Influence of Platelet-derived Growth Factor on Lens Epithelial Cell Proliferation and Differentiation

The expression pattern of platelet-derived growth factor (PDGF) and its receptor suggest a role in lens cell proliferation. PDGF is strongly expressed in the iris and ciliary body, situated opposite the proliferative cells of the lens epithelium which express the PDGF- &#102 receptor. In this study, using lens epithelial explant cultures, we report that PDGF can induce a dose and time dependent increase in lens cell DNA synthesis. Culturing lens explants with both PDGF and FGF (a mitogen and differentiation factor for lens cells) resulted in responses greater than those induced by either growth factor alone. PDGF did not induce any changes typical of fibre differentiation; however, in combination with FGF it potentiated the fibre differentiating activity of FGF. Results obtained in this study support previous indications that PDGF has an important role in regulating lens cell proliferation. In addition, PDGF may have a role in potentiating FGF-induced lens fibre differentiation in vivo.     

The conserved lymphokine element 0 is a powerful activator and target for corticosteroid inhibition in human interleukin-5 transcription

The role of eosinophilia in allergic disorders indicates hIL-5 as a potential target for therapy. The conservation of hIL-5 gene proximal elements suggests they are important in controlling expression. Corticosteroids are important in the treatment of allergy, and are powerful inhibitors of IL-5 expression. This study aimed at understanding the role of hIL-5 conserved proximal elements, and elucidating the target of corticosteroid activity, in hIL-5 gene expression. Methods used include transient transfection of PBMC and PER117 cells with hIL-5 deletion constructs, EMSA, Western Blotting, and RT-PCR.

The conserved proximal CLE0/TATA elements driving a reporter gene gave similar or higher expression than a 500 bp promoter in primary human T cells and a T-cell line. Two and three copies of IL-5 CLE0 upstream of the silent IL-4 minimal promoter gave 30–45 fold increases in expression in forward orientation, but little activity in reverse orientation. Consequently, CLE0 is a powerful activator but not a classical enhancer. Deletion analysis identified CLE0 as the key element in the inhibition of IL-5 reporter constructs by dexamethasone, and RT-PCR analysis indicated that GILZ expression correlated with dexamethasone-induced inhibition of IL-5. Ectopic expression of GILZ, confirmed by western blotting, gave a 90% inhibition of promoter constructs in absence of dexamethasone. CLE0 is a powerful activator sufficient for the inducible expression of IL-5, and functions when moved upstream in a heterologous promoter. CLE0 is also the main target for IL-5 inhibition by dexamethasone, and we present evidence consistent with a role of GILZ in this.     

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma

Objective:Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma.Methods:A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection.Results:Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS.Conclusion:Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC.Advances in knowledge:We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.     

Monitoring Dietary Intake and Physical Activity Electronically: Feasibility,Usability, and Ecological Validity of a Mobile-Based Ecological Momentary Assessment Tool

Background

Despite the growing body of research on complex lifestyle behaviors (eg, Dietary Intake [DI] and Physical Activity [PA]), monitoring of these behaviors has been hampered by a lack of suitable methods. A possible solution to this deficiency is mobile-based Ecological Momentary Assessment (mEMA), which enables researchers to collect data on participants’ states in real-time by means of a smartphone application. However, feasibility, usability, and ecological validity need to be anticipated and managed in order to enhance the validity of mEMA.

Objective

To examine the feasibility, usability, and ecological validity of a mEMA application (app) with regard to DI and PA among Dutch vocational education students.

Methods

The students (n=30) participated in the mEMA study for seven consecutive days. They downloaded the mEMA app on their smartphone. Feasibility and usability of the mEMA app were evaluated by completing an online evaluation after seven days of participation. Ecological validity was measured by assessing the degree to which the content of the mEMA app approximated the real-world setting that was being examined, through several multiple-choice questions.

Results

Compliance rates, as registered by the mEMA app, declined 46% over a seven-day period, while self-reported compliance, as measured with an online evaluation questionnaire afterwards, indicated a smaller decrease in compliance (29%). The students evaluated the mEMA app as feasible and usable. Ecological validity analyses showed that all DI and almost all PA multiple-choice options were covered with the compound response categories.

