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19 pages, 967 KB  
Article
Real-World Laboratory Analysis of Molecular Biomarkers in Multiple Sclerosis Centers in Central-Eastern European Countries Covering 107 Million Inhabitants
by Anett Járdánházy, Thomas Berger, Harald Hegen, Bernhard Hemmer, Halina Bartosik-Psujek, Vanja Basic Kes, Achim Berthele, Jelena Drulovic, Mario Habek, Dana Horakova, Alenka Horvat Ledinek, Eva Kubala Havrdova, Melinda Magyari, Konrad Rejdak, Cristina Tiu, Peter Turcani, Krisztina Bencsik, Zsigmond Tamás Kincses and László Vécsei
Int. J. Mol. Sci. 2025, 26(17), 8274; https://doi.org/10.3390/ijms26178274 - 26 Aug 2025
Viewed by 610
Abstract
A multicenter molecular biomarker survey was conducted in Multiple Sclerosis (MS) centers across Central-Eastern European countries, encompassing a population of 107 million. Our aim was to provide a “snapshot” for future studies investigating the use of molecular biomarkers in MS. A self-report questionnaire [...] Read more.
A multicenter molecular biomarker survey was conducted in Multiple Sclerosis (MS) centers across Central-Eastern European countries, encompassing a population of 107 million. Our aim was to provide a “snapshot” for future studies investigating the use of molecular biomarkers in MS. A self-report questionnaire was distributed via email to MS centers in seven Central-Eastern European countries (Croatia, Czech Republic, Poland, Romania, Serbia, Slovakia, and Slovenia) and to four reference centers (two in Austria, one in Germany, and one in Denmark), focusing on cerebrospinal fluid (CSF) analysis and molecular biomarkers in MS. Responding centers routinely request CSF oligoclonal band (OCB) testing in suspected MS cases, although no consensus exists on the number of CSF-restricted bands required to define OCB positivity, either within or between countries. More than half of the surveyed centers in the Czech Republic, Slovakia, Slovenia, and the reference centers request kappa free light chain (κFLC) testing in patients with suspected MS. Neurofilament light chain (NfL) is frequently used as a molecular biomarker for MS in Romania, Slovakia, and the reference centers. In summary, besides the use of CSF-specific OCB there is no consensus among the surveyed countries regarding the use of molecular biomarkers in MS. Full article
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18 pages, 259 KB  
Article
Religious Pluralism and Identity Among Descendants of Bosnian Migrants in Slovenia
by Ana Ješe Perković
Religions 2025, 16(7), 911; https://doi.org/10.3390/rel16070911 - 16 Jul 2025
Viewed by 396
Abstract
This article examines the religious practices of descendants of Bosnian migrants in Slovenia, a country that stands out as one of the most secular in Europe. While Bosnia and Herzegovina is known for its complex religious pluralism, where religious institutions play a crucial [...] Read more.
This article examines the religious practices of descendants of Bosnian migrants in Slovenia, a country that stands out as one of the most secular in Europe. While Bosnia and Herzegovina is known for its complex religious pluralism, where religious institutions play a crucial role in nation-building, Slovenia presents a contrasting context of secularization. Applying Peter Berger’s theory of religious pluralism, which suggests that pluralism weakens traditional religious authority, this study explores how descendants of Bosnian migrants navigate their religious identities in a secular environment. Although their identities have been shaped by the Yugoslav wars and the post-war redefinition of ethnicity through religion, younger generations are also influenced by broader social processes in Slovenia, including secularization, integration, and exposure to multiple belief systems. Using a qualitative research approach based on semi-structured interviews, this case study investigates the preservation and transformation of religious traditions among Bosnian migrant descendants and how these practices influence their identity. The findings highlight how migration and adaptation to a different socio-cultural environment shape religious practices across generations, contributing to broader discussions on religious choice, identity, and pluralism in contemporary societies. Full article
18 pages, 290 KB  
Article
“Limit Situations” and Sociological Theory: Implications for the Study of Vulnerability and Engaged Spirituality
by Benedetta Nicoli
Religions 2025, 16(5), 656; https://doi.org/10.3390/rel16050656 - 21 May 2025
Viewed by 439
Abstract
This paper aims to advance sociological theory by systematizing the concept of “limit situation”, a term that Berger employs throughout his work, though only in a hinted and unsystematic manner. To achieve this objective, the paper develops a theoretical framework that incorporates different [...] Read more.
