Introduction: The dentist's main working area is the head and neck region, which is innervated by the cranial nerves. On a daily basis, dentists must administer local anaesthesia to ensure pain-free treatment and differentiate between dental pain and neuropathies to avoid mistreatment. Therefore, neuroanatomical training, especially on the cranial nerves, is of immense importance for clinical practice. In order to adopt the curriculum, it is essential to constantly evaluate the quality of the training and to investigate whether there is a correlation between the students' performance and the relevance of the subfields to their work. Material and methods: To address this issue, the results of MC exams in the neuroanatomy course for dental students at Charit & eacute;-Universit & auml;tsmedizin Berlin from winter semester 2014/2015 to winter semester 2019/2020 were analysed. Each question was assigned to a specific subfield of neuroanatomy. We then compared cranial nerves and cranial nerve nuclei (clinically relevant) with the remaining subfields (clinically less/not relevant) to investigate whether students performed better in anatomy subfields that are more aligned with the clinical practice of a dentist. We also conducted an anonymous survey (n=201) of the dental students. Results: From winter semester 2014/2015 to winter semester 2019/2020, students performed significantly (***, p< 0.001) better on the clinically relevant questions of the MC examination than on the less/not clinically relevant questions. However, when looking at each of the eleven semesters separately, only three semesters actually performed significantly better on the clinically relevant questions. Our survey also showed that students perceived the subfield of cranial nerves and cranial nerve nuclei to be the most relevant and studied it more intensively out of their own interest. Discussion: The study showed that students perceived the subfield of cranial nerves and cranial nerve nuclei to be the most relevant. However, there was no direct correlation between student performance and clinically relevant questions. Using student performance alone as an indicator of relevance is not optimal, as factors such as motivation to learn can have a significant impact. Conclusion: Greater clinical relevance influences what students learn more intensively out of their own interest, but does not influence the results of the MC examination in favour of the subspecialty. Based on the available evidence, it is recommended that the structure of the neuroanatomy course be reconsidered.
Weniger anzeigenPredicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function. We measured uDKK3/crea ratios (uDKK3/crea) from 95 deceased and 46 living kidney donors. Prenephrectomy uDKK3/crea levels were 100x higher in deceased than in living donors (9888 pg/mg vs 113 pg/mg; P < .001). Among deceased donor transplantations, recipients were stratified by their corresponding uDKK3/crea donor levels ranging below (group A, n68) or above (group B, n65) median. The primary end point of best estimated glomerular filtration rate (eGFR) within the first 3 months after kidney transplantation was superior in group A (56.3 mL/min/1.73 m2) than that in group B (44.2 mL/min/1.73 m2; P-.0139). Second, the composite clinical end point consisting of death, allograft failure or eGFR decline >50% occurred less frequent in group A. By mixed linear regression modeling, donor uDKK3/crea remained an independent predictor of eGFR after transplantation, with a slope of-4.282 mL/min/1.73 m2 per logarithmic increase in donor uDKK3/crea. In summary, uDKK3 may serve as a noninvasive, donor-dependent biomarker for assessing organ quality and future allograft function.
Weniger anzeigenPosttransplant diabetes mellitus (PTDM) and prediabetes represent serious complications after kidney transplantation and are associated with increased cardiovascular morbidity and mortality. We assessed the predictive performance of continuous glucose monitoring (CGM) compared with plasma glucose and hemoglobin A1c in 46 kidney transplant recipients (KTRs) without known preexisting diabetes mellitus. CGM (14-day recording duration) was performed on days 8, 30, 45, 60, 90, and 180 posttransplant. Eight patients (17%) developed PTDM and nine (20%) impaired glucose tolerance (IGT), as diagnosed by oral glucose tolerance test (oGTT)-derived 2-hour plasma glucose (2hPG) or glucose- lowering therapy on day 90. CGM-readouts percent of time >140 mg/dL (%TAR (140 mg/dL)) and percent of time >180 mg/dL (%TAR (180 mg/dL)) showed excellent in-sample test characteristics regarding PTDM from day 8 onward (days 8-90 receiver operating characteristic area under the curve: 0.88-0.99) and regarding PTDM/IGT with the commencement of maintenance immunosuppression from day 30 onward (days 30-90 receiver operating characteristic area under the curve: 0.88-0.91). Exploratory CGM-% TAR (140 mg/dL)-screening thresholds of 31.8% on day 8 and 13.2% on day 30 yielded sensitivities/specificities of 88%/83% for PTDM and 94%/78% for PTDM/IGT on day 90, respectively. Although our findings need to be replicated in studies with larger sample sizes, CGM bears promising potential to facilitate clinical practice and research regarding PTDM.
