Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Antimicrobial Agents and Chemotherapy
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Susceptibility

Antifungal Susceptibility Profile of Human-Pathogenic Species of Lichtheimia

Ana Alastruey-Izquierdo, Isabel Cuesta, Grit Walther, Manuel Cuenca-Estrella, Juan Luis Rodriguez-Tudela
Ana Alastruey-Izquierdo
1Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Isabel Cuesta
1Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Grit Walther
2CBS-KNAW Fungal Biodiversity Centre, Utrecht, Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manuel Cuenca-Estrella
1Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juan Luis Rodriguez-Tudela
1Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jlrtudela@isciii.es
DOI: 10.1128/AAC.01270-09
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

Forty-four isolates belonging to human pathogenic species of Lichtheimia were tested against nine antifungal agents by using the EUCAST methodology. No remarkable differences were found between the clinical species, although L. ramosa showed slightly higher MICs for all drugs. Amphotericin B was the most active drug. Among azole drugs, posaconazole had the best activity in vitro and voriconazole was inactive. Echinocandins showed activity for some isolates, suggesting a potential role in combination therapy.

In recent years, the number of zygomycosis cases (mucormycosis) has grown, probably due to the increasing population at risk (14). The course of zygomycosis infection progresses rapidly and is potentially fatal, with mortality and morbidity rates remaining high. A gold-standard therapy has not yet been found, and amphotericin B remains the agent of choice (6). Treatment usually requires a combination of measures, including antifungal treatment, surgical intervention, and control of the underlying risk factors (13). Patient outcome has improved using posaconazole as salvage therapy (7, 18). Echinocandins have been used in combination therapies, highlighting the potential utility of other antifungals.

Lichtheimia is the third-most-frequent genus isolated in these infections and is responsible for approximately 5% of cases (4, 14). This genus has undergone several taxonomical changes in recent years. Thus, Lichtheimia species were originally classified in the genus Absidia. However, molecular phylogenetic analyses revealed that they belonged to a separate genus, named Mycocladus (8), that had to be renamed as Lichtheimia (9). Based on morphological, physiological, and molecular data, five species were proposed in this genus (3), L. corymbifera, L. ornata, L. ramosa, L. hyalospora, and L. sphaerocystis, of which only the first three are clinically relevant. In the last decades, L. corymbifera and L. ramosa have been treated as synonymous, and subsequently, previous publications on the in vitro susceptibility profile of “Absidia corymbifera” may refer either to L. corymbifera or to L. ramosa. In our setting, L. ramosa is more common than L. corymbifera. The aim of this study was to ascertain the antifungal susceptibility profile of clinical Lichtheimia species.

Strains.

Forty-three clinical isolates and one environmental isolate of Lichtheimia species were obtained between 1999 and 2009 in the Mycology Laboratory of the Spanish National Centre for Microbiology. Twenty-four strains were identified as L. ramosa, 19 strains as L. corymbifera, and one isolate as L. ornata by internal transcribed spacer (ITS) sequence comparison by Alastruey-Izquierdo et al. (3). Sixteen strains were isolated from respiratory sites, 15 from superficial sites, one from gastric juice, one from peritoneal drainage, and one from hospital air. The origin of 10 strains was unknown.

Antifungal susceptibility testing.

Microdilution testing was performed following the EUCAST standard methodology (16). Inoculum preparations were performed by means of counting spores in a hematocytometer (1, 12, 15). Aspergillus fumigatus ATCC 2004305 and A. flavus ATCC 2004304 were used as quality control strains (11).

The antifungal agents used in the study were amphotericin B (Sigma-Aldrich Quimica, Madrid, Spain), itraconazole (Janssen Pharmaceutica, Madrid), voriconazole (Pfizer S.A., Madrid), ravuconazole (Bristol-Myers Squibb, Princeton, NJ), posaconazole (Merck & Co., Inc., Rahway, NJ), terbinafine (Novartis, Basel, Switzerland), caspofungin (Merck & Co., Inc.), micafungin (Astellas Pharma, Inc., Tokyo, Japan), and anidulafungin (Pfizer S.A.). The final concentrations tested ranged from 16 to 0.03 mg/liter for amphotericin B, terbinafine, caspofungin, micafungin, and anidulafungin and from 8 to 0.015 mg/liter for itraconazole, voriconazole, ravuconazole, and posaconazole. The plates were incubated at 35°C for 48 h in a humid atmosphere. Visual readings were performed at 24 and 48 h with the help of a mirror. The endpoint for amphotericin B, itraconazole, voriconazole, ravuconazole, posaconazole, and terbinafine was the antifungal concentration that produced complete inhibition of visual growth at 24 and 48 h. For the echinocandins, the endpoint was the antifungal concentration that produced a visible change in the morphology of the hyphae compared with the morphology of the hyphae in the growth control well (minimum effective concentration [MEC]) (5, 10).