This paper aims to advance sociological theory by systematizing the concept of “limit situation”, a term that Berger employs throughout his work, though only in a hinted and unsystematic manner. To achieve this objective, the paper develops a theoretical framework that incorporates different contributions and perspectives. Within this framework, the concept of “limit situation” translates into an analytical tool for the sociological study of vulnerability, particularly in relation to engaged spirituality. The concept is tested through an empirical study based on in-depth interviews with founders, workers, and volunteers from organizations that provide care for individuals facing vulnerability. The analysis shows that encounters with vulnerability, under specific circumstances, create a liminal situation that promotes spirituality at both existential and operational levels. This process informs the value systems of the involved actors and activates specific social practices and relationships. Full article
(This article belongs to the Special Issue Engaged Spiritualities: Theories, Practices, and Future Directions)
25 pages, 1960 KB  
Article
Evaluating Sorafenib (SORA-2) as Second-Line Treatment for Unresectable Hepatocellular Carcinoma: A European Retrospective Multicenter Study
by Christian Möhring, Moritz Berger, Farsaneh Sadeghlar, Xin Zhou, Taotao Zhou, Malte Benedikt Monin, Kateryna Shmanko, Sabrina Welland, Friedrich Sinner, Birgit Schwacha-Eipper, Ulrike Bauer, Christoph Roderburg, Angelo Pirozzi, Najib Ben Khaled, Peter Schrammen, Lorenz Balcar, Matthias Pinter, Thomas J. Ettrich, Anna Saborowski, Marie-Luise Berres, Enrico N. De Toni, Tom Lüdde, Lorenza Rimassa, Ursula Ehmer, Marino Venerito, Iuliana-Pompilia Radu, Ingo G. H. Schmidt-Wolf, Arndt Weinmann, Arndt Vogel, Matthias Schmid, Jörg C. Kalff, Christian P. Strassburg and Maria A. Gonzalez-Carmonaadd Show full author list remove Hide full author list
Cancers 2025, 17(6), 972; https://doi.org/10.3390/cancers17060972 - 13 Mar 2025
Viewed by 1829
Abstract
Background/Objectives: Systemic treatment for unresectable hepatocellular carcinoma (HCC) has rapidly advanced, with immune checkpoint inhibitors now the preferred first-line option. However, with multiple agents available and no established treatment sequence, selecting the most suitable second-line (2L) therapy remains challenging. While sorafenib is frequently [...] Read more.
Background/Objectives: Systemic treatment for unresectable hepatocellular carcinoma (HCC) has rapidly advanced, with immune checkpoint inhibitors now the preferred first-line option. However, with multiple agents available and no established treatment sequence, selecting the most suitable second-line (2L) therapy remains challenging. While sorafenib is frequently chosen for 2L treatment, comprehensive data supporting its use is limited. This study evaluates the effectiveness of sorafenib as 2L therapy and factors influencing outcomes following first-line treatment failure in advanced HCC patients. Methods: This is a retrospective, multicenter study, including 81 patients with unresectable HCC from 12 European centers who received sorafenib as 2L treatment. Median overall survival (mOS), median progression-free survival (mPFS), radiological response to treatment, and toxicity were evaluated. Univariable and multivariable analyses were performed to identify potential predictors of clinical benefit. Results: In this cohort, some patients were treated with 2L sorafenib mOS for 7.4 months (95% CI: 6.6–13.6) and other patients were treated with mPFS for 3.7 months (95% CI: 3.0–4.8). Multivariable analysis revealed the best median OS for patients with CP A and AFP levels < 400 ng/mL (15.5 months). Adverse events (AE) of grade ≥ 3 were reported in 59.4% of patients. Conclusions: In this real-world cohort of European patients with unresectable HCC, the outcome of sorafenib treatment in the 2L setting was comparable to that of the other established 2L treatment options in patients with preserved liver function and good performance status. This study contributes to the understanding of the role of sorafenib in the 2L setting and underscores the need for further research to identify predictive factors for response and survival in order to optimize treatment algorithms for advanced HCC. Full article
(This article belongs to the Special Issue Clinical Studies in Gastrointestinal Malignancies)
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6 pages, 813 KB  
Case Report
Precision Oncology Approach for Urachal Carcinoma: A Clinical Case Report
by Dániel Juhász, Anita Csizmarik, János Szalontai, Attila Keszthelyi, Bálint Dér, András Kubik, Miklós Szűcs, István Kenessey, Iris E. Ertl, Walter Berger, Bernhard Englinger, Shahrokh F. Shariat, Péter Nyirády and Tibor Szarvas
Int. J. Mol. Sci. 2024, 25(24), 13315; https://doi.org/10.3390/ijms252413315 - 12 Dec 2024
Cited by 2 | Viewed by 1609
Abstract
Urachal cancer (UrC) is a rare disease which is mostly diagnosed late due to symptoms caused by its local invasion to the urinary bladder. Given the lack of clinical trials and guideline recommendations for systemic treatment, a molecularly informed precision oncology approach is [...] Read more.