Conclusions

The mEMA app offers the opportunity to assess complex health behaviors (eg, DI and PA) in real-time settings, in which specifically routinized behaviors are involved. However, the mEMA app faced several challenges that needed to be overcome in order to improve its validity. Overall, the present study showed that the mEMA app is a usable and ecologically valid tool to measure DI and PA behaviors among vocational education students, but compliance is still limited.     

More than a decade after live donor nephrectomy: a prospective cohort study

Previously reported short‐term results after live kidney donation show no negative consequences for the donor. The incidence of new‐onset morbidity takes years to emerge, making it highly likely that this will be missed during short‐term follow‐up. Therefore, evidence on long‐term outcome is essential. A 10‐year follow‐up on renal function, hypertension, quality of life (QOL), fatigue, and survival was performed of a prospective cohort of 100 donors. After a median follow‐up time of 10 years, clinical data were available for 97 donors and QOL data for 74 donors. Nine donors died during follow‐up of unrelated causes to donation, and one donor was lost to follow‐up. There was a significant decrease in kidney function of 12.9 ml/min (P < 0.001) at follow‐up. QOL showed significant clinically relevant decreases of 10‐year follow‐up scores in SF‐36 dimensions of physical function (P < 0.001), bodily pain (P = 0.001), and general health (P < 0.001). MFI‐20 scores were significantly higher for general fatigue (P < 0.001), physical fatigue (P < 0.001), reduced activity (P = 0.019), and reduced motivation (P = 0.030). New‐onset hypertension was present in 25.6% of the donors. Donor outcomes are excellent 10 years post‐donation. Kidney function appears stable, and hypertension does not seem to occur more frequently compared to the general population.     

Disease Detection or Public Opinion Reflection? Content Analysis of Tweets,Other Social Media,and Online Newspapers During the Measles Outbreak in the Netherlands in 2013

Background

In May 2013, a measles outbreak began in the Netherlands among Orthodox Protestants who often refuse vaccination for religious reasons.

Objective

Our aim was to compare the number of messages expressed on Twitter and other social media during the measles outbreak with the number of online news articles and the number of reported measles cases to answer the question if and when social media reflect public opinion patterns versus disease patterns.

Methods

We analyzed measles-related tweets, other social media messages, and online newspaper articles over a 7-month period (April 15 to November 11, 2013) with regard to topic and sentiment. Thematic analysis was used to structure and analyze the topics.

Results

There was a stronger correlation between the weekly number of social media messages and the weekly number of online news articles (P<.001 for both tweets and other social media messages) than between the weekly number of social media messages and the weekly number of reported measles cases (P=.003 and P=.048 for tweets and other social media messages, respectively), especially after the summer break. All data sources showed 3 large peaks, possibly triggered by announcements about the measles outbreak by the Dutch National Institute for Public Health and the Environment and statements made by well-known politicians. Most messages informed the public about the measles outbreak (ie, about the number of measles cases) (93/165, 56.4%) followed by messages about preventive measures taken to control the measles spread (47/132, 35.6%). The leading opinion expressed was frustration regarding people who do not vaccinate because of religious reasons (42/88, 48%).

Conclusions

The monitoring of online (social) media might be useful for improving communication policies aiming to preserve vaccination acceptability among the general public. Data extracted from online (social) media provide insight into the opinions that are at a certain moment salient among the public, which enables public health institutes to respond immediately and appropriately to those public concerns. More research is required to develop an automatic coding system that captures content and user’s characteristics that are most relevant to the diseases within the National Immunization Program and related public health events and can inform official responses.     

A Study on the Utilization of Coal Fly Ash Derived Grog in Clay Ceramics

Grog is an additive material that plays important roles in ceramic making. It improves the fabrication process of green bodies as well as the physical properties of fired bodies. Few low-cost materials and wastes have found their application as grog in recent years, thus encouraging the replacement of commercial grogs with cost-saving materials. Coal fly ash, a combustion waste produced by coal-fired power plant, has the potential to be converted into grog owing to its small particle sizes and high content of silica and alumina. In this study, grog was derived from coal fly ash and mixed with kaolin clay to produce ceramics. Effects of the grog addition on the resultant ceramics were investigated. It was found that, to a certain extent, the grog addition reduced the firing shrinkage and increased the total porosity of the ceramics. The dimensional stability of the ceramics at a firing temperature of 1200 °C was also not noticeably affected by the grog. However, the grog addition in general had negative effects on the biaxial flexural strength and refractoriness of the ceramics.