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Article ; Online: Parental Experience of the Children with Gastrointestinal Stoma in Kanti Children Hospital, a Tertiary Level Children Hospital in Nepal

Smriti Manandhar / Sarala Shrestha / Sangita Shrestha / Mankeshari Maharjan

Journal of Karnali Academy of Health Sciences, Vol 6, Iss

2023 Volume 2

Abstract: Background: The gastrointestinal stomas are seen as the obligatory condition for the treatment of children with gastrointestinal malfunction where their parents have to face various challenges. The lived experience of parents having children with ... ...

Abstract	Background: The gastrointestinal stomas are seen as the obligatory condition for the treatment of children with gastrointestinal malfunction where their parents have to face various challenges. The lived experience of parents having children with gastrointestinal stomas was explored in this study. Methods: Qualitative phenomenological research design was used. Data were gathered by interviewing total 11 mothers with children having stoma for at least 2 weeks and admitted in a hospital. Thematic analysis was done with obtained data. Results: Six major emergent themes from the study were the parent’s journey with child’s health, challenges faced, resilience in caring the child, change in family life, support system and socio-cultural perception and influence. Conclusion: Parents of the children with the stoma face a range of problems and challenges. So, to sustain a better and conducive life of the parent and their children with stoma, parental resilience must be enhanced by developing an integrated support in the journey of the parenthood.
Keywords	Gastrointestinal stoma ; Children ; Parental experience ; Medicine (General) ; R5-920
Subject code	360
Language	English
Publishing date	2023-08-01T00:00:00Z
Publisher	Karnali Academy of Health Sciences
Document type	Article ; Online
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Article ; Online: The Risk Factors of Cerebral Palsy among the Children Attending a Children's Hospital.

Mishra, Tulashi Adhikari / Shrestha, Sarala / Prajapati Manandhar, Bina / Sharma, Pratima

Journal of Nepal Health Research Council

2022 Volume 19, Issue 4, Page(s) 778–783

Abstract: Background: Cerebral Palsy is a disorder of movement and posture caused by nonprogressive abnormal brain function. It is a lifelong condition and one of the most common causes of physical disability in children. The objective of this study was to find ... ...

Abstract	Background: Cerebral Palsy is a disorder of movement and posture caused by nonprogressive abnormal brain function. It is a lifelong condition and one of the most common causes of physical disability in children. The objective of this study was to find out the risk factors associated with cerebral palsy among children. Methods: A case control study was carried out among 330 children where cases and controls were taken in the ratio of 1:2. Cases included children diagnosed with cerebral palsy and attending neurological out-patient department of a Children's Hospital in Kathmandu, Nepal and control included children not having cerebral palsy and attending medical out-patient department of the same hospital for other medical problems. The data were collected from November 29, 2017 to May 20, 2018 by using a pretested interview schedule. The findings were analyzed using frequency, percentage, mean, standard deviation and chi square test and odds ratio. Results: Findings revealed that about one-fourth (24.5%) cases were diagnosed to have CP within one year of age. In terms of sex majority (63.6%) of the cases were male and majority were the first born children. Findings also revealed that infection during pregnancy (OR:2.9, CI: 1.1-7.5), family history of cerebral palsy (OR:5.6, CI: 1.4-21.8), instrumental delivery (OR: 10.9, CI:2.3-50.6), not crying immediately after birth (OR: 17.3, CI: 8.6-34.6), were significantly associated with cerebral palsy. Conclusions: Most of the identified risk factors are preventable and controllable through proper antenatal and skilled intranatal care. Thus, every pregnant woman should receive proper care during pregnancy as well as during delivery for the prevention of the identified risk factors.
MeSH term(s)	Case-Control Studies ; Cerebral Palsy/epidemiology ; Cerebral Palsy/etiology ; Child ; Female ; Hospitals ; Humans ; Male ; Nepal/epidemiology ; Pregnancy ; Risk Factors
Language	English
Publishing date	2022-03-13
Publishing country	Nepal
Document type	Journal Article
ZDB-ID	2551251-1
ISSN	1999-6217 ; 1999-6217
ISSN (online)	1999-6217
ISSN	1999-6217
DOI	10.33314/jnhrc.v19i04.3808
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Article ; Online: The Risk Factors of Cerebral Palsy among the Children Attending a Children’s Hospital

