 cattle, of which 9 and 26 received 10 and 5 sheep doses, respectively, were followed for 200 days for humoral immune responses. Additionally, maternal antibodies in colostrum-fed calves were investigated. The humoral immune responses of naive and previously vaccinated cattle were compared to determine the effects of annual re-vaccination. Furthermore, the compatibility of the VNT and ELISA tests was analyzed. According to the results, on day 30 post-vaccination, 19 and 13 out of 35 cattle were positive for VNT and ELISA, respectively. The number of seropositive cattle was higher in the group that had been vaccinated in previous years than in naive cattle. No significant differences were observed in the number of positive cattle between the groups vaccinated with the 5- and 10- doses. In colostrum-fed calves grouped according to age, the seropositivity rate was 87 % (41/47) in the one-week-old group, while this rate was only 18 % (3/16) in the 3-month-old group. It was determined that vaccination at different stages in the last four months of pregnancy did not cause any difference in the number of seropositive calves in one-week-old calves fed with colostrum. The concordance between VNT and ELISA tests was lower in 5-dose vaccinated group than 10-dose vaccinated and colostrum-fed calves groups. This study provides insights into the effect of the vaccination strategy followed by Türkiye during its combat of LSD and revealed that annual repeated vaccination using heterologous vaccine has significant positive effects on humoral immun response at the herd level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Published
2024
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40. Intraoral findings of a patient with Nablus mask-like facial syndrome and dental treatment approaches: a case report and literature review.

Author

Bas A, Sarac F, and Derelioglu S

Subjects
Humans, Face abnormalities, Dental Care, Blepharophimosis diagnosis, Blepharophimosis genetics, Craniofacial Abnormalities diagnosis, Craniofacial Abnormalities genetics
Abstract

Nablus mask-like facial syndrome (NMLFS) (OMIM: 608156) is an extremely rare genetic syndrome first reported by Ahmad Teebi in 2000. Although it is a rare condition, it is characterized by distinctive facial features such as, expressionless facial appearance, tight, glistening facial skin, low anterior hairline, sparse eyebrows, small palpebral fissures (blepharophimosis), hypertolerism, bulbous nose with prominent columella, abnormally short nose and flat nasal bridge, abnormal ear configuration, bilateral longitudinal cheek dimples, everted lower lip, long philtrum, and maxillary hypoplasia. In addition, a happy and friendly disposition is considered to be the common symptom of this syndrome. Previous studies revealing the intraoral findings of this rare symptom are inadequate and the present report is the first one that presents a dental case involving Nablus syndrome in detail. The aim of this report is to contribute to the current literature through our oral findings in an NMFLS patient, presented at our clinic with toothache and through our treatment approach., Competing Interests: The authors declare no conflict of interest., (©2023 The Author(s). Published by MRE Press.)

Published
2023
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41. Process development for an effective COVID-19 vaccine candidate harboring recombinant SARS-CoV-2 delta plus receptor binding domain produced by Pichia pastoris.

Author

Kalyoncu S, Yilmaz S, Kuyucu AZ, Sayili D, Mert O, Soyturk H, Gullu S, Akinturk H, Citak E, Arslan M, Taskinarda MG, Tarman IO, Altun GY, Ozer C, Orkut R, Demirtas A, Tilmensagir I, Keles U, Ulker C, Aralan G, Mercan Y, Ozkan M, Caglar HO, Arik G, Ucar MC, Yildirim M, Yildirim TC, Karadag D, Bal E, Erdogan A, Senturk S, Uzar S, Enul H, Adiay C, Sarac F, Ekiz AT, Abaci I, Aksoy O, Polat HU, Tekin S, Dimitrov S, Ozkul A, Wingender G, Gursel I, Ozturk M, and Inan M

Subjects
Animals, Humans, Mice, SARS-CoV-2 genetics, Mice, Transgenic, Saccharomyces cerevisiae, Antibodies, Viral, Antibodies, Neutralizing, COVID-19 Vaccines, COVID-19 prevention & control
Abstract