Weniger anzeigenRegeneration of large bone defects remains a clinical challenge until today. While existing biomaterials are predominantly addressing bone healing via direct, intramembranous ossification (IO), bone tissue formation via a cartilage phase, so-called endochondral ossification (EO) has been shown to be a promising alternative strategy. However, pure biomaterial approaches for EO induction are sparse and the knowledge how material components can have bioactive contribution to the required cartilage formation is limited. Here, we combined a previously developed purely architecture-driven biomaterial approach with the release of therapeutic metal ions from tailored silicate microparticles. The delivery platform was free of calcium phosphates (CaP) that are known to support IO but not EO and was employed for the release of lithium (Li), magnesium (Mg), strontium (Sr) or zinc (Zn) ions. We identified an ion-specific cellular response in which certain metal ions strongly enhanced cell recruitment into the material and showed superior chondrogenesis and deposition collagen II by human mesenchymal stromal cells (MSCs). At the same time, in some cases microparticle incorporation altered the mechanical properties of the biomaterial with consequences for cell-induced biomaterial contraction and scaffold wall deformation. Collectively, the results suggest that the incorporation of metal-doped silicate microparticles has the potential to further improve the bioactivity of architectured biomaterials for bone defect healing via EO. Statement of significance: Endochondral bone healing, a process that resembles embryonic skeletal development, has gained prominence in regenerative medicine. However, most therapeutic biomaterial strategies are not optimized for endochondral bone healing but instead target direct bone formation through IO. Here, we report on a novel approach to accelerate biomaterial-guided endochondral bone healing by combining cell-guiding collagen scaffolds with therapeutic metal-doped silicate microparticles. While other strategies, such as hypoxia-mimic drugs and iron-chelating biomaterials, have been documented in the literature before to enhance EO, our approach uniquely implements enhanced bioactivity into a previously developed biomaterial strategy for bone defect regeneration. Enhanced cell recruitment into the material and more pronounced chondrogenesis were observed for specific hybrid scaffold formulations, suggesting a high relevance of this new biomaterial for improved endochondral bone healing.
Weniger anzeigenMagnesium as a biodegradable material offers promising results in recent studies of different maxillofacial fracture models. To overcome adverse effects caused by the fast corrosion of pure magnesium in fluid surroundings, various alloys, and surface modifications are tested in animal models. In specified cases, magnesium screws already appeared for clinical use in maxillofacial surgery. The present study aims to compare the bone healing outcome in a non-load-bearing fracture scenario of the forehead in sheep when fixed with standard-sized WE43 magnesium fixation plates and screws with plasma electrolytic oxidation (PEO) surface modification in contrast to titanium osteosynthesis. Surgery was performed on 24 merino mix sheep. The plates and screws were explanted en-bloc with the surrounding tissue after four and twelve weeks. The outcome of bone healing was investigated with micro-computed tomography, histological, immunohistological, and fluorescence analysis. There was no significant difference between groups concerning the bone volume, bone volume/ total volume, and newly formed bone in volumetric and histological analysis at both times of investigation. The fluorescence analysis revealed a significantly lower signal in the magnesium group after one week, although there was no difference in the number of osteoclasts per mm(2). The magnesium group had significantly fewer vessels per mm(2) in the healing tissue. In conclusion, the non-inferiority of WE43-based magnesium implants with PEO surface modification was verified concerning fracture healing under non-load-bearing conditions in a defect model. Statement of significance Titanium implants, the current gold standard of fracture fixation, can lead to adverse effects linked to the implant material and often require surgical removal. Therefore, degradable metals like the magnesium alloy WE43 with plasma electrolytic oxidation (PEO) surface modification gained interest. Yet, miniplates of this alloy with PEO surface modification have not been examined in a fracture defect model of the facial skeleton in a large animal model. This study shows, for the first time, the non-inferiority of magnesium miniplates compared to titanium miniplates. In radiological and histological analysis, bone healing was undisturbed. Magnesium miniplates can reduce the number of interventions for implant removal, thus reducing the risk for the patient and minimizing the costs.
