Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Potential Application of Cephalosporins Carried in Organic or Inorganic Nanosystems against Gram-Negative Pathogens

Author(s): Brenda Maria Silva Bezerra, Sara Efigênia Dantas de Mendonça y Araujo, Analara Cordeiro de Macêdo, Kammila Martins Nicolau Costa, Mariana Rillo Sato and João Augusto Oshiro-Junior*

Volume 29, Issue 31, 2022

Published on: 23 May, 2022

Page: [5212 - 5229] Pages: 18

DOI: 10.2174/0929867329666220329201817

Price: $65

Abstract

Cephalosporins are β-lactam antibiotics, classified into five generations and extensively used in clinical practice against infections caused by Gram-negative pathogens, including Enterobacteriaceae and P. aeruginosa. Commercially, conventional pharmaceutical forms require high doses to ensure clinical efficacy. Additionally, β-lactam resistance mechanisms, such as the production of enzymes (called extended-spectrum β-lactamases) and the low plasma half-life of these antibiotics, have been challenging in clinical therapy based on the use of cephalosporins. In this context, its incorporation into nanoparticles, whether organic or inorganic, is an alternative to temporally and spatially control the drug release and improve its pharmacokinetic and pharmacodynamic limitations. Considering this, the present review unites the cephalosporins encapsulated into organic and inorganic nanoparticles against resistant and nonresistant enterobacteria. We divide cephalosporin generation into subtopics in which we discuss all molecules approved by regulatory agencies. In addition, changes in the side chains at positions R1 and R2 of the central structure of cephalosporins for all semisynthetic derivatives developed were discussed and presented, as the changes in these groups are related to modifications in pharmacological and pharmacokinetic properties, respectively. Ultimately, we exhibit the advances and differences in the release profile and in vitro activity of cephalosporins incorporated in different nanoparticles.

Keywords: Cephalosporins, nanoparticles, antimicrobial activity, infections, enterobacteriaceae, P. aeruginosa, organic or inorganic Nanosystems, gram-negative pathogens.

[1]
Han, Y.; Zhang, J.; Hu, C. A systematic toxicity evaluation of cephalosporins via transcriptomics in zebrafish and in silico ADMET studies. Food Chem. Toxicol., 2018, 116(Pt B), 264-271.
[http://dx.doi.org/10.1016/j.fct.2018.04.046] [PMID: 29689360]
[2]
Tauzin, M.; Ouldali, N.; Béchet, S.; Caeymaex, L.; Cohen, R. Pharmacokinetic and pharmacodynamic considerations of cephalosporin use in children. Expert Opin. Drug Metab. Toxicol., 2019, 15(11), 869-880.
[http://dx.doi.org/10.1080/17425255.2019.1678585] [PMID: 31597049]
[3]
Turner, J.V.; Maddalena, D.J.; Cutler, D.J.; Agatonovic-Kustrin, S. Multiple pharmacokinetic parameter prediction for a series of cephalosporins. J. Pharm. Sci., 2003, 92(3), 552-559.
[http://dx.doi.org/10.1002/jps.10314] [PMID: 12587116]
[4]
Bergan, T. Pharmacokinetic properties of the cephalosporins. Drugs, 1987, 34(Suppl. 2), 89-104.
[http://dx.doi.org/10.2165/00003495-198700342-00008] [PMID: 3319507]
[5]
Harrison, C.J.; Bratcher, D. Cephalosporins: A review. Pediatr. Rev., 2008, 29(8), 264-267.
[PMID: 18676578]
[6]
Iredell, J.; Brown, J.; Tagg, K. Antibiotic resistance in Enterobacteriaceae: Mechanisms and clinical implications. BMJ, 2016, 352, h6420.
[http://dx.doi.org/10.1136/bmj.h6420] [PMID: 26858245]
[7]
United Nations meeting on antimicrobial resistance. Bull. World Health Organ., 2016, 94(9), 638-639.
[http://dx.doi.org/10.2471/BLT.16.020916] [PMID: 27708467]
[8]
de Oliveira, M.S.; Oshiro-Junior, J.A.; Sato, M.R.; Conceição, M.M.; Medeiros, A.C.D. Polymeric nanoparticle associated with ceftriaxone and extract of Schinopsis brasiliensis engler against Multiresistant enterobacteria. Pharmaceutics, 2020, 12(8), 695.
[http://dx.doi.org/10.3390/pharmaceutics12080695] [PMID: 32718016]
[9]
de Oliveira, M.S.; Oshiro-Junior, J.A.; Dantas, M.M.; da Fonsêca, N.F.; Ramos, H.A.; da Silva, J.V.B.; de Medeiros, A.C.D. An overview of the antimicrobial activity of polymeric nanoparticles against enterobacteriaceae. Curr. Pharm. Des., 2021, 27(10), 1311-1322.
[http://dx.doi.org/10.2174/1381612826666201029095327] [PMID: 33121399]
[10]
Zhang, S.; Gao, H.; Bao, G. Physical principles of nanoparticle cellular endocytosis. ACS Nano, 2015, 9(9), 8655-8671.