Table 1 shows the geometric mean (GM) and range of the MICs for the three Lichtheimia species. Since time plays a critical role in the management of these infections and most members of the Mucorales are fast-growing fungi, it has been recommended that MIC results be given for this fungal group at 24 h (2). However, we provide results at both 24 and 48 h because it is not yet clear whether all resistant strains can be detected after 24 h. Although no remarkable differences were found between L. corymbifera and L. ramosa, the latter species showed slightly higher MICs to most drugs. The greatest differences were found for itraconazole (the GM of the MIC of L. ramosa was 2.38 mg/liter and of L. corymbifera was 1.035 mg/liter at 48 h). The MICs of L. ornata were based on one isolate, and therefore, no conclusions could be obtained and more isolates are needed to evaluate the action of antifungals against this species. Amphotericin B was the most active drug, showing a GM of 0.07 mg/liter at 24 h. Among the azoles, voriconazole was inactive, whereas posaconazole had the highest activity (GM of MICs of 0.34 mg/liter at 24 h). Although itraconazole has shown poor activity against most zygomycetes (2), several isolates of Lichtheimia showed low MICs to this drug. These results concur with previous reports where L. corymbifera showed the lowest MICs to itraconazole among zygomycetes species (2, 6, 17). Terbinafine showed low MICs for most of the strains, although some isolates had MICs of >2 mg/liter. Regarding echinocandins, three out of 19 strains of L. corymbifera and three out of 24 of L. ramosa showed low MICs at 24 h. Anidulafungin was the echinocandin showing the best activity, especially against L. ramosa, where 10 out of 24 strains showed MICs of ≤2 mg/liter, pointing out the potential utility of this drug in combination therapies.

View this table:
  • View inline
  • View popup
TABLE 1.

Antifungal susceptibility results for clinical isolates of Lichtheimia spp.

More data are needed in order to obtain a clear picture of the susceptibility profile and clinical importance of these species. Little is known about their prevalence, and there are no studies regarding epidemiology, pattern of disease, risk factors, etc. The treatment of systemic fungal infections has undergone changes in the last years, as several new antifungal agents are available. Because of the existence of these therapy alternatives, it is clear that not all fungal infections should be treated in the same manner. Consequently, the correct identification and susceptibility testing of fungal species are increasingly important. We strongly recommend sending all strains of Lichtheimia species involved in human infections to reference laboratories where those isolates can be properly identified to species level and where antifungal susceptibility testing can be performed. The importance of these species could thus be ascertained.

Nucleotide sequence accession numbers.

The GenBank nucleotide sequence accession numbers for ITS sequences from all the strains used in this work are as follows: CNM-CM4337:GQ342852, CNM-CM4427:GQ342853, CNM-CM4261:GQ342854, CNM-CM4849:GQ342855, CNM-CM4253:GQ342860, CNM-CM4228:GQ342861, CNM-CM4119:GQ342862, CNM-CM2166:GQ342863, CNM-CM5171:GQ342864, CNM-CM1638:GQ342866, CNM-CM4849:GQ342868, CNM-CM3590:GQ342869, CNM-CM5111:GQ342871, CNM-CM3148:GQ342872, CNM-CM4537:GQ342873, CNM-CM4978:GQ342892CNM-CM1503:HM104192, CNM-CM2071:HM104193, CNM-CM3013:HM104194, CNM-CM3346:HM104195, CNM-CM3415:HM104196, CNM-CM4374:HM104197, CNM-CM4671:HM104198, CNM-CM4738:HM104199, CNM-CM5039:HM104200, CNM-CM5166:HM104201, CNM-CM5175:HM104202, CNM-CM5222:HM104203, CNM-CM5223:HM104204, CNM-CM5224:HM104205, CNM-CM5256:HM104206, CNM-CM5358:HM104207, CNM-CM5396:HM104208, CNM-CM5397:HM104209, CNM-CM5398:HM104210, CNM-CM5399:HM104211, CNM-CM5400:HM104212, CNM-CM5538:HM104213, CNM-CM5565:HM104214, CNM-CM5581:HM104215, CNM-CM5637:HM104216, CNM-CM5677:HM104217, CNM-CM5738:HM104218, CNM-CM5848:HM104219, CNM-CM5861:HM104220, CNM-CM5984:HM104221.

ACKNOWLEDGMENTS

Ana Alastruey has a predoctoral fellowship from Fondo de Investigaciones Sanitarias (grant FI05/00856). Isabel Cuesta has a contract from the Spanish Network for Research into Infectious Diseases (REIPI RD06/0008). This work was supported in part by research projects PI05/32 from the Instituto de Salud Carlos III and by the Spanish Network for Research in Infectious Diseases (REIPI RD06/0008).