Weniger anzeigenMagnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) are complementary imaging techniques that detect disease based on viscoelasticity and water mobility, respectively. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering the clinical translation of combined DWI-MRE markers. We used DWI-MRE to study 129 biomaterial samples including native and cross-linked collagen, glycosaminoglycans (GAGs) with different sulfation levels, and decellularized specimens of pancreas and liver, all with different proportions of solid tissue, or solid fractions. We developed a theoretical framework of the relationship between mechanical loss and tissue-water mobility based on two parameters, solid and fluid viscosity. These parameters revealed distinct DWI-MRE property clusters characterizing weak, moderate, and strong water-network interactions. Sparse networks interacting weakly with water, such as collagen or diluted decellularized tissue, resulted in marginal changes in water diffusion over increasing solid viscosity. In contrast, dense networks with larger solid fractions exhibited both free and hindered water diffusion depending on the polarity of the solid components. For example, polar and highly sulfated GAGs as well as native soft tissues hindered water diffusion despite relatively low solid viscosity. Our results suggest that two fundamental properties of tissue networks, solid fraction and network polarity, critically influence solid and fluid viscosity in biological tissues. Since clinical DWI and MRE are sensitive to these viscosity parameters, the framework we present here can be used to detect tissue remodeling and architectural changes in the setting of diagnostic imaging. Statement of significance The viscoelastic properties of biological tissues provide a wealth of information on the vital state of cells and host matrix. Combined measurement of viscoelasticity and water diffusion by medical imaging is sensitive to tissue microarchitecture. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering full exploitation of these properties as a combined clinical biomarker. Therefore, we analyzed the parameter space accessible by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) and developed a theoretical framework for the relationship between water mobility and mechanical parameters in biomaterials. Our theory of solid material properties related to particle motion can be translated to clinical radiology using clinically established MRE and DWI.
Weniger anzeigenFailure -resistant designs are particularly crucial for bones subjected to rapid loading, as is the case for the ambush -hunting northern pike (Esox lucius). These fish have slim and low -density osteocyte-lacking bones. As part of the swallowing mechanism, the cleithrum bone opens and closes the jaw. The cleithrum needs sufficient strength and damage tolerance, to withstand years of repetitive rapid gape -and -suck cycles of feeding. The thin wing -shaped bone comprises anisotropic layers of mineralized collagen fibers that exhibit periodic variations in mineral density on the mm and micrometer length scales. Wavy collagen fibrils interconnect these layers yielding a highly anisotropic structure. Hydrated cleithra exhibit Young's moduli spanning 3-9 GPa where the yield stress of -40 MPa increases markedly to exceed -180 MPa upon drying. This 5x observation of increased strength corresponds to a change to brittle fracture patterns. It matches the emergence of compressive residual strains of -0.15% within the mineral crystals due to forces from shrinking collagen layers. Compressive stresses on the nanoscale, combined with the layered anisotropic microstructure on the mm length scale, jointly confer structural stability in the slender and lightweight bones. By employing a range of X-ray, electron and optical imaging and mechanical characterization techniques, we reveal the structure and properties that make the cleithra impressively damage resistant composites.
