Plectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC; PleΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the PleΔIEC colon.
Purpose Electromagnetic tracking (EMT) is a versatile and viable technique for various quality assurance (QA) tasks in interstitial brachytherapy (iBT). As the duration of EMT measurements in iBT is on the order of minutes, they can be strongly affected by patient motion, especially breathing, which gives rise to motion artefacts. Since the centrepiece of EMT‐related QA in iBT is to assess the geometry of the iBT implant or applicator, the absence of adequate motion compensation techniques could impede the use of EMT for QA purposes. A common way to compensate for this is to reference the data to either external or internal reference sensors (ERS, IRS) which are fixated on the patient's body or inside the applicator and therefore move with the patient. The purpose of the presented study is to provide a quantitative and in‐depth analysis on the use of reference sensors for motion compensation. Methods First, the need for adequate motion compensation is identified both qualitatively and quantitatively using a phantom subjected to simulated breathing motion. An evaluation routine is developed to assess the influence of motion compensation using reference sensors on the acquired EMT data. The evaluation metric is based on the observed displacement of the EMT sensor from its mean position while dwelling at a dwell position (DP) for a dwell time of 1 s. After that, the routine is applied to a cohort of 54 breast cancer patients treated with iBT, and the quality of an ERS based compensation approach is assessed. In a subgroup of four patients, an IRS is inserted into the iBT implant and IRS‐based compensation is compared to the ERS‐based approach. Moreover, a correlation analysis of the ERS and IRS approach is performed, also including respiratory signals derived from the trajectories of the different reference sensors. Results It was found that motion compensation with ERS effectively reduced the mean sensor displacement per DP to median values as low as 0.11 mm in both phantom and patient measurements, which is below the precision of the EMT system (0.48 mm). Compensation using the IRS yielded comparable results and was as good as compensation with ERS. The results obtained from both approaches showed a strong correlation. Also the respiratory signals calculated from the different reference sensors were well correlated in most cases. Conclusion These results indicate that motion compensation with ERS can effectively remove motion artefacts in EMT data. While compensation with an IRS leads to comparable results, the IRS occupies one catheter whose geometry hence cannot be assessed. The use of ERS has proven to be both effective and practical in clinical routine.
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