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Authors = David Werner ORCID = 0000-0002-6741-1256

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19 pages, 3064 KiB  
Article
HR-pQCT and 3D Printing for Forensic and Orthopaedic Analysis of Gunshot-Induced Bone Damage
by Richard Andreas Lindtner, Lukas Kampik, Werner Schmölz, Mateus Enzenberg, David Putzer, Rohit Arora, Bettina Zelger, Claudia Wöss, Gerald Degenhart, Christian Kremser, Michaela Lackner, Anton Kasper Pallua, Michael Schirmer and Johannes Dominikus Pallua
Biomedicines 2025, 13(7), 1742; https://doi.org/10.3390/biomedicines13071742 - 16 Jul 2025
Viewed by 281
Abstract
Background/Objectives: Recent breakthroughs in three-dimensional (3D) printing and high-resolution imaging have opened up new possibilities in personalized medicine, surgical planning, and forensic reconstruction. This study breaks new ground by evaluating the integration of high-resolution peripheral quantitative computed tomography (HR-pQCT) with multimodal imaging and [...] Read more.
Background/Objectives: Recent breakthroughs in three-dimensional (3D) printing and high-resolution imaging have opened up new possibilities in personalized medicine, surgical planning, and forensic reconstruction. This study breaks new ground by evaluating the integration of high-resolution peripheral quantitative computed tomography (HR-pQCT) with multimodal imaging and additive manufacturing to assess a chronic, infected gunshot injury in the knee joint of a red deer. This unique approach serves as a translational model for complex skeletal trauma. Methods: Multimodal imaging—including clinical CT, MRI, and HR-pQCT—was used to characterise the extent of osseous and soft tissue damage. Histopathological and molecular analyses were performed to confirm the infectious agent. HR-pQCT datasets were segmented and processed for 3D printing using PolyJet, stereolithography (SLA), and fused deposition modelling (FDM). Printed models were quantitatively benchmarked through 3D surface deviation analysis. Results: Imaging revealed comminuted fractures, cortical and trabecular degradation, and soft tissue involvement, consistent with chronic osteomyelitis. Sphingomonas sp., a bacterium that forms biofilms, was identified as the pathogen. Among the printing methods, PolyJet and SLA demonstrated the highest anatomical accuracy, whereas FDM exhibited greater geometric deviation. Conclusions: HR-pQCT-guided 3D printing provides a powerful tool for the anatomical visualisation and quantitative assessment of complex bone pathology. This approach not only enhances diagnostic precision but also supports applications in surgical rehearsal and forensic analysis. It illustrates the potential of digital imaging and additive manufacturing to advance orthopaedic and trauma care, inspiring future research and applications in the field. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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10 pages, 478 KiB  
Article
Knee Loading Asymmetries During Descent and Ascent Phases of Squatting After ACL Reconstruction
by Manuel Angel Romero Padron, Alyx Jorgensen, David M. Werner, Matthew Alan Tao and Elizabeth Wellsandt
Appl. Sci. 2025, 15(14), 7780; https://doi.org/10.3390/app15147780 - 11 Jul 2025
Viewed by 283
Abstract
Asymmetries are common during squats following anterior cruciate ligament reconstruction (ACLR). This study examined interlimb loading differences between squat phases at 6 months post-ACLR. Thirty-five participants performed bodyweight squats at self-selected speed and were analyzed using 3D motion capture. Vertical ground reaction force [...] Read more.