Recombinant protein-based SARS-CoV-2 vaccines are needed to fill the vaccine equity gap. Because protein-subunit based vaccines are easier and cheaper to produce and do not require special storage/transportation conditions, they are suitable for low-/middle-income countries. Here, we report our vaccine development studies with the receptor binding domain of the SARS-CoV-2 Delta Plus strain (RBD-DP) which caused increased hospitalizations compared to other variants. First, we expressed RBD-DP in the Pichia pastoris yeast system and upscaled it to a 5-L fermenter for production. After three-step purification, we obtained RBD-DP with > 95% purity from a protein yield of > 1 g/L of supernatant. Several biophysical and biochemical characterizations were performed to confirm its identity, stability, and functionality. Then, it was formulated in different contents with Alum and CpG for mice immunization. After three doses of immunization, IgG titers from sera reached to > 10 6 and most importantly it showed high T-cell responses which are required for an effective vaccine to prevent severe COVID-19 disease. A live neutralization test was performed with both the Wuhan strain (B.1.1.7) and Delta strain (B.1.617.2) and it showed high neutralization antibody content for both strains. A challenge study with SARS-CoV-2 infected K18-hACE2 transgenic mice showed good immunoprotective activity with no viruses in the lungs and no lung inflammation for all immunized mice., (© 2023. The Author(s).)

Published
2023
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42. Effects of Cilostazol on the Myocardium in an Obese Wistar Rat Model of Ischemia-Reperfusion Injury.

Author

Demir T, Sahin M, Ilal Mert FT, and Sarac F

Subjects
Rats, Animals, Rats, Wistar, Cilostazol pharmacology, Cilostazol metabolism, Myocardium metabolism, Plasminogen Activator Inhibitor 1 metabolism, Reperfusion Injury drug therapy, Reperfusion Injury prevention & control, Reperfusion Injury metabolism
Abstract

Objectives: This study aims to determine the protective effect of cilostazol on myocardium in obese Wistar rats with induced ischemia-reperfusion injury (IRI)., Methods: Four groups with 10 Wistar rats were included: 1] Sham Group: IRI was not established in normal weight-Wistar rats. 2] Control Group: IRI but no cilostazol in normal weight-Wistar rats. 3] Cilostazol in normal weight-Wistar rats: IRI and cilostazol was administered. 4] Cilostazol in obese- Wistar rats: IRI and cilostazol was administered., Results: Tissue adenosine triphosphate (ATP) levels were significantly higher and superoxide dismutase (SOD) levels significantly lower in the control group than in the sham group and normal weight cilostazol group (p=0.024 and p=0.003). Fibrinogen levels were 198 mg/dL in the sham group, 204 mg/dL in the control group, and 187 mg/dL in the normal-weight cilostazol group (p=0.046). Additionally, plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in the control group (p=0.047). The level of ATP was significantly lower in the normal-weight cilostazol group than in the obese group (104 vs 131.2 nmol/g protein, p=0.043). PAI-1 level was 2.4 ng/mL in the normal weight cilostazol group and 3.7 ng/mL in the obese cilostazol group (p=0.029). Normal-weight Wistar rats with cilostazol had significantly better histologic outcomes than the control group and obese Wistar rats (p=0.001 and p=0.001)., Conclusion: Cilostazol has a protective effect on myocardial cells in IRI models by decreasing inflammation. The protective role of cilostazol was reduced in obese Wistar rats compared with normal-weight Wistar rats., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Published
2023
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43. Assessment of Permanent First Molars in Children Aged 7 to 10 Years Old.

