Serum mucosa-associated epithelial chemokine (MEC/CCL28) in atopic dermatitis: a specific marker for severity

Background Mucosa‐associated epithelial chemokine (MEC; CCL28) is considered to be pivotal in mediating the migration of CC chemokine receptor 3‐ and 10‐ (CCR3‐ and CCR10)‐expressing, skin‐homing, memory, cutaneous lymphocyte‐associated antigen‐positive (CLA⁺) T cells. CCL28 is selectively and continuously expressed by epidermal keratinocytes, but highly upregulated in inflammatory skin diseases, such as atopic dermatitis (AD). Aim This controlled longitudinal study was designed to evaluate the expression of CCL28 in serum in childhood AD and bronchial asthma (BA), and its possible relationship to disease severity and activity. Methods Serum CCL28 levels were measured in 36 children with AD, 23 with BA, 14 with both conditions, and 21 healthy age‐ and sex‐matched controls. Sixteen patients in the AD group were followed up and resampled for serum CCL28 after clinical remission. Serum CCL28 levels were correlated with some AD disease activity and severity variables. Results Serum CCL28 levels in AD, whether during flare [median, 1530 pg/mL; mean ± standard deviation (SD) = 1590.4 ± 724.3 pg/mL] or quiescence (median, 1477 pg/mL; mean ± SD = 1575.2 ± 522.1 pg/mL), were significantly higher than those in healthy children (median, 301 pg/mL; mean ± SD = 189.6 ± 92.8 pg/mL); however, the levels during flare and quiescence were statistically comparable. The serum levels in BA (median, 340 pg/mL; mean ± SD = 201.6 ± 109.5 pg/mL) were significantly lower than those in the AD group, and comparable with those in healthy controls. Serum CCL28 levels in severe AD were significantly higher than those in mild and moderate cases, and correlated positively with the calculated severity scores [Leicester Sign Score (LSS) and Scoring Atopic Dermatitis (SCORAD)]. CCL28 levels during the exacerbation of AD were positively correlated with the corresponding values during remission, the peripheral absolute eosinophil counts, and serum lactate dehydrogenase levels. Serum CCL28 levels were not correlated with the serum total immunoglobulin E values in AD. Conclusions Our data reinforce the concept that CCL28 might contribute to the pathogenesis of AD, probably through the selective migration and infiltration of effector/memory T‐helper‐2 cells in the skin. CCL28 may also represent an objective prognostic marker for disease severity. Further studies may pave the way for CCL28 antagonism among adjuvant therapeutic strategies.     

Inhibition of the sodium/potassium ATPase impairs N-glycan expression and function

Aberrant N-linked glycans promote the malignant potential of cells by enhancing the epithelial-to-mesenchymal transition and the invasive phenotype. To identify small molecule inhibitors of N-glycan biosynthesis, we developed a chemical screen based on the ability of the tetravalent plant lectin L-phytohemagglutinin (L-PHA) to bind and crosslink surface glycoproteins with beta1,6GlcNAc-branched complex type N-glycans and thereby induce agglutination and cell death. In this screen, Jurkat cells were treated with a library of off-patent chemicals (n = 1,280) to identify molecules that blocked L-PHA-induced death. The most potent hit from this screen was the cardiac glycoside (CG) dihydroouabain. In secondary assays, a panel of CGs was tested for their effects on L-PHA-induced agglutination and cell death. All of the CGs tested inhibited L-PHA-induced death in Jurkat cells, and the most potent CG tested was digoxin with an EC(50) of 60 +/- 20 nmol/L. Digoxin also increased the fraction of some concanavalin A-binding N-glycans. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, digoxin specifically increased GlcNAc(1)Man(3)GlcNAc(2)Fuc(1) and GlcNAc(2)Man(3)GlcNAc(2)Fuc(1) oligosaccharides demonstrating an impairment of the N-glycan pathway. Consistent with this effect on the N-glycan pathway, digoxin inhibited N-glycosylation-mediated processes of tumor cell migration and invasion. Furthermore, digoxin prevented distant tumor formation in two mouse models of metastatic prostate cancer. Thus, taken together, our high throughput screen identified CGs as modifiers of the N-glycan pathway. These molecules can be used as tools to better understand the role of N-glycans in normal and malignant cells. Moreover, these results may partly explain the anticancer effect of CGs in cardiovascular patients.     

