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Article: MUG CCArly: A Novel Autologous 3D Cholangiocarcinoma Model Presents an Increased Angiogenic Potential.

Schrom, Silke / Kleinegger, Florian / Anders, Ines / Hebesberger, Thomas / Karner, Christina / Liesinger, Laura / Birner-Gruenberger, Ruth / Renner, Wilfried / Pichler, Martin / Grillari, Regina / Aigelsreiter, Ariane / Rinner, Beate

Cancers

2023 Volume 15, Issue 6

Abstract: Cholangiocarcinoma (CCA) are characterized by their desmoplastic and hypervascularized tumor microenvironment (TME), which is mainly composed of tumor cells and cancer-associated fibroblasts (CAFs). CAFs play a pivotal role in general and CCA tumor ... ...

Abstract	Cholangiocarcinoma (CCA) are characterized by their desmoplastic and hypervascularized tumor microenvironment (TME), which is mainly composed of tumor cells and cancer-associated fibroblasts (CAFs). CAFs play a pivotal role in general and CCA tumor progression, angiogenesis, metastasis, and the development of treatment resistance. To our knowledge, no continuous human in vivo-like co-culture model is available for research. Therefore, we aimed to establish a new model system (called MUG CCArly) that mimics the desmoplastic microenvironment typically seen in CCA. Proteomic data comparing the new CCA tumor cell line with our co-culture tumor model (CCTM) indicated a higher gene expression correlation of the CCTM with physiological CCA characteristics. A pro-angiogenic TME that is typically observed in CCA could also be better simulated in the CCTM group. Further analysis of secreted proteins revealed CAFs to be the main source of these angiogenic factors. Our CCTM MUG CCArly represents a new, reproducible, and easy-to-handle 3D CCA model for preclinical studies focusing on CCA-stromal crosstalk, tumor angiogenesis, and invasion, as well as the immunosuppressive microenvironment and the involvement of CAFs in the way that drug resistance develops.
Language	English
Publishing date	2023-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15061757
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Article ; Online: Development of a localization-based algorithm for the prediction of leg ulcer etiology.

Deinsberger, Julia / Moschitz, Irina / Marquart, Elias / Manz-Varga, Alexander Konstantin / Gschwandtner, Michael E / Brugger, Jonas / Rinner, Christoph / Böhler, Kornelia / Tschandl, Philipp / Weber, Benedikt

Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG

2023 Volume 21, Issue 11, Page(s) 1339–1349

Abstract: Background: Diagnostic work-up of leg ulcers is time- and cost-intensive. This study aimed at evaluating ulcer location as a diagnostic criterium and providing a diagnostic algorithm to facilitate differential diagnosis.: Patients and methods: The ... ...

Abstract	Background: Diagnostic work-up of leg ulcers is time- and cost-intensive. This study aimed at evaluating ulcer location as a diagnostic criterium and providing a diagnostic algorithm to facilitate differential diagnosis. Patients and methods: The study consisted of 277 patients with lower leg ulcers. The following five groups were defined: Venous leg ulcer, arterial ulcers, mixed ulcer, arteriolosclerosis, and vasculitis. Using computational surface rendering, predilection sites of different ulcer types were evaluated. The results were integrated in a multinomial logistic regression model to calculate the likelihood of a specific diagnosis depending on location, age, bilateral involvement, and ulcer count. Additionally, neural network image analysis was performed. Results: The majority of venous ulcers extended to the medial malleolar region. Arterial ulcers were most frequently located on the dorsal aspect of the forefoot. Arteriolosclerotic ulcers were distinctly localized at the middle third of the lower leg. Vasculitic ulcers appeared to be randomly distributed and were markedly smaller, multilocular and bilateral. The multinomial logistic regression model showed an overall satisfactory performance with an estimated accuracy of 0.68 on unseen data. Conclusions: The presented algorithm based on ulcer location may serve as a basic tool to narrow down potential diagnoses and guide further diagnostic work-up.
MeSH term(s)	Humans ; Ulcer ; Leg Ulcer/diagnosis ; Leg Ulcer/etiology ; Varicose Ulcer/diagnosis ; Leg ; Algorithms
Language	English
Publishing date	2023-09-01
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2093479-8
ISSN	1610-0387 ; 1610-0379
ISSN (online)	1610-0387
ISSN	1610-0379
DOI	10.1111/ddg.15192
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Article ; Online: Entwicklung eines Lokalisations-basierten Algorithmus zur Vorhersage der Ätiologie von Ulcera cruris.

Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG

2023 Volume 21, Issue 11, Page(s) 1339–1350

Language	German
Publishing date	2023-11-09
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2093479-8
ISSN	1610-0387 ; 1610-0379
ISSN (online)	1610-0387
ISSN	1610-0379
DOI	10.1111/ddg.15192_g
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Article ; Online: Drug combination screening as a translational approach toward an improved drug therapy for chordoma.

Scheipl, Susanne / Barnard, Michelle / Lohberger, Birgit / Zettl, Richard / Brcic, Iva / Liegl-Atzwanger, Bernadette / Rinner, Beate / Meindl, Claudia / Fröhlich, Eleonore

Cellular oncology (Dordrecht)

2021 Volume 44, Issue 6, Page(s) 1231–1242

Abstract: Purpose: Drug screening programmes have revealed epidermal growth factor receptor inhibitors (EGFR: Methods: We screened 133 clinically approved anticancer drugs as single agents and in combination with two EGFR: Results: Drugs that were active as ...

Abstract	Purpose: Drug screening programmes have revealed epidermal growth factor receptor inhibitors (EGFR Methods: We screened 133 clinically approved anticancer drugs as single agents and in combination with two EGFR Results: Drugs that were active as single agents (n = 45) included TKIs, HDAC and proteasome inhibitors, and cytostatic drugs. Six combinations were analysed in a matrix format: n = 4 resulted in a significantly increased cell killing (crizotinib, dabrafenib, panobinostat and doxorubicin), and n = 2 exhibited no or negligible effects (regorafenib, venetoclax). Clival chordoma cell lines were more responsive to combined EGFR-MET inhibition. EGFR-MET cross-talk (e.g. via TGF-α secretion) likely accounts for the synergistic effects of EGFR-MET inhibition. Conclusion: Our screen revealed promising combinations with EGFR
MeSH term(s)	Afatinib/pharmacology ; Afatinib/therapeutic use ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Autocrine Communication ; Cell Line, Tumor ; Chordoma/drug therapy ; Crizotinib/pharmacology ; Crizotinib/therapeutic use ; Drug Approval ; Drug Screening Assays, Antitumor ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/metabolism ; Hepatocyte Growth Factor/metabolism ; Humans ; Ligands ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-met/metabolism ; Transforming Growth Factor alpha/metabolism ; Translational Research, Biomedical ; United States ; United States Food and Drug Administration ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Antineoplastic Agents ; Ligands ; Protein Kinase Inhibitors ; Transforming Growth Factor alpha ; Vascular Endothelial Growth Factor A ; Afatinib (41UD74L59M) ; Crizotinib (53AH36668S) ; Hepatocyte Growth Factor (67256-21-7) ; ErbB Receptors (EC 2.7.10.1) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
Language	English
Publishing date	2021-09-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2595109-9
ISSN	2211-3436 ; 1875-8606 ; 2211-3428
ISSN (online)	2211-3436
ISSN	1875-8606 ; 2211-3428
DOI	10.1007/s13402-021-00632-x
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Article: Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model.

Garofalo, Mariangela / Wieczorek, Magdalena / Anders, Ines / Staniszewska, Monika / Lazniewski, Michal / Prygiel, Marta / Zasada, Aleksandra Anna / Szczepińska, Teresa / Plewczynski, Dariusz / Salmaso, Stefano / Caliceti, Paolo / Cerullo, Vincenzo / Alemany, Ramon / Rinner, Beate / Pancer, Katarzyna / Kuryk, Lukasz

Frontiers in oncology

2023 Volume 13, Page(s) 1259314

Abstract: Introduction: Malignant mesothelioma is a rare and aggressive form of cancer. Despite improvements in cancer treatment, there are still no curative treatment modalities for advanced stage of the malignancy. The aim of this study was to evaluate the anti- ...