Author

Urvasizoglu G, Bas A, Sarac F, Celikel P, Sengul F, and Derelioglu S

Abstract

Background: Dental caries is a chronic, infectious and preventable disease that is very common around the world. It has been observed that dental caries affect not only the majority of adults but also 60% to 90% of children. Permanent first molars (PFM) are the most commonly decayed teeth observed in children. Aim: The aim of this study is to evaluate the decayed, missing filled teeth (DMFT) scores of PFMs in the early post-eruptive stage, within the scope of the United Nations Agenda for 2030 Sustainable Development Goals, thereby raising awareness for the prevention and treatment of permanent tooth decay. Methods: This descriptive cross-sectional epidemiological study was conducted in Erzurum between the years 2015−2016 by collecting data from children aged 7−10 years (17,208). In addition to the decayed, filled and missing data of the students’ 6-year-molars, their ages, genders, frequencies of both tooth brushing and dental office visits were evaluated. The relationship between the variables was analyzed with chi-square. Result: The present study analyzed the data of a total of 11,457 children, 5704 girls and 5753 boys with a mean age of 8.74 ± 1.18. There was a statistically significant difference between the PFMs 16, 26, 36 and 46 regarding the number of healthy, decayed, missing and restored teeth (p < 0.001). Conclusion: In this study, the prevalence of caries in the PFMs of children aged 7−10 years was 15.9% and the mean DMFT was 0.79 ± 1.39. This result showed that PFMs might develop carious lesions and even be lost within three years in the early post-eruptive stage.

Published
2022
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44. [Shedding of SARS-CoV-2 Virus in COVID-19 Patients and Neutralizing Antibody Level].

Author

Ayhancı T, Toptan H, Özer YE, Uzar S, Enül H, Adıay C, Sarac F, Dheir H, Köroğlu M, Hasöksüz M, and Altındiş M

Subjects
Antibodies, Neutralizing, Antibodies, Viral, COVID-19 Vaccines, Humans, Immunoglobulin G, RNA, Viral, SARS-CoV-2, COVID-19
Abstract

The coronavirus disease 2019 (COVID-19) turned into a pandemic shortly after emerging in December 2019, in the city of Wuhan, China. In this study, it was aimed to investigate the presence of severe acute respiratory system coronavirus-2 (SARS-CoV-2) RNA in various clinical samples and the scattering profile of the virus and the variation of anti-SARS-CoV-2 IgG and neutralizing antibody levels over time in infected patients during and after the period of COVID-19 disease. The study included COVID-19 patients from the community (CCP) (n= 47) (May-June 2020) and healthcare workers (HCWP) (n= 30) (November-December 2020). To investigate the presence of SARS-CoV-2 in clinical samples, oropharynx (OF), nasopharynx (NF), sputum, stool, blood and urine samples were taken from the CCP group on days 0, 3, 7, 14 and 28. For the detection of anti SARS-CoV-2 IgG and neutralizing antibodies serum samples were taken from the CCP group on days 0, 3, 7, 14, 28, 60, 90 and 120 and on days 14, 28, 60, 90, 120 and 150 from HCWP group. Virus RNA was detected by reverse transcription polymerase chain reaction (RT-PCR), anti SARS-CoV-2 IgG antibody levels by enzyme-linked immunosorbent assay (ELISA), neutralizing antibody levels (NAb) by cell culture neutralization and representative neutralization test (sVNT) methods. With the onset of the vaccination program in our country, 11 of the HCWP group patients had SARS-CoV-2 vaccine after the second month serum samples were taken, the remaining HCWP group patients did not get vaccinated during the study period. SARS-CoV-2 RNA was detected with the highest rates in NF (100%), stool (65.8%), sputum (45.7%), OF (41.3%), blood (5.3%), and urine (2.2%) samples, respectively. It was found that viral shedding continued for 14 days in respiratory tract samples and up to 60 days in stool samples, and no virus was detected in blood samples after the third day. It was observed that the viral load was highest at the time of diagnosis in both upper and lower respiratory tract samples, peaking on the seventh day in stool samples and following an irregular course throughout the disease. Anti-SARS-CoV-2 IgG antibody positivity was found in 41.4% of CCP group patients on the first day of diagnosis, and seroconversion was observed in all patients at the fourth month. During the study period, seropositivity was detected in only 82.1% of the patients in the HCWP group. It was observed that the IgG antibody levels peaked at the 7th day in the CCP group patients and at the third month in the HCWP group patients (S/Co: 9.6 and 2.8, respectively). Anti-SARS-CoV-2 IgG antibody levels detected in the CCP group were found to be significantly higher than the HCWP group (p<0.05). At the end of the first month, NAb was detected in all (100%) patients in the CCP group. It was found that NAb titers peaked (1/256) on the 28th day and showed a decreasing trend from the second month. NAb median titers were observed to peak earlier in the severe HCWP group (14 days in the severe group, 28 days in the mild group, p> 0.05). It was observed that 6 (26.1%) of HCWP group patients had low, 11 (47.8%) moderate, 6 (26.1%) high titers of representative NAb. The distribution of representative NAb levels by vaccine status was examined and no statistically significant difference was found (p= 0.400, p= 0.077 and p= 0.830, respectively). As a result; SARS-CoV-2 RNA was detected in many samples such as sputum, stool, blood and urine, and it was observed that viral shedding in stool samples could continue for months. Anti-SARS-CoV-2 IgG antibody positivity was observed in most of the patients in the fourth month, and it was found that the antibody titers decreased after the third month. It was determined that protective antibody levels continued in the fourth month. These findings are important in vaccination strategies and in the fight against the pandemic. However, considering the emergence of new mutant forms of the virus in today's conditions where the pandemic continues, more detailed and comprehensive studies are needed for viral shedding and antibody titer studies.

