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Article ; Online: Multi-Omic Blood Biomarkers as Dynamic Risk Predictors in Late-Onset Alzheimer's Disease.

Bhalala, Oneil G / Watson, Rosie / Yassi, Nawaf

International journal of molecular sciences

2024 Volume 25, Issue 2

Abstract: Late-onset Alzheimer's disease is the leading cause of dementia worldwide, accounting for a growing burden of morbidity and mortality. Diagnosing Alzheimer's disease before symptoms are established is clinically challenging, but would provide therapeutic ...

Abstract	Late-onset Alzheimer's disease is the leading cause of dementia worldwide, accounting for a growing burden of morbidity and mortality. Diagnosing Alzheimer's disease before symptoms are established is clinically challenging, but would provide therapeutic windows for disease-modifying interventions. Blood biomarkers, including genetics, proteins and metabolites, are emerging as powerful predictors of Alzheimer's disease at various timepoints within the disease course, including at the preclinical stage. In this review, we discuss recent advances in such blood biomarkers for determining disease risk. We highlight how leveraging polygenic risk scores, based on genome-wide association studies, can help stratify individuals along their risk profile. We summarize studies analyzing protein biomarkers, as well as report on recent proteomic- and metabolomic-based prediction models. Finally, we discuss how a combination of multi-omic blood biomarkers can potentially be used in memory clinics for diagnosis and to assess the dynamic risk an individual has for developing Alzheimer's disease dementia.
MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Alzheimer Disease/genetics ; Genome-Wide Association Study ; Multiomics ; Proteomics ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-01-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25021231
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Article ; Online: Diagnostic challenges for dementia in Australia: are blood-based biomarkers the solution?

Loveland, Paula M / Watson, Rosie / Yassi, Nawaf

Internal medicine journal

2023 Volume 52, Issue 12, Page(s) 2181–2185

Abstract: The burden of dementia will increase as the Australian population ages and grows in coming decades. Early and accurate diagnosis remains challenging, and disproportionately so for particular groups, including rural communities. Recent advances in ... ...

Abstract	The burden of dementia will increase as the Australian population ages and grows in coming decades. Early and accurate diagnosis remains challenging, and disproportionately so for particular groups, including rural communities. Recent advances in technology, however, now allow reliable measurement of blood biomarkers that could improve diagnosis in a range of settings. We discuss the most promising biomarker candidates for translation into clinical practice and research in the near future.
MeSH term(s)	Humans ; Dementia/diagnosis ; Australia ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-05-03
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2045436-3
ISSN	1445-5994 ; 1444-0903
ISSN (online)	1445-5994
ISSN	1444-0903
DOI	10.1111/imj.15973
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Zs.A 792: 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 ; Online: Tau as a Biomarker of Neurodegeneration.

Holper, Sarah / Watson, Rosie / Yassi, Nawaf

International journal of molecular sciences

2022 Volume 23, Issue 13

Abstract: Less than 50 years since tau was first isolated from a porcine brain, its detection in femtolitre concentrations in biological fluids is revolutionizing the diagnosis of neurodegenerative diseases. This review highlights the molecular and technological ... ...

Abstract	Less than 50 years since tau was first isolated from a porcine brain, its detection in femtolitre concentrations in biological fluids is revolutionizing the diagnosis of neurodegenerative diseases. This review highlights the molecular and technological advances that have catapulted tau from obscurity to the forefront of biomarker diagnostics. Comprehensive updates are provided describing the burgeoning clinical applications of tau as a biomarker of neurodegeneration. For the clinician, tau not only enhances diagnostic accuracy, but holds promise as a predictor of clinical progression, phenotype, and response to drug therapy. For patients living with neurodegenerative disorders, characterization of tau dysregulation could provide much-needed clarity to a notoriously murky diagnostic landscape.
MeSH term(s)	Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/metabolism ; Animals ; Biomarkers ; Brain/metabolism ; Swine ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; tau Proteins
Language	English
Publishing date	2022-06-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23137307
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Article ; Online: Tau as a Biomarker of Neurodegeneration

Sarah Holper / Rosie Watson / Nawaf Yassi

International Journal of Molecular Sciences, Vol 23, Iss 7307, p

2022 Volume 7307

Abstract	Less than 50 years since tau was first isolated from a porcine brain, its detection in femtolitre concentrations in biological fluids is revolutionizing the diagnosis of neurodegenerative diseases. This review highlights the molecular and technological advances that have catapulted tau from obscurity to the forefront of biomarker diagnostics. Comprehensive updates are provided describing the burgeoning clinical applications of tau as a biomarker of neurodegeneration. For the clinician, tau not only enhances diagnostic accuracy, but holds promise as a predictor of clinical progression, phenotype, and response to drug therapy. For patients living with neurodegenerative disorders, characterization of tau dysregulation could provide much-needed clarity to a notoriously murky diagnostic landscape.
Keywords	tau ; neurodegeneration ; Alzheimer’s disease ; biomarker ; cerebrospinal fluid ; tauopathy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Cerebral amyloid angiopathy: clinical presentations and management challenges in the Australian context.

