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Article: Theranostic gold in a gold cage nanoparticle for photothermal ablation and photoacoustic imaging of skin and oral infections.

Hajfathalian, Maryam / de Vries, Christiaan R / Hsu, Jessica C / Amirshaghaghi, Ahmad / Dong, Yuxi C / Ren, Zhi / Liu, Yuan / Huang, Yue / Li, Yong / Knight, Simon / Jonnalagadda, Pallavi / Zlitni, Aimen / Grice, Elizabeth / Bollyky, Paul L / Koo, Hyun / Cormode, David P

bioRxiv : the preprint server for biology

2023

Abstract: Biofilms are structured communities of microbial cells embedded in a self-produced matrix of extracellular polymeric substances. Biofilms are associated with many health issues in humans, including chronic wound infections and tooth decay. Current ... ...

Abstract	Biofilms are structured communities of microbial cells embedded in a self-produced matrix of extracellular polymeric substances. Biofilms are associated with many health issues in humans, including chronic wound infections and tooth decay. Current antimicrobials are often incapable of disrupting the polymeric biofilm matrix and reaching the bacteria within. Alternative approaches are needed. Here, we describe a unique structure of dextran coated gold in a gold cage nanoparticle that enables photoacoustic and photothermal properties for biofilm detection and treatment. Activation of these nanoparticles with a near infrared laser can selectively detect and kill biofilm bacteria with precise spatial control and in a short timeframe. We observe a strong biocidal effect against both Streptococcus mutans and Staphylococcus aureus biofilms in mouse models of oral plaque and wound infections respectively. These effects were over 100 times greater than that seen with chlorhexidine, a conventional antimicrobial agent. Moreover, this approach did not adversely affect surrounding tissues. We conclude that photothermal ablation using theranostic nanoparticles is a rapid, precise, and non-toxic method to detect and treat biofilm-associated infections.
Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.05.539604
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Article ; Online: Theranostic gold-in-gold cage nanoparticles enable photothermal ablation and photoacoustic imaging in biofilm-associated infection models.

Hajfathalian, Maryam / de Vries, Christiaan R / Hsu, Jessica C / Amirshaghaghi, Ahmad / Dong, Yuxi C / Ren, Zhi / Liu, Yuan / Huang, Yue / Li, Yong / Knight, Simon Ab / Jonnalagadda, Pallavi / Zlitni, Aimen / Grice, Elizabeth A / Bollyky, Paul L / Koo, Hyun / Cormode, David P

The Journal of clinical investigation

2023 Volume 133, Issue 21

Abstract	Biofilms are structured communities of microbial cells embedded in a self-produced matrix of extracellular polymeric substances. Biofilms are associated with many health issues in humans, including chronic wound infections and tooth decay. Current antimicrobials are often incapable of disrupting the polymeric biofilm matrix and reaching the bacteria within. Alternative approaches are needed. Here, we described a complex structure of a dextran-coated gold-in-gold cage nanoparticle that enabled photoacoustic and photothermal properties for biofilm detection and treatment. Activation of these nanoparticles with a near infrared laser could selectively detect and kill biofilm bacteria with precise spatial control and in a short timeframe. We observed a strong biocidal effect against both Streptococcus mutans and Staphylococcus aureus biofilms in mouse models of oral plaque and wound infections, respectively. These effects were over 100 times greater than those seen with chlorhexidine, a conventional antimicrobial agent. Moreover, this approach did not adversely affect surrounding tissues. We concluded that photothermal ablation using theranostic nanoparticles is a rapid, precise, and nontoxic method to detect and treat biofilm-associated infections.
MeSH term(s)	Animals ; Mice ; Anti-Bacterial Agents ; Biofilms ; Gold/pharmacology ; Gold/chemistry ; Nanoparticles/chemistry ; Photoacoustic Techniques ; Precision Medicine ; Wound Infection
Chemical Substances	Anti-Bacterial Agents ; Gold (7440-57-5)
Language	English
Publishing date	2023-11-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI168485
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Article ; Online: Phages in vaccine design and immunity; mechanisms and mysteries.

de Vries, Christiaan R / Chen, Qingquan / Demirdjian, Sally / Kaber, Gernot / Khosravi, Arya / Liu, Dan / Van Belleghem, Jonas D / Bollyky, Paul L

Current opinion in biotechnology

2020 Volume 68, Page(s) 160–165

Abstract: Bacteriophages have attracted extensive interest in vaccine design. This includes the use of phage display technology to select antigens, the use of engineered phages displaying target antigens in vaccine formulations, and phage DNA vaccines. However, ... ...