Urachal cancer (UrC) is a rare disease which is mostly diagnosed late due to symptoms caused by its local invasion to the urinary bladder. Given the lack of clinical trials and guideline recommendations for systemic treatment, a molecularly informed precision oncology approach is a viable option for UrC already in the early lines of systemic treatment. While single case experiences may provide valuable reference for later decision-making, well-documented clinical experience with off-label targeted treatments is limited to a few patients. Here, we report a case of a 31-year-old female UrC patient who underwent intensive therapy with three surgeries and five lines of systemic treatments, including chemo-, checkpoint inhibitor and tyrosine kinase inhibitor therapies. In addition, next-generation sequencing (NGS) analysis and an ex vivo drug-screening analysis were performed on patient-derived tumor cells and the results were implemented into the therapeutic decision-making. Finally, serum carcinoembryonic antigen (CEA) levels proved to be helpful for therapy monitoring during the whole follow-up period. Full article
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11 pages, 1174 KB  
Article
Paper-and-Pencil vs. Electronic Patient Records: Analyzing Time Efficiency, Personnel Requirements, and Usability Impacts on Healthcare Administration
by Matthias Fabian Berger, Johanna Petritsch, Andrzej Hecker, Sabrina Pustak, Birgit Michelitsch, Chiara Banfi, Lars-Peter Kamolz and David Benjamin Lumenta
J. Clin. Med. 2024, 13(20), 6214; https://doi.org/10.3390/jcm13206214 - 18 Oct 2024
Cited by 1 | Viewed by 5642
Abstract
Background: This study investigates the impact of transitioning from paper and pencil (P&P) methods to electronic patient records (EPR) on workflow and usability in surgical ward rounds. Methods: Surgical ward rounds were audited by two independent observers to evaluate the effects of transitioning [...] Read more.
Background: This study investigates the impact of transitioning from paper and pencil (P&P) methods to electronic patient records (EPR) on workflow and usability in surgical ward rounds. Methods: Surgical ward rounds were audited by two independent observers to evaluate the effects of transitioning from P&P to EPR. Key observations included the number of medical personnel and five critical workflow aspects before and after EPR implementation. Additionally, usability was assessed using the System Usability Scale (SUS) and the Post-Study System Usability Questionnaire (PSSUQ). Results: A total of 192 P&P and 160 EPR observations were analyzed. Physicians experienced increased administrative workload with EPR, while nurses adapted more easily. Ward teams typically consisted of two physicians and three or four nurses. Usability scores rated the system as “Not Acceptable” across all professional groups. Conclusions: The EPR system introduced usability challenges, particularly for physicians, despite potential benefits like improved data access. Usability flaws hindered system acceptance, highlighting the need for better workflow integration. Addressing these issues could improve efficiency and reduce administrative strain. As artificial intelligence becomes more integrated into clinical practice, healthcare professionals must critically assess AI-driven tools to ensure safe and effective patient care. Full article
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14 pages, 5946 KB  
Technical Note
Characterizing and Implementing the Hamamatsu C12880MA Mini-Spectrometer for Near-Surface Reflectance Measurements of Inland Waters
by Andreas Jechow, Jan Bumberger, Bert Palm, Paul Remmler, Günter Schreck, Igor Ogashawara, Christine Kiel, Katrin Kohnert, Hans-Peter Grossart, Gabriel A. Singer, Jens C. Nejstgaard, Sabine Wollrab, Stella A. Berger and Franz Hölker
Sensors 2024, 24(19), 6445; https://doi.org/10.3390/s24196445 - 5 Oct 2024
Viewed by 4934
Abstract
In recent decades, inland water remote sensing has seen growing interest and very strong development. This includes improved spatial resolution, increased revisiting times, advanced multispectral sensors and recently even hyperspectral sensors. However, inland waters are more challenging than oceanic waters due to their [...] Read more.
