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  • 1
    Online Resource
    Online Resource
    20 Years of ICF—International Classification of Functioning, Disability and Health: Uses and Applications around the World
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 18 ( 2022-09-08), p. 11321-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 18 ( 2022-09-08), p. 11321-
    Abstract: The International Classification of Functioning Disability and Health (ICF) was approved in 2001 and, since then, several studies reported the increased interest about its use in different sectors. A recent overview that summarizes its applications is lacking. This study aims to provide an updated overview about 20 years of ICF application through an international online questionnaire, developed by the byline authors, and sent to each World Health Organization Collaborating Centers of the Family of International Classifications (WHO-FIC CCs). Data was collected during October 2020 and December 2021 and descriptive content analyses were used to report main results. Results show how, in most of the respondent countries represented by WHO-FIC CCs, ICF was mainly used in clinical practice, policy development and social policy, and in education areas. Despite its applications in different sectors, ICF use is not mandatory in most countries but, where used, it provides a biopsychosocial framework for policy development in health, functioning and disability. The study provides information about the needs related to ICF applications, that can be useful to organize targeted intervention plans. Furthermore, this survey methodology can be re-proposed periodically to monitor the use of the ICF in the future.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph191811321
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 2
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    Online Resource
    Development and Degeneration of the Intervertebral Disc—Insights from Across Species
    MDPI AG ; 2023
    In:  Veterinary Sciences Vol. 10, No. 9 ( 2023-08-24), p. 540-
    Details
    In: Veterinary Sciences, MDPI AG, Vol. 10, No. 9 ( 2023-08-24), p. 540-
    Abstract: Back pain caused by intervertebral disc (IVD) degeneration has a major socio-economic impact in humans, yet historically has received minimal attention in species other than humans, mice and dogs. However, a general growing interest in this unique organ prompted the expansion of IVD research in rats, rabbits, cats, horses, monkeys, and cows, further illuminating the complex nature of the organ in both healthy and degenerative states. Application of recent biotechnological advancements, including single cell RNA sequencing and complex data analysis methods has begun to explain the shifting inflammatory signaling, variation in cellular subpopulations, differential gene expression, mechanical loading, and metabolic stresses which contribute to age and stress related degeneration of the IVD. This increase in IVD research across species introduces a need for chronicling IVD advancements and tissue biomarkers both within and between species. Here we provide a comprehensive review of recent single cell RNA sequencing data alongside existing case reports and histo/morphological data to highlight the cellular complexity and metabolic challenges of this unique organ that is of structural importance for all vertebrates.
    Type of Medium: Online Resource
    ISSN: 2306-7381
    URL: Article
    DOI: 10.3390/vetsci10090540
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2768971-2
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  • 3
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    Online Resource
    Quantitative Single-Cell Transcript Assessment of Biomarkers Supports Cellular Heterogeneity in the Bovine IVD
    MDPI AG ; 2019
    In:  Veterinary Sciences Vol. 6, No. 2 ( 2019-05-12), p. 42-
    Details
    In: Veterinary Sciences, MDPI AG, Vol. 6, No. 2 ( 2019-05-12), p. 42-
    Abstract: Severe and chronic low back pain is often associated with intervertebral disc (IVD) degeneration. While imposing a considerable socio-economic burden worldwide, IVD degeneration is also severely impacting on the quality of life of affected individuals. Cell-based regenerative medicine approaches have moved into clinical trials, yet IVD cell identities in the mature disc remain to be fully elucidated and tissue heterogeneity exists, requiring a better characterization of IVD cells. The bovine coccygeal IVD is an accepted research model to study IVD mechano-biology and disc homeostasis. Recently, we identified novel IVD biomarkers in the outer annulus fibrosus (AF) and nucleus pulposus (NP) of the mature bovine coccygeal IVD through RNA in situ hybridization (AP-RISH) and z-proportion test. Here we follow up on Lam1, Thy1, Gli1, Gli3, Noto, Ptprc, Scx, Sox2 and Zscan10 with fluorescent RNA in situ hybridization (FL-RISH) and confocal microscopy. This permits sub-cellular transcript localization and the addition of quantitative single-cell derived values of mRNA expression levels to our previous analysis. Lastly, we used a Gaussian mixture modeling approach for the exploratory analysis of IVD cells. This work complements our earlier cell population proportion-based study, confirms the previously proposed biomarkers and indicates even further heterogeneity of cells in the outer AF and NP of a mature IVD.