Asymmetries are common during squats following anterior cruciate ligament reconstruction (ACLR). This study examined interlimb loading differences between squat phases at 6 months post-ACLR. Thirty-five participants performed bodyweight squats at self-selected speed and were analyzed using 3D motion capture. Vertical ground reaction force impulse (vGRFi), external knee flexion moment impulse (KFMi) and hip-to-knee flexion moment impulse ratio (HKRi) were calculated, along with interlimb ratios (ILR). Squat phase durations were also recorded. Paired t-tests and ANCOVA (controlling for time) were used to compare biomechanical variables across squat phases. Greater asymmetry was observed during ascent for vGRFi ILR (p = 0.045), KFMi ILR (p < 0.001) and HKRi ILR (p = 0.006). The ascent phase was faster than descent (p = 0.036). After adjusting for time, phase-related differences in ILRs were no longer significant. These findings suggest that greater limb and knee-specific loading asymmetries occur during the ascent phase of squats but may be influenced by movement speed. Importantly, significant knee-specific loading asymmetries persisted regardless of squat phase. At 6 months post-ACLR, addressing neuromuscular control and movement speed during rehabilitation may help reduce biomechanical imbalances during closed kinetic chain exercises. Full article
(This article belongs to the Special Issue Applied Biomechanics and Sports Sciences)
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19 pages, 4983 KiB  
Article
The Role of Chair Design in Dental Ergonomics: A Kinematic Assessment of Movement and Ergonomic Risk
by Fabian Holzgreve, Jasmin Preuß, Christina Erbe, Werner Betz, Eileen M. Wanke, Gerhard Oremek, Doerthe Brueggmann, Albert Nienhaus, David A. Groneberg, Christian Maurer-Grubinger and Daniela Ohlendorf
Bioengineering 2025, 12(4), 353; https://doi.org/10.3390/bioengineering12040353 - 29 Mar 2025
Viewed by 948
Abstract
Introduction: Dental professionals are susceptible to musculoskeletal disorders due to unphysiological postures during treatment, which can be mitigated by the choice of a work chair to improve ergonomic working posture. Methods: In this study, the influence of five different work chairs on the [...] Read more.
Introduction: Dental professionals are susceptible to musculoskeletal disorders due to unphysiological postures during treatment, which can be mitigated by the choice of a work chair to improve ergonomic working posture. Methods: In this study, the influence of five different work chairs on the ergonomic risk assessment using RULA and the working behaviour of 22 right-handed dentists was investigated. To this end, dental treatment was simulated on a phantom head, with the body posture recorded using an inertial motion capture system. The resulting kinematic data were converted into a continuous RULA scheme, and statistical methods (Friedman test with Conover–Iman comparisons and statistical parametric mapping) were used to compare the chairs. The significance level was set at p ≤ 0.05. Results: The RULA analysis revealed no significant differences between the task chairs that were tested; however, it should be noted that all of the task chairs exhibited an increased ergonomic risk (RULA ≥ 5), which indicates an increased risk of musculoskeletal disorders. Significant multiple comparisons (SPM analysis) between the selected chairs of the relative occurrence of total joint angles were between Chair 1 vs. 5 (p ≤ 0.03 for shoulder left flexion–extension), Chair 2 vs. 4 (p ≤ 0.03 for shoulder right flexion–extension), Chair 1 vs. 3 (p ≤ 0.03 for trunk right flexion–extension, 0.04 for trunk lateral flexion and 0.05 for elbow left flexion–extension), Chair 3 vs. 4 (p ≤ 0.05 for shoulder left flexion–extension and 0.01 shoulder right flexion–extension), and between Chair 2 vs. 3 (p ≤ 0.05 for elbow left flexion–extension). Discussion: The study’s findings indicate that the selection of work chairs did not have a significant impact on the ergonomic risk, which remained consistently high across all the chairs. Nevertheless, the analysis of joint angles demonstrated that the Ghopec chair was more frequently associated with greater joint angles, with only a few significant deviations. However, it should be noted that these significant differences in joint angles occurred only sporadically, did not demonstrate a clear and consistent trend across all the chairs, and have no clinical impact. Overall, the results confirm that the working posture of the dentists has a potential risk of developing musculoskeletal disorders, while the ergonomic design of the work chairs plays a rather subordinate role. Full article
(This article belongs to the Section Biomechanics and Sports Medicine)
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3 pages, 146 KiB  
Opinion
Challenges and Opportunities for Urban Water That Is Fit to Play in
by David Werner
Hydrology 2025, 12(4), 75; https://doi.org/10.3390/hydrology12040075 - 28 Mar 2025
Viewed by 595
Abstract
As cities in Europe and beyond recognize the flood protection, recreational, and biodiversity benefits of blue-green spaces, human interaction with urban water is increasing. This trend raises public health concerns that must be addressed by the scientific community, regulators, and the water industry. [...] Read more.