Weniger anzeigenThe persistence of viruses in human semen following acute infection can contribute to the ongoing transmission of a disease or cause resurgence after an outbreak has been declared ended. Viral persistence in semen affects embryonic development and male fertility, and the development of drugs and vaccines. We conducted a systematic review of viral persistence in semen in accordance with PRISMA guidelines. 373 original studies were included in this Review after screening 29 739 articles from five databases. Evidence was found of detection of 22 viruses in human semen following acute infection, including pathogens with pandemic potential. In addition to collating the largest evidence base to date on viral detection in semen following acute infection, this Review reports the maximal and median viral persistence (in days) after the onset of illness and evidence for sexual transmission and viability of the viruses in semen. Finally, the Review presents research gaps that need to be prioritised to guide further study of the dynamics of viral persistence in semen.
Weniger anzeigenBackground Mycobacterium chelonae is a rare cause of infective endocarditis that is difficult to diagnose and treat. After we found M chelonae in a series of patients, we aimed to investigate its role in cardiovascular prosthesis dysfunction and contamination of bioprostheses as a possible cause of infection. Methods In this collaborative microbiological study, we report on nine patients treated in three cardiovascular surgical departments in Germany, who were found to have M chelonae infection after receiving BioIntegral bioprostheses. We performed fl uorescence in-situ hybridisation (FISH) combined with broad-range 16S rRNA gene amplification and sequencing (FISHseq) on samples of native cardiovascular tissue and explanted bioprosthetic material, as well as on 12 unused BioIntegral prostheses. We confirmed FISHseq fi ndings with histological examination by staining for acid-fast bacilli, and M chelonae was differentiated from M abscessus by molecular techniques. Findings Between Dec 1, 2020, and Feb 28, 2022, we identified M chelonae in BioIntegral bioprostheses from three initial patients treated in Berlin that were explanted following dysfunction or suspected endocarditis, visualising morphologically intact FISH-positive mycobacteria. Despite negative mycobacterial culture, we also detected M chelonae in all 12 unused BioIntegral prostheses. The competent authorities in the EU prompted an alert, leading to the identification of six additional patients between March 1, 2022, and July 31, 2023. To fi nd other cases of M chelonae endocarditis, we reviewed the FISHseq results of 1237 cardiovascular samples that were analysed between Jan 1, 2015, and Aug 31, 2022, including 295 samples from 228 bioprostheses supplied by other manufacturers. M chelonae was only detected in six of 41 patients who had received BioIntegral products. Interpretation Bioprostheses manufactured by BioIntegral Surgical might be colonised by M chelonae, which can lead to implant dysfunction. These infections are likely to be missed by conventional routine diagnostics and should be considered in patients with BioIntegral implants and suspected infection or dysfunction. Cases should be reported to public health and regulatory authorities. Routine safety testing of bioprostheses during manufacture should be reconsidered. Funding German Federal Ministry of Education and Research.
Weniger anzeigenObjectives: Change in body weight during the COVID-19 pandemic as an unintended side effect of lockdown measures has been predominantly reported for younger and middle-aged adults. However, information on older adults for which weight loss is known to result in adverse outcomes, is scarce. In this study we describe the body weight change in older adults before, during, and after the COVID-19 lockdown measures and explore putative associated factors with a focus on the period that includes the first six months of the COVID-19 containment measures. Design: Prospective cohort study with three follow-up examinations over the course of 10 years. Setting and Participants: In this study, we analyzed the longitudinal weight change of 472 participants of the Berlin Aging Study II (mean age of 67.5 years at baseline). Measurements: Body weight was assessed at four time points. Additionally, differences between subgroups characterized by socio-economic, cognitive, and psychosocial variables as well as morbidity burden, biological age markers (epigenetic clocks, telomere length), and frailty were compared. Results: On average, women and men lost 0.87% (n = 227) and 0.5% (n = 245) of their body weight per year in the study period covering the first six months of the COVID-19 pandemic. Weight loss among men was particularly pronounced among groups characterized by change in physical activity due to COVID-19 lockdown, low positive affect, premature epigenetic age (7-CpG clock), diagnosed metabolic syndrome, and a more masculine gender score (all variables: p < 0.05, n = 245). Conclusion: During the COVID-19 pandemic, older participants lost weight with a 2.5-times (women) and 2-times (men) higher rate than what is expected in this age.