[http://dx.doi.org/10.1021/acsnano.5b03184] [PMID: 26256227]
[11]
Barros, R.M.; de Oliveira, M.S.; Costa, K.M.N.; Sato, M.R.; Santos, K.L.M.; de L Damasceno, B.P.G.; Cuberes, T.; Oshiro-Junior, J.A. Physicochemical characterization of bioactive compounds in nanocarriers. Curr. Pharm. Des., 2020, 26(33), 4163-4173.
[http://dx.doi.org/10.2174/1381612826666200310144533] [PMID: 32156229]
[12]
Alves, L.P.; da Silva Oliveira, K.; da Paixão Santos, J.A.; da Silva Leite, J.M.; Rocha, B.P.; de Lucena Nogueira, P.; de Araújo Rêgo, R.I.; Oshiro-Junior, J.A.; Damasceno, B.P.G. Review on developments and prospects of anti-inflammatory in microemulsions. J. Drug Deliv. Sci. Technol., 2020, 60(102008), 102008.
[http://dx.doi.org/10.1016/j.jddst.2020.102008]
[13]
Boraschi, D.; Italiani, P.; Palomba, R.; Decuzzi, P.; Duschl, A.; Fadeel, B.; Moghimi, S.M. Nanoparticles and innate immunity: New perspectives on host defence. Semin. Immunol., 2017, 34, 33-51.
[http://dx.doi.org/10.1016/j.smim.2017.08.013] [PMID: 28869063]
[14]
Oshiro-Júnior, J. A.; Rodero, C.; Hanck-Silva, G.; Sato, M. R.; Alves, R. C.; Eloy, J. O.; Chorilli, M. Stimuli-responsive drug delivery nanocarriers in the treatment of breast cancer. Curr. Med. Chem., 2020, 27(15), 2494-2513.
[15]
Khameneh, B.; Diab, R.; Ghazvini, K.; Fazly Bazzaz, B.S.; Alves, R.C.; Eloy, J.O.; Chorilli, M. Breakthroughs in bacterial resistance mechanisms and the potential ways to combat them. Microb. Pathog., 2016, 95, 32-42.
[http://dx.doi.org/10.1016/j.micpath.2016.02.009] [PMID: 26911646]
[16]
de Assis, K.M.A.; de A Rêgo, R.I.; de Melo, D.F.; da Silva, L.M.; Oshiro-Júnior, J.A.; Formiga, F.R.; Pires, V.C.; de Lima, Á.A.N.; Converti, A.; de L Damasceno, B.P.G. Therapeutic potential of Melaleuca alternifolia essential oil in new drug delivery systems. Curr. Pharm. Des., 2020, 26(33), 4048-4055.
[http://dx.doi.org/10.2174/1381612826666200305124041] [PMID: 32133957]
[17]
Danhier, F.; Feron, O.; Préat, V. To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J. Control. Release, 2010, 148(2), 135-146.
[http://dx.doi.org/10.1016/j.jconrel.2010.08.027] [PMID: 20797419]
[18]
Radovic-Moreno, A.F.; Lu, T.K.; Puscasu, V.A.; Yoon, C.J.; Langer, R.; Farokhzad, O.C. Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted delivery of antibiotics. ACS Nano, 2012, 6(5), 4279-4287.
[http://dx.doi.org/10.1021/nn3008383] [PMID: 22471841]
[19]
Silvestre, A.L.P.; Oshiro-Júnior, J.A.; Garcia, C.; Turco, B.O.; da Silva Leite, J.M.; de Lima Damasceno, B.P.G.; Soares, J.C.M.; Chorilli, M. Monoclonal antibodies carried in drug delivery nanosystems as a strategy for cancer treatment. Curr. Med. Chem., 2021, 28(2), 401-418.
[http://dx.doi.org/10.2174/0929867327666200121121409] [PMID: 31965938]
[20]
Sato, M.R.; Oshiro-Junior, J.A.; Souza, P.C.; Campos, D.L.; Pereira-Da-Silva, M.A.; Pavan, F.R.; Da Silva, P.B.; Chorilli, M. Copper(II) complex-loaded castor oil-based nanostructured lipid carriers used against Mycobacterium tuberculosis: Development, characterisation, in vitro and in vivo biological assays. Pharmazie, 2019, 74(12), 715-720.
[http://dx.doi.org/10.1691/ph.2019.9110] [PMID: 31907109]
[21]
Yeh, Y-C.; Huang, T-H.; Yang, S-C.; Chen, C-C.; Fang, J-Y. Nano-based drug delivery or targeting to eradicate bacteria for infection mitigation: A review of recent advances. Front Chem., 2020, 8, 286.
