3D-MRI rendering of the anatomical structures related to acupuncture points of the Dai mai, Yin qiao mai and Yang qiao mai meridians within the context of the WOMED concept of lateral tension: implications for musculoskeletal disease

BACKGROUND: A conceptual model of lateral muscular tension in patients presenting thyroid associated ophthalmopathy (TAO) has been recently described. Clinical improvement has been achieved by using acupuncture on points belonging to the so-called extraordinary meridians. The aim of this study was to characterize the anatomical structures related to these acupuncture points by means of 3D MRI image rendering relying on external markers. METHODS: The investigation was carried out the index case patient of the lateral tension model. A licensed medical acupuncture practitioner located the following acupuncture points: 1) Yin qiao mai meridian (medial ankle): Kidney 3, Kidney 6, the plantar Kidney 6 (Nan jing description); 2) Yang qiao mai meridian (lateral ankle): Bladder 62, Bladder 59, Bladder 61, and the plantar Bladder 62 (Nan jing description); 3) Dai mai meridian (wait): Liver 13, Gall bladder 26, Gall bladder 27, Gall bladder 28, and Gall bladder 29. The points were marked by taping a nitro-glycerin capsule on the skin. Imaging was done on a Siemens Magnetom Avanto MR scanner using an array head and body coil. Mainly T1-weighted imaging sequences, as routinely used for patient exams, were used to obtain multi-slice images. The image data were rendered in 3D modus using dedicated software (Leonardo, Siemens). RESULTS: Points of the Dai mai meridian – at the level of the waist – corresponded to the obliquus externus abdominis and the obliquus internus abdominis. Points of the Yin qiao mai meridian – at the medial side of the ankle – corresponded to tendinous structures of the flexor digitorum longus as well as to muscular structures of the abductor hallucis on the foot sole. Points of the Yang qiao mai meridian – at the lateral side of the ankle – corresponded to tendinous structures of the peroneus brevis, the peroneous longus, and the lateral surface of the calcaneus and close to the foot sole to the abductor digiti minimi. CONCLUSION: This non-invasive MRI investigation has revealed the anatomical relations of acupuncture points belonging to 3 of the so-called extraordinary meridians. We conclude that the clinically developed "WOMED concept of lateral tension" is related to tendino-muscular structures

Isolation of neoantigen-specific human T cell receptors from different human and murine repertoires

(1) Background: Mutation-specific T cell receptor (TCR)-based adoptive T cell therapy represents a truly tumor-specific immunotherapeutic strategy. However, isolating neoepitope-specific TCRs remains a challenge. (2) Methods: We investigated, side by side, different TCR repertoires-patients' peripheral lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs), PBLs of healthy donors, and a humanized mouse model-to isolate neoepitope-specific TCRs against eight neoepitope candidates from a colon cancer and an ovarian cancer patient. Neoepitope candidates were used to stimulate T cells from different repertoires in vitro to generate neoepitope-specific T cells and isolate the specific TCRs. (3) Results: We isolated six TCRs from healthy donors, directed against four neoepitope candidates and one TCR from the murine T cell repertoire. Endogenous processing of one neoepitope, for which we isolated one TCR from both human and mouse-derived repertoires, could be shown. No neoepitope-specific TCR could be generated from the patients' own repertoire. (4) Conclusion: Our data indicate that successful isolation of neoepitope-specific TCRs depends on various factors such as the heathy donor's TCR repertoire or the presence of a tumor microenvironment allowing neoepitope-specific immune responses of the host. We show the advantage and feasibility of using healthy donor repertoires and humanized mouse TCR repertoires to generate mutation-specific TCRs with different specificities, especially in a setting when the availability of patient material is limited

Epithelial calcineurin controls microbiota-dependent intestinal tumor development.

Inflammation-associated pathways are active in intestinal epithelial cells (IECs) and contribute to the pathogenesis of colorectal cancer (CRC). Calcineurin, a phosphatase required for the activation of the nuclear factor of activated T cells (NFAT) family of transcription factors, shows increased expression in CRC. We therefore investigated the role of calcineurin in intestinal tumor development. We demonstrate that calcineurin and NFAT factors are constitutively expressed by primary IECs and selectively activated in intestinal tumors as a result of impaired stratification of the tumor-associated microbiota and toll-like receptor signaling. Epithelial calcineurin supports the survival and proliferation of cancer stem cells in an NFAT-dependent manner and promotes the development of intestinal tumors in mice. Moreover, somatic mutations that have been identified in human CRC are associated with constitutive activation of calcineurin, whereas nuclear translocation of NFAT is associated with increased death from CRC. These findings highlight an epithelial cell-intrinsic pathway that integrates signals derived from the commensal microbiota to promote intestinal tumor development.This work was supported by the Deutsche Forschungsgemeinschaft (DFG) grants ZE814/5-1 (S.Z.), BA2863/5-1 (J.F.B.) and CH279/5-1 (T.C.), the European Research Council (ERC) starting grant 336528 (S.Z.), a Postdoctoral Fellowship Award from the Crohn's and Colitis Foundation of America (S.Z.), the European Commission (Marie Curie International Reintegration grant 256363; S.Z.), the DFG Excellence Cluster 'Inflammation at Interfaces' (S.Z. and J.F.B.), the DFG Excellence Cluster 'Center for Regenerative Therapies' (S.Z.); the US National Institutes of Health grants DK044319 (R.S.B.), DK051362 (R.S.B.), DK053056 (R.S.B.) and DK088199 (R.S.B.), the Harvard Digestive Diseases Center (HDDC) grant DK0034854 (R.S.B.), and the AIRC grant IG-14233 (M.E.B.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nm.407

A Multispecialty Evaluation of Thiel Cadavers for Surgical Training

Background: Changes in UK legislation allow for surgical procedures to be performed on cadavers. The aim of this study was to assess Thiel cadavers as high-fidelity simulators and to examine their suitability for surgical training. Methods: Surgeons from various specialties were invited to attend a 1 day dissection workshop using Thiel cadavers. The surgeons completed a baseline questionnaire on cadaveric simulation. At the end of the workshop, they completed a similar questionnaire based on their experience with Thiel cadavers. Comparing the answers in the pre- and post-workshop questionnaires assessed whether using Thiel cadavers had changed the surgeons’ opinions of cadaveric simulation. Results: According to the 27 participants, simulation is important for surgical training and a full-procedure model is beneficial for all levels of training. Currently, there is dissatisfaction with existing models and a need for high-fidelity alternatives. After the workshop, surgeons concluded that Thiel cadavers are suitable for surgical simulation (p = 0.015). Thiel were found to be realistic (p < 0.001) to have reduced odour (p = 0.002) and be more cost-effective (p = 0.003). Ethical constraints were considered to be small. Conclusion: Thiel cadavers are suitable for training in most surgical specialties

Which stabilization technique corrects anatomy best in patients with AC-separation? An experimental study

In ten human cadaveric shoulder specimens four different parameters were documented prior to, and after, dissecting all passive stabilizers. These included the vertical, horizontal and mediolateral acromioclavicular distance, as well as the clavicular rotation. In addition, the same parameters were documented after acromioclavicular (AC) reconstruction using eight different techniques. The results showed a good reconstruction of the vertical ac-distance. Most of the techniques, especially the coracoid-sling procedure, led to a significant anterior displacement of the clavicle in relation to the scapula. To a lesser degree, most of the conventional procedures also resulted in a lateralization of the acromion and/or clavicular rotation. A bone anchor system for distal fixation in the base of the coracoid process and a medialized hole in the clavicle restored anatomy best. This new technique therefore is recommended for anatomical AC-reconstruction