A non‐fatal case of invasive zygomycete (Lichtheimia corymbifera) infection in an allogeneic haematopoietic cell transplant recipient

Post‐transplant infections in allogeneic haematopoietic cell transplant (allo‐HCT) recipients often have severe consequences. This is especially the case when dealing with zygomycete infections where the result is often fatal. A major problem when dealing with zygomycete infections is the need for an accurate and fast diagnosis as the phylum is highly resistant towards the conventional antifungals. We herein describe a non‐fatal case of Lichtheimia corymbifera infection in an allo‐HCT recipient.     

Guidelines and considerations for conducting experiments using tissue microarrays

Tissue microarrays (TMAs) represent a powerful method for undertaking large‐scale tissue‐based biomarker studies. While TMAs offer several advantages, there are a number of issues specific to their use which need to be considered when employing this method. Given the investment in TMA‐based research, guidance on design and execution of experiments will be of benefit and should help researchers new to TMA‐based studies to avoid known pitfalls. Furthermore, a consensus on quality standards for TMA‐based experiments should improve the robustness and reproducibility of studies, thereby increasing the likelihood of identifying clinically useful biomarkers. In order to address these issues, the National Cancer Research Institute Biomarker and Imaging Clinical Studies Group organized a 1‐day TMA workshop held in Nottingham in May 2012. The document herein summarizes the conclusions from the workshop. It includes guidance and considerations on all aspects of TMA‐based research, including the pre‐analytical stages of experimental design, the analytical stages of data acquisition, and the postanalytical stages of data analysis. A checklist is presented which can be used both for planning a TMA experiment and interpreting the results of such an experiment. For studies of cancer biomarkers, this checklist could be used as a supplement to the REMARK guidelines.     

Interpreting the Tinnitus Questionnaire (German version): what individual differences are clinically important?

Objective: Reporting of clinical significance is recommended because findings can be statistically significant without being relevant to patients. For aiding clinical interpretation of the Tinnitus Questionnaire (TQ), many investigators use a 5-point change cut-off as a minimal clinically important difference (MCID). But there are shortcomings in how this value was originally determined. Design: The MCID was evaluated by analysing retrospective clinical data on the TQ (German version). Following recommended standards, multiple estimates were computed using anchor- and distribution-based statistical methods. These took into account not only patients’ experience of clinical improvement, but also measurement reliability. Study sample: Pre- and post-intervention scores were assessed for 202 patients. Results: Our six estimates ranged from 5 to 21 points in TQ change score from pre- to post- intervention. The 5-point TQ change score was obtained using a method that considered change between groups, and did not account for measurement error or bias. The size of the measurement error was considerable, and this comprises interpretation of individual patient change scores. Conclusions: To enhance confidence that a TQ change over time in individual patients is clinically meaningful, we advise at least the median MCID of 12 points.     

Which Vitamin D Oral Supplement is Best for Postmenopausal Women?

Next to a healthy calcium and protein rich diet and exercise, vitamin D supplementation is a key pillar of osteoporosis prevention among postmenopausal women. This article reviews the recent recommendations on vitamin D by the IOF (2010), the Institute of Medicine (2010), and the US Endocrine Society (2011), including the evidence to support these recommendations for fracture and fall prevention. The recent recommendations agree that supplementation should be performed with vitamin D3 or vitamin D2, and that a minimal serum 25-hydroxyvitamin D threshold of 50?nmol/l (20 ng/ml)should be achieved to overcome vitamin D deficiency. In contrast to the Institute of Medicine, the IOF and the US Endocrine Society recommend vitamin D also for the prevention of falls, and state that for fracture prevention a higher serum 25-hydroxyvitamin D threshold of 75?nmol/l (30?ng/ml) should be targeted.     

Activation of RhoA,B,C by Yersinia Cytotoxic Necrotizing Factor (CNFy) Induces Apoptosis in LNCaP Prostate Cancer Cells

Prostate cancer is the most common malignancy, accounting for about 25% of all incident cases among men in industrialized countries. The human androgen-dependent prostate cancer cell line LNCaP, which is derived from a metastatic lesion of human prostatic adenocarcinoma, is frequently used to study prostate cancer associated signaling pathways in vitro. Recently it was described that Rho GTPase activation in these cells leads to apoptotic responses. We used the bacterial toxins CNFy and CNF1, which specifically and directly activate Rho GTPases by deamidation of a single glutamine. We asked whether these Rho activators could induce apoptosis in LNCaP cells. Our results indicate that RhoA activation, induced by CNFy, does lead to intrinsic apoptosis of the cells. Analysis of the underlying signaling pathway reveals that apoptosis induction requires the activity of Rho kinase (ROCK) and myosin activation, an apoptotic pathway previously identified in cancer stem cells.