[http://dx.doi.org/10.3389/fchem.2020.00286] [PMID: 32391321]
[22]
Dantas Lopes Dos Santos, D.; Besegato, J.F.; de Melo, P.B.G.; Oshiro, J.A., Jr.; Chorilli, M.; Deng, D.; Bagnato, V.S.; Rastelli, A.N. Curcumin-loaded pluronic® F-127 micelles as a drug delivery system for curcumin-mediated photodynamic therapy for oral application. Photochem. Photobiol., 2021, 97(5), 1072-1088.
[23]
Santos, K.L.M.; Barros, R.M.; da Silva Lima, D.P.; Nunes, A.M.A.; Sato, M.R.; Faccio, R.; de Lima Damasceno, B.P.G.; Oshiro-Junior, J.A. Prospective application of phthalocyanines in the photodynamic therapy against microorganisms and tumor cells: A mini-review. Photodiagn. Photodyn. Ther., 2020, 32(102032), 102032.
[http://dx.doi.org/10.1016/j.pdpdt.2020.102032] [PMID: 33017659]
[24]
Cephalosporins and Enterobacteriaceae. Available from: https://pubmed.ncbi.nlm.nih.gov/?term=cephalosporins+and+enterobacteriaceae&filter=simsearch3.fft&filter=datesearch.y_10 (Accessed on: Jan 27, 2021).
[25]
Cephalosporins and Enterobacteriaceae and Nanoparticles. Available from: https://pubmed.ncbi.nlm.nih.gov/?term=cephalosporins+and+enterobacteriaceae+and+nanoparticles&filter=simsearch3.fft&filter=datesearch.y_10 (Accessed on: Jan 27, 2021).
[26]
Lima, L.M.; Silva, B.N.M.D.; Barbosa, G.; Barreiro, E.J. β-lactam antibiotics: An overview from a medicinal chemistry perspective. Eur. J. Med. Chem., 2020, 208(112829), 112829.
[http://dx.doi.org/10.1016/j.ejmech.2020.112829] [PMID: 33002736]
[27]
Pedroso, T.M.; Salgado, H.R.N. Validation of Cefazolin Sodium by UV-Spectrophotometric Method. Phys. chem., 2013, 3(1), 11-20.
[http://dx.doi.org/10.5923/j.pc.20130301.03]
[28]
Mahdi, B.M. Role of antimicrobial agents in the management of perianal abscess. In: New Concepts in the Management of Septic Perianal Conditions; Elsevier, Amsterdam, 2018, pp. 71-77.
[http://dx.doi.org/10.1016/B978-0-12-816111-1.00007-0]
[29]
Gustaferro, C.A.; Steckelberg, J.M. Cephalosporin antimicrobial agents and related compounds. Mayo Clinic Proceedings, 2019, 66(10), 1064-1073.
[http://dx.doi.org/10.1016/S0025-6196(12)61731-5] [PMID: 1921490]
[30]
Dąbrowska, M.; Starek, M.; Komsta, Ł.; Szafrański, P.; Stasiewicz-Urban, A.; Opoka, W. Assessment of the chromatographic lipophilicity of eight cephalosporins on different stationary phases. Eur. J. Pharm. Sci., 2017, 101, 115-124.
[http://dx.doi.org/10.1016/j.ejps.2017.01.034] [PMID: 28137472]
[31]
Ribeiro, A.R.; Sures, B.; Schmidt, T.C. Cephalosporin antibiotics in the aquatic environment: A critical review of occurrence, fate, ecotoxicity and removal technologies. Environ. Pollut., 2018, 241, 1153-1166.
[http://dx.doi.org/10.1016/j.envpol.2018.06.040] [PMID: 30029325]
[32]
Jamil, B.; Habib, H.; Abbasi, S.; Nasir, H.; Rahman, A.; Rehman, A.; Bokhari, H.; Imran, M. Cefazolin loaded chitosan nanoparticles to cure multi drug resistant Gram-negative pathogens. Carbohydr. Polym., 2016, 136, 682-691.
[http://dx.doi.org/10.1016/j.carbpol.2015.09.078] [PMID: 26572401]
[33]
Munir, M.U.; Ihsan, A.; Javed, I.; Ansari, M.T.; Bajwa, S.Z.; Bukhari, S.N.A.; Ahmed, A.; Malik, M.Z.; Khan, W.S. Controllably biodegradable hydroxyapatite nanostructures for Cefazolin delivery against antibacterial resistance. ACS Omega, 2019, 4(4), 7524-7532.
[http://dx.doi.org/10.1021/acsomega.9b00541]
[34]
Jubeh, B.; Breijyeh, Z.; Karaman, R. Antibacterial prodrugs to overcome bacterial resistance. Molecules, 2020, 25(7), 1-16.
[http://dx.doi.org/10.3390/molecules25071543] [PMID: 32231026]
[35]
Doerr, B.I.; Glomot, R.; Kief, H.; Kramer, M.; Sakaguchi, T. Toxicology of cefotaxime in comparison to other cephalosporins. J. Antimicrob. Chemother., 1980, 6(Suppl. A), 79-82.