As cities in Europe and beyond recognize the flood protection, recreational, and biodiversity benefits of blue-green spaces, human interaction with urban water is increasing. This trend raises public health concerns that must be addressed by the scientific community, regulators, and the water industry. Advances in measurement and modelling have made continuous city-scale water quality monitoring for real-time risk communication a realistic goal. Achieving this goal requires quality-assured data on hydrology, water quality, drainage infrastructure, and land use, along with robust mechanistic models and a deeper understanding of human behaviour. Full article
4 pages, 158 KiB  
Editorial
Special Issue on Scheduling Theory and Algorithms for Sustainable Manufacturing
by Alexandre Dolgui, David Lemoine, María I. Restrepo and Frank Werner
Algorithms 2025, 18(1), 15; https://doi.org/10.3390/a18010015 - 3 Jan 2025
Viewed by 1029
Abstract
The following Special Issue was initiated at the 10th IFAC triennial conference MIM 2022 (https://hub [...] Full article
(This article belongs to the Special Issue Scheduling Theory and Algorithms for Sustainable Manufacturing)
14 pages, 2601 KiB  
Article
Endoscopic In Vivo Hyperspectral Imaging for Head and Neck Tumor Surgeries Using a Medically Approved CE-Certified Camera with Rapid Visualization During Surgery
by Ayman Bali, Thomas Bitter, Marcela Mafra, Jonas Ballmaier, Mussab Kouka, Gerlind Schneider, Anna Mühlig, Nadja Ziller, Theresa Werner, Ferdinand von Eggeling, Orlando Guntinas-Lichius and David Pertzborn
Cancers 2024, 16(22), 3785; https://doi.org/10.3390/cancers16223785 - 10 Nov 2024
Cited by 2 | Viewed by 1832
Abstract
Background: In vivo visualization of malignant tumors remains the main challenge during head and neck cancer surgery. This can result in inadequate tumor margin assessment and incomplete tumor resection, adversely affecting patient outcomes. Hyperspectral imaging (HSI) is a promising approach to address [...] Read more.
Background: In vivo visualization of malignant tumors remains the main challenge during head and neck cancer surgery. This can result in inadequate tumor margin assessment and incomplete tumor resection, adversely affecting patient outcomes. Hyperspectral imaging (HSI) is a promising approach to address this issue. However, its application in surgery has been limited by the lack of medically approved HSI devices compliant with MDR regulations, as well as challenges regarding the integration into the surgical workflow. Methods: In this feasibility study, we employed endoscopic HSI during surgery to visualize the tumor sites of 12 head and neck cancer patients. We optimized the HSI workflow to minimize time required during surgery and to reduce the adaptation period needed for surgeons to adjust to the new workflow. Additionally, we implemented data processing to enable real-time classification and visualization of HSI within the intraoperative setting. HSI evaluation was conducted using principal component analysis and k-means clustering, with this clustering validated through comparison with expert annotations. Results: Our complete HSI workflow requires two to three minutes, with each HSI measurement—including evaluation and visualization—taking less than 10 s, achieving an accuracy of 79%, sensitivity of 72%, and specificity of 84%. Medical personnel became proficient with the HSI system after two surgeries. Conclusions: This study presents an HSI workflow for in vivo tissue differentiation during head and neck cancer surgery, providing accurate and visually accessible results within minimal time. This approach enhances the in vivo evaluation of tumor margins, leading to more clear margins and, consequently, improved patient outcomes. Full article
(This article belongs to the Section Methods and Technologies Development)
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12 pages, 1538 KiB  
Brief Report
STAR LIGHT Study: XBB.1.5 COVID-19 mRNA Vaccines Boost Systemic but Not Mucosal Immunity Against the SARS-CoV-2 JN.1 Variant in Patients with Chronic Liver Disease
by Simon Woelfel, Daniel Junker, Irina Bergamin, Pamela Meyer-Herbon, Roman Stillhard, Nicole Graf, Georg Leinenkugel, Joel Dütschler, Marius König, Livia Kammerlander, Rahel Häuptle, Sarah Zwyssig, Claudia Krieger, Samuel Truniger, Seraina Koller, Katline Metzger-Peter, Nicola Frei, STAR SIGN Study Investigators, Werner C. Albrich, Matthias Friedrich, Christine Bernsmeier, Jan Hendrik Niess, Wolfgang Korte, Justus J. Bürgi, Alex Dulovic, Nicole Schneiderhan-Marra, David Semela and Stephan Brandadd Show full author list remove Hide full author list
Vaccines 2024, 12(11), 1241; https://doi.org/10.3390/vaccines12111241 - 31 Oct 2024
Cited by 1 | Viewed by 2007
Abstract
Background: Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied. Methods: We present the first [...] Read more.