Tulashi Adhikari Mishra / Sarala Shrestha / Bina Prajapati Manandhar / Pratima Sharma

Journal of Nepal Health Research Council, Vol 19, Iss

2022 Volume 04

Abstract	Background: Cerebral Palsy is a disorder of movement and posture caused by nonprogressive abnormal brain function. It is a lifelong condition and one of the most common causes of physical disability in children. The objective of this study was to find out the risk factors associated with cerebral palsy among children. Methods: A case control study was carried out among 330 children where cases and controls were taken in the ratio of 1:2. Cases included children diagnosed with cerebral palsy and attending neurological out-patient department of a Children’s Hospital in Kathmandu, Nepal and control included children not having cerebral palsy and attending medical out-patient department of the same hospital for other medical problems. The data were collected from November 29, 2017 to May 20, 2018 by using a pretested interview schedule. The findings were analyzed using frequency, percentage, mean, standard deviation and chi square test and odds ratio. Results: Findings revealed that about one-fourth (24.5%) cases were diagnosed to have CP within one year of age. In terms of sex majority (63.6%) of the cases were male and majority were the first born children. Findings also revealed that infection during pregnancy (OR:2.9, CI: 1.1-7.5), family history of cerebral palsy (OR:5.6, CI: 1.4-21.8), instrumental delivery (OR: 10.9, CI:2.3-50.6), not crying immediately after birth (OR: 17.3, CI: 8.6-34.6), were significantly associated with cerebral palsy. Conclusions: Most of the identified risk factors are preventable and controllable through proper antenatal and skilled intranatal care. Thus, every pregnant woman should receive proper care during pregnancy as well as during delivery for the prevention of the identified risk factors. Keywords: Cerebral palsy; children; risk factors
Keywords	Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Nepal Health Research Council
Document type	Article ; Online
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Article ; Online: Emerging role of RUNX3 in the regulation of tumor microenvironment.

Manandhar, Sarala / Lee, You Mie

BMB reports

2018 Volume 51, Issue 4, Page(s) 174–181

Abstract: A number of genes have been therapeutically targeted to relieve cancer, but cancer relapse is still a growing issue. The concept that the surrounding tumor environment is critical for the progression of cancer may foster an answer to the issue of cancer ... ...

Abstract	A number of genes have been therapeutically targeted to relieve cancer, but cancer relapse is still a growing issue. The concept that the surrounding tumor environment is critical for the progression of cancer may foster an answer to the issue of cancer malignancy. Runt domain transcription factors (RUNX1, 2, and 3) are evolutionarily conserved and have been intensively studied for their roles in normal development and pathological conditions. During tumor growth, a hypoxic microenvironment and infiltration of the tumor by immune cells are common phenomena. In this review, we briefly introduce the consequences of hypoxia and immune cell infiltration into the tumor microenvironment with a focus on RUNX3 as a critical regulator. Furthermore, based on our current knowledge of the functional role of RUNX3 in hypoxia and immune cell maintenance, a probable therapeutic intervention is suggested for the effective management of tumor growth and malignancy. [BMB Reports 2018; 51(4): 174-181].
MeSH term(s)	Animals ; Carcinogenesis/genetics ; Carcinogenesis/metabolism ; Cell Hypoxia/physiology ; Core Binding Factor Alpha 3 Subunit/genetics ; Core Binding Factor Alpha 3 Subunit/metabolism ; DNA Methylation ; Disease Progression ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Inflammation/metabolism ; Tumor Microenvironment/physiology
Chemical Substances	Core Binding Factor Alpha 3 Subunit ; Hypoxia-Inducible Factor 1, alpha Subunit
Language	English
Publishing date	2018-02-12
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	2410389-5
ISSN	1976-670X ; 1976-6696
ISSN (online)	1976-670X
ISSN	1976-6696
DOI	10.5483/bmbrep.2018.51.4.033
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Article: Roles of RUNX in Hypoxia-Induced Responses and Angiogenesis.