Published
2022
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45. Comparison and efficacy of two different sheep pox vaccines prepared from the Bakırköy strain against lumpy skin disease in cattle.

Author

Uzar S, Sarac F, Gulyaz V, Enul H, Yılmaz H, and Turan N

Abstract

Purpose: Lumpy skin disease (LSD) is a highly contagious and economically important viral infection of cattle, which leads to financial losses in the livestock industry of affected countries. Vaccination is the most effective control measure to prevent the disease. Heterologous sheep pox (SP) vaccine was used against LSD in Turkey. In this research, it was aimed to adapt SP Bakırköy vaccine strain attenuated in lamb kidney cells to Madin-Darby bovine kidney (MDBK) cells to provide better protection than commercial SP vaccine in cattle., Materials and Methods: To evaluate safety and efficacy of vaccines, while animals were immunized with 10 doses (10 4.75 50% tissue culture infectious dose [TCID 50 ]) and 5 doses of SP vaccine (10 4 TCID 50 ) produced in MDBK cells, others were immunized with commercial Penpox-M vaccine (10 3.9 TCID 50 ). Two cattle were kept as unvaccinated. At day 31 post-vaccination, all animals were challenged with the virulent LSD virus. Blood and swab samples were taken on certain days post-inoculation. Logarithmic differences challenge virus titers between vaccinated and unvaccinated animals were calculated., Results: The clinical sign was not observed in animals immunized with 10 doses of SP vaccine. The differences between the animals immunized with SP vaccine and control group was less than log 2.5 and the viremia occurred in immunized animals. The difference in titer was higher than log 2.5 in animals immunized with the Penpox-M, and viremia did not occur., Conclusion: SP vaccine strain propagated in MDBK cells and can be used for immunization to prevent LSD infections. However, SP vaccine strain propagated in MDBK showed poor protection as compared to Penpox-M., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Korean Vaccine Society.)

Published
2022
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46. Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection.