Swarup, Oshi / Barker, James L / Watson, Rosie / Davis, Stephen M / Campbell, Bruce C V / Yassi, Nawaf

Internal medicine journal

2023 Volume 53, Issue 6, Page(s) 907–916

Abstract: Cerebral amyloid angiopathy (CAA) is a disease with several clinical manifestations. It is characterised by amyloid-beta deposition in cerebral blood vessels, making them prone to bleeding. The incidence of CAA increases with age and may be associated or ...

Abstract	Cerebral amyloid angiopathy (CAA) is a disease with several clinical manifestations. It is characterised by amyloid-beta deposition in cerebral blood vessels, making them prone to bleeding. The incidence of CAA increases with age and may be associated or co-exist with intraparenchymal neurodegenerative proteinopathies, which makes it an increasingly relevant condition for adult physicians in all areas of medical practice. The vast majority of cases of CAA are sporadic with a small minority of familial cases. CAA is asymptomatic in many older adults but increases the risk of fatal intracerebral or subarachnoid haemorrhage. We review the existing literature on CAA and summarise the key findings. We specifically explore clinical challenges relevant to CAA, particularly in diagnosis, management of intracranial haemorrhage and management of concurrent medical conditions.
MeSH term(s)	Humans ; Aged ; Australia/epidemiology ; Cerebral Amyloid Angiopathy/diagnosis ; Cerebral Amyloid Angiopathy/epidemiology ; Cerebral Amyloid Angiopathy/therapy ; Subarachnoid Hemorrhage ; Intracranial Hemorrhages/complications ; Incidence ; Cerebral Hemorrhage/complications ; Cerebral Hemorrhage/diagnosis ; Cerebral Hemorrhage/epidemiology ; Magnetic Resonance Imaging
Language	English
Publishing date	2023-01-13
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	2045436-3
ISSN	1445-5994 ; 1444-0903
ISSN (online)	1445-5994
ISSN	1444-0903
DOI	10.1111/imj.15999
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Zs.A 792: 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)
Zs.MO 424: Show issues

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Article ; Online: Lessons from a population-based bladder cancer registry: exploring why survival is not improving.

Tempo, Jake A / Sii, Samuel / Ischia, Joseph / Bolton, Damien M / D'Onise, Katina / Meng, Rosie / Watson, David I / O'Callaghan, Michael

BJU international

2024

Abstract: Objective: To explore the causes of the decrease in bladder cancer survival that has occurred over the past four decades.: Methods: We extracted data from the South Australian Cancer Registry. Data from the period 1 January 1977 to 31 December 2020 ... ...

Abstract	Objective: To explore the causes of the decrease in bladder cancer survival that has occurred over the past four decades. Methods: We extracted data from the South Australian Cancer Registry. Data from the period 1 January 1977 to 31 December 2020 were extracted to explore changes in incidence and survival among a total of 8356 patients diagnosed with ≥pT1 disease. Invasive bladder cancer was defined as ≥pT1 in this study. Results: Invasive bladder cancer age-standardized incidence decreased from 7.20 cases per 100 000 people in 1977 to 5.85 cases per 100 000 in 2020. The mean age at diagnosis increased from 68 years to 76 years. The crude incidence for patients aged 80 years and over increased by 3.3% per year (95% confidence interval [CI] 2.1 to 4.6). Overall survival decreased over the study period (hazard ratio [HR] 1.22 [95% CI 1.09 to 1.35]), however, survival increased after adjusting for age at diagnosis (HR 0.80 [95% CI 0.76 to 0.94]). Despite a decrease in non-bladder cancer-specific deaths in older people, there was no change in the bladder cancer-specific death rate in older people (HR 0.94 [95% CI 0.70 to 1.26]). Male sex was associated with higher survival (HR 0.87 [95% CI 0.83 to 0.92]), whereas socioeconomic advantage was not. Conclusions: Invasive bladder cancer survival has decreased over the past 40 years, with the age structure of the population being a significant contributing factor. Patient summary: We looked at why bladder cancer survival is decreasing using a large cancer registry with information from 1977 to 2020. We found that people are now more likely to be diagnosed at an older age. Older people often live for a shorter time with bladder cancer compared to younger people. Bladder cancer survival has decreased because there are more older people with the disease than previously.
Language	English
Publishing date	2024-02-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1462191-5
ISSN	1464-410X ; 1464-4096 ; 1358-8672
ISSN (online)	1464-410X
ISSN	1464-4096 ; 1358-8672
DOI	10.1111/bju.16286
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Ui VI Zs.107: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 13: Show issues

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Article ; Online: Melatonin does not reduce delirium severity in hospitalized older adults: Results of a randomized placebo-controlled trial.

