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The EU Directive 2010/63/EU changed the requirements regarding the use of laboratory animals and raised important issues related to assessing the severity of all procedures undertaken on laboratory animals. However, quantifiable parameters to assess severity are rare, and improved assessment strategies need to be developed. Hence, a Sheep Grimace Scale (SGS) was herein established by observing and interpreting sheep facial expressions as a consequence of pain and distress following unilateral tibia osteotomy. The animals were clinically investigated and scored five days before surgery and at 1, 3, 7, 10, 14 and 17 days afterwards. Additionally, cortisol levels in the saliva of the sheep were determined at the respective time points. For the SGS, video recording was performed, and pictures of the sheep were randomized and scored by blinded observers. Osteotomy in sheep resulted in an increased clinical severity score from days 1 to 17 post-surgery and elevated salivary cortisol levels one day post-surgery. An analysis of facial expressions revealed a significantly increased SGS on the day of surgery until day 3 post-surgery; this elevated level was sustained until day 17. Clinical severity and SGS scores correlated positively with a Pearson´s correlation coefficient of 0.47. Further investigations regarding the applicability of the SGS revealed a high inter-observer reliability with an intraclass correlation coefficient of 0.92 and an accuracy of 68.2%. In conclusion, the SGS represents a valuable approach for severity assessment that may help support and refine a widely used welfare assessment for sheep during experimental procedures, thereby meeting legislation requirements and minimizing the occurrence of unrecognized distress in animal experimentation. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) up-regulates the human leukocyte antigen (HLA) class I antigen presentation machinery (APM). This appears counterintuitive with immune evasion in EBV-associated tumours like nasopharyngeal carcinoma (NPC).Methods: Latent membrane protein 1-transfected epithelial cell lines were used as a model system to study the impact of LMP1 and c-Myc on HLA class I components. The expression of components of the HLA class I APM, c-Myc and Ki-67 was analysed in LMP1+ and LMP1- NPC by immunohistochemistry.Results: In epithelial cells, LMP1 up-regulated HLA class I APM. This effect could be counteracted by c-Myc, which itself was up-regulated by LMP1 apparently through IL6 induction and Jak3/STAT3 activation. Studies of NPC biopsies revealed down-regulation of HLA class I APM expression. No difference was observed between LMP1+ and LMP1- NPC. However, expression of Ki-67 and c-Myc were up-regulated in LMP1+ tumours.Conclusion: These findings raise the possibility that c-Myc activation in NPC might antagonise the effect of LMP1 on HLA class I expression thus contributing to immune escape of tumour cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To discuss a unique method of treatment for a patient with diffuse idiopathic skeletal hyperostosis (DISH) and the long-term result of this treatment. CLINICAL FEATURES: The patient had a long-standing history of low back pain and stiffness caused by DISH. Coexisting conditions consisted of right-hand paresthesia because of a thalamic stroke, osteoporosis, Barrett's esophagus, thyroid and parathyroid disease, and hypercholesterolemia. INTERVENTION AND OUTCOME: The patient received chiropractic manipulation and drop table adjustments, along with range-of-motion exercise, extension exercise, and standing lumbar extension traction. The magnitude of lumbar lordotic alignment and Ferguson's angle improved with treatment. The patient's subjective perception of pain significantly improved, as documented with the use of numeric rating scales. Flexibility and activities of daily living were also improved. The effect was maintained for 19 months after termination of the active rehabilitative treatment period. CONCLUSION: A paucity of literature exists regarding the chiropractic management of patients with a diagnosis of DISH. Chiropractors should be encouraged to report on their clinical experiences in treating patients with varied conditions and disorders. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The translocator protein (TSPO) is overexpressed in high-grade glioma and can be visualized in vivo by TSPO PET even in areas without MRI contrast enhancement. Here, we assessed the value of TSPO PET using the high-affinity TSPO ligand 18F-GE-180 in primary irradiation (RT) and re-irradiation (reRT) treatment planning.Materials/methods: Radiation treatment plans of high-grade glioma patients, examined with the TSPO PET tracer 18F-GE-180 prior to RT and reRT between 08/2016 and 01/2019, were included. PET based biological tumor volumes (BTV) were built on basis of tumor-to-background activity thresholds of 1.6, 1.8, and 2.0. Consensus GTVs (cGTV) based on GTV volumes delineated on MRI by 4 independent observers were generated using the simultaneous truth and performance level estimation (STAPLE) algorithm. Conformity of cGTV with BTV1.6, BTV1.8 and BTV2.0 were assessed by Sørensen-Dice coefficient (SDC) and conformity index (CI). Minimal clinical target volume (CTV) margins including the whole BTV into the cGTV were calculated.Results: Target volumes of 35 RT and 16 reRT plans were assessed. Volumes of cGTVs were smaller than the corresponding volumes of BTV1.6, BTV1.8 and BTV2.0 in the primary RT plans (median volumes 22.6 vs. 67.4, 50.7, 39.1 cm³; P < 0.001, P < 0.001, P = 0.018; Wilcoxon-Test) and reRT plans (median volumes 22.7 vs. 80.5, 55.0, 41.6 cm³; P = 0.001, P = 0.007, P = 0.134; Wilcoxon-Test). Conformity between BTVs and cGTV calculated by SDC and CI for thresholds 1.6, 1.8 and 2.0 were low in median in the RT (SDC: 0.51, 0.55, 0.58; CI: 0.35, 0.38, 0.41) and reRT setting (SDC: 0.38, 0.40, 0.40; CI 0.24, 0.25, 0.25). Median minimal CTV margins to include the entire BTV in the expanded cGTV volume was smaller in the RT setting (16, 12, 10 mm) than in the reRT setting (> 20, 17.5, 11 mm) for thresholds 1.6, 1.8 and 2.0.Conclusion: TSPO PET based BTVs showed highest conformity and best comparability in terms of size with MRI based GTVs for the threshold 2.0 both in the primary and reRT setting. Recurrence pattern analyses are needed to assess the clinical relevance of TSPO PET in glioma RT and reRT treatment planning.Author Disclosure: D.F. Fleischmann: None. M. Buettner: None. M. Unterrainer: None. S. Corradini: None. B. Zollner: None. J. Hofmaier: None. R. Bodensohn: None. N. Thon: None. C. Belka: None. P. Bartenstein: None. N. Albert: None. M. Niyazi: None. [ABSTRACT FROM AUTHOR]

Background: Tumour infiltrating lymphocytes (TIL) are generally considered to represent a host immune response directed against tumour antigens. TIL are also increasingly recognised as possible prognostic parameters. However, the effects observed are variable indicating that results cannot be extrapolated from type of tumour to another. Moreover, it has been suggested that primary solid tumours may be ignored by the immune system and that a meaningful immune response is only mounted in regional lymph nodes.Methods: We have examined the local distribution of immune cells in tumour-related compartments in head and neck squamous cell carcinomas (HNSCC). In a second step, the prognostic impact of these cells on disease-free survival (DFS) was analysed. A total of 198 tissue cores from 33 patients were evaluated using tissue mircroarray technique and immunohistochemistry. Tumour-infiltrating immune cells were identified using antibodies specific for CD3, CD8, GranzymeB, FoxP3, CD20 and CD68 and quantified using an image analysis system.Results: We demonstrate a relative expansion of FoxP3+ regulatory T-cells (Treg) and of cytotoxic T-cells among tumour infiltrating T-cells. We also show that intratumoural CD20+ B-cells are significantly more frequent in metastatic deposits than in primary tumours. Furthermore, we observed a reduced number of peritumoural CD8+ T-cells in metastatic lymph nodes as compared to univolved regional nodes suggesting a local down-modulation of cellular immunity. All other immune cells did not show significant alterations in distribution. We did not observe an association of tumour infiltrating immune cells at the primary site with outcome. However, increased numbers of intraepithelial CD8+ TIL in metastatic tumours as well as large numbers of peritumoural B-cells in lymph node metastases were associated with favourable outcome. Unexpectedly, no effect on patient outcome was observed for Treg in any compartment.Conclusion: Our results suggest that alterations in lymphocyte distribution in regional lymph nodes rather than at the primary tumour site may be relevant for patient prognosis. Moreover, we demonstrate that in addition to cellular immunity humoral immune responses may be clinically relevant in anti-tumour immunity. [ABSTRACT FROM AUTHOR]