Background: Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied. Methods: We present the first evaluation of XBB.1.5 COVID-19 vaccine immunogenicity against the SARS-CoV-2 JN.1 variant in patients with CLD. Serum anti-receptor binding domain (RBD) IgG, neutralization, and saliva anti-RBD IgG and IgA against wild-type SARS-CoV-2 (WT) and the XBB.1.5, EG.5.1, BA.2.86, and JN.1 variants were quantified before and 2–4 weeks following a fourth dose of XBB.1.5 mRNA vaccines. Results: Vaccination boosted anti-RBD IgG and neutralization against all tested variants including JN.1 (each p < 0.001). Following immunization, neutralization was lower against JN.1 compared to WT, XBB.1.5, and EG.5.1 (p < 0.001, p < 0.001, and p < 0.01, respectively). Vaccination reduced neutralization failure rates against BA.2.86 and JN.1 (each p < 0.05). The evasion of vaccine-induced antibodies by the tested variants was low, indicated by the positive correlation between anti-RBD IgG and neutralization. At mucosal sites, vaccination boosted anti-RBD IgG (each p < 0.01) but failed to induce infection-blocking IgA (each p > 0.05). Conclusion: XBB.1.5 vaccines protect CLD patients against recent SARS-CoV-2 variants, but developing vaccines with optimized mucosal immunogenicity is required to prevent SARS-CoV-2 transmission and recurrent seasonal COVID-19 outbreaks. Full article
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16 pages, 2836 KiB  
Article
Does the Addition of Low-Dose Antibiotics Compromise the Mechanical Properties of Polymethylmethacrylate (PMMA)?
by Valentina Egger, Dietmar Dammerer, Gerald Degenhart, Johannes D. Pallua, Werner Schmölz, Martin Thaler, Klaus-Dieter Kühn, Michael Nogler and David Putzer
Polymers 2024, 16(16), 2378; https://doi.org/10.3390/polym16162378 - 22 Aug 2024
Cited by 7 | Viewed by 1115
Abstract
The increasing numbers of total joint replacements and related implant-associated infections demand solutions, which can provide a high-dose local delivery of antibiotics. Antibiotic-loaded bone cement (ALBC) is an accepted treatment method for infected joint arthroplasties. The mechanical properties of low-dose gentamicin-loaded bone cement [...] Read more.
The increasing numbers of total joint replacements and related implant-associated infections demand solutions, which can provide a high-dose local delivery of antibiotics. Antibiotic-loaded bone cement (ALBC) is an accepted treatment method for infected joint arthroplasties. The mechanical properties of low-dose gentamicin-loaded bone cement (BC) in medium- and high-viscosity versions were compared to unloaded BC using a vacuum mixing system. As an additional control group, manual mixed unloaded BC was used. In a uniaxial compression test, ultimate compressive strength, compressive yield strength, and compression modulus of elasticity, as well as ultimate and yield strain, were determined according to ISO 5833-2022 guidelines. All groups exceeded the minimum compressive strength (70 MPa) specified in the ISO 5833 guidelines. Both ALBC groups showed a similar ultimate compressive and yield strength to the unloaded BC. The results showed that vacuum mixing increased the compression strength of BC. ALBC showed similar compressive strength to their non-antibiotic counterparts when vacuum mixing was performed. Added low-dose gentamicin acted as a plasticizer on bone cement. From a biomechanical point of view, the usage of gentamicin-based ALBC formulations is viable. Full article
(This article belongs to the Special Issue Physicochemical Properties of Polymer Composites)
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21 pages, 1468 KiB  
Article
Ergonomic Analysis of Dental Work in Different Oral Quadrants: A Motion Capture Preliminary Study among Endodontists
by Sophie Feige, Fabian Holzgreve, Laura Fraeulin, Christian Maurer-Grubinger, Werner Betz, Christina Erbe, Albert Nienhaus, David A. Groneberg and Daniela Ohlendorf
Bioengineering 2024, 11(4), 400; https://doi.org/10.3390/bioengineering11040400 - 19 Apr 2024
Cited by 6 | Viewed by 2798
Abstract
Background: Dentists, including endodontists, frequently experience musculoskeletal disorders due to unfavourable working postures. Several measures are known to reduce the ergonomic risk; however, there are still gaps in the research, particularly in relation to dental work in the different oral regions (Quadrants 1–4). [...] Read more.