Lee, Sun Hee / Manandhar, Sarala / Lee, You Mie

Advances in experimental medicine and biology

2017 Volume 962, Page(s) 449–469

Abstract: During the past two decades, Runt domain transcription factors (RUNX1, 2, and 3) have been investigated in regard to their function, structural elements, genetic variants, and roles in normal development and pathological conditions. The Runt family ... ...

Abstract	During the past two decades, Runt domain transcription factors (RUNX1, 2, and 3) have been investigated in regard to their function, structural elements, genetic variants, and roles in normal development and pathological conditions. The Runt family proteins are evolutionarily conserved from Drosophila to mammals, emphasizing their physiological importance. A hypoxic microenvironment caused by insufficient blood supply is frequently observed in developing organs, growing tumors, and tissues that become ischemic due to impairment or blockage of blood vessels. During embryonic development and tumor growth, hypoxia triggers a stress response that overcomes low-oxygen conditions by increasing erythropoiesis and angiogenesis and triggering metabolic changes. This review briefly introduces hypoxic conditions and cellular responses, as well as angiogenesis and its related signaling pathways, and then describes our current knowledge on the functions and molecular mechanisms of Runx family proteins in hypoxic responses, especially in angiogenesis.
MeSH term(s)	Animals ; Core Binding Factor alpha Subunits/metabolism ; Erythropoiesis/physiology ; Humans ; Hypoxia/metabolism ; Hypoxia/pathology ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/pathology ; Signal Transduction/physiology
Chemical Substances	Core Binding Factor alpha Subunits
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-981-10-3233-2_27
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Article ; Online: Exostosin 1 regulates cancer cell stemness in doxorubicin-resistant breast cancer cells.

Manandhar, Sarala / Kim, Chang-Gu / Lee, Sun-Hee / Kang, Soo Hyun / Basnet, Nikita / Lee, You Mie

Oncotarget

2017 Volume 8, Issue 41, Page(s) 70521–70537

Abstract: Cancer stem cells (CSCs) are associated with cancer recurrence following radio/chemotherapy owing to their high resistance to therapeutic intervention. In this study, we investigated the role of exostoxin 1 (EXT1), an endoplasmic reticulum (ER)-residing ... ...

Abstract	Cancer stem cells (CSCs) are associated with cancer recurrence following radio/chemotherapy owing to their high resistance to therapeutic intervention. In this study, we investigated the role of exostoxin 1 (EXT1), an endoplasmic reticulum (ER)-residing type II transmembrane glycoprotein, in cancer cell stemness. DNA microarray analysis revealed that doxorubicin-resistant MCF7/ADR cells have high levels of EXT1 expression compared to its parental cell line, MCF7. These cells showed significantly higher populations of CSCs and larger populations of aldehyde dehydrogenase (ALDH
Language	English
Publishing date	2017-09-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.19737
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Article ; Online: CCN1 interlinks integrin and hippo pathway to autoregulate tip cell activity.

Park, Myo-Hyeon / Kim, Ae Kyung / Manandhar, Sarala / Oh, Su-Young / Jang, Gun-Hyuk / Kang, Li / Lee, Dong-Won / Hyeon, Do Young / Lee, Sun-Hee / Lee, Hye Eun / Huh, Tae-Lin / Suh, Sang Heon / Hwang, Daehee / Byun, Kyunghee / Park, Hae-Chul / Lee, You Mie

eLife

2019 Volume 8

Abstract: CCN1 (CYR61) stimulates active angiogenesis in various tumours, although the mechanism is largely unknown. Here, we report that CCN1 is a key regulator of endothelial tip cell activity in angiogenesis. Microvessel networks and directional vascular cell ... ...