    Type of Medium: Online Resource
    ISSN: 2306-7381
    URL: Article
    DOI: 10.3390/vetsci6020042
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2768971-2
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  • 4
    Online Resource
    Online Resource
    Cross-Sectional and Longitudinal Effects of PCB Exposure on Human Stress Hormones in the German HELPcB Surveillance Program
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 13 ( 2020-06-30), p. 4708-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 13 ( 2020-06-30), p. 4708-
    Abstract: Multiple pathological associations are attributed to PCBs (polychlorinated biphenyls). Research shows a positive association of PCBs with dehydroepiandrosterone sulfate (DHEAS) concentration but the results on the stress hormone cortisol have been inconsistent so far. This study is the first to examine not only the cross-sectional but also the longitudinal effects of PCB exposure on the stress hormones DHEAS and cortisol. Over a period of three years, 112 former employees occupationally exposed to PCBs were tested for their body burden with different types of PCBs (lower and higher chlorinated, dioxin-like and hydroxylated) and for their stress hormone concentration. Highly exposed employees showed a significantly higher risk for higher DHEAS values. Multiple linear regression analysis revealed a positive relationship between the exposure to lower chlorinated PCBs and DHEAS. Mixed models also revealed a significantly positive correlation between lower chlorinated PCBs with DHEAS when controlled for a cross-section. However, an effect for cortisol was not found. These results suggest a causal pathophysiological relationship between PCB exposure and DHEAS concentration, but not with cortisol. The health consequences of high DHEAS concentrations are discussed.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17134708
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 5
    Online Resource
    Online Resource
    Depressive Symptoms After PCB Exposure: Hypotheses for Underlying Pathomechanisms via the Thyroid and Dopamine System
    MDPI AG ; 2019
    In:  International Journal of Environmental Research and Public Health Vol. 16, No. 6 ( 2019-03-16), p. 950-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 16, No. 6 ( 2019-03-16), p. 950-
    Abstract: Polychlorinated biphenyls’ (PCB) exposure has been reported to be associated with depressive symptoms, which is correlated to lower dopamine- (DA) and thyroxine-concentrations (T4). T4 is necessary for DA-synthesis and it binds to transthyretin (TTR) being transported into the brain. PCBs can displace T4 by binding to TTR itself, being transported into the brain and disturbing DA-synthesis, where depressive symptoms might occur. Consequently, the free T4-concentration (fT4) increases when PCBs bind to TTR. The interaction of PCBs with fT4 and its associations with the main DA metabolite, homovanillic acid (HVA), and depressive symptoms were investigated. In total, 116 participants (91.6% men) were investigated, who took part in three annual examinations (t1–t3) of the HELPcB health surveillance program. Blood was collected for measuring PCBs, hydroxy PCBs (OH-PCBs), and fT4 and urine for HVA. Depressive Symptoms were assessed with a standardized questionnaire. Interactions were tested cross-sectionally with multiple hierarchical regressions and longitudinally with mixed effect models. Related to HVA, an interaction was cross-sectionally found for lower-chlorinated PCBs (LPCBs) and dioxin-like PCBs (dlPCBs); longitudinally only for LPCBs. Related to depressive symptoms, the interaction was found for LPCBs, dlPCBs, and OH-PCBs; longitudinally again only for LPCBs. The results give first hints that a physiological process involving the thyroid and DA system is responsible for depressive symptoms after PCB exposure.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph16060950
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2175195-X
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  • 6
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    Online Resource
    Analogues of Natural Chalcones as Efficient Inhibitors of AKR1C3
    MDPI AG ; 2022
    In:  Metabolites Vol. 12, No. 2 ( 2022-01-21), p. 99-
    Details
    In: Metabolites, MDPI AG, Vol. 12, No. 2 ( 2022-01-21), p. 99-
    Abstract: Naturally occurring substances are valuable resources for drug development. In this respect, chalcones are known to be antiproliferative agents against prostate cancer cell lines through various mechanisms or targets. Based on the literature and preliminary results, we aimed to study and optimise the efficiency of a series of chalcones to inhibit androgen-converting AKR1C3, known to promote prostate cancer. A total of 12 chalcones with different substitution patterns were synthesised. Structure–activity relationships associated with these modifications on AKR1C3 inhibition were analysed by performing enzymatic assays and docking simulations. In addition, the selectivity and cytotoxicity of the compounds were assessed. In enzymatic assays, C-6′ hydroxylated derivatives were more active than C-6′ methoxylated derivatives. In contrast, C-4 methylation increased activity over C-4 hydroxylation. Docking results supported these findings with the most active compounds fitting nicely in the binding site and exhibiting strong interactions with key amino acid residues. The most effective inhibitors were not cytotoxic for HEK293T cells and selective for 17β-hydroxysteroid dehydrogenases not primarily involved in steroid hormone metabolism. Nevertheless, they inhibited several enzymes of the steroid metabolism pathways. Favourable substitutions that enhanced AKR1C3 inhibition of chalcones were identified. This study paves the way to further develop compounds from this series or related flavonoids with improved inhibitory activity against AKR1C3.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    URL: Article
    DOI: 10.3390/metabo12020099
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662251-8
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  • 7
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    Online Resource
    The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 6 ( 2022-03-12), p. 3073-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 6 ( 2022-03-12), p. 3073-
    Abstract: Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23063073
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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