Background: Dentists, including endodontists, frequently experience musculoskeletal disorders due to unfavourable working postures. Several measures are known to reduce the ergonomic risk; however, there are still gaps in the research, particularly in relation to dental work in the different oral regions (Quadrants 1–4). Methods: In this study (of a pilot character), a total of 15 dentists (8 male and 7 female) specialising in endodontics were measured while performing root canal treatments on a phantom head. These measurements took place in a laboratory setting using an inertial motion capture system. A slightly modified Rapid Upper Limb Assessment (RULA) coding system was employed for the analysis of kinematic data. The significance level was set at p = 0.05. Results: The ergonomic risk for the entire body was higher in the fourth quadrant than in the first quadrant for 80% of the endodontists and higher than in the second quadrant for 87%. For 87% of the endodontists, the ergonomic risk for the right side of the body was significantly higher in the fourth quadrant compared to the first and second quadrant. The right arm was stressed more in the lower jaw than in the upper jaw, and the neck also showed a greater ergonomic risk in the fourth quadrant compared to the first quadrant. Conclusion: In summary, both the total RULA score and scores for the right- and lefthand sides of the body ranged between 5 and 6 out of a possible 7 points. Considering this considerable burden, heightened attention, especially to the fourth quadrant with a significantly higher ergonomic risk compared to Quadrants 1 and 2, may be warranted. Full article
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10 pages, 6249 KiB  
Article
AI-Based Detection of Oral Squamous Cell Carcinoma with Raman Histology
by Andreas Weber, Kathrin Enderle-Ammour, Konrad Kurowski, Marc C. Metzger, Philipp Poxleitner, Martin Werner, René Rothweiler, Jürgen Beck, Jakob Straehle, Rainer Schmelzeisen, David Steybe and Peter Bronsert
Cancers 2024, 16(4), 689; https://doi.org/10.3390/cancers16040689 - 6 Feb 2024
Cited by 6 | Viewed by 2527
Abstract
Stimulated Raman Histology (SRH) employs the stimulated Raman scattering (SRS) of photons at biomolecules in tissue samples to generate histological images. Subsequent pathological analysis allows for an intraoperative evaluation without the need for sectioning and staining. The objective of this study was to [...] Read more.
Stimulated Raman Histology (SRH) employs the stimulated Raman scattering (SRS) of photons at biomolecules in tissue samples to generate histological images. Subsequent pathological analysis allows for an intraoperative evaluation without the need for sectioning and staining. The objective of this study was to investigate a deep learning-based classification of oral squamous cell carcinoma (OSCC) and the sub-classification of non-malignant tissue types, as well as to compare the performances of the classifier between SRS and SRH images. Raman shifts were measured at wavenumbers k1 = 2845 cm−1 and k2 = 2930 cm−1. SRS images were transformed into SRH images resembling traditional H&E-stained frozen sections. The annotation of 6 tissue types was performed on images obtained from 80 tissue samples from eight OSCC patients. A VGG19-based convolutional neural network was then trained on 64 SRS images (and corresponding SRH images) and tested on 16. A balanced accuracy of 0.90 (0.87 for SRH images) and F1-scores of 0.91 (0.91 for SRH) for stroma, 0.98 (0.96 for SRH) for adipose tissue, 0.90 (0.87 for SRH) for squamous epithelium, 0.92 (0.76 for SRH) for muscle, 0.87 (0.90 for SRH) for glandular tissue, and 0.88 (0.87 for SRH) for tumor were achieved. The results of this study demonstrate the suitability of deep learning for the intraoperative identification of tissue types directly on SRS and SRH images. Full article
(This article belongs to the Special Issue Recent Advances in Oncology Imaging)
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14 pages, 2351 KiB  
Review
Reconstruction of the Anterior Skull Base Using the Nasoseptal Flap: A Review
by Michael T. Werner, Desmond Yeoh, Judd H. Fastenberg, Mark B. Chaskes, Aron Z. Pollack, John A. Boockvar, David J. Langer, Randy S. D’Amico, Jason A. Ellis, Brett A. Miles and Charles C. L. Tong
Cancers 2024, 16(1), 169; https://doi.org/10.3390/cancers16010169 - 29 Dec 2023
Cited by 6 | Viewed by 4062
Abstract
The nasoseptal flap is a workhorse reconstructive option for anterior skull base defects during endonasal surgery. This paper highlights the versatility of the nasoseptal flap. After providing a brief historical perspective, this review will focus on the relevant primary literature published in the [...] Read more.