In recent decades, inland water remote sensing has seen growing interest and very strong development. This includes improved spatial resolution, increased revisiting times, advanced multispectral sensors and recently even hyperspectral sensors. However, inland waters are more challenging than oceanic waters due to their higher complexity of optically active constituents and stronger adjacency effects due to their small size and nearby vegetation and built structures. Thus, bio-optical modeling of inland waters requires higher ground-truthing efforts. Large-scale ground-based sensor networks that are robust, self-sufficient, non-maintenance-intensive and low-cost could assist this otherwise labor-intensive task. Furthermore, most existing sensor systems are rather expensive, precluding their employability. Recently, low-cost mini-spectrometers have become widely available, which could potentially solve this issue. In this study, we analyze the characteristics of such a mini-spectrometer, the Hamamatsu C12880MA, and test it regarding its application in measuring water-leaving radiance near the surface. Overall, the measurements performed in the laboratory and in the field show that the system is very suitable for the targeted application. Full article
(This article belongs to the Special Issue Feature Papers in Remote Sensors 2024–2025)
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12 pages, 2505 KB  
Article
Evaluation of a Video-Based Concept for Hand Hygiene Education of Parents in a Neonatal Intensive Care Unit
by Judith Rittenschober-Böhm, Johanna Strassl, Maria Kletecka-Pulker, Péter Szerémy, Tamás Haidegger, Tamás Ferenci, Angelika Berger and Michael Wagner
Healthcare 2024, 12(17), 1766; https://doi.org/10.3390/healthcare12171766 - 4 Sep 2024
Cited by 1 | Viewed by 2079
Abstract
Background: Current clinical guidelines support family-centered care in Neonatal Intensive Care Units (NICUs). This implies parents should also be involved in the most critical patient safety measures. Hand hygiene is the single most important tool to prevent healthcare-associated infections and related long-term effects. [...] Read more.
Background: Current clinical guidelines support family-centered care in Neonatal Intensive Care Units (NICUs). This implies parents should also be involved in the most critical patient safety measures. Hand hygiene is the single most important tool to prevent healthcare-associated infections and related long-term effects. Although often studied in healthcare workers, the hand hygiene compliance of parents is rarely assessed. The aim of this study was to evaluate the effectiveness of an educational video, available in ten different languages, in teaching parents hand hygiene techniques in a NICU, lowering the burden on the staff. Methods: Parents in the intervention group were educated through a video; the control group received personal instruction from healthcare workers. The primary outcome parameter was the predicted probability of passing a subsequent hand scan. Results: The quality of hand hygiene among parents educated through the video was at least as good as that of those who received instruction from a healthcare worker, demonstrated by a higher predicted probability of passing the hand scan (43.8% vs. 57.1% in male and 67.9% vs. 75.9% in female participants). The feedback from the intervention group was predominantly positive, with most parents (62%) expressing a preference for video-based education. Conclusion: Implementing a video-based approach seems to be effective for educating parents about hand hygiene in a NICU and was well accepted by the parents. This method offers a consistent standard of hand hygiene education, helps to overcome language barriers, and can also be used as regular reminder of the importance and proper technique of hand hygiene. Full article
(This article belongs to the Special Issue The 10th Anniversary of Healthcare—Perinatal and Neonatal Medicine)
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47 pages, 11537 KB  
Review
Monitoring Water Diversity and Water Quality with Remote Sensing and Traits
by Angela Lausch, Lutz Bannehr, Stella A. Berger, Erik Borg, Jan Bumberger, Jorg M. Hacker, Thomas Heege, Michael Hupfer, András Jung, Katja Kuhwald, Natascha Oppelt, Marion Pause, Franziska Schrodt, Peter Selsam, Fabian von Trentini, Michael Vohland and Cornelia Glässer
Remote Sens. 2024, 16(13), 2425; https://doi.org/10.3390/rs16132425 - 1 Jul 2024
Cited by 13 | Viewed by 6180
Abstract
Changes and disturbances to water diversity and quality are complex and multi-scale in space and time. Although in situ methods provide detailed point information on the condition of water bodies, they are of limited use for making area-based monitoring over time, as aquatic [...] Read more.