Lange, Peter W / Turbić, Alisa / Soh, Cheng Hwee / Clayton-Chubb, Daniel / Lim, Wen Kwang / Conyers, Rachel / Watson, Rosie / Maier, Andrea B

Journal of the American Geriatrics Society

2024

Abstract: Background: Delirium is common in older inpatients, causing distress, cognitive decline, and death. Current therapies are unsatisfactory, limited by lack of efficacy and adverse effects. There is an urgent need for effective delirium treatment. Sleep ... ...

Abstract	Background: Delirium is common in older inpatients, causing distress, cognitive decline, and death. Current therapies are unsatisfactory, limited by lack of efficacy and adverse effects. There is an urgent need for effective delirium treatment. Sleep wake cycle is disturbed in delirium; endogenous Melatonin is perturbed, and exogenous Melatonin is a safe and effective medication for sleep disorders. This study aims to determine the effect of oral Melatonin 5 mg immediate release (IR) nightly for five nights on the severity of delirium in older (≥65 years) medical inpatients. Methods: This was a double-blinded, randomized controlled trial in general internal medicine units of a tertiary teaching hospital. Older inpatients with Confusion Assessment Method positive, hyperactive or mixed delirium within 48 h of admission or onset of in-hospital delirium were included. The primary outcome was change in delirium severity measured with the Memorial Delirium Assessment Scale (MDAS). A previous pilot trial showed 120 participants randomized 1:1 to Melatonin or Placebo would provide 90% power to demonstrate a 3-point reduction in the MDAS. Results: One hundred and twenty participants were randomized, 61 to Melatonin 5 mg and 59 to Placebo. The medication was well tolerated. The mean MDAS improvement was 4.9 (SD 7.6) in the Melatonin group and 5.4 (SD 7.2) in the Placebo group, p-value 0.42, a non-significant difference. A post-hoc analysis showed length of stay (LOS) was shorter in the intervention group (median 9 days [Interquartile Range (IQR) 4, 12] vs. Placebo group 10 [IQR 6, 16] p-value = 0.033, Wilcoxon Rank Sum test). Conclusions: This trial does not support the hypothesis that Melatonin reduces the severity of delirium. This may be due to no effect of Melatonin, a smaller effect than anticipated, an effect not captured on a multidimensional delirium assessment scale, or a type II statistical error. Melatonin may improve LOS; this hypothesis should be studied.
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	80363-7
ISSN	1532-5415 ; 0002-8614
ISSN (online)	1532-5415
ISSN	0002-8614
DOI	10.1111/jgs.18825
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Article ; Online: Investigation of Inflammation in Lewy Body Dementia: A Systematic Scoping Review.

Loveland, Paula M / Yu, Jenny J / Churilov, Leonid / Yassi, Nawaf / Watson, Rosie

International journal of molecular sciences

2023 Volume 24, Issue 15

Abstract: Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD ( ... ...

Abstract	Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson's disease dementia) and, secondly, identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease and other neurodegenerative diseases. A systematic scoping review was performed by searching major electronic databases (MEDLINE, Embase, Web of Science, and PSYCHInfo) to identify relevant human studies. Of the 2509 results screened, 80 studies were included. Thirty-six studies analyzed postmortem brain tissue, and 44 investigated living subjects with cerebrospinal fluid, blood, and/or brain imaging assessments. Largely cross-sectional data were available, although two longitudinal clinical studies investigated prodromal Lewy body disease. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, and lymphocytes) and inflammatory molecules (cytokines, etc.). Results of the included studies identified innate and adaptive immune system contributions to inflammation associated with Lewy body pathology and clinical disease features. Different signals in early and late-stage disease, with possible late immune senescence and dystrophic glial cell populations, were identified. The strength of these associations is limited by the varying methodologies, small study sizes, and cross-sectional nature of the data. Longitudinal studies investigating associations with clinical and other biomarker outcomes are needed to improve understanding of inflammatory activity over the course of LBD. This could identify markers of disease activity and support therapeutic development.
MeSH term(s)	Humans ; Lewy Body Disease/pathology ; Dementia ; Neurodegenerative Diseases ; Cross-Sectional Studies ; Parkinson Disease/cerebrospinal fluid ; Inflammation ; alpha-Synuclein/cerebrospinal fluid
Chemical Substances	alpha-Synuclein
Language	English
Publishing date	2023-07-28
Publishing country	Switzerland
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241512116
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Article ; Online: Prevalence of cerebral microbleeds in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia: A systematic review and meta-analysis.