The nasoseptal flap is a workhorse reconstructive option for anterior skull base defects during endonasal surgery. This paper highlights the versatility of the nasoseptal flap. After providing a brief historical perspective, this review will focus on the relevant primary literature published in the last ten years. We will touch upon new applications of the flap, how the flap has been modified to expand its reach and robustness, and some of the current limitations. We will conclude by discussing what the future holds for improving upon the design and use of the nasoseptal flap in anterior skull base reconstruction. Full article
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18 pages, 2130 KiB  
Article
User Perceptions of Avatar-Based Patient Monitoring for Intensive Care Units: An International Exploratory Sequential Mixed-Methods Study
by Justyna Lunkiewicz, Greta Gasciauskaite, Tadzio Raoul Roche, Samira Akbas, Christoph B. Nöthiger, Michael T. Ganter, Patrick Meybohm, Sebastian Hottenrott, Kai Zacharowski, Florian Jürgen Raimann, Eva Rivas, Manuel López-Baamonde, Elisabeth Anna Beller, David Werner Tscholl and Lisa Bergauer
Diagnostics 2023, 13(21), 3391; https://doi.org/10.3390/diagnostics13213391 - 6 Nov 2023
Cited by 1 | Viewed by 2350
Abstract
Visual Patient Avatar ICU is an innovative approach to patient monitoring, enhancing the user’s situation awareness in intensive care settings. It dynamically displays the patient’s current vital signs using changes in color, shape, and animation. The technology can also indicate patient-inserted devices, such [...] Read more.
Visual Patient Avatar ICU is an innovative approach to patient monitoring, enhancing the user’s situation awareness in intensive care settings. It dynamically displays the patient’s current vital signs using changes in color, shape, and animation. The technology can also indicate patient-inserted devices, such as arterial lines, central lines, and urinary catheters, along with their insertion locations. We conducted an international, multi-center study using a sequential qualitative-quantitative design to evaluate users’ perception of Visual Patient Avatar ICU among physicians and nurses. Twenty-five nurses and twenty-five physicians from the ICU participated in the structured interviews. Forty of them completed the online survey. Overall, ICU professionals expressed a positive outlook on Visual Patient Avatar ICU. They described Visual Patient Avatar ICU as a simple and intuitive tool that improved information retention and facilitated problem identification. However, a subset of participants expressed concerns about potential information overload and a sense of incompleteness due to missing exact numerical values. These findings provide valuable insights into user perceptions of Visual Patient Avatar ICU and encourage further technology development before clinical implementation. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics Technology and Applications)
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38 pages, 4754 KiB  
Review
Challenges in Permeability Assessment for Oral Drug Product Development
by Mirko Koziolek, Patrick Augustijns, Constantin Berger, Rodrigo Cristofoletti, David Dahlgren, Janneke Keemink, Pär Matsson, Fiona McCartney, Marco Metzger, Mario Mezler, Janis Niessen, James E. Polli, Maria Vertzoni, Werner Weitschies and Jennifer Dressman
Pharmaceutics 2023, 15(10), 2397; https://doi.org/10.3390/pharmaceutics15102397 - 28 Sep 2023
Cited by 15 | Viewed by 4984
Abstract
Drug permeation across the intestinal epithelium is a prerequisite for successful oral drug delivery. The increased interest in oral administration of peptides, as well as poorly soluble and poorly permeable compounds such as drugs for targeted protein degradation, have made permeability a key [...] Read more.
Drug permeation across the intestinal epithelium is a prerequisite for successful oral drug delivery. The increased interest in oral administration of peptides, as well as poorly soluble and poorly permeable compounds such as drugs for targeted protein degradation, have made permeability a key parameter in oral drug product development. This review describes the various in vitro, in silico and in vivo methodologies that are applied to determine drug permeability in the human gastrointestinal tract and identifies how they are applied in the different stages of drug development. The various methods used to predict, estimate or measure permeability values, ranging from in silico and in vitro methods all the way to studies in animals and humans, are discussed with regard to their advantages, limitations and applications. A special focus is put on novel techniques such as computational approaches, gut-on-chip models and human tissue-based models, where significant progress has been made in the last few years. In addition, the impact of permeability estimations on PK predictions in PBPK modeling, the degree to which excipients can affect drug permeability in clinical studies and the requirements for colonic drug absorption are addressed. Full article
(This article belongs to the Special Issue Recent Advances in Oral Biopharmaceutics)
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15 pages, 3044 KiB  
Article
Comparison of the Declared Nutrient Content of Plant-Based Meat Substitutes and Corresponding Meat Products and Sausages in Germany
by Corinna Gréa, Anna Dittmann, David Wolff, Romy Werner, Christin Turban, Silvia Roser, Ingrid Hoffmann and Stefan Storcksdieck genannt Bonsmann
Nutrients 2023, 15(18), 3864; https://doi.org/10.3390/nu15183864 - 5 Sep 2023
Cited by 5 | Viewed by 3657
Abstract
Plant-based meat substitutes (PBMS) are becoming increasingly popular due to growing concerns about health, animal welfare, and environmental issues associated with animal-based foods. The aim of this study was to compare the declared energy and nutrient contents of PBMS with corresponding meat products [...] Read more.