Changes and disturbances to water diversity and quality are complex and multi-scale in space and time. Although in situ methods provide detailed point information on the condition of water bodies, they are of limited use for making area-based monitoring over time, as aquatic ecosystems are extremely dynamic. Remote sensing (RS) provides methods and data for the cost-effective, comprehensive, continuous and standardised monitoring of characteristics and changes in characteristics of water diversity and water quality from local and regional scales to the scale of entire continents. In order to apply and better understand RS techniques and their derived spectral indicators in monitoring water diversity and quality, this study defines five characteristics of water diversity and quality that can be monitored using RS. These are the diversity of water traits, the diversity of water genesis, the structural diversity of water, the taxonomic diversity of water and the functional diversity of water. It is essential to record the diversity of water traits to derive the other four characteristics of water diversity from RS. Furthermore, traits are the only and most important interface between in situ and RS monitoring approaches. The monitoring of these five characteristics of water diversity and water quality using RS technologies is presented in detail and discussed using numerous examples. Finally, current and future developments are presented to advance monitoring using RS and the trait approach in modelling, prediction and assessment as a basis for successful monitoring and management strategies. Full article
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10 pages, 198 KB  
Article
Secular Religiosity: Heretical Imperative, Jewish Imponderables
by Paul Robert Mendes-Flohr
Religions 2024, 15(6), 725; https://doi.org/10.3390/rel15060725 - 13 Jun 2024
Viewed by 991
Abstract
The article develops a concept of “secular religiosity” to characterize “post-traditional” Jewish affiliation as an individual and private matter, which the sociologist Peter Berger casts as a “heretical imperative” to make autonomous, individual choices. The waning of the heteronomous authority of rabbinic Judaism, [...] Read more.
The article develops a concept of “secular religiosity” to characterize “post-traditional” Jewish affiliation as an individual and private matter, which the sociologist Peter Berger casts as a “heretical imperative” to make autonomous, individual choices. The waning of the heteronomous authority of rabbinic Judaism, yielded theological and hermeneutic strategies to address the “secular religiosity” of individuals who sought to affirm distinctive Jewish spiritual and devotional practices. The article concludes by adumbrating two contrasting paradigmatic strategies exemplified by Franz Rosenzweig and Martin Buber respectively. Full article
(This article belongs to the Special Issue Heretical Religiosity)
6 pages, 983 KB  
Correction
Correction: Fadil et al. Isotope Ratio Outlier Analysis (IROA) for HPLC–TOFMS-Based Metabolomics of Human Urine. Metabolites 2022, 12, 741
by Fadi Fadil, Claudia Samol, Raffaela S. Berger, Fabian Kellermeier, Wolfram Gronwald, Peter J. Oefner and Katja Dettmer
Metabolites 2024, 14(6), 293; https://doi.org/10.3390/metabo14060293 - 23 May 2024
Cited by 1 | Viewed by 798
Abstract
It was pointed out to us that we had not followed exactly the IROA TruQuant IQQ Workflow Kit protocol in the experimental part of our work [...] Full article
13 pages, 1190 KB  
Article
Evaluation of the Effects of an Undenatured Collagen Type-2-Based Nutraceutical (ARTHROSHINE® HA²) on Recovery Time after TPLO in Dogs: A Prospective, Randomized Study with Objective Gait Analysis as the Primary Outcome Measure
by Maria Assies, Björn Berger, Bente Stegen, Thomas Rohwedder, Marcus Doherr and Peter Böttcher
Animals 2024, 14(2), 298; https://doi.org/10.3390/ani14020298 - 18 Jan 2024
Viewed by 4100
Abstract
This randomized, prospective clinical trial investigates the impact of a novel undenatured collagen type 2 (T2NDC)-based nutraceutical, ARTHROSHINE® HA² (AS), on postoperative rehabilitation following Tibial Plateau Leveling Osteotomy (TPLO) in 50 dogs with unilateral cranial cruciate ligament rupture (CCLR). The patients were [...] Read more.