Abstract	Introduction: Malignant mesothelioma is a rare and aggressive form of cancer. Despite improvements in cancer treatment, there are still no curative treatment modalities for advanced stage of the malignancy. The aim of this study was to evaluate the anti-tumor efficacy of a novel combinatorial therapy combining AdV5/3-D24-ICOSL-CD40L, an oncolytic vector, with an anti-PD-1 monoclonal antibody. Methods: The efficacy of the vector was confirmed Results and discussion: Anticancer efficacy was attributed to reduced tumour volume and increased infiltration of tumour infiltrating lymphocytes, including activated cytotoxic T-cells (GrB+CD8+). Additionally, a correlation between tumour volume and activated CD8+ tumour infiltrating lymphocytes was observed. These findings were confirmed by transcriptomic analysis carried out on resected human tumour tissue, which also revealed upregulation of CD83 and CRTAM, as well as several chemokines (CXCL3, CXCL9, CXCL11) in the tumour microenvironment. Furthermore, according to observations, the combinatorial therapy had the strongest effect on reducing mesothelin and MUC16 levels. Gene set enrichment analysis suggested that the combinatorial therapy induced changes to the expression of genes belonging to the "adaptive immune response" gene ontology category. Combinatorial therapy with oncolytic adenovirus with checkpoint inhibitors may improve anticancer efficacy and survival by targeted cancer cell destruction and triggering of immunogenic cell death. Obtained results support further assessment of the AdV5/3-D24-ICOSL-CD40L in combination with checkpoint inhibitors as a novel therapeutic perspective for mesothelioma treatment.
Language	English
Publishing date	2023-11-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1259314
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Article ; Online: Targeting epigenetic features in clear cell sarcomas based on patient-derived cell lines.

Karner, Christina / Anders, Ines / Vejzovic, Djenana / Szkandera, Joanna / Scheipl, Susanne / Deutsch, Alexander J A / Weiss, Larissa / Vierlinger, Klemens / Kolb, Dagmar / Kühberger, Stefan / Heitzer, Ellen / Habisch, Hansjörg / Zhang, Fangrong / Madl, Tobias / Reininger-Gutmann, Birgit / Liegl-Atzwanger, Bernadette / Rinner, Beate

Journal of translational medicine

2023 Volume 21, Issue 1, Page(s) 54

Abstract: Background: Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. ...

Abstract	Background: Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated. Methods: Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine N-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test. Results: The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the IC Conclusions: MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS.
MeSH term(s)	Humans ; Sarcoma, Clear Cell/genetics ; Sarcoma, Clear Cell/metabolism ; Sarcoma, Clear Cell/pathology ; Cell Line ; Enzyme Inhibitors ; Arginine/genetics ; Arginine/metabolism ; Arginine/therapeutic use ; Epigenesis, Genetic ; Cell Line, Tumor ; Protein-Arginine N-Methyltransferases/genetics ; Protein-Arginine N-Methyltransferases/metabolism ; Protein-Arginine N-Methyltransferases/therapeutic use ; Repressor Proteins/genetics
Chemical Substances	Enzyme Inhibitors ; Arginine (94ZLA3W45F) ; PRMT1 protein, human (EC 2.1.1.319) ; Protein-Arginine N-Methyltransferases (EC 2.1.1.319) ; Repressor Proteins
Language	English
Publishing date	2023-01-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-022-03843-4
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Article ; Online: A reinforcement learning model for AI-based decision support in skin cancer.

Barata, Catarina / Rotemberg, Veronica / Codella, Noel C F / Tschandl, Philipp / Rinner, Christoph / Akay, Bengu Nisa / Apalla, Zoe / Argenziano, Giuseppe / Halpern, Allan / Lallas, Aimilios / Longo, Caterina / Malvehy, Josep / Puig, Susana / Rosendahl, Cliff / Soyer, H Peter / Zalaudek, Iris / Kittler, Harald

Nature medicine

2023 Volume 29, Issue 8, Page(s) 1941–1946

Abstract: We investigated whether human preferences hold the potential to improve diagnostic artificial intelligence (AI)-based decision support using skin cancer diagnosis as a use case. We utilized nonuniform rewards and penalties based on expert-generated ... ...