Over the past 5 years, M.C.-E. has received grant support from Astellas Pharma, bioMérieux, Gilead Sciences, Merck Sharp and Dohme, Pfizer, Schering Plough, Soria Melguizo S.A., the European Union, the ALBAN program, the Spanish Agency for International Cooperation, the Spanish Ministry of Culture and Education, the Spanish Health Research Fund, the Instituto de Salud Carlos III, the Ramon Areces Foundation, and the Mutua Madrileña Foundation. He has been an advisor/consultant to the Pan American Health Organization, Gilead Sciences, Merck Sharp and Dohme, Pfizer, and Schering Plough. He has been remunerated for talks on behalf of Gilead Sciences, Merck Sharp and Dohme, Pfizer, and Schering Plough.

Over the past 5 years, J.L.R.-T. has received grant support from Astellas Pharma, Gilead Sciences, Merck Sharp and Dohme, Pfizer, Schering Plough, Soria Melguizo S.A., the European Union, the Spanish Agency for International Cooperation, the Spanish Ministry of Culture and Education, the Spanish Health Research Fund, the Instituto de Salud Carlos III, the Ramon Areces Foundation, and the Mutua Madrileña Foundation. He has been an advisor/consultant to the Pan American Health Organization, Gilead Sciences, Merck Sharp and Dohme, Mycognostica, Pfizer, and Schering Plough. He has received payment for talks on behalf of Gilead Sciences, Merck Sharp and Dohme, Pfizer, and Schering Plough.

FOOTNOTES

    • Received 7 September 2009.
    • Returned for modification 19 September 2009.
    • Accepted 18 April 2010.
  • Copyright © 2010 American Society for Microbiology