Weniger anzeigenBackground Since the pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the leading trigger for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Evidence indicates that auto- immunity plays an important pathophysiological role. We aimed to evaluate the effectiveness of IA treatment in postCOVID ME/CFS patients. Methods This pre-post study included 20 post-coronavirus disease 2019 (COVID) ME/CFS patients found to have elevated (32 adrenergic autoantibodies ((32 AR-AB) between October 2022 and October 2023. Patients, with a median disease duration of 22 months (IQR: 15-31), were treated with five immunoadsorption sessions at Charit & eacute;- Universit & auml;tsmedizin Berlin, Germany. Seven were male and 13 female, with a median age of 40 years (IQR: 36-51). The primary end point was the change in the Short Form (36) Health Survey physical functioning domain (SF36 PF) from baseline to four weeks post immunoadsorption. Key symptoms were assessed via questionnaires over six months. Handgrip strength and EndoPAT (R) measurements were used to evaluate muscle fatigue and vascular dysfunction. Seven patients who worsened after an initial response received a second cycle. Findings The treatment was generally well tolerated, reducing total immunoglobulin G by 79% (CI: 73-84%) and (32 AR-AB by 77% (CI: 58-95%). Patients demonstrated a mean increase in the SF36 PF of 17.75 points (CI: 13.41-26.16), with the greatest improvement occurring between months two and three, and significant gains maintained through month six. 14/20 (70%) patients were categorized as responders with an increase in the SF36 PF of >= ten points. Further lasting improvements were reported in fatigue, post-exertional malaise, pain, cognitive, autonomic, and immunological symptoms. Female patients had increased repeat handgrip strength at month six. Interpretation Immunoadsorption may improve symptoms in post-COVID ME/CFS patients. The beneficial effects of IgG depletion suggest a significant role for autoantibodies and disturbed B-cell function in the condition's pathophysiology.
Weniger anzeigenHuman-derived experimental systems such as induced pluripotent stem cell (iPSC)-derived models are useful tools to study mechanisms and potential therapeutic approaches for mitochondrial disorders. Here, we generated two iPSC lines from fibroblasts of patients carrying mutations at MT-ATP6 (m.8993 T>G). One patient with 96 % heteroplasmy suffered from Neuropathy, Ataxia, and Retinitis pigmentosa (NARP) syndrome, while the other patient with a homoplasmic mutation suffered from Maternally Inherited Leigh Syndrome (MILS). For reprogramming, we delivered reprogramming factors using Sendai virus and evaluated the pluripotency characteristics of the derived iPSCs. The degree of heteroplasmy remained stable after reprogramming.
Weniger anzeigenSerotonin (5-HT) is crucial for regulating brain functions such as mood, sleep, and cognition. This study presents a comprehensive transcriptomic analysis of 5-HT receptors (Htrs) across z4 million cells in the adult mouse brain using single-cell RNA sequencing (scRNA-seq) data from the Allen Institute. We observed differential transcription patterns of all 14 Htr subtypes, revealing diverse prevalence and distribution across cell classes. Remarkably, we found that 65.84% of cells transcribe RNA of at least one Htr, with frequent co-transcription of multiple Htrs, underscoring the complexity of the 5-HT system even at the single-cell dimension. Leveraging a multiplexed error-robust fluorescence in situ hybridization (MERFISH) dataset provided by Harvard University of z10 million cells, we analyzed the spatial distribution of each Htr, confirming previous findings and uncovering novel transcription patterns. To aid in exploring Htr transcription, we provide an online interactive visualizer.