[http://dx.doi.org/10.1093/jac/6.suppl_A.79] [PMID: 6252183]
[36]
Hari, N.; Thomas, T.K.; Nair, A.J. Comparative study on the synergistic action of differentially synthesized silver nanoparticles with β-cephem antibiotics and chloramphenicol. J. Nanosci., 2014, 2014, 1-8.
[http://dx.doi.org/10.1155/2014/201482]
[37]
Castle, S.S. Cephalexin. In: xPharm: The Comprehensive Pharmacology Reference; Elsevier, Amsterdam, 2007, pp. 1-5.
[http://dx.doi.org/10.1016/B978-008055232-3.61417-5]
[38]
Rayegan, A.; Allafchian, A.; Abdolhosseini Sarsari, I.; Kameli, P. Synthesis and characterization of basil seed mucilage coated Fe3O4 magnetic nanoparticles as a drug carrier for the controlled delivery of cephalexin. Int. J. Biol. Macromol., 2018, 113, 317-328.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.02.134] [PMID: 29481957]
[39]
Vivekanandan, K.E.; Raj, K.G.; Kumaresana, S.; Pandib, M. Biosynthesis of silver nanoparticle activity against bacterial strain, cephalexin antibiotic synergistic activity. Int. J. Curr. Sci., 2012, 4, 1-7.
[40]
Singh, P.; Raja, R. B. Synergistic effect of silver nanoparticles with the cephalexin antibiotic against the test strains. Biores. Bull., 2012, 2(4), 171-179.
[41]
Öztürk, A.A.; Aygül, A. Design of cefaclor monohydrate containing nanoparticles with extended antibacterial effect by nano-spray dryer: A nanoenglobing study. J. Res. Pharm., 2020, 24(1), 1-12.
[42]
Belveyre, T.; Guerci, P.; Pape, E.; Thilly, N.; Hosseini, K.; Brunaud, L.; Gambier, N.; Meistelman, C.; Losser, M-R.; Birckener, J.; Scala-Bertola, J.; Novy, E. Observational, prospective single-center study of antibiotic prophylaxis with high-dose cefoxitin in bariatric surgery. Antimicrob. Agents Chemother., 2019, 63(12), e01613-19.
[http://dx.doi.org/10.1128/AAC.01613-19] [PMID: 31591127]
[43]
Cefoxitin. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/441199 (Accessed on: May 24, 2021)
[44]
Refat, M.S.; Sharshar, T.; Elsabawy, K.M.; El-Sayed, M.Y.; Adam, A.M.A. Synthesis of new drug model has an effective antimicrobial and antitumors by combination of cephalosporin antibiotic drug with silver(I) ion in nano scale range: chemical, physical and biological studies. J. Mol. Liq., 2017, 244, 169-181.
[http://dx.doi.org/10.1016/j.molliq.2017.09.005]
[45]
Jamil, B.; Habib, H.; Abbasi, S.A.; Ihsan, A.; Nasir, H.; Imran, M. Development of cefotaxime impregnated chitosan as nano-antibiotics: De novo strategy to combat biofilm forming multi-drug resistant pathogens. Front. Microbiol., 2016, 7, 1-11.
[http://dx.doi.org/10.3389/fmicb.2016.00330] [PMID: 27047457]
[46]
Halawani, E.M.; Hassan, A.M.; Gad El-Rab, S.M.F. Nanoformulation of biogenic cefotaxime-conjugated-silver nanoparticles for enhanced antibacterial efficacy against multidrug-resistant bacteria and anticancer studies. Int. J. Nanomedicine, 2020, 15, 1889-1901.
[http://dx.doi.org/10.2147/IJN.S236182] [PMID: 32256066]
[47]
Arora, B.; Murar, M.; Dhumale, V. Antimicrobial potential of tio2nanoparticles against MDR Pseudomonas aeruginosa. J. Exp. Nanosci., 2015, 10(11), 819-827.
[http://dx.doi.org/10.1080/17458080.2014.902544]
[48]
Hasanova, U.A.; Ramazanov, M.A.; Maharramov, A.M.; Eyvazova, Q.M.; Agamaliyev, Z.A.; Parfyonova, Y.V.; Hajiyeva, S.F.; Hajiyeva, F.V.; Veliyeva, S.B. Nano-coupling of cephalosporin antibiotics with Fe3o4 nanoparticles: Trojan horse approach in antimicrobial chemotherapy of infections caused by Klebsiella spp. J. Biomater. Nanobiotechnol., 2015, 06(03), 225-235.
[http://dx.doi.org/10.4236/jbnb.2015.63021]
[49]
Panáček, A.; Smékalová, M.; Večeřová, R.; Bogdanová, K.; Röderová, M.; Kolář, M.; Kilianová, M.; Hradilová, Š.; Froning, J.P.; Havrdová, M.; Prucek, R.; Zbořil, R.; Kvítek, L. Silver nanoparticles strongly enhance and restore bactericidal activity of inactive antibiotics against multiresistant Enterobacteriaceae. Colloids Surf. B Biointerfaces, 2016, 142, 392-399.