This randomized, prospective clinical trial investigates the impact of a novel undenatured collagen type 2 (T2NDC)-based nutraceutical, ARTHROSHINE® HA² (AS), on postoperative rehabilitation following Tibial Plateau Leveling Osteotomy (TPLO) in 50 dogs with unilateral cranial cruciate ligament rupture (CCLR). The patients were randomly allocated to either group A, receiving AS once daily for 24 weeks post-TPLO surgery, or group B, without any supplementation. Frequency matching was applied to enhance group comparability. Assessment of outcomes included computerized gait analysis and a validated owner questionnaire. AS supplementation was well received, without any reported side effect. Consistently, patients in group A exhibited significantly higher peak vertical force values during all follow-up assessments. By the 12-week mark, gait analysis indicated a return to a physiological gait pattern in group A, while group B achieved this normalization only by the 24-week point. The administration of AS post-TPLO surgery demonstrates promise in enhancing limb function, leading to faster restoration of a physiological gait pattern. The inclusion of AS, a T2NDC-based nutraceutical, in the post-TPLO rehabilitation protocol may contribute to improved limb function and an expedited recovery, potentially facilitating a quicker return to normalcy. It is noteworthy that subjective owner perceptions did not differ between the two groups. Full article
(This article belongs to the Special Issue Sports Medicine and Rehabilitation in Companion Animals)
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16 pages, 293 KB  
Article
The Health/Salvation Nexus: Religion, New Forms of Spirituality, Medicine and the Problem of “Theodicy”
by Antonio Camorrino
Religions 2024, 15(1), 97; https://doi.org/10.3390/rel15010097 - 11 Jan 2024
Cited by 1 | Viewed by 1873
Abstract
The health/salvation nexus can be better understood if analyzed through the transformations that have affected the social relationship with the sacred in Western society. These changes have caused relevant implications concerning the sphere of “ultimate meaning”, in the words of Peter Berger. Today, [...] Read more.
The health/salvation nexus can be better understood if analyzed through the transformations that have affected the social relationship with the sacred in Western society. These changes have caused relevant implications concerning the sphere of “ultimate meaning”, in the words of Peter Berger. Today, we are witnessing a weakening of legitimized “theodicies” capable of promising—according to Max Weber—salvation and guaranteeing “just equalization”, that is, compensation or metaphysical condemnation for worldly conduct. However, this occurs to different extents depending on whether we are in the field of Western religions or new forms of spirituality. Medicine deserves a separate discussion. The hypothesis is that the health/salvation nexus leans towards salvation in the case of Western religions; towards health in the case of medicine; and, in the case of new forms of spirituality it leans neither exactly towards health nor exactly towards salvation: new forms of spirituality promise more than the achievement of health, but less than the achievement of salvation. Ultimately, the health/salvation nexus is structured differently depending on how much Western religions, new forms of spirituality and medicine are able to respond, more or less effectively, to the questions of “theodicy” and of “ultimate meaning”. I use the term of “theodicy” in the way Max Weber and Peter Berger conceived it: therefore, this concept can also be usefully applied to non-theistic and secular worldviews. Full article
19 pages, 4697 KB  
Article
Loss of Sec-1 Family Domain-Containing 1 (scfd1) Causes Severe Cardiac Defects and Endoplasmic Reticulum Stress in Zebrafish
by Inken G. Huttner, Celine F. Santiago, Arie Jacoby, Delfine Cheng, Gunjan Trivedi, Stephen Cull, Jasmina Cvetkovska, Renee Chand, Joachim Berger, Peter D. Currie, Kelly A. Smith and Diane Fatkin
J. Cardiovasc. Dev. Dis. 2023, 10(10), 408; https://doi.org/10.3390/jcdd10100408 - 22 Sep 2023
Cited by 4 | Viewed by 2357
Abstract
Dilated cardiomyopathy (DCM) is a common heart muscle disorder that frequently leads to heart failure, arrhythmias, and death. While DCM is often heritable, disease-causing mutations are identified in only ~30% of cases. In a forward genetic mutagenesis screen, we identified a novel zebrafish [...] Read more.
