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| 2. |
- Preis, S, et al.
(author)
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Munich atopy prediction study (MAPS): protocol for a prospective birth cohort addressing clinical and molecular risk factors for atopic dermatitis in early childhood
- 2022
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In: BMJ open. - : BMJ. - 2044-6055. ; 12:9, s. e059256-
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Journal article (peer-reviewed)abstract
- The pathogenesis of atopic diseases is highly complex, and the exact mechanisms leading to atopic dermatitis (AD) onset in infants remain mostly enigmatic. In addition to an interdependent network of components of skin development in young age and skin barrier dysfunction underlying AD development that is only partially understood, a complex interplay between environmental factors and lifestyle habits with skin barrier and immune dysregulation is suspected to contribute to AD onset. This study aims to comprehensively evaluate individual microbiome and immune responses in the context of environmental determinants related the risk of developing AD in the first 4 years of a child’s life.Methods and analysesThe ‘Munich Atopic Prediction Study’ is a comprehensive clinical and biological investigation of a prospective birth cohort from Munich, Germany. Information on pregnancy, child development, environmental factors, parental exposures to potential allergens and acute or chronic diseases of children and parents are collected by questionnaires together with a meticulous clinical examination by trained dermatologists focusing on allergies, skin health, and in particular signs of AD at 2 months after birth and then every 6 months. In addition, skin barrier functions are assessed through cutometry, corneometry and transepidermal water loss at every visit. These measurements are completed with allergy diagnostics and extensive microbiome analyses from stool and skin swabs as well as transcriptome analyses using skin microbiopsies.The aim is to assess the relevance of different known and yet unknown risk factors of AD onset and exacerbations in infants and to identify possible accessible and robust biomarkers.Ethics and disseminationThe study is approved by the Ethical Committee of the Medical Faculty of the Technical University of Munich (reference 334/16S). All relevant study results will be presented at national and international conferences and in peer-reviewed journals.
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| 3. |
- Chouraki, V, et al.
(author)
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Plasma amyloid-β and risk of Alzheimer's disease in the Framingham Heart Study.
- 2015
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:3
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Journal article (peer-reviewed)abstract
- BACKGROUND: Plasma amyloid-β (Aβ) peptide levels have been examined as a low-cost accessible marker for risk of incident Alzheimer's disease (AD) and dementia, but results have varied between studies. We reassessed these associations in one of the largest, prospective, community-based studies to date. METHODS: A total of 2189 dementia-free, Framingham Study participants aged >60 years (mean age, 72 ± 8 years; 56% women) had plasma Aβ1-42 and Aβ1-40 measured and were followed prospectively (mean, 7.6 ± 3.0 years) for dementia/AD. RESULTS: Increased plasma Aβ1-42 levels were associated with lower risk of dementia (Aβ1-42: hazard ratio [HR] = 0.80 [0.71‒0.90], P < .001; Aβ1-42-to-Aβ1-40 ratio: HR = 0.86 [0.76‒0.98], P = .027) and AD (Aβ1-42: HR = 0.79 [0.69‒0.90], P < .001; Aβ1-42-to-Aβ1-40 ratio: HR = 0.83 [0.72‒0.96], P = .012). CONCLUSION: Our results suggest that lower plasma Aβ levels are associated with risk of incident AD and dementia. They encourage further evaluation of plasma Aβ levels as a biomarker for risk of developing clinical AD and dementia. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 5. |
- Amin, Muhammad Umair, et al.