Abstract	CCN1 (CYR61) stimulates active angiogenesis in various tumours, although the mechanism is largely unknown. Here, we report that CCN1 is a key regulator of endothelial tip cell activity in angiogenesis. Microvessel networks and directional vascular cell migration patterns were deformed in
MeSH term(s)	Animals ; Cysteine-Rich Protein 61/genetics ; Cysteine-Rich Protein 61/metabolism ; Endothelial Cells/physiology ; Gene Expression Regulation ; Human Umbilical Vein Endothelial Cells ; Humans ; Integrin alphaVbeta3/metabolism ; Mice, Transgenic ; Neovascularization, Pathologic ; Protein Interaction Maps ; Signal Transduction ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Zebrafish
Chemical Substances	Cysteine-Rich Protein 61 ; Integrin alphaVbeta3 ; KDR protein, human (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
Language	English
Publishing date	2019-08-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.46012
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Article: Effect of stable inhibition of NRF2 on doxorubicin sensitivity in human ovarian carcinoma OV90 cells.

Manandhar, Sarala / Lee, Sangwhan / Kwak, Mi-Kyoung

Archives of pharmacal research

2010 Volume 33, Issue 5, Page(s) 717–726

Abstract: The transcription factor NRF2 defends the cell from oxidative stress by up-regulating a large number of antioxidant genes through its binding with antioxidant response element on gene promoters. Cancer cells are known to possess high levels of ... ...

Abstract	The transcription factor NRF2 defends the cell from oxidative stress by up-regulating a large number of antioxidant genes through its binding with antioxidant response element on gene promoters. Cancer cells are known to possess high levels of antioxidant genes that increases survival in cancer microenvironment of oxidative stress, particularly in the treatment with anticancer agents. In the current study we have examined the role of the NRF2 in doxorubicin sensitivity and tumor growth by establishing stable cell line expressing NRF2 shRNA in the human ovarian carcinoma cell line OV90. On knockdown of NRF2 through NRF2-specific shNRF2 expressing lentiviral plasmid, antioxidant response element-driven luciferase activity as well as the expression of NRF2-target genes were significantly suppressed compared to nonspecific scrambled RNA (scRNA) expressing cells. In addition, shNRF2 expressing OV90-shNRF2 cells showed a reduction in total GSH levels by 82% and cell growth was observed to be significantly retarded compared to scRNA control cells. Furthermore, stable inhibition of NRF2 sensitized OV90 cells were seen following doxorubicin treatment as shown by the analysis with MTT assay and propidium iodide-fluorescence-activated cell sorting. OV90-shNRF2 cells showed higher levels of cell death and apoptosis in response to doxorubicin than OV90-scRNA cells. While, when BALBc (nu/nu) mice with OV90 tumor xenograft in the flanks were injected with NRF2 shRNA containing viral particles and treated with doxorubicin a pattern of retardation in tumor growth was seen in shRNA group compared to scRNA group, but this difference was not statistically significant. In conclusion, we propose that the NRF2 signaling might be a molecular target to repress tumor growth and enhance cytotoxic effects of anticancer agent in cancer cells.
MeSH term(s)	Animals ; Antibiotics, Antineoplastic/pharmacology ; Apoptosis/drug effects ; Cell Line ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Doxorubicin/pharmacology ; Drug Screening Assays, Antitumor/methods ; Gene Knockdown Techniques/methods ; Glutathione/metabolism ; Humans ; Mice ; Mice, Nude ; NF-E2-Related Factor 2/antagonists & inhibitors ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Reactive Oxygen Species/metabolism
Chemical Substances	Antibiotics, Antineoplastic ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; RNA, Small Interfering ; Reactive Oxygen Species ; Doxorubicin (80168379AG) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2010-05
Publishing country	Korea (South)
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	447623-2
ISSN	1976-3786 ; 0253-6269
ISSN (online)	1976-3786
ISSN	0253-6269
DOI	10.1007/s12272-010-0511-z
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Article ; Online: CCN1 interlinks integrin and hippo pathway to autoregulate tip cell activity

