IL-9 exerts biological function on antigen-experienced murine T cells and exacerbates colitis induced by adoptive transfer

IL-9 is involved in various T cell-dependent inflammatory models including colitis, encepahlitis, and asthma. However, the regulation and specificity of IL-9 responsiveness by T cells during immune responses remains poorly understood. Here, we addressed this question using two different models: experimental colitis induced by transfer of naive CD4⁺CD45RB^high T cells into immunodeficient mice, and OVA-specific T cell activation. In the colitis model, constitutive IL-9 expression exacerbated inflammation upon transfer of CD4⁺CD45RB^high T cells from WT but not from Il9r^−/− mice, indicating that IL-9 acts directly on T cells. Suprisingly, such naïve CD4⁺CD45RB^high T cells failed to express the Il9r or respond to IL-9 in vitro, in contrast with CD4⁺CD45RB^low T cells. By using OVA-specific T cells, we observed that T cells acquired the capacity to respond to IL-9 along with CD44 upregulation, after long-lasting (5 to 12 days) in vivo antigenic stimulation. Il9r expression was associated with Th2 and Th17 phenotypes. Interestingly, in contrast to the IL-2 response, antigen restimulation downregulated IL-9 responsiveness. Taken together, our results demonstrate that IL-9 does not act on naïve T cells but that IL-9 responsiveness is acquired by CD4⁺ T cells after in vivo activation and acquisition of memory markers such as CD44.     

A humanized tissue-engineered in vivo model to dissect interactions between human prostate cancer cells and human bone

Currently used xenograft models for prostate cancer bone metastasis lack the adequate tissue composition necessary to study the interactions between human prostate cancer cells and the human bone microenvironment. We introduce a tissue engineering approach to explore the interactions between human tumor cells and a humanized bone microenvironment. Scaffolds, seeded with human primary osteoblasts in conjunction with BMP7, were implanted into immunodeficient mice to form humanized tissue engineered bone constructs (hTEBCs) which consequently resulted in the generation of highly vascularized and viable humanized bone. At 12 weeks, PC3 and LNCaP cells were injected into the hTEBCs. Seven weeks later the mice were euthanized. Micro-CT, histology, TRAP, PTHrP and osteocalcin staining results reflected the different characteristics of the two cell lines regarding their phenotypic growth pattern within bone. Microvessel density, as assessed by vWF staining, showed that tumor vessel density was significantly higher in LNCaP injected hTEBC implants than in those injected with PC3 cells (p < 0.001). Interestingly, PC3 cells showed morphological features of epithelial and mesenchymal phenotypes suggesting a cellular plasticity within this microenvironment. Taken together, a highly reproducible humanized model was established which is successful in generating LNCaP and PC3 tumors within a complex humanized bone microenvironment. This model simulates the conditions seen clinically more closely than any other model described in the literature to date and hence represents a powerful experimental platform that can be used in future work to investigate specific biological questions relevant to bone metastasis.     

The Assessment of Eating Behaviour in Children Who Are Obese: A Psychological Approach. A Position Paper from the European Childhood Obesity Group

ObjectiveThis paper introduces health professionals to the different psychological models thought to influence eating behaviour in the absence of hunger in children who are obese and to propose a method of assessing these behaviours in practice.MethodsClinical researchers from the European Childhood Obesity Group (ECOG) adopted an evidence-based approach to examine the literature concerning the assessment of eating behaviour in children who are obese. Studies published in English were filtered out of the medical and psychological literature from 1960 to the present, and the resulting bibliography was searched for relevant articles. Key themes from the current evidence were compiled and classified according to the underpinning psychological models. Based on the current evidence and the authors'' combined clinical experience, a three-staged approach to assessment was agreed by consensus.ResultsValid and reliable tools for assessing and monitoring each of the three identified models (Dietary Restraint Theory, Emotional Eating and the Diathesis-Stress Model) are suggested for use in clinical practice, and the ECOG three-staged approach to assessing eating behaviours in the absence of hunger is described.ConclusionsThis paper presents practical guidance on how to assess eating behaviour in the absence of hunger in children who are clinically obese and suggests a focus for future research.Key Words: Children, Obesity, Psychological assessment, Eating behaviour     

Rosiglitazone treatment alleviates inflammation and improves liver function in overweight women with polycystic ovary syndrome: a randomized placebo-controlled study

In a randomized, placebo-controlled study, we studied the effects of 4 months' treatment with rosiglitazone on low-grade inflammation, liver function, lipid levels, and blood pressure in 30 overweight women with polycystic ovary syndrome. Rosiglitazone significantly decreased serum C-reactive protein levels, white blood cell count, and alanine aminotransferase enzyme activity but did not affect lipid or blood pressure levels. Placebo had no effect on any parameters.     

Prescription,Compliance, and Burden Associated with Salt-Restricted Diets in Heart Failure Patients: Results from the French National OFICSel Observatory

(1) Background: There is much debate about the use of salt-restricted diet for managing heart failure (HF). Dietary guidelines are inconsistent and lack evidence. (2) Method: The OFICSel observatory collected data about adults hospitalised for HF. The data, collected using study-specific surveys, were used to describe HF management, including diets, from the cardiologists’ and patients’ perspectives. Cardiologists provided the patients’ clinical, biological, echocardiography, and treatment data, while the patients provided dietary, medical history, sociodemographic, morphometric, quality of life, and burden data (burden scale in restricted diets (BIRD) questionnaire). The differences between the diet recommended by the cardiologist, understood by the patient, and the estimated salt intake (by the patient) and diet burden were assessed. (3) Results: Between March and June 2017, 300 cardiologists enrolled 2822 patients. Most patients (90%) were recommended diets with <6 g of salt/day. Mean daily salt consumption was 4.7 g (standard deviation (SD): 2.4). Only 33% of patients complied with their recommended diet, 34% over-complied, and 19% under-complied (14% unknown). Dietary restrictions in HF patients were associated with increased burden (mean BIRD score of 8.1/48 [SD: 8.8]). (4) Conclusion: Healthcare professionals do not always follow dietary recommendations, and their patients do not always understand and comply with diets recommended. Restrictive diets in HF patients are associated with increased burden. An evidence-based approach to developing and recommending HF-specific diets is required.