Abstract	We investigated whether human preferences hold the potential to improve diagnostic artificial intelligence (AI)-based decision support using skin cancer diagnosis as a use case. We utilized nonuniform rewards and penalties based on expert-generated tables, balancing the benefits and harms of various diagnostic errors, which were applied using reinforcement learning. Compared with supervised learning, the reinforcement learning model improved the sensitivity for melanoma from 61.4% to 79.5% (95% confidence interval (CI): 73.5-85.6%) and for basal cell carcinoma from 79.4% to 87.1% (95% CI: 80.3-93.9%). AI overconfidence was also reduced while simultaneously maintaining accuracy. Reinforcement learning increased the rate of correct diagnoses made by dermatologists by 12.0% (95% CI: 8.8-15.1%) and improved the rate of optimal management decisions from 57.4% to 65.3% (95% CI: 61.7-68.9%). We further demonstrated that the reward-adjusted reinforcement learning model and a threshold-based model outperformed naïve supervised learning in various clinical scenarios. Our findings suggest the potential for incorporating human preferences into image-based diagnostic algorithms.
MeSH term(s)	Humans ; Artificial Intelligence ; Algorithms ; Skin Neoplasms/diagnosis ; Skin Neoplasms/pathology ; Melanoma/diagnosis ; Melanoma/pathology ; Carcinoma, Basal Cell/diagnosis
Language	English
Publishing date	2023-07-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-023-02475-5
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: High risk of peri-implant disease in periodontal Ehlers-Danlos Syndrome. A case series.

Rinner, Alexander / Zschocke, Johannes / Schossig, Anna / Gröbner, Rebekka / Strobl, Heinrich / Kapferer-Seebacher, Ines

Clinical oral implants research

2018 Volume 29, Issue 11, Page(s) 1101–1106

Abstract: Objectives: Periodontal Ehlers-Danlos syndrome (pEDS) has recently been delineated as a molecularly defined cause of early severe periodontitis. Here we report that implant treatment failed in three affected individuals from one family.: Materials and ...

Abstract	Objectives: Periodontal Ehlers-Danlos syndrome (pEDS) has recently been delineated as a molecularly defined cause of early severe periodontitis. Here we report that implant treatment failed in three affected individuals from one family. Materials and methods: Longitudinal data before and after implant treatment were examined for three individuals with genetically confirmed pEDS in the course of a large-scale pedigree analysis. Results: Most detailed information was available for individual 1 in whom first periodontal bone loss was diagnosed at age 16 years. Rapid progression resulted in multiple tooth extractions at age 23 years and interforaminal placement of four implants. After primary implant success, peri-implant bone loss accompanied by highly inflamed tissues and receding gums led to explantation five years later. In individual 2, severe periodontitis was diagnosed at age 15 years and resulted in extraction of all mandibular teeth at age 28 years. Four interforaminal implants were placed. Peri-implant bone loss was diagnosed four years later, when up to three implant threads were exposed. Individual 3 showed complete tooth loss at age 29 years. He was restored with ten implants and removable prosthesis. Peri-implant bone loss was diagnosed radiologically eight years later, when seven implant threads were exposed. Conclusion: This is the first report on severe peri-implant bone loss in pEDS. Retention of teeth as long as possible is the primary objective in pEDS as satisfying prosthetic solutions are missing. Further evaluation of dental management in individuals with pEDS is needed to develop concise treatment guidelines.
Language	English
Publishing date	2018-10-08
Publishing country	Denmark
Document type	Case Reports
ZDB-ID	1067626-0
ISSN	1600-0501 ; 0905-7161
ISSN (online)	1600-0501
ISSN	0905-7161
DOI	10.1111/clr.13373
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Article ; Online: Workability, quality of life and cardiovascular risk markers in aging nightshift workers: a pilot study.