Abstract	Bacteriophages have attracted extensive interest in vaccine design. This includes the use of phage display technology to select antigens, the use of engineered phages displaying target antigens in vaccine formulations, and phage DNA vaccines. However, the development of these approaches is limited in part by uncertainty regarding the underlying mechanisms by which phages elicit immunity. This has stymied the clinical development of this technology. Here we review the immunology of phage vaccines and highlight the gaps in our knowledge regarding the underlying mechanisms. First, we review the basic biology of phages and their use in vaccines. Next we discuss what is known about the mechanisms of immunity against engineered phages and phage DNA. Finally, we highlight the gaps in our understanding regarding the immunogenicity of these preparations. We argue that mechanistic insight into the immunology of phage vaccines is essential for the further development and clinical utility of these technologies.
MeSH term(s)	Bacteriophages/genetics ; Cell Surface Display Techniques ; Vaccines
Chemical Substances	Vaccines
Language	English
Publishing date	2020-12-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1052045-4
ISSN	1879-0429 ; 0958-1669
ISSN (online)	1879-0429
ISSN	0958-1669
DOI	10.1016/j.copbio.2020.11.002
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Article ; Online: Theranostic gold-in-gold cage nanoparticles enable photothermal ablation and photoacoustic imaging in biofilm-associated infection models

Maryam Hajfathalian / Christiaan R. de Vries / Jessica C. Hsu / Ahmad Amirshaghaghi / Yuxi C. Dong / Zhi Ren / Yuan Liu / Yue Huang / Yong Li / Simon A.B. Knight / Pallavi Jonnalagadda / Aimen Zlitni / Elizabeth A. Grice / Paul L. Bollyky / Hyun Koo / David P. Cormode

The Journal of Clinical Investigation, Vol 133, Iss

2023 Volume 21

Abstract	Biofilms are structured communities of microbial cells embedded in a self-produced matrix of extracellular polymeric substances. Biofilms are associated with many health issues in humans, including chronic wound infections and tooth decay. Current antimicrobials are often incapable of disrupting the polymeric biofilm matrix and reaching the bacteria within. Alternative approaches are needed. Here, we described a complex structure of a dextran-coated gold-in-gold cage nanoparticle that enabled photoacoustic and photothermal properties for biofilm detection and treatment. Activation of these nanoparticles with a near infrared laser could selectively detect and kill biofilm bacteria with precise spatial control and in a short timeframe. We observed a strong biocidal effect against both Streptococcus mutans and Staphylococcus aureus biofilms in mouse models of oral plaque and wound infections, respectively. These effects were over 100 times greater than those seen with chlorhexidine, a conventional antimicrobial agent. Moreover, this approach did not adversely affect surrounding tissues. We concluded that photothermal ablation using theranostic nanoparticles is a rapid, precise, and nontoxic method to detect and treat biofilm-associated infections.
Keywords	Infectious disease ; Therapeutics ; Medicine ; R
Subject code	616
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	American Society for Clinical Investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Delayed Inoculation Model of Chronic Pseudomonas aeruginosa Wound Infection.

de Vries, Christiaan R / Sweere, Johanna M / Ishak, Heather / Sunkari, Vivekananda / Bach, Michelle S / Liu, Dan / Manasherob, Robert / Bollyky, Paul L

Journal of visualized experiments : JoVE

2020 , Issue 156

Abstract: Pseudomonas aeruginosa (P. aeruginosa) is a major nosocomial pathogen of increasing relevance to human health and disease, particularly in the setting of chronic wound infections in diabetic and hospitalized patients. There is an urgent need for chronic ... ...

Abstract	Pseudomonas aeruginosa (P. aeruginosa) is a major nosocomial pathogen of increasing relevance to human health and disease, particularly in the setting of chronic wound infections in diabetic and hospitalized patients. There is an urgent need for chronic infection models to aid in the investigation of wound pathogenesis and the development of new therapies against this pathogen. Here, we describe a protocol that uses delayed inoculation 24 hours after full-thickness excisional wounding. The infection of the provisional wound matrix present at this time forestalls either rapid clearance or dissemination of infection and instead establishes chronic infection lasting 7-10 days without the need for implantation of foreign materials or immune suppression. This protocol mimics a typical temporal course of post-operative infection in humans. The use of a luminescent P. aeruginosa strain (PAO1:lux) allows for quantitative daily assessment of bacterial burden for P. aeruginosa wound infections. This novel model may be a useful tool in the investigation of bacterial pathogenesis and the development of new therapies for chronic P. aeruginosa wound infections.
MeSH term(s)	Animals ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Pseudomonas Infections/microbiology ; Pseudomonas Infections/pathology ; Pseudomonas aeruginosa/pathogenicity ; Wound Infection/microbiology ; Wound Infection/pathology
Language	English
Publishing date	2020-02-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/60599
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Article ; Online: The Safety and Toxicity of Phage Therapy: A Review of Animal and Clinical Studies.

