Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy

Loss of pancreatic beta cells is the central feature of all forms of diabetes. Current therapies fail to halt the declined beta cell mass. Thus, strategies to preserve beta cells are imperatively needed. In this study, we identified paired box 6 (PAX6) as a critical regulator of beta cell survival. Under diabetic conditions, the human beta cell line EndoC-βH1, db/db mouse and human islets displayed dampened insulin and incretin signalings and reduced beta cell survival, which were alleviated by PAX6 overexpression. Adeno-associated virus (AAV)-mediated PAX6 overexpression in beta cells of streptozotocin-induced diabetic mice and db/db mice led to a sustained maintenance of glucose homeostasis. AAV-PAX6 transduction in human islets reduced islet graft loss and improved glycemic control after transplantation into immunodeficient diabetic mice. Our study highlights a previously unappreciated role for PAX6 in beta cell survival and raises the possibility that ex vivo PAX6 gene transfer into islets prior to transplantation might enhance islet graft function and transplantation outcome

An International Reading Literacy Study: Factor Structure of the Chinese Version of the Student Questionnaire (PIRLS-SQCV 2011)

The student questionnaire (PIRLS-SQ 2011) of the Progress in International Reading Literacy Study (PIRLS) was designed to gather information from pupils on reading literacy development as to aspects of pupils’ self-lives, home, and school lives across countries/districts. In order to serve the purposes of research and international comparison, the questionnaire was translated into various languages. Using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), the current study investigates the psychometric properties of the Chinese version of the student questionnaire (PIRLS-SQCV 2011) and identifies its underlying factor structure among Chinese fourth-grade pupils in Hong Kong. A 10-factor structure model was identified and much resemblance could be drawn to the original PIRLS structure. While the similarity allows international comparisons of studies in different places following the PIRLS strategy, the findings of this study add to extant literature on the relationship between student factors and reading achievement.published_or_final_versio

Lycium barbarum polysaccharides reduce neuronal damage, blood-retinal barrier disruption and oxidative stress in retinal ischemia/reperfusion injury

Neuronal cell death, glial cell activation, retinal swelling and oxidative injury are complications in retinal ischemia/ reperfusion (I/R) injuries. Lycium barbarum polysaccharides (LBP), extracts from the wolfberries, are good for "eye health" according to Chinese medicine. The aim of our present study is to explore the use of LBP in retinal I/R injury. Retinal I/R injury was induced by surgical occlusion of the internal carotid artery. Prior to induction of ischemia, mice were treated orally with either vehicle (PBS) or LBP (1 mg/kg) once a day for 1 week. Paraffin-embedded retinal sections were prepared. Viable cells were counted; apoptosis was assessed using TUNEL assay. Expression levels of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), poly(ADP-ribose) (PAR) and nitrotyrosine (NT) were investigated by immunohistochemistry. The integrity of blood-retinal barrier (BRB) was examined by IgG extravasations. Apoptosis and decreased viable cell count were found in the ganglion cell layer (GCL) and the inner nuclear layer (INL) of the vehicle-treated I/R retina. Additionally, increased retinal thickness, GFAP activation, AQP4 up-regulation, IgG extravasations and PAR expression levels were observed in the vehicle-treated I/R retina. Many of these changes were diminished or abolished in the LBP-treated I/R retina. Pre-treatment with LBP for 1 week effectively protected the retina from neuronal death, apoptosis, glial cell activation, aquaporin water channel up-regulation, disruption of BRB and oxidative stress. The present study suggests that LBP may have a neuroprotective role to play in ocular diseases for which I/R is a feature. © 2011 Li et al.published_or_final_versio

The Clinical Utility of SUDOSCAN in Chronic Kidney Disease in Chinese Patients with Type 2 Diabetes

published_or_final_versio

Paired box 6 programs essential exocytotic genes in the regulation of glucose-stimulated insulin secretion and glucose homeostasis