Author

Yilmaz IC, Ipekoglu EM, Bulbul A, Turay N, Yildirim M, Evcili I, Yilmaz NS, Guvencli N, Aydin Y, Gungor B, Saraydar B, Bartan AG, Ibibik B, Bildik T, Baydemir İ, Sanli HA, Kayaoglu B, Ceylan Y, Yildirim T, Abras I, Ayanoglu IC, Cam SB, Ciftci Dede E, Gizer M, Erganis O, Sarac F, Uzar S, Enul H, Adiay C, Aykut G, Polat H, Yildirim IS, Tekin S, Korukluoglu G, Zeytin HE, Korkusuz P, Gursel I, and Gursel M

Subjects
Animals, Antibodies, Neutralizing, Antibodies, Viral, COVID-19 Vaccines, HEK293 Cells, Humans, SARS-CoV-2, COVID-19, Vaccines, Virus-Like Particle
Abstract

Background: Vaccines that incorporate multiple SARS-CoV-2 antigens can further broaden the breadth of virus-specific cellular and humoral immunity. This study describes the development and immunogenicity of SARS-CoV-2 VLP vaccine that incorporates the four structural proteins of SARS-CoV-2., Methods: VLPs were generated in transiently transfected HEK293 cells, purified by multimodal chromatography, and characterized by tunable-resistive pulse sensing, AFM, SEM, and TEM. Immunoblotting studies verified the protein identities of VLPs. Cellular and humoral immune responses of immunized animals demonstrated the immune potency of the formulated VLP vaccine., Results: Transiently transfected HEK293 cells reproducibly generated vesicular VLPs that were similar in size to and expressing all four structural proteins of SARS-CoV-2. Alum adsorbed, K3-CpG ODN-adjuvanted VLPs elicited high titer anti-S, anti-RBD, anti-N IgG, triggered multifunctional Th1-biased T-cell responses, reduced virus load, and prevented lung pathology upon live virus challenge in vaccinated animals., Conclusion: These data suggest that VLPs expressing all four structural protein antigens of SARS-CoV-2 are immunogenic and can protect animals from developing COVID-19 infection following vaccination., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Published
2022
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48. Rat Model Investigation on the Role of Biomarkers in Hepatic Ischemia-Reperfusion Injury.

Author

Yildirim D, Sarac F, Degerli MS, Cakir M, Akturk OM, Özcevik H, Isik Saglam ZM, and Gecer MO

Abstract

Objectives: Liver function is affected by ischemiareperfusion. Ischemia-reperfusion injury to the liver often follows hepatobiliary surgery. Here, we investigated biomarkers of liver ischemia-reperfusion injury using an animal model., Materials and Methods: For this study, 24 male Sprague Dawley rats (146-188 g) were divided into 4 groups: group A was the control group, group B was the partial hepatic ischemia-reperfusion group, group C was the total hepatic ischemia-reperfusion group, and group D was the intermittent total hepatic ischemiareperfusion group. Laboratory liver function levels were measured before ischemia, after ischemia, and after reperfusion. We used liver and renal biopsies for histopathological examination at the end of the study., Results: After clamping and reperfusion, alanine aminotransferase and cystatin C levels in groups B, C, and D were significantly higher than levels in group A. In group B, after clamping, neutrophil gelatinaseassociated lipocalin levels were higher than in groups A and D, with significantly higher level than in group D after reperfusion. Neutrophil gelatinase-associated lipocalin levels decreased significantly in groups B, C, and D after reperfusion. There was significantly greater hepatic damage in groups B, C, and D compared with group A but no significant differences in renal injury scores among the groups. There was a significant positive correlation between hepatic damage and renal injury. With regard to histopathological examination versus laboratory results, a statistically significant positive correlation was shown between grade of hepatic damage and serum alanine aminotransferase and cystatin C levels. Similarly, there was a positive correlation between renal damage score and alanine aminotransferase level., Conclusions: In our animal model, alanine amino - transferase and cystatin C levels tended to increase with ischemia-reperfusion injury levels but neutrophil gelatinase-associated lipocalin decreased during reperfusion. In liver ischemia, we suggest that neutrophil gelatinase-associated lipocalin may be an important biomarker for distinguishing the reperfusion phase.

Published
2021
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49. The diagnostic role of testicular fatty acid-binding protein in testicular ischemia: A randomized controlled experimental study.