Liu, Dan / Van Belleghem, Jonas D / de Vries, Christiaan R / Burgener, Elizabeth / Chen, Qingquan / Manasherob, Robert / Aronson, Jenny R / Amanatullah, Derek F / Tamma, Pranita D / Suh, Gina A

Viruses

2021 Volume 13, Issue 7

Abstract: Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a ... ...

Abstract	Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English language publications from 2008-2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimize safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found some adverse events associated with phage therapy, but serious events were extremely rare. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.
MeSH term(s)	Animals ; Bacterial Infections/therapy ; Bacteriophages/pathogenicity ; Clinical Trials as Topic ; Disease Models, Animal ; Humans ; Mice ; Phage Therapy/adverse effects ; Phage Therapy/methods
Language	English
Publishing date	2021-06-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13071268
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Article ; Online: Microbial Cell-Free DNA Identifies the Causative Pathogen in Infective Endocarditis and Remains Detectable Longer Than Conventional Blood Culture in Patients with Prior Antibiotic Therapy.

Eichenberger, Emily M / Degner, Nicholas / Scott, Erick R / Ruffin, Felicia / Franzone, John / Sharma-Kuinkel, Batu / Shah, Pratik / Hong, David / Dalai, Sudeb C / Blair, Lily / Hollemon, Desiree / Chang, Eliza / Ho, Carine / Wanda, Lisa / de Vries, Christiaan R / Fowler, Vance G / Ahmed, Asim A

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2022 Volume 76, Issue 3, Page(s) e1492–e1500

Abstract: Background: The diagnosis of infective endocarditis (IE) can be difficult, particularly if blood cultures fail to yield a pathogen. This study evaluates the potential utility of microbial cell-free DNA (mcfDNA) as a tool to identify the microbial ... ...

Abstract	Background: The diagnosis of infective endocarditis (IE) can be difficult, particularly if blood cultures fail to yield a pathogen. This study evaluates the potential utility of microbial cell-free DNA (mcfDNA) as a tool to identify the microbial etiology of IE. Methods: Blood samples from patients with suspected IE were serially collected. mcfDNA was extracted from plasma and underwent next-generation sequencing. Reads were aligned against a library containing DNA sequences belonging to >1400 different pathogens. mcfDNA from organisms present above a statistical threshold were reported and quantified in molecules per milliliter (MPM). Additional mcfDNA was collected on each subject every 2-3 days for a total of 7 collections or until discharge. Results: Of 30 enrolled patients with suspected IE, 23 had definite IE, 2 had possible IE, and IE was rejected in 5 patients by modified Duke Criteria. Only the 23 patients with definite IE were included for analysis. Both mcfDNA and blood cultures achieved a sensitivity of 87%. The median duration of positivity from antibiotic treatment initiation was estimated to be approximately 38.1 days for mcfDNA versus 3.7 days for blood culture (proportional odds, 2.952; P = .02771), using a semiparametric survival analysis. mcfDNA (log10) levels significantly declined (-0.3 MPM log10 units, 95% credible interval -0.45 to -0.14) after surgical source control was performed (pre- vs postprocedure, posterior probability >0.99). Conclusion: mcfDNA accurately identifies the microbial etiology of IE. Sequential mcfDNA levels may ultimately help to individualize therapy by estimating a patient's burden of infection and response to treatment.
MeSH term(s)	Humans ; Blood Culture ; Anti-Bacterial Agents/therapeutic use ; Cell-Free Nucleic Acids ; Endocarditis, Bacterial/diagnosis ; Endocarditis/diagnosis ; Endocarditis/drug therapy
Chemical Substances	Anti-Bacterial Agents ; Cell-Free Nucleic Acids
Language	English
Publishing date	2022-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciac426
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Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: A delayed inoculation model of chronic Pseudomonas aeruginosa wound infection

de Vries, Christiaan R / Sweere, Johanna M / Ishak, Heather / Sunkari, Vivekananda / Bach, Michelle S / Liu, Dan / Manasherob, Robert / Bollyky, Paul L