Plant-based meat substitutes (PBMS) are becoming increasingly popular due to growing concerns about health, animal welfare, and environmental issues associated with animal-based foods. The aim of this study was to compare the declared energy and nutrient contents of PBMS with corresponding meat products and sausages available on the German market. Mandatory nutrition labelling data of 424 PBMS and 1026 meat products and sausages, surveyed in 2021 and 2020, respectively, as part of the German national monitoring of packaged food were used to test for differences in energy and nutrient contents. Principal component analysis (PCA) was used to describe characteristics in the energy and nutrient contents. The comparison showed that most of the PBMS subcategories had significantly lower contents of fat and saturated fat but higher contents of carbohydrate and sugar than corresponding meat subcategories. For salt, the only striking difference was that PBMS salamis had lower salt content than meat salamis. Overall, the PCA revealed protein as a main characteristic for most PBMS categories, with the protein content being equivalent to or, in most protein-based PBMS, even higher than in the corresponding meat products. The wide nutrient content ranges within subcategories, especially for salt, reveal the need and potential for reformulation. Full article
(This article belongs to the Section Nutrition and Public Health)
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15 pages, 3649 KiB  
Article
Whole-Genome Sequencing Identified New Structural Variations in the DMD Gene That Cause Duchenne Muscular Dystrophy in Two Girls
by Natalie Pluta, Arpad von Moers, Astrid Pechmann, Werner Stenzel, Hans-Hilmar Goebel, David Atlan, Beat Wolf, Indrajit Nanda, Ann-Kathrin Zaum and Simone Rost
Int. J. Mol. Sci. 2023, 24(17), 13567; https://doi.org/10.3390/ijms241713567 - 1 Sep 2023
Cited by 3 | Viewed by 2339
Abstract
Dystrophinopathies are the most common muscle diseases, especially in men. In women, on the other hand, a manifestation of Duchenne muscular dystrophy is rare due to X-chromosomal inheritance. We present two young girls with severe muscle weakness, muscular dystrophies, and creatine kinase (CK) [...] Read more.
Dystrophinopathies are the most common muscle diseases, especially in men. In women, on the other hand, a manifestation of Duchenne muscular dystrophy is rare due to X-chromosomal inheritance. We present two young girls with severe muscle weakness, muscular dystrophies, and creatine kinase (CK) levels exceeding 10,000 U/L. In the skeletal muscle tissues, dystrophin staining reaction showed mosaicism. The almost entirely skewed X-inactivation in both cases supported the possibility of a dystrophinopathy. Despite standard molecular diagnostics (including multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS) gene panel sequencing), the genetic cause of the girls’ conditions remained unknown. However, whole-genome sequencing revealed two reciprocal translocations between their X chromosomes and chromosome 5 and chromosome 19, respectively. In both cases, the breakpoints on the X chromosomes were located directly within the DMD gene (in introns 54 and 7, respectively) and were responsible for the patients’ phenotypes. Additional techniques such as Sanger sequencing, conventional karyotyping and fluorescence in situ hybridization (FISH) confirmed the disruption of DMD gene in both patients through translocations. These findings underscore the importance of accurate clinical data combined with histopathological analysis in pinpointing the suspected underlying genetic disorder. Moreover, our study illustrates the viability of whole-genome sequencing as a time-saving and highly effective method for identifying genetic factors responsible for complex genetic constellations in Duchenne muscular dystrophy (DMD). Full article
(This article belongs to the Special Issue New Perspectives in Molecular Diagnosis of Neuromuscular Disorders)
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