REFERENCES

  1. 1.↵
    Aberkane, A., M. Cuenca-Estrella, A. Gomez-Lopez, E. Petrikkou, E. Mellado, A. Monzon, and J. L. Rodriguez-Tudela. 2002. Comparative evaluation of two different methods of inoculum preparation for antifungal susceptibility testing of filamentous fungi. J. Antimicrob. Chemother.50:719-722.
    OpenUrlCrossRefPubMedWeb of Science
  2. 2.↵
    Alastruey-Izquierdo, A., M. V. Castelli, I. Cuesta, A. Monzon, M. Cuenca-Estrella, and J. L. Rodriguez-Tudela. 2009. Activity of posaconazole and other antifungal agents against Mucorales strains identified by sequencing of internal transcribed spacers. Antimicrob. Agents Chemother.53:1686-1689.
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    Alastruey-Izquierdo, A., K. Hoffmann, G. S. de Hoog, J. L. Rodriguez-Tudela, K. Voigt, E. Bibashi, and G. Walther. 2010. Species recognition and clinical relevance of the zygomycetous genus Lichtheimia (syn. Absidia pro parte,Mycocladus). J. Clin. Microbiol.48:2154-2170.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    Alvarez, E., D. A. Sutton, J. Cano, A. W. Fothergill, A. Stchigel, M. G. Rinaldi, and J. Guarro. 2009. Spectrum of zygomycete species identified from clinically significant specimens in the United States. J. Clin. Microbiol.47:1650-1656.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    Arikan, S., M. Lozano-Chiu, V. Paetznick, and J. H. Rex. 2001. In vitro susceptibility testing methods for caspofungin against Aspergillus and Fusarium isolates. Antimicrob. Agents Chemother.45:327-330.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    Dannaoui, E., J. Meletiadis, J. W. Mouton, J. F. Meis, and P. E. Verweij. 2003. In vitro susceptibilities of zygomycetes to conventional and new antifungals. J. Antimicrob. Chemother.51:45-52.
    OpenUrlCrossRefPubMedWeb of Science
  7. 7.↵
    Greenberg, R. N., K. Mullane, J. A. van Burik, I. Raad, M. J. Abzug, G. Anstead, R. Herbrecht, A. Langston, K. A. Marr, G. Schiller, M. Schuster, J. R. Wingard, C. E. Gonzalez, S. G. Revankar, G. Corcoran, R. J. Kryscio, and R. Hare. 2006. Posaconazole as salvage therapy for zygomycosis. Antimicrob. Agents Chemother.50:126-133.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    Hoffmann, K., S. Discher, and K. Voigt. 2007. Revision of the genus Absidia (Mucorales, Zygomycetes) based on physiological, phylogenetic, and morphological characters; thermotolerant Absidia spp. form a coherent group, Mycocladiaceae fam. nov. Mycol. Res.111:1169-1183.
    OpenUrlCrossRefPubMedWeb of Science
  9. 9.↵
    Hoffmann, K., G. Walther, and K. Voigt. 2009. Mycocladus vs. Lichtheimia: a correction (Lichtheimiaceae fam. nov. Mucorales,Mucoromycotina). Mycol. Res.113:275-278.
    OpenUrlCrossRef
  10. 10.↵
    Kurtz, M. B., I. B. Heath, J. Marrinan, S. Dreikorn, J. Onishi, and C. Douglas. 1994. Morphological effects of lipopeptides against Aspergillus fumigatus correlate with activities against (1,3)-β-d-glucan synthase. Antimicrob. Agents Chemother.38:1480-1489.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    National Committee for Clinical Laboratory Standards. 2002. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi. Approved standard M38-A. NCCLS, Wayne, PA.
  12. 12.↵
    Petrikkou, E., J. L. Rodriguez-Tudela, M. Cuenca-Estrella, A. Gomez, A. Molleja, and E. Mellado. 2001. Inoculum standardization for antifungal susceptibility testing of filamentous fungi pathogenic for humans. J. Clin. Microbiol.39:1345-1347.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    Ribes, J. A., C. L. Vanover-Sams, and D. J. Baker. 2000. Zygomycetes in human disease. Clin. Microbiol. Rev.13:236-301.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    Roden, M. M., T. E. Zaoutis, W. L. Buchanan, T. A. Knudsen, T. A. Sarkisova, R. L. Schaufele, M. Sein, T. Sein, C. C. Chiou, J. H. Chu, D. P. Kontoyiannis, and T. J. Walsh. 2005. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin. Infect. Dis.41:634-653.
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    Rodriguez-Tudela, J. L., E. Chryssanthou, E. Petrikkou, J. Mosquera, D. W. Denning, and M. Cuenca-Estrella. 2003. Interlaboratory evaluation of hematocytometer method of inoculum preparation for testing antifungal susceptibilities of filamentous fungi. J. Clin. Microbiol.41:5236-5237.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    Rodriguez-Tudela, J. L., J. P. Donnelly, M. C. Arendrup, S. Arikan, F. Barchiesi, J. Bille, E. Chryssanthou, M. Cuenca-Estrella, E. Danaoui, D. Denning, W. Fegeler, P. Gaustad, C. Lass-Florl, C. Moore, M. Richardson, A. Schmalreck, J. A. Velegraki, and P. Verweij. 2008. EUCAST Technical Note on the method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia-forming moulds—Subcommittee on antifungal susceptibility testing (AFST) of the ESCMID European committee for antimicrobial susceptibility testing (EUCAST). Clin. Microbiol. Infect.14:982-984.
    OpenUrlCrossRefPubMedWeb of Science
  17. 17.↵
    Singh, J., D. Rimek, and R. Kappe. 2005. In vitro susceptibility of 15 strains of zygomycetes to nine antifungal agents as determined by the NCCLS M38-A microdilution method. Mycoses48:246-250.
    OpenUrlCrossRefPubMedWeb of Science
  18. 18.↵
    van Burik, J. A., R. S. Hare, H. F. Solomon, M. L. Corrado, and D. P. Kontoyiannis. 2006. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin. Infect. Dis.42:e61-e65.
    OpenUrlCrossRefPubMedWeb of Science
View Abstract
PreviousNext
Back to top
Download PDF
Citation Tools
Antifungal Susceptibility Profile of Human-Pathogenic Species of Lichtheimia
Ana Alastruey-Izquierdo, Isabel Cuesta, Grit Walther, Manuel Cuenca-Estrella, Juan Luis Rodriguez-Tudela
Antimicrobial Agents and Chemotherapy Jun 2010, 54 (7) 3058-3060; DOI: 10.1128/AAC.01270-09

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Antifungal Susceptibility Profile of Human-Pathogenic Species of Lichtheimia
(Your Name) has forwarded a page to you from Antimicrobial Agents and Chemotherapy
(Your Name) thought you would be interested in this article in Antimicrobial Agents and Chemotherapy.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Antifungal Susceptibility Profile of Human-Pathogenic Species of Lichtheimia
Ana Alastruey-Izquierdo, Isabel Cuesta, Grit Walther, Manuel Cuenca-Estrella, Juan Luis Rodriguez-Tudela
Antimicrobial Agents and Chemotherapy Jun 2010, 54 (7) 3058-3060; DOI: 10.1128/AAC.01270-09
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • Strains.
    • Antifungal susceptibility testing.
    • Nucleotide sequence accession numbers.
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

antifungal agents
Mucorales

Related Articles

Cited By...

About

  • About AAC
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • AAC Podcast
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #AACJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0066-4804; Online ISSN: 1098-6596