Dilated cardiomyopathy (DCM) is a common heart muscle disorder that frequently leads to heart failure, arrhythmias, and death. While DCM is often heritable, disease-causing mutations are identified in only ~30% of cases. In a forward genetic mutagenesis screen, we identified a novel zebrafish mutant, heart and head (hahvcc43), characterized by early-onset cardiomyopathy and craniofacial defects. Linkage analysis and next-generation sequencing identified a nonsense variant in the highly conserved scfd1 gene, also known as sly1, that encodes sec1 family domain-containing 1. Sec1/Munc18 proteins, such as Scfd1, are involved in membrane fusion regulating endoplasmic reticulum (ER)/Golgi transport. CRISPR/Cas9-engineered scfd1vcc44 null mutants showed severe cardiac and craniofacial defects and embryonic lethality that recapitulated the phenotype of hahvcc43 mutants. Electron micrographs of scfd1-depleted cardiomyocytes showed reduced myofibril width and sarcomere density, as well as reticular network disorganization and fragmentation of Golgi stacks. Furthermore, quantitative PCR analysis showed upregulation of ER stress response and apoptosis markers. Both heterozygous hahvcc43 mutants and scfd1vcc44 mutants survived to adulthood, showing chamber dilation and reduced ventricular contraction. Collectively, our data implicate scfd1 loss-of-function as the genetic defect at the hahvcc43 locus and provide new insights into the role of scfd1 in cardiac development and function. Full article
(This article belongs to the Section Basic and Translational Cardiovascular Research)
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22 pages, 26292 KB  
Article
ABCD1 Transporter Deficiency Results in Altered Cholesterol Homeostasis
by Agnieszka Buda, Sonja Forss-Petter, Rong Hua, Yorrick Jaspers, Mark Lassnig, Petra Waidhofer-Söllner, Stephan Kemp, Peter Kim, Isabelle Weinhofer and Johannes Berger
Biomolecules 2023, 13(9), 1333; https://doi.org/10.3390/biom13091333 - 31 Aug 2023
Cited by 8 | Viewed by 3829
Abstract
X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder, is caused by mutations in the peroxisomal transporter ABCD1, resulting in the accumulation of very long-chain fatty acids (VLCFA). Strongly affected cell types, such as oligodendrocytes, adrenocortical cells and macrophages, exhibit high cholesterol turnover. Here, [...] Read more.
X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder, is caused by mutations in the peroxisomal transporter ABCD1, resulting in the accumulation of very long-chain fatty acids (VLCFA). Strongly affected cell types, such as oligodendrocytes, adrenocortical cells and macrophages, exhibit high cholesterol turnover. Here, we investigated how ABCD1 deficiency affects cholesterol metabolism in human X-ALD patient-derived fibroblasts and CNS tissues of Abcd1-deficient mice. Lipidome analyses revealed increased levels of cholesterol esters (CE), containing both saturated VLCFA and mono/polyunsaturated (V)LCFA. The elevated CE(26:0) and CE(26:1) levels remained unchanged in LXR agonist-treated Abcd1 KO mice despite reduced total C26:0. Under high-cholesterol loading, gene expression of SOAT1, converting cholesterol to CE and lipid droplet formation were increased in human X-ALD fibroblasts versus healthy control fibroblasts. However, the expression of NCEH1, catalysing CE hydrolysis and the cholesterol transporter ABCA1 and cholesterol efflux were also upregulated. Elevated Soat1 and Abca1 expression and lipid droplet content were confirmed in the spinal cord of X-ALD mice, where expression of the CNS cholesterol transporter Apoe was also elevated. The extent of peroxisome-lipid droplet co-localisation appeared low and was not impaired by ABCD1-deficiency in cholesterol-loaded primary fibroblasts. Finally, addressing steroidogenesis, progesterone-induced cortisol release was amplified in X-ALD fibroblasts. These results link VLCFA to cholesterol homeostasis and justify further consideration of therapeutic approaches towards reducing VLCFA and cholesterol levels in X-ALD. Full article
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