[http://dx.doi.org/10.1016/j.colsurfb.2016.03.007] [PMID: 26970828]
[50]
Shaikh, S.; Rizvi, S.M.D.; Shakil, S.; Hussain, T.; Alshammari, T.M.; Ahmad, W.; Tabrez, S.; Al-Qahtani, M.H.; Abuzenadah, A.M. Synthesis and characterization of cefotaxime conjugated gold nanoparticles and their use to target drug-resistant CTX-M-producing bacterial pathogens. J. Cell. Biochem., 2017, 118(9), 2802-2808.
[http://dx.doi.org/10.1002/jcb.25929] [PMID: 28181300]
[51]
Freitas, R. M. Mechanism of action, pharmacological effects and adverse reactions of ceftriaxone: A literature review. Rev. eletrônica Farm, 2014, 11(3), 48-57.
[52]
Kumar, S.; Bhanjana, G.; Kumar, A.; Taneja, K.; Dilbaghi, N.; Kim, K-H. Synthesis and optimization of ceftriaxone-loaded solid lipid nanocarriers. Chem. Phys. Lipids, 2016, 200, 126-132.
[http://dx.doi.org/10.1016/j.chemphyslip.2016.09.002] [PMID: 27697513]
[53]
Ebrahimi, S.; Farhadian, N.; Karimi, M.; Ebrahimi, M. Enhanced bactericidal effect of ceftriaxone drug encapsulated in nanostructured lipid carrier against gram-negative Escherichia coli bacteria: Drug formulation, optimization, and cell culture study. Antimicrob. Resist. Infect. Control, 2020, 9(28), 1-12.
[http://dx.doi.org/10.1186/s13756-020-0690-4] [PMID: 32041660]
[54]
Mushtaq, S.; Khan, J.A.; Rabbani, F.; Latif, U.; Arfan, M.; Yameen, M.A. Biocompatible biodegradable polymeric antibacterial nanoparticles for enhancing the effects of a third-generation cephalosporin against resistant bacteria. J. Med. Microbiol., 2017, 66(3), 318-327.
[http://dx.doi.org/10.1099/jmm.0.000445] [PMID: 28150580]
[55]
Shanmuganathan, R.; MubarakAli, D.; Prabakar, D.; Muthukumar, H.; Thajuddin, N.; Kumar, S.S.; Pugazhendhi, A. An enhancement of antimicrobial efficacy of biogenic and ceftriaxone-conjugated silver nanoparticles: Green approach. Environ. Sci. Pollut. Res. Int., 2018, 25(11), 10362-10370.
[http://dx.doi.org/10.1007/s11356-017-9367-9] [PMID: 28600792]
[56]
Carmen Chifiriuc, M.; Mihaiescu, D.; Ilinca, E.; Marutescu, L.; Mihaescu, G.; Mihai Grumezescu, A. Influence of hybrid inorganic/organic mesoporous and nanostructured materials on the cephalosporins’ efficacy on different bacterial strains. IET Nanobiotechnol., 2012, 6(4), 156-161.
[http://dx.doi.org/10.1049/iet-nbt.2011.0066] [PMID: 23101869]
[57]
Heesterbeek, D.A.C.; Martin, N.I.; Velthuizen, A.; Duijst, M.; Ruyken, M.; Wubbolts, R.; Rooijakkers, S.H.M.; Bardoel, B.W. Complement-dependent outer membrane perturbation sensitizes Gram-negative bacteria to Gram-positive specifc antibiotics. Sci. Reports., 2019, 9, 1-10.
[http://dx.doi.org/10.1038/s41598-019-38577-9] [PMID: 30816122]
[58]
Ceftazidime. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/5481173 (Accessed on: May 24, 2021).
[59]
Al-Amiery, A.A.; Al-Bayati, R.I.H.; Saour, K.Y.; Radi, M.F. Cytotoxicity, antioxidant, and antimicrobial activities of novel 2-quinolone derivatives derived from coumarin. Res. Chem. Intermed., 2012, 38(2), 559-569.
[http://dx.doi.org/10.1007/s11164-011-0371-2]
[60]
Singh, A.K.; Shukla, S.K.; Quraishi, M.A. Corrosion behaviour of mild steel in sulphuric acid solution in presence of ceftazidime. Int. J. Electrochem. Sci., 2011, 6, 5802-5814.
[61]
Isaei, E.; Mansouri, S.; Mohammadi, F.; Taheritarigh, S.; Mohammadi, Z. Novel combinations of synthesized ZnO NPs and ceftazidime: Evaluation of their activity against standards and new clinically isolated Pseudomonas aeruginosa. Avicenna J. Med. Biotechnol., 2016, 8(4), 169-174.
[PMID: 27920884]
[62]
Philpott, C.D.; Droege, C.A.; Droege, M.E.; Healy, D.P.; Courter, J.D.; Ernst, N.E.; Harger, N.J.; Foertsch, M.J.; Winter, J.B.; Carter, K.E.; Van Fleet, S.L.; Athota, K.; Mueller, E.W. Pharmacokinetics and pharmacodynamics of extended-infusion cefepime in critically ill patients receiving continuous renal replacement therapy: A prospective, open-label study. Pharmacotherapy, 2019, 39(11), 1066-1076.