Weniger anzeigenBackground: Spine surgical training faces increasing challenges due to restricted working hours and greater sub specialization. Modern simulators offer a promising approach to teaching both simple and complex spinal procedures. This study evaluated the acceptance and efficacy of spine simulator training using a lumbar herniated disc model tested by 16 neurosurgical residents (PGY-1-6), and compared 3D and 2D teaching methods. Methods: Sixteen residents utilized the Realists RealSpine L4/L5 disc simulator with both microscope and exoscope. A mixed-methods analysis assessed the efficacy and acceptance of the training. Six PGY-1 residents participated in a learning curve study, divided into exoscopic and microscopic cohorts. Each group watched a tutorial in either 3D or 2D, followed by 3 surgical sessions. Endpoints included surgical progress within 30 minutes and complication rates. Microsurgical skills and mental concepts were evaluated on a numeric Likert Scale. Results: Participants rated the simulator training favorably, with a median score of 8/10 across 6 categories. The learning curve study showed a 30% improvement in microsurgical performance. The completion rate of herniated disc removal increased from 50% at T2 to 100% at T3 and T4. Significant improvement in mental concept was observed (p = .035), with slightly better consolidation in the exoscope group. Self-assessments revealed significantly improved skills across all participants. Conclusions: Spine simulator training was well-received and resulted in improvements in both mental concept and microsurgical performance, with enhanced outcomes in the 3D teaching/exoscope group. This study supports the integration of spine simulators into spine surgical residency, particularly for early-stage training, to improve both cognitive and practical surgical skills.
Weniger anzeigenThe circle of Willis (CoW) is a network of cerebral arteries with significant inter-individual anatomical variations. Deep learning has been used to characterize and quantify the status of the CoW in various applications for the diagnosis and treatment of cerebrovascular disease. In medical imaging, the performance of deep learning models is limited by the diversity and size of training datasets. To address medical data scarcity, generative AI models have been applied to generate synthetic vessel neuroimaging data. However, the proposed methods produce synthetic data with limited anatomical fidelity or downstream utility in tasks concerning vessel characteristics. We adapted the StyleGANv2 architecture to 3D to synthesize Time-of-Flight Magnetic Resonance Angiography (TOF MRA) volumes of the CoW. For generative modeling, we used 1782 individual TOF MRA scans from 6 open source datasets. To train the adapted 3D StyleGAN model with limited data we employed differentiable data augmentations, used mixed precision and a cropped region of interest of size 32 x 128 x 128 to tackle computational constraints. The performance was evaluated quantitatively using the Fre<acute accent>chet Inception Distance (FID), MedicalNet distance (MD) and Area Under the Curve of the Precision and Recall Curve for Distributions (AUC-PRD). Qualitative analysis was performed via a visual Turing test. We demonstrated the utility of generated data in a downstream task of multiclass semantic segmentation of CoW arteries. Vessel segmentation performance was assessed quantitatively using the Dice coefficient and the Hausdorff distance. The best-performing 3D StyleGANv2 architecture generated high-quality and diverse synthetic TOF MRA volumes (FID: 12.17, MD: 0.00078, AUC-PRD: 0.9610). Multiclass vessel segmentation models trained on synthetic data alone achieved comparable performance to models trained using real data in most arteries. The addition of synthetic data to a baseline training set improved segmentation performance in underrepresented artery segments, similar to the addition of real data. In conclusion, generative modeling of the Circle of Willis via synthesis of 3D TOF MRA data paves the way for generalizable deep learning applications in cerebrovascular disease. In the future, the extensions of the provided methodology to other medical imaging problems or modalities with the inclusion of pathological datasets has the potential to advance the development of more robust AI models for clinical applications.
