In Vitro Th17-Polarized Human CD4+ T Cells Exacerbate Xenogeneic Graft-versus-Host Disease

Acute graft-versus-host disease (aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation. The role of Th17 cells in its pathophysiology remains a matter of debate. In this study, we assessed whether enrichment of human peripheral blood mononuclear cells (PBMCs) with in vitro Th17-polarized CD4⁺ T cells would exacerbate xenogeneic GVHD (xGVHD) into NOD-scid IL-2Rγ null (NSG) mice. Naive human CD4⁺ T cells were stimulated under Th17-skewing conditions for 8 to 10 days and then coinjected in NSG mice with fresh PBMCs from the same donor. We observed that Th17-polarized cells engrafted and migrated toward xGVHD target organs. They also acquired a double-expressing IL-17A⁺IFNγ⁺ profile in vivo. Importantly, cotransfer of Th17-polarized cells (1?×?10⁶) with PBMCs (1?×?10⁶) exacerbated xGVHD compared with transplantation of PBMCs alone (2?×?10⁶). Furthermore, PBMC cotransfer with Th17-polarized cells was more potent for xGVHD induction than cotransfer with naive CD4⁺ T cells stimulated in nonpolarizing conditions (Th0 cells, 1?×?10⁶?+?1?×?10⁶ PBMCs) or with Th1-polarized cells (1?×?10⁶?+?1?×?10⁶ PBMCs). In summary, our results suggest that human Th17-polarized cells can cooperate with PBMCs and be pathogenic in the NSG xGVHD model.     

Dual-energy X-ray absorptiometry and biochemical markers of bone turnover after autologous stem cell transplantation in myeloma

Objectives: To evaluate the effect of high‐dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) on bone turnover and bone mineral density in a cohort of 39 consecutive patients with multiple myeloma (MM). Methods: Phosphorus and calcium parameters, bone turnover markers, and bone mineral density were studied. Timepoints were diagnosis (T1), just before ASCT (T2), 6 months (T3) after ASCT, and 1 yr (T4) after ASCT. Results: No bone mineral loss was shown on dual‐energy X‐ray absorptiometry (DXA) at T1 (lumbar Z‐score ?0.02, femoral neck Z‐score 0.77) or during follow‐up. Chronic vitamin D deficiency (25OHD3 11.7 ± 7.7 ng/mL at T1) and relative hyperparathyroidism from T2 to T4 were observed. In spite of this moderate hyperparathyroidism, serum C‐telopeptide of type I collagen (CTX) decreased significantly between T1 and T4. Bone alkaline phosphatase levels were low at diagnosis and showed no significant change after ASCT, unlike DKK1 levels that were high at diagnosis and decreased 6 months after ASCT in patients not previously treated with bisphosphonates. Conclusion: Bone demineralization is moderate in multiple myeloma. ASCT induces a decrease in bone resorption but no changes in bone formation, remaining low despite the decrease in DKK1. Bone mineral loss, evaluated by DXA, is moderate in multiple myeloma. High‐dose chemotherapy followed by ASCT leads to decreased bone resorption but osteoblastic bone formation remains low, in spite of reduced circulating DKK1.     

Study of the uses of Information and Communication Technologies by Pain Treatment Unit Physicians

Adequate use of Information and Communication Technologies (ICTs) in health has been shown to save the patient and caregiver time, improve access to the health system, improve diagnosis and control of disease or treatment. All this results in cost savings, and more importantly, they help improve the quality of service and the lives of patients. The purpose of this study is to analyse the differences in the uses of this ICTs between those physicians that belong to Pain Treatment Units (PU) and other physicians that work in pain not linked to these PUs. An online survey, generated by Netquest online survey tool, was sent to both groups of professionals and the data collected was statistical analysed through a logistic regression methodology which is the Logit binomial model. Our results show that those physicians that belong to PUs use ICTs more frequently and consider it more relevant to their clinical practice.     

Automated segmentation of the aorta from phase contrast MR images: Validation against expert tracing in healthy volunteers and in patients with a dilated aorta

Purpose:

To assess if segmentation of the aorta can be accurately achieved using the modulus image of phase contrast (PC) magnetic resonance (MR) acquisitions.

Materials and Methods:

PC image sequences containing both the ascending and descending aorta of 52 subjects were acquired using three different MR scanners. An automated segmentation technique, based on a 2D+t deformable surface that takes into account the features of PC aortic images, such as flow‐related effects, was developed. The study was designed to: 1) assess the variability of our approach and its robustness to the type of MR scanner, and 2) determine its sensitivity to aortic dilation and its accuracy against an expert manual tracing.

Results:

Interobserver variability in the lumen area was 0.59 ± 0.92% for the automated approach versus 10.09 ± 8.29% for manual segmentation. The mean Dice overlap measure was 0.945 ± 0.014. The method was robust to the aortic size and highly correlated (r = 0.99) with the manual tracing in terms of aortic area and diameter.

Conclusion:

A fast and robust automated segmentation of the aortic lumen was developed and successfully tested on images provided by various MR scanners and acquired on healthy volunteers as well as on patients with a dilated aorta. J. Magn. Reson. Imaging 2010;31:881–888. ©2010 Wiley‐Liss, Inc.     

Mucin-bacterial interactions in the human oral cavity and digestive tract

Mucins are a family of heavily glycosylated proteins that are the major organic components of the mucus layer, the protective layer covering the epithelial cells in many human and animal organs, including the entire gastro-intestinal tract. Microbes that can associate with mucins benefit from this interaction since they can get available nutrients, experience physico-chemical protection and adhere, resulting in increased residence time. Mucin-degrading microorganisms, which often are found in consortia, have not been extensively characterized as mucins are high molecular weight glycoproteins that are hard to study because of their size, complexity and heterogeneity. The purpose of this review is to discuss how advances in mucus and mucin research, and insight in the microbial ecology promoted our understanding of mucin degradation. Recent insight is presented in mucin structure and organization, the microorganisms known to use mucin as growth substrate, with a specific attention on Akkermansia muciniphila, and the molecular basis of microbial mucin degradation owing to availability of genome sequences.     

Postcesarean Infection

In 1998, 20.2% of the approximately 4 million births in the United States occurred via cesarean delivery. Routine antibiotic prophylaxis has significantly reduced morbidity, yet each year between 41,000 and 206,000 women develop a subsequent infection of the uterus or surgical incision. A thorough understanding of the pathophysiology and complex interaction of risk factors for metritis and wound infection is vital for perinatal nurses. Nurses have a critical role in the identification and treatment of postcesarean infection.     

Hypofractionation in radiotherapy

Major changes in cancer radiotherapy have followed a greater understanding of the biological effects of radiation on tumours and normal tissues. Clinical radiotherapy is today a solid body of knowledge with well defined scientific foundations. Key concepts in current radiobiology include lethal and sublethal injuries, dose-effect coefficients, α/β ratios, acute and late response, biologically equivalent dose, fraction dose, irradiation time and tumour regeneration between others. Effects of irradiation time and dose per fraction on tumours versus normal tissues are of special importance. Dose per fraction must be considered for analysis of effects in normal late-responding tissues. In contrast, both dose per fraction and irradiation time influence the response to radiation of malignant tumours and acute-responding tissues. Finally, the ability to quantify relationships between radiation dose and biological effect has been of particular value in the development of radiotherapy. This is illustrated by the growing use of high doses per fraction for the treatment of some cancers. *Supported by an unrestricted educational grant from Roche Farma S.A.