[http://dx.doi.org/10.1002/phar.2332] [PMID: 31549737]
[63]
Cefepime. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/5479537 (Accessed on: May 24, 2021).
[64]
Ahmed, F.Y.; Farghaly Aly, U.; Abd El-Baky, R.M.; Waly, N.G.F.M. Comparative study of antibacterial effects of titanium dioxide nanoparticles alone and in combination with antibiotics on MDR Pseudomonas aeruginosa strains. Int. J. Nanomedicine, 2020, 15, 3393-3404.
[http://dx.doi.org/10.2147/IJN.S246310] [PMID: 32523339]
[65]
Ficai, D.; Grumezescu, V.; Fufă, O.M.; Popescu, R.C.; Holban, A.M.; Ficai, A.; Grumezescu, A.M.; Mogoanta, L.; Mogosanu, G.D.; Andronescu, E. Antibiofilm coatings based on PLGA and nanostructured cefepime-functionalized magnetite. Nanomaterials, 2018, 8(9), 1-21.
[http://dx.doi.org/10.3390/nano8090633] [PMID: 30134515]
[66]
Medeiros, T.S.; Moreira, L.M.C.C.; Oliveira, T.M.T.; Melo, D.F.; Azevedo, E.P.; Gadelha, A.E.G.; Fook, M.V.L.; Oshiro-Júnior, J.A.; Damasceno, B.P.G.L. Bemotrizinol-loaded carnauba wax-based nanostructured lipid carriers for sunscreen: Optimization, characterization, and in vitro evaluation. AAPS PharmSciTech, 2020, 21(8), 1-13.
[http://dx.doi.org/10.1208/s12249-020-01821-x] [PMID: 33073311]
[67]
Ghafelehbashi, R.; Akbarzadeh, I.; Tavakkoli Yaraki, M.; Lajevardi, A.; Fatemizadeh, M.; Heidarpoor Saremi, L. Preparation, physicochemical properties, in vitro evaluation and release behavior of cephalexin-loaded niosomes. Int. J. Pharm., 2019, 569(118580), 1-8.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118580] [PMID: 31374239]
[68]
Asfour, H.Z. Cefotaxime combined ellagic acid in a liposomal form for more stable and antimicrobial effective formula. Am. J. Microbiol. Res., 2017, 5(5), 113-117.
[http://dx.doi.org/10.12691/ajmr-5-5-4]
[69]
Torres, I.M.S.; Bento, E.B.; Almeida, L. da C.; de Sá, L.Z.C.M.; Lima, E.M. Preparation, characterization and in vitro antimicrobial activity of liposomal ceftazidime and cefepime against Pseudomonas aeruginosa strains. Braz. J. Microbiol., 2012, 43(3), 984-992.
[http://dx.doi.org/10.1590/S1517-83822012000300020] [PMID: 24031917]
[70]
Selvadoss, P.P.; Nellore, J.; Ravindrran, M.B.; Sekar, U. Novel pyochelin-based PEGylated liposomes for enhanced delivery of antibiotics against resistant clinical isolates of Pseudomonas aeruginosa. Artif. Cells Nanomed. Biotechnol., 2018, 46(8), 2043-2053.
[http://dx.doi.org/10.1080/21691401.2017.1408119] [PMID: 29179607]
[71]
Selvadoss, P.P.; Nellore, J.; Ravindrran, M.B.; Sekar, U.; Tippabathani, J. Enhancement of antimicrobial activity by liposomal oleic acid-loaded antibiotics for the treatment of multidrug-resistant Pseudomonas aeruginosa. Artif. Cells Nanomed. Biotechnol., 2018, 46(2), 268-273.
[http://dx.doi.org/10.1080/21691401.2017.1307209] [PMID: 28362119]
[72]
Moyá, M.L.; López-López, M.; Lebrón, J.A.; Ostos, F.J.; Pérez, D.; Camacho, V.; Beck, I.; Merino-Bohórquez, V.; Camean, M.; Madinabeitia, N.; López-Cornejo, P. Preparation and characterization of new liposomes. Bactericidal activity of Cefepime encapsulated into cationic liposomes. Pharmaceutics, 2019, 11(2), 1-12.
[http://dx.doi.org/10.3390/pharmaceutics11020069] [PMID: 30736367]
[73]
Chiari-Andréo, B.G.; Abuçafy, M.P.; Manaia, E.B.; da Silva, B.L.; Rissi, N.C.; Oshiro-Júnior, J.A.; Chiavacci, L.A. Drug delivery using theranostics: An overview of its use, advantages and safety assessment. Curr. Nanosci., 2020, 16(1), 3-14.