Weniger anzeigenPurpose: To generate perfusion parameter maps from Time-of-flight magnetic resonance angiography (TOF-MRA) images using artificial intelligence to provide an alternative to traditional perfusion imaging techniques. Materials and methods: This retrospective study included a total of 272 patients with cerebrovascular diseases; 200 with acute stroke (from 2010 to 2018), and 72 with steno-occlusive disease (from 2011 to 2014). For each patient the TOF MRA image and the corresponding Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) were retrieved from the datasets. The authors propose an adapted generative adversarial network (GAN) architecture, 3D pix2pix GAN, that generates common perfusion maps (CBF, CBV, MTT, TTP, Tmax) from TOF-MRA images. The performance was evaluated by the structural similarity index measure (SSIM). For a subset of 20 patients from the acute stroke dataset, the Dice coefficient was calculated to measure the overlap between the generated and real hypoperfused lesions with a time-to-maximum (Tmax) > 6 s. Results: The GAN model exhibited high visual overlap and performance for all perfusion maps in both datasets: acute stroke (mean SSIM 0.88-0.92, mean PSNR 28.48-30.89, mean MAE 0.02-0.04 and mean NRMSE 0.14-0.37) and steno-occlusive disease patients (mean SSIM 0.83-0.98, mean PSNR 23.62-38.21, mean MAE 0.01-0.05 and mean NRMSE 0.03-0.15). For the overlap analysis for lesions with Tmax>6 s, the median Dice coefficient was 0.49. Conclusion: Our AI model can successfully generate perfusion parameter maps from TOF-MRA images, paving the way for a non-invasive alternative for assessing cerebral hemodynamics in cerebrovascular disease patients. This method could impact the stratification of patients with cerebrovascular diseases. Our results warrant more extensive refinement and validation of the method.
Weniger anzeigenCrohn's disease (CD) is an inflammatory bowel disease that can affect any part of the gastrointestinal tract, frequently involving the terminal ileum. While colonic mucus alterations in CD patients have been described, terminal ileal mucus and its mechanobiological properties have been neglected. Our study is the first of its kind to decipher the viscoelastic and network properties of ileal mucus. With that aim, oscillatory rheological shear measurements based on an airway mucus protocol that was thoroughly validated for ileal mucus were performed. Our pilot study analyzed terminal ileum mucus from controls (n = 14) and CD patients (n = 14). Mucus network structure was visualized by scanning electron microscopy. Interestingly, a statistically significant increase in viscoelasticity as well as a decrease in mesh size was observed in ileal mucus from CD patients compared to controls. Furthermore, rheological data were analyzed in relation to study participants' clinical characteristics, revealing a noteworthy trend between non-smokers and smokers. In conclusion, this study provides the first data on the viscoelastic properties and structure of human ileal mucus in the healthy state and Crohn's disease, demonstrating significant alterations between groups and highlighting the need for further research on mucus and its effect on the underlying epithelial barrier.
Weniger anzeigenMetabolic dysfunction-associated fatty liver disease (MAFLD), the leading cause of end-stage liver disease in developed countries, is expected to increase over the next decade. Characterized by hepatic steatosis, MAFLD is commonly studied in animal models. Here, we generated a human induced pluripotent stem cell (iPSC) line from a patient homozygous of the protective MTARC1 gene variant rs2642438:A. This line displays a normal karyotype and typical pluripotent stem cell morphology and can differentiate into all three germ layers in vitro.
Weniger anzeigenBcl-2-associated X protein ( BAX ) and Blc-2 homologous antagonist killer 1 ( BAK ) are two pro-apoptotic members of BCL2 family. Here, two BAX / BAK double knockout human induced pluripotent stem cell lines (iPSC) we generated using CRISPR-Cas9 to generate apoptosis incompetent cell lines. The resulting cell lines were karyotypically normal, had typical morphology and expressed typical markers for the undifferentiated state.
Phenotypic and compositional changes of immune cells in cerebrospinal fluid (CSF) can be used as biomarkers to help diagnose and track disease activity for neuroinflammatory and neurodegenerative diseases. Here, we present a workflow to perform high -dimensional immune profiling at single -cell resolution using cytometry by time -of -flight (CyTOF) on cells isolated from the CSF of patients with neuroinflammation. We describe steps for sample collection and preparation, barcoding to allow for multiplexing, and downstream data analysis using R. For complete details on the use and execution of this protocol, please refer to Ferna<acute accent>ndez-Zapata et al. 1
Weniger anzeigen