Myo-Hyeon Park / Ae kyung Kim / Sarala Manandhar / Su-Young Oh / Gun-Hyuk Jang / Li Kang / Dong-Won Lee / Do Young Hyeon / Sun-Hee Lee / Hye Eun Lee / Tae-Lin Huh / Sang Heon Suh / Daehee Hwang / Kyunghee Byun / Hae-Chul Park / You Mie Lee

eLife, Vol

2019 Volume 8

Abstract	CCN1 (CYR61) stimulates active angiogenesis in various tumours, although the mechanism is largely unknown. Here, we report that CCN1 is a key regulator of endothelial tip cell activity in angiogenesis. Microvessel networks and directional vascular cell migration patterns were deformed in ccn1-knockdown zebrafish embryos. CCN1 activated VEGFR2 and downstream MAPK/PI3K signalling pathways, YAP/TAZ, as well as Rho effector mDia1 to enhance tip cell activity and CCN1 itself. VEGFR2 interacted with integrin αvβ3 through CCN1. Integrin αvβ3 inhibitor repressed tip cell number and sprouting in postnatal retinas from endothelial cell-specific Ccn1 transgenic mice, and allograft tumours in Ccn1 transgenic mice showed hyperactive vascular sprouting. Cancer patients with high CCN1 expression have poor survival outcomes and positive correlation with ITGAV and ITGB3 and high YAP/WWTR1. Thus, our data underscore the positive feedback regulation of tip cells by CCN1 through integrin αvβ3/VEGFR2 and increased YAP/TAZ activity, suggesting a promising therapeutic intervention for pathological angiogenesis.
Keywords	Cyr61 ; integrinαvβ3 ; VEGFR2 ; YAP/TAZ ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Acquisition of doxorubicin resistance in ovarian carcinoma cells accompanies activation of the NRF2 pathway.

Shim, Gi-seong / Manandhar, Sarala / Shin, Dong-ha / Kim, Tae-Hyoung / Kwak, Mi-Kyoung

Free radical biology & medicine

2009 Volume 47, Issue 11, Page(s) 1619–1631

Abstract: It has been firmly established that the transcription factor NRF2 is a critical element in the survival of healthy cells in response to oxidative stress because it up-regulates a wide array of antioxidant genes by binding to the antioxidant-response ... ...

Abstract	It has been firmly established that the transcription factor NRF2 is a critical element in the survival of healthy cells in response to oxidative stress because it up-regulates a wide array of antioxidant genes by binding to the antioxidant-response element (ARE). However, adaptive activation of the NRF2 system after an exposure of cancer cells to chemotherapy can be hypothesized, implying the acquisition of chemoresistance by tumors. In this study we have investigated the potential role of NRF2 signaling in the development of acquired resistance to doxorubicin. The human ovarian carcinoma cell line A2780, which is highly sensitive to doxorubicin, showed low levels of ARE binding and ARE-driven luciferase activity, as well as repressed expression of its target genes compared with resistant ovarian carcinoma SKOV3 and OV90 cells. Doxorubicin-resistant A2780DR cells, established after exposure to stepwise increasing concentrations of doxorubicin, displayed a refractoriness to doxorubicin-induced cell death. Acquisition of doxorubicin resistance in A2780 cells was accompanied by an elevation in NRF2 activity and consequent increase in the expression of the catalytic subunit of gamma-glutamylcysteine ligase and total GSH content. A critical role for NRF2 in the acquired chemoresistance of A2780DR cells could be confirmed by the restoration of doxorubicin sensitivity after stable expression of NRF2-specific shRNA in A2780DR cells, whereas inhibition of NRF2 could not further enhance doxorubicin sensitivity in the parental A2780 cells. These results suggest that the level of NRF2 activity might be a determining factor for doxorubicin sensitivity in ovarian carcinoma cell lines and adaptive activation of the NRF2 system can participate in the development of acquired resistance to anthracycline therapy.
MeSH term(s)	Apoptosis/drug effects ; Cell Line, Tumor ; Doxorubicin/pharmacology ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Female ; Glutamate-Cysteine Ligase/genetics ; Glutamate-Cysteine Ligase/metabolism ; Humans ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Oxidative Stress ; Protein Binding ; RNA, Small Interfering/genetics ; Response Elements/genetics ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Transcriptional Activation
Chemical Substances	NF-E2-Related Factor 2 ; RNA, Small Interfering ; Doxorubicin (80168379AG) ; Glutamate-Cysteine Ligase (EC 6.3.2.2)
Language	English
Publishing date	2009-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2009.09.006
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