[http://dx.doi.org/10.2174/1573413715666190618162321]
[74]
Gatadi, S.; Madhavi, Y.V.; Nanduri, S. Nanoparticle drug conjugates treating microbial and viral infections: A review. J. Mol. Struct., 2021, 1228(129750), 129750.
[http://dx.doi.org/10.1016/j.molstruc.2020.129750]
[75]
Amini, S.M. Preparation of antimicrobial metallic nanoparticles with bioactive compounds. Mater. Sci. Eng. C, 2019, 103(109809), 109809.
[http://dx.doi.org/10.1016/j.msec.2019.109809] [PMID: 31349497]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version350msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[20:18:34] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[20:18:34] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[20:18:34] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[20:18:34] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[20:18:34] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (109ms)time
  • Application (241ms)time
  • 1 x Application (68.91%)
    241ms
    1 x Booting (31.09%)
    109ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated164ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('314556225','',1,1740514714,1740514714) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740514714
      900μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('314556225','/article/122013',1,1740514714,1740514714)
      130μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 314556225 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314556225) limit 1
      10.79msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 314556225
      • 1: 314556225
      • 2: 314556225
      • 3: 314556225
      • 4: 314556225
      • 5: 314556225
      • 6: 314556225
      • 7: 314556225
      • 8: 314556225
      • 9: 314556225
      • 10: 314556225
      • 11: 314556225
      • 12: 314556225
      • 13: 314556225
      • 14: 314556225
      • 15: 314556225
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=122013
      620μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 25 limit 1
      700μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 25
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and sj.journal_id!=25 group by `j`.`nid`) as `aggregate_table`
      1.28msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and sj.journal_id!=25 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.05msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      3.34msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.75msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '122013'
      790μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 122013
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '122013'
      1msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 122013
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '122013' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      3.12msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 122013
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      230μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      420μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 25 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      30.99msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      45.04msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      38.26msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 122013 limit 1
      290μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 122013
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 122013 and content_type = 'article' order by status desc limit 1
      300μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 202793 limit 1
      850μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 202793
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      230μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      340μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CMC
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '122013' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      360μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '11698' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      260μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3240' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      270μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314556225 and j.to_ip >=314556225 )) and ((j.from_date <= 1740514714 and j.to_date >= 1740514714 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3240) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314556225 and j.to_ip >=314556225 )) and ((j.from_date <= 1740514714 and j.to_date >= 1740514714 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3240) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314556225 and j.to_ip >=314556225 )) and ((j.from_date <= 1740514714 and j.to_date >= 1740514714 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3240)
      12.41msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314556225 and j.to_ip >=314556225 )) and ((j.from_date <= 1740514714 and j.to_date >= 1740514714 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11698) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314556225 and j.to_ip >=314556225 )) and ((j.from_date <= 1740514714 and j.to_date >= 1740514714 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11698) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314556225 and j.to_ip >=314556225 )) and ((j.from_date <= 1740514714 and j.to_date >= 1740514714 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11698)
      650μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314556225 and j.to_ip >=314556225 )) and ((j.from_date <= 1740514714 and j.to_date >= 1740514714 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 122013) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314556225 and j.to_ip >=314556225 )) and ((j.from_date <= 1740514714 and j.to_date >= 1740514714 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 122013) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314556225 and j.to_ip >=314556225 )) and ((j.from_date <= 1740514714 and j.to_date >= 1740514714 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 122013)
      580μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '5212' and is_uploaded = 1 and issue_id = 11698 order by cast(first_page as SIGNED) desc limit 1
      460μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 5212
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '5229' and is_uploaded = 1 and issue_id = 11698 order by cast(first_page as SIGNED) asc limit 1
      400μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 5229
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      170μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      200μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 122013 limit 1
      2.33msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 122013
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 25 and `b`.`banner_from_date` <= 1740514714 and `b`.`banner_to_date` >= 1740514714 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.16msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740514714
      • 4: 1740514714
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 25 and `b`.`banner_from_date` <= 1740514714 and `b`.`banner_to_date` >= 1740514714 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.13msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1740514714
      • 4: 1740514714
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='965eb27604ca941a6021beadd0cd3c4c'
      240μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
    App\Models\MultiLangArticle
    1MultiLangArticle.php#?