The paired box 6 (PAX6) transcription factor is crucial for normal pancreatic islet development and function. Heterozygous mutations of PAX6 are associated with impaired insulin secretion and early-onset diabetes mellitus in humans. However, the molecular mechanism of PAX6 in controlling insulin secretion in human beta cells and its pathophysiological role in type 2 diabetes (T2D) remain ambiguous. We investigated the molecular pathway of PAX6 in the regulation of insulin secretion and the potential therapeutic value of PAX6 in T2D by using human pancreatic beta cell line EndoC-βH1, the db/db mouse model, and primary human pancreatic islets. Through loss- and gain-of-function approaches, we uncovered a mechanism by which PAX6 modulates glucose-stimulated insulin secretion (GSIS) through a cAMP response element–binding protein (CREB)/Munc18-1/2 pathway. Moreover, under diabetic conditions, beta cells and pancreatic islets displayed dampened PAX6/CREB/Munc18-1/2 pathway activity and impaired GSIS, which were reversed by PAX6 replenishment. Adeno-associated virus–mediated PAX6 overexpression in db/db mouse pancreatic beta cells led to a sustained amelioration of glycemic perturbation in vivo but did not affect insulin resistance. Our study highlights the pathophysiological role of PAX6 in T2D-associated beta cell dysfunction in humans and suggests the potential of PAX6 gene transfer in preserving and restoring beta cell function

From design to implementation - The Joint Asia Diabetes Evaluation (JADE) program: A descriptive report of an electronic web-based diabetes management program

<p>Abstract</p> <p>Background</p> <p>The Joint Asia Diabetes Evaluation (JADE) Program is a web-based program incorporating a comprehensive risk engine, care protocols, and clinical decision support to improve ambulatory diabetes care.</p> <p>Methods</p> <p>The JADE Program uses information technology to facilitate healthcare professionals to create a diabetes registry and to deliver an evidence-based care and education protocol tailored to patients' risk profiles. With written informed consent from participating patients and care providers, all data are anonymized and stored in a databank to establish an Asian Diabetes Database for research and publication purpose.</p> <p>Results</p> <p>The JADE electronic portal (e-portal: <url>http://www.jade-adf.org</url>) is implemented as a Java application using the Apache web server, the mySQL database and the Cocoon framework. The JADE e-portal comprises a risk engine which predicts 5-year probability of major clinical events based on parameters collected during an annual comprehensive assessment. Based on this risk stratification, the JADE e-portal recommends a care protocol tailored to these risk levels with decision support triggered by various risk factors. Apart from establishing a registry for quality assurance and data tracking, the JADE e-portal also displays trends of risk factor control at each visit to promote doctor-patient dialogues and to empower both parties to make informed decisions.</p> <p>Conclusions</p> <p>The JADE Program is a prototype using information technology to facilitate implementation of a comprehensive care model, as recommended by the International Diabetes Federation. It also enables health care teams to record, manage, track and analyze the clinical course and outcomes of people with diabetes.</p

The Complexity of Vascular and Non-Vascular Complications of Diabetes: The Hong Kong Diabetes Registry

Diabetes is a complex disease characterized by chronic hyperglycemia and multiple phenotypes. In 1995, we used a doctor-nurse-clerk team and structured protocol to establish the Hong Kong Diabetes Registry in a quality improvement program. By 2009, we had accrued 2616 clinical events in 9588 Chinese type 2 diabetic patients with a follow-up duration of 6 years. The detailed phenotypes at enrollment and follow-up medications have allowed us to develop a series of risk equations to predict multiple endpoints with high sensitivity and specificity. In this prospective database, we were able to validate findings from clinical trials in real practice, confirm close links between cardiovascular and renal disease, and demonstrate the emerging importance of cancer as a leading cause of death. In addition to serving as a tool for risk stratification and quality assurance, ongoing data analysis of the registry also reveals secular changes in disease patterns and identifies unmet needs

Tuberculin screening of some selected Fulani lactating cows in north-central Nigeria

The prevalence of mycobacterial infection among lactating Fulani cows was investigated in the Federal Capital Territory, Abuja and Kaduna State of Nigeria. Tuberculin testing using single comparative intradermal tuberculin test showed a 14.6 % positive, 4 % doubtful, and 81.4 % negative reactors. Mycobacterial infection was found to be present in the nomadic (constantly moving) and seminomadic (limited movement) management systems studied but management showed no significant effect on the prevalence of the disease. However, the prevalence was significantly higher in older age groups than the younger ones (P < 0.05).Peer reviewedSubmitted Versio

Oxygen-related band gap state in single crystal rubrene

A molecular exciton signature is established and investigated under different ambient conditions in rubrene single crystals. An oxygen-related band gap state is found to form in the ambient atmosphere. This state acts as an acceptor center and assists in the fast dissociation of excitons, resulting in a higher dark and photoconductivity of oxidized rubrene. The band gap state produces a well-defined photoluminescence band at an energy 0.25 eV below the energy of the 0-0 molecular exciton transition. Two-photon excitation spectroscopy shows that the states are concentrated