Author

Yeniocak S, Sarac F, Erbin A, Yazicioglu M, Olgac V, Koldas M, Uzun O, and Akkoc I

Subjects
Animals, Male, Rats, Fatty Acid-Binding Proteins, Ischemia diagnosis, Rats, Wistar, Spermatic Cord Torsion diagnosis, Testis
Abstract

Objective: To investigate the diagnostic value of testicular fatty acid-binding protein (T-FABP) in acute testicular ischemia and prolonged ischemia. METHODS: The study included a total of 28 prepubertal male Wistar-Hannover rats. The animals were randomly divided into 4 groups as torsion groups (group I; min 30; 7 rats, group II; min 120; 7 rats, group III; min 240; 7 rats) and control group (group IV; 7 rats). In each group, the left testis was separated from the gubernaculum by blunt dissection together with the tunica vaginalis and spermatic cord, and then exposed. In the control group, the blood samples and left testicular tissues were collected at min 240 after extraction. In torsion groups, the left testis was rotated together with its cord elements,720° in a clockwise direction for the induction of an extravaginal TT model. The blood samples were obtained at min 30, 120, and 240 in the torsion groups. Bilateral testicular tissues were collected via orchiectomy for histopathological examination in all groups. RESULTS: The mean plasma T-FABP level in group III (torsion, min 240) was significantly higher than those of other groups. The T-FABP level at min 240 had a sensitivity and specificity of 100% and 85%, respectively, at a cut-off value of 1.059. A significant difference was found between the torsion groups and the control group with regard to histopathological scores. CONCLUSIONS: The increased T-FABP levels in testicular ischemia seem to be correlated with testicular necrosis rather than acute ischemia.

Published
2021

50. Ischemia Modified Albumin and D-dimer in the Diagnosis of Testicular Torsion: An Experimental Model.

Author

Sarac F, Yeniocak S, Erbin A, Yucetas E, Altundal K, Ucpinar B, Saygili A, and Koldas M

Subjects
Animals, Biomarkers metabolism, Disease Models, Animal, Male, Rats, Rats, Wistar, Spermatic Cord Torsion metabolism, Early Diagnosis, Fibrin Fibrinogen Degradation Products metabolism, Serum Albumin, Human metabolism, Spermatic Cord pathology, Spermatic Cord Torsion diagnosis
Abstract

Purpose: We aimed to investigate the potential early diagnostic value of ischemia modified albumin (IMA) and D-dimer in testicular torsion., Material and Methods: A total of 42 prepubertal Wistar-Hannover rats (26-30 days old, weighing 75-125 grams) were used in the study. They were randomly divided into 2 groups as torsion (21 rats) and control (21 rats). Both torsion and control groups were subdivided into three subgroups as 30th, 120th and 240th minutes. Intraperitoneal injection of 70 mg/kg ketamine (Ketalar, Pfizer, Istanbul, Turkey) plus 10 mg/kg of xylazine (Rompun, Bayer, Istanbul, Turkey) were used for general anesthesia. In the control group, scrotal incision was made and the left testis gently extracted. Then, intracardiac blood and testicular tissue were obtained at 30th, 120th and 240th minutes. In torsion group, testicular ischemia was achieved by rotating left testis 720° clockwise and maintained by fixing the testis. Blood and testicular samples were obtained at 30th, 120th and 240th minutes. All animals were sacrificed after completion of the study., Results: There was a statistically significant difference between the IMA and D-dimer levels at 30th, 120th and 240th minutes of torsion group when compared with the control group (p = .001). When compared in terms of pathological changes at 30th, 120th and 240th minutes, significant difference was found for all 3 periods (p = 0.039, p = 0.014, p = 0.03, respectively). The D-dimer and IMA estimated torsion with reasonable accuracy [Area under the curve (AUC)= 0.771 (p = 0.003, 95% confidental interval: 0.620-0.922) and AUC = 0.706 (95% confidental interval: 0.549-0.863, p = 0.022), respectively., Conclusion: The elevated D-dimer and IMA serum levels observed in the experimental testicular torsion modelseem to have a potential role as a serum marker in the early diagnosis of testicular torsion.

Published
2019
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