Chin, Kai Sin / Holper, Sarah / Loveland, Paula / Churilov, Leonid / Yassi, Nawaf / Watson, Rosie

Neurobiology of aging

2023 Volume 134, Page(s) 74–83

Abstract: Cerebral microbleeds (CMB) are often associated with vascular risk factors and/or cerebral amyloid angiopathy and are frequently identified in people with dementia. The present study therefore aimed to estimate the pooled prevalence and associations of ... ...

Abstract	Cerebral microbleeds (CMB) are often associated with vascular risk factors and/or cerebral amyloid angiopathy and are frequently identified in people with dementia. The present study therefore aimed to estimate the pooled prevalence and associations of CMB in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), using meta-analytic methods. Sixty-five MRI studies were included after a systematic search on major electronic databases. We found that the prevalence of CMB was comparable across the three dementia subtypes (31-36%) and was highly influenced by the MRI techniques used. CMB in AD were associated with a history of hypertension and amyloid-β burden. In contrast, CMB in DLB, despite being predominantly lobar, were associated with hypertension, but not amyloid-β burden. These findings suggest that the underlying pathophysiology of CMB in DLB might differ from that of AD. There was substantially larger number of AD studies identified and more studies evaluating CMB in Lewy body dementias are warranted.
MeSH term(s)	Humans ; Alzheimer Disease/epidemiology ; Alzheimer Disease/complications ; Lewy Body Disease/complications ; Lewy Body Disease/epidemiology ; Dementia/epidemiology ; Dementia/etiology ; Parkinson Disease/complications ; Parkinson Disease/epidemiology ; Prevalence ; Amyloid beta-Peptides ; Cerebral Hemorrhage/diagnostic imaging ; Cerebral Hemorrhage/epidemiology ; Cerebral Hemorrhage/complications ; Hypertension/complications
Chemical Substances	Amyloid beta-Peptides
Language	English
Publishing date	2023-11-19
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2023.11.006
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Zs.A 1685: 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)
Zs.MG 10: Show issues

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Article ; Online: The influence of cerebrovascular disease in dementia with Lewy bodies and Parkinson's disease dementia.

Hijazi, Zina / Yassi, Nawaf / O'Brien, John T / Watson, Rosie

European journal of neurology

2022 Volume 29, Issue 4, Page(s) 1254–1265

Abstract: Background and purpose: Lewy body dementia (LBD), including dementia with Lewy bodies (DLB) and Parkinson's disease dementia, is a common form of neurodegenerative dementia. The frequency and influence of comorbid cerebrovascular disease is not ... ...

Abstract	Background and purpose: Lewy body dementia (LBD), including dementia with Lewy bodies (DLB) and Parkinson's disease dementia, is a common form of neurodegenerative dementia. The frequency and influence of comorbid cerebrovascular disease is not understood but has potentially important clinical management implications. Methods: A systematic literature search was conducted (MEDLINE and Embase) for studies including participants with DLB and/or Parkinson's disease dementia assessing cerebrovascular lesions (imaging and pathological studies). They included white matter changes, cerebral amyloid angiopathy, cerebral microbleeds (CMB), macroscopic infarcts, microinfarcts and intracerebral haemorrhage. Results: Of 4411 articles, 63 studies were included. Cerebrovascular lesions commonly studied included white matter changes (41 studies) and CMB (18 studies). There was an increased severity of white matter changes on magnetic resonance imaging (visualized as white matter hyperintensities), but not neuropathology, in LBD compared to Parkinson's disease without dementia and age-matched controls. CMB prevalence in DLB was highly variable but broadly similar to Alzheimer's disease (0%-48%), with a lobar predominance. No relationship was found between large cortical or small subcortical infarcts or intracerebral haemorrhage and the presence of LBD. Conclusion: The underlying mechanisms of white matter hyperintensities in LBD require further exploration, as their increased severity in LBD was not supported by neuropathological examination of white matter. CMB in LBD had a similar prevalence to Alzheimer's disease. There is a need for larger studies assessing the influence of cerebrovascular lesions on clinical symptoms, disease progression and outcomes.
MeSH term(s)	Alzheimer Disease ; Cerebrovascular Disorders/complications ; Cerebrovascular Disorders/diagnostic imaging ; Cerebrovascular Disorders/epidemiology ; Dementia/epidemiology ; Dementia/etiology ; Humans ; Lewy Body Disease/complications ; Lewy Body Disease/diagnosis ; Lewy Body Disease/epidemiology ; Parkinson Disease/complications ; Parkinson Disease/epidemiology ; Parkinson Disease/pathology
Language	English
Publishing date	2022-01-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.15211
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