Jordakieva, Galateja / Markovic, Lovro / Rinner, Walter / Santonja, Isabel / Lee, Seungjune / Pilger, Alexander / Perkman, Thomas / Grabovac, Igor / Schernhammer, Eva / Crevenna, Richard / Papantoniou, Kyriaki / Godnic-Cvar, Jasminka

Wiener klinische Wochenschrift

2021 Volume 134, Issue 7-8, Page(s) 276–285

Abstract: Background: In aging healthcare professionals, multiple stressors such as night work may affect life and work satisfaction and risk for chronic diseases (e.g. cardiovascular disease [CVD]). In this pilot study we compared workability, quality of life ( ... ...

Abstract	Background: In aging healthcare professionals, multiple stressors such as night work may affect life and work satisfaction and risk for chronic diseases (e.g. cardiovascular disease [CVD]). In this pilot study we compared workability, quality of life (QoL), and CVD risk markers between night shift and day workers. Methods: We included 70 hospital employees (mean age 52 ± 4 years, 91.4% female): 32 rotating night shift workers (> 3 nights/month) and 38 permanent day workers. In addition to sociodemographic, lifestyle, and sleep characteristics, we assessed i) workability index (WAI), ii) QoL (World Health Organization Quality of Life [WHOQOL-Bref]) and iii) CVD risk markers, i.e. carotid ultrasound measurements, and biomarkers (NTproBNP, CRP, IL‑6, LDL, ferritin, copper, zinc, and selenium). WAI, QoL, and CVD risk markers were compared between night and day workers. In a subgroup of participants (N = 38) with complete data, we used quantile regression analysis to estimate age and multivariate adjusted differences in biomarker levels. Results: We found no differences in the domains of QoL (physical health, psychological, social relationships, and environment) and WAI scores between night and day workers. Night shift workers were less likely to report excellent workability than day workers, although differences were not statistically significant. Night shift workers reported more sleep problems (73.1% vs. 55.6%) and tended to have lower zinc levels and higher inflammatory markers (CRP, IL‑6, ferritin), but differences were not significant after adjusting for potential confounders. Conclusions: Workability, QoL and CVD markers did not significantly differ between rotating night shift and day workers in this small pilot study. Sleep problems and inflammatory marker levels carry implications for occupational health.
MeSH term(s)	Aging ; Biomarkers ; Cardiovascular Diseases/epidemiology ; Cross-Sectional Studies ; Female ; Ferritins ; Heart Disease Risk Factors ; Humans ; Interleukin-6 ; Male ; Middle Aged ; Pilot Projects ; Quality of Life ; Risk Factors ; Sleep Wake Disorders ; Work Schedule Tolerance ; Zinc
Chemical Substances	Biomarkers ; Interleukin-6 ; Ferritins (9007-73-2) ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2021-09-06
Publishing country	Austria
Document type	Journal Article
ZDB-ID	200462-8
ISSN	1613-7671 ; 0043-5325 ; 0300-5178
ISSN (online)	1613-7671
ISSN	0043-5325 ; 0300-5178
DOI	10.1007/s00508-021-01928-6
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Zs.A 902: Show issues

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Book: Oversexed and underfucked

Osswald-Rinner, Iris

über die gesellschaftliche Konstruktion der Lust

(Erlebniswelten)

2011

Author's details	Iris Osswald-Rinner
Series title	Erlebniswelten
Keywords	Lust/Social aspects ; Sex/Social aspects ; Sex (Psychology) ; Analyse ; Ratgeber ; Lust ; Wandel ; Sexualverhalten ; Soziale Konstruktion
Language	German
Size	271 S., Ill., graph. Darst.
Edition	1. Aufl.
Publisher	VS, Verl. für Sozialwiss
Publishing place	Wiesbaden
Document type	Book
Note	Literaturverz. S. [253] - 271
ISBN	3531181858 ; 9783531181851
Database	Former special subject collection: coastal and deep sea fishing

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