Journal of visualized experiments. 2020 Feb. 20, , no. 156

2020

Abstract	Pseudomonas aeruginosa (P. aeruginosa) is a major nosocomial pathogen of increasing relevance to human health and disease, particularly in the setting of chronic wound infections in diabetic and hospitalized patients. There is an urgent need for chronic infection models to aid in the investigation of wound pathogenesis and the development of new therapies against this pathogen. Here, we describe a protocol that uses delayed inoculation 24 hours after full-thickness excisional wounding. The infection of the provisional wound matrix present at this time forestalls either rapid clearance or dissemination of infection and instead establishes chronic infection lasting 7–10 days without the need for implantation of foreign materials or immune suppression. This protocol mimics a typical temporal course of post-operative infection in humans. The use of a luminescent P. aeruginosa strain (PAO1:lux) allows for quantitative daily assessment of bacterial burden for P. aeruginosa wound infections. This novel model may be a useful tool in the investigation of bacterial pathogenesis and the development of new therapies for chronic P. aeruginosa wound infections.
Keywords	Pseudomonas aeruginosa ; cross infection ; human diseases ; human health ; luminescence ; microbial load ; models ; pathogenesis ; pathogens ; patients
Language	English
Dates of publication	2020-0220
Size	p. e60599.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/60599
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Hormonal control during infancy and testicular adrenal rest tumor development in males with congenital adrenal hyperplasia: a retrospective multicenter cohort study.

Schröder, Mariska A M / Neacşu, Mihaela / Adriaansen, Bas P H / Sweep, Fred C G J / Ahmed, S Faisal / Ali, Salma R / Bachega, Tânia A S S / Baronio, Federico / Birkebæk, Niels Holtum / de Bruin, Christiaan / Bonfig, Walter / Bryce, Jillian / Clemente, Maria / Cools, Martine / Elsedfy, Heba / Globa, Evgenia / Guran, Tulay / Güven, Ayla / Amr, Nermine Hussein /

Janus, Dominika / Taube, Nina Lenherr / Markosyan, Renata / Miranda, Mirela / Poyrazoğlu, Şükran / Rees, Aled / Salerno, Mariacarolina / Stancampiano, Marianna Rita / Vieites, Ana / de Vries, Liat / Yavas Abali, Zehra / Span, Paul N / Claahsen-van der Grinten, Hedi L

European journal of endocrinology

2023 Volume 189, Issue 4, Page(s) 460–468

Abstract: Importance: Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic ... ...

Abstract	Importance: Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development. Objective: This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. Design and participants: This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. Results: TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. Conclusions and relevance: A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life.
MeSH term(s)	Adolescent ; Humans ; Male ; Adrenal Hyperplasia, Congenital/genetics ; Adrenal Rest Tumor/epidemiology ; Adrenal Rest Tumor/etiology ; Cohort Studies ; Testicular Neoplasms/epidemiology ; Testicular Neoplasms/complications ; Child
Language	English
Publishing date	2023-10-30
Publishing country	England
Document type	Multicenter Study ; Journal Article
ZDB-ID	1183856-5
ISSN	1479-683X ; 0804-4643
ISSN (online)	1479-683X
ISSN	0804-4643
DOI	10.1093/ejendo/lvad143
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Uh III Zs.147: Show issues

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Article ; Online: Pf Bacteriophage and Their Impact on Pseudomonas Virulence, Mammalian Immunity, and Chronic Infections.

Secor, Patrick R / Burgener, Elizabeth B / Kinnersley, M / Jennings, Laura K / Roman-Cruz, Valery / Popescu, Medeea / Van Belleghem, Jonas D / Haddock, Naomi / Copeland, Conner / Michaels, Lia A / de Vries, Christiaan R / Chen, Qingquan / Pourtois, Julie / Wheeler, Travis J / Milla, Carlos E / Bollyky, Paul L

Frontiers in immunology

2020 Volume 11, Page(s) 244

Abstract: Pf bacteriophage are temperate phages that infect the ... ...

Abstract	Pf bacteriophage are temperate phages that infect the bacterium
MeSH term(s)	Animals ; Bacteriophages/physiology ; Biofilms ; Chronic Disease ; Drug Resistance, Microbial ; Humans ; Mammals ; Pseudomonas Infections/immunology ; Pseudomonas Infections/transmission ; Pseudomonas Infections/virology ; Pseudomonas aeruginosa/physiology ; Virulence
Language	English
Publishing date	2020-02-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.00244
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