        _token
        cqBmWWdsN38c5sUPjyFWctUBEN4OtcCFKTfWmwUn
        uc_cart_id
        965eb27604ca941a6021beadd0cd3c4c
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/122013" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/122013
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6Ikp2d0kvbERHRUdsVGxhRktnWDJuQ1E9PSIsInZhbHVlIjoiVytUK2h6THkxdGhmVkJhZk52ZlRPay9MTEFaKy9SQzhqMXRKTFl0L2g2ND0iLCJtYWMiOiJjNGFkNzJmNGMxMGNiM2MwYTMwZTJlNWEyMzhiMzg3ZTgzZDQyM2E3NmEzZGQzNmI0N2UwMDlhOWMwZjc2ZTFiIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Ikp2d0kvbERHRUdsVGxhRktnWDJuQ1E9PSIsInZhbHVlIjoiVytUK2h6THkxdGhmVkJhZk52ZlRPay9MTEFaKy9SQzhqMXRKTFl0L2g2ND0iLCJtYWMiOiJjNGFkNzJmNGMxMGNi" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 20:18:34 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IldYd2lEOTVHS0ZCblpnb0hmbWorN1E9PSIsInZhbHVlIjoic2gxR3RxOGtDSGd0TmEydU9md1NFdEI4SG1jWnlIN0xGbk5MMTVmZG9FVXZTTHBHOHpRTzgzWksxclhuVndlUDR5SHl4YWVKemRNNUpQYmxkSHNIVldmN0VUbDF5RjQ5Tmx5Z1NKM0JtQlg1UVRDQzZ0TWJ6d1RaUTRTcGsrR3QiLCJtYWMiOiJmZTUzY2ExNGEzMTQ4ZDhjOWEwYjllNmQxOGUxNDFiMDc2OTU1OWE1YzY3MGFhOTNjOWM2NTIyYmY5NjRjN2Q0IiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 08:18:34 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IldYd2lEOTVHS0ZCblpnb0hmbWorN1E9PSIsInZhbHVlIjoic2gxR3RxOGtDSGd0TmEydU9md1NFdEI4SG1jWnlIN0xGbk5MMTVmZG9FVXZTTHBHOHpRTzgzWksxclhuVndlUDR5SHl4Y" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkFxYllEdENyU3hML2xjZkJkUnRGeEE9PSIsInZhbHVlIjoiWFhmSEQ3d2tNaytPYnYvZHR6c2hKWFlueGdMenMvMi9SZ1hzOEFWRGk4THhlYW9kT2I1cFozSGFTd3lIaEFuRkxEeVkzVzViUTVwaGpZTG1ib09EVXd2aXhwRW93eEhUdERJOGVCQWF4R3I1VlRYSEIwVWRYOHlIOTVIbXdxOEgiLCJtYWMiOiIzNmI2YThiZDY4MjIwNGRjN2U3ZWZhNjlmNDNjZjJlOTlhNmE5OWZiNmZkMzdkYzc0NGQzMzMyNTAxY2ViOGIxIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IkFxYllEdENyU3hML2xjZkJkUnRGeEE9PSIsInZhbHVlIjoiWFhmSEQ3d2tNaytPYnYvZHR6c2hKWFlueGdMenMvMi9SZ1hzOEFWRGk4THhlYW9kT2I1cFozSGF" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IldYd2lEOTVHS0ZCblpnb0hmbWorN1E9PSIsInZhbHVlIjoic2gxR3RxOGtDSGd0TmEydU9md1NFdEI4SG1jWnlIN0xGbk5MMTVmZG9FVXZTTHBHOHpRTzgzWksxclhuVndlUDR5SHl4YWVKemRNNUpQYmxkSHNIVldmN0VUbDF5RjQ5Tmx5Z1NKM0JtQlg1UVRDQzZ0TWJ6d1RaUTRTcGsrR3QiLCJtYWMiOiJmZTUzY2ExNGEzMTQ4ZDhjOWEwYjllNmQxOGUxNDFiMDc2OTU1OWE1YzY3MGFhOTNjOWM2NTIyYmY5NjRjN2Q0IiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 08:18:34 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IldYd2lEOTVHS0ZCblpnb0hmbWorN1E9PSIsInZhbHVlIjoic2gxR3RxOGtDSGd0TmEydU9md1NFdEI4SG1jWnlIN0xGbk5MMTVmZG9FVXZTTHBHOHpRTzgzWksxclhuVndlUDR5SHl4Y" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkFxYllEdENyU3hML2xjZkJkUnRGeEE9PSIsInZhbHVlIjoiWFhmSEQ3d2tNaytPYnYvZHR6c2hKWFlueGdMenMvMi9SZ1hzOEFWRGk4THhlYW9kT2I1cFozSGFTd3lIaEFuRkxEeVkzVzViUTVwaGpZTG1ib09EVXd2aXhwRW93eEhUdERJOGVCQWF4R3I1VlRYSEIwVWRYOHlIOTVIbXdxOEgiLCJtYWMiOiIzNmI2YThiZDY4MjIwNGRjN2U3ZWZhNjlmNDNjZjJlOTlhNmE5OWZiNmZkMzdkYzc0NGQzMzMyNTAxY2ViOGIxIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IkFxYllEdENyU3hML2xjZkJkUnRGeEE9PSIsInZhbHVlIjoiWFhmSEQ3d2tNaytPYnYvZHR6c2hKWFlueGdMenMvMi9SZ1hzOEFWRGk4THhlYW9kT2I1cFozSGF" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "cqBmWWdsN38c5sUPjyFWctUBEN4OtcCFKTfWmwUn" "uc_cart_id" => "965eb27604ca941a6021beadd0cd3c4c" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/122013" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 20:18:34GET/article/122013514362