Inflammatory breast cancer in Tunisia: reassessment of incidence and clinicopathological features

Inflammatory breast cancer (IBC) is a clinical diagnosis characterized by a peculiar geographic distribution in incidence, being particularly common in Tunisia and the region of North Africa. The peculiar aspects of the disease in this region may provide some insights on the biological characteristics of the disease. We updated and revised the data from our single-institution experience using the more stringent diagnostic criteria of the International Union Against Cancer (UICC) based on the tumor-node-metastasis (TNM) classification. The new analysis included 419 newly diagnosed cases of IBC evaluated between 1975 and 1996 that were subdivided into three groups: group A (118 cases classified as T4d in 1990-1996); group B (175 cases reported as Pev 2 or 3 in 1975-81 and restaged as T4d); and group C (126 cases classified Pev 2 or 3 in 1975-81 and restaged as T4b). The frequency of IBC cases classified as T4d in the various series was 5.7% for group A (118/2,073) and 13.3% for group B (175/1,317), while T4b represented 9% for group C (126/1,317). The analysis demonstrated worse 5-year overall survival rates for groups A and B (8.5% and 11.3%, respectively) compared to group C (25.6%). Interestingly, using a more uniform classification criteria, the incidence of IBC was 5% to 7% compared to previous historical reports of up to 50% of newly diagnosed cases of breast cancer in Tunisia.     

Clinical Research Recession: Training Needs Perception Among Medical Students

Clinical research is an integrated part of medical education. There is a noticeable decrease in the number of physician-scientists in developing countries, which is reflected by a decrease in research output and publications from these countries. We conducted a survey aiming to identify the gaps in clinical research training from the perspective of medical students. The results can be used to customize future clinical research trainings. The survey tool was divided into six modules which represent the cornerstones of clinical research based on similar surveys done for the same purpose. For each module, questions covered the perceived knowledge of its aspects and how much relevant the responder thought it was to clinical research. Five hundred one candidates have filled the survey. Evidence-based medicine (EBM) had the highest knowledge score of 2.20/4, while “clinical trials execution” knowledge got the lowest score of 1.64/4. Responders perceived EBM as the most relevant aspect of clinical research (3.39/4), while research ethics received the lowest score 3.18/4. “Clinical trials execution” had the largest gap of a difference calculated as 1.60, while EBM had the lowest gap of 1.20. More attention must be paid to clinical research training for medical students in developing countries. These trainings have to be customized to focus on clinical trial execution, research methodology, and biostatistics. In parallel, awareness campaigns targeted toward the medical community emphasizing the importance of the ethics as an aspect of clinical research should be established.     

Additional value of qualitative strain ultrasound elastography and strain ratio in predicting thyroid malignancy

Objective

To detect if strain ultrasound elastography and strain ratio have additional value to the conventional grey scale ultrasound in predicting thyroid malignancy.

Role of positron emission tomography computed tomography in screening metastasis of renal cell carcinoma

Purpose

To demonstrate role of PET-CT (positron emission tomography-computed tomography) in screening for local and distant metastatic deposits from primary renal cell carcinoma and enhancing its advantages over other imaging modalities.

Problem of living liver donation in the absence of deceased liver transplantation program: Mansoura experience

We report our experience with potential donors for living donor liver transplantation (LDLT), which is the first report from an area where there is no legalized deceased donation program. This is a single center retrospective analysis of potential living donors (n = 1004) between May 2004 and December 2012. This report focuses on the analysis of causes, duration, cost, and various implications of donor exclusion (n = 792). Most of the transplant candidates (82.3%) had an experience with more than one excluded donor (median = 3). Some recipients travelled abroad for a deceased donor transplant (n = 12) and some died before finding a suitable donor (n = 14). The evaluation of an excluded donor is a time-consuming process (median = 3 d, range 1 d to 47 d). It is also a costly process with a median cost of approximately 70 USD (range 35 USD to 885 USD). From these results, living donor exclusion has negative implications on the patients and transplant program with ethical dilemmas and an economic impact. Many strategies are adopted by other centers to expand the donor pool; however, they are not all applicable in our locality. We conclude that an active legalized deceased donor transplantation program is necessary to overcome the shortage of available liver grafts in Egypt.     

Demographic,clinical and radiological characteristics of seronegative spondyloarthritis Egyptian patients: A rheumatology clinic experience in Mansoura

Introduction

Seronegative spondyloarthritis (SpA) is a group of chronic potentially disabling diseases that affect mainly axial joints in addition to extra-articular manifestations such as enthesitis, dactylitis and uveitis.