(author)
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Co-delivery of carbonic anhydrase IX inhibitor and doxorubicin as a promising approach to address hypoxia-induced chemoresistance
- 2022
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In: Drug Delivery. - : Informa UK Limited. - 1071-7544 .- 1521-0464. ; 29:1, s. 2072-2085
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Journal article (peer-reviewed)abstract
- Hypoxia, an oxygen-deprived condition of the tumor, is one of the major reasons for resistance to chemotherapy. Carbonic anhydrases are generally involved in pH homeostasis in normal conditions, but in solid tumors having a strong relation with hypoxia, the carbonic anhydrase IX (CA-IX) enzyme is overexpressed and results in an extracellular acidic environment. For most weakly basic anticancer drugs, including doxorubicin (Dox), the ionization in an acidic environment limits their cellular uptake, and consequently, the tumor exposure to the drug at sub-therapeutic concentration comes out as chemoresistance. Herein, a combined drug delivery system of liposomes and mesoporous silica nanoparticles (MSNPs) was developed for the co-delivery of the CA-IX enzyme inhibitor and Dox in hypoxic condition. The unique structure of MSNPs with higher surface area was utilized for higher drug loading and sustained release of Dox. Additionally, the biocompatible nature of liposomal coating as a second loading site for the CA-IX enzyme inhibitor has provided gatekeeping effects at pore opening to avoid premature drug release. Lipid coated MSNPs as a co-delivery system for Dox and the CA-IX inhibitor have synergistic cytotoxic effects against MDA-MB 231 breast cancer cells in hypoxic conditions. These findings assure the potential of this drug delivery system to overcome hypoxia-related chemoresistance.
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| 6. |
- Baumeister, Hannah, et al.
(author)
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A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings
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In: Brain : a journal of neurology. - 1460-2156. ; 147:7, s. 2400-2413
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Journal article (peer-reviewed)abstract
- Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± SD age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (CU; n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (SCD; n = 342), mild cognitive impairment (MCI; n = 118), or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid AD biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5), as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test if baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and MCI conversion rates of CU and SCD participants. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy first affected the medial temporal lobes, followed by further temporal and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological AD biomarker levels, APOE ε4 carriership, and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive AD biomarkers and was associated with more generalised cognitive impairment. Limbic-predominant atrophy, in all and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of MCI conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, both on the subject and group level, were excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for AD in applied settings. The implementation of atrophy subtype- and stage-specific end-points may increase the statistical power of pharmacological trials targeting early AD.
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| 7. |
- Furberg, Helena, et al.
(author)
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
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Journal article (peer-reviewed)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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| 9. |
- Knaapila, Matti, et al.
(author)
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Control over phase behavior and solution structure of hairy-rod polyfluorene by means of side-chain length and branching
- 2008
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In: Physical Review E (Statistical, Nonlinear, and Soft Matter Physics). - 1539-3755. ; 77:5
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Journal article (peer-reviewed)abstract
- We present guidelines on how the solution structure of pi-conjugated hairy-rod polyfluorenes is controlled by the side-chain length and branching. First, the semiquantitative mean-field theory is formulated to predict the phase behavior of the system as a function of side-chain beads (N). The phase transition at N=N* separates a lyotropic phase with solvent coexistence (N < N*) and a metastable membrane phase (N > N*). The membrane phase transforms into the isotropic phase of dissolved rodlike polymers at the temperature T-mem*(N), which decreases both with N and with the degree of side-chain branching. This picture is complemented by polymer demixing with the transition temperature T-IN*(N), which decreases with N. For N < N*, the lyotropic phase turns isotropic with increasing T at T-IN*. For N > N*, stable membranes are predicted for T-IN*< T < T-mem* and metastable membranes with nematic coexistence for T < T-IN*. Second, in experiment, samples of poly(9,9-dialkylfluorene) with N=6-10 were mixed in methylcyclohexane. For N=8 the side-chain branching was controlled by (9,9-dioctylfluorene)/(9,9-bis(2-ethylhexyl)fluorene) (F8/F2/6) random copolymers. The proportion of F8 to F2/6 repeat units was 100:0, 95:5, 90:10, 50:50, and 0:100. In accordance with the theory, lyotropic, membrane, and isotropic phases with the corresponding phase transitions were observed. For N < N*similar to 6 only the lyotropic phase is present for attainable temperatures. The membrane and isotropic phases are present for N > N*. T-mem*(N) decreases from 340 K to 280 K for N >= 8. For copolymers, the membrane phase is found when the fraction of F8 units is at least 90%, T-mem* decreasing with this fraction. The membrane phase contains three material types: loose sheets of two polymer layers, a better packed beta phase, and dissolved polymer. For N >= 7 and T < T-mem* the tendency for membrane formation becomes stronger with increasing temperature.
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| 10. |
- Preis, S, et al.
(author)
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A "hellish" Experience
- 2023
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In: JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT. - 1610-0379. ; 21, s. 145-146
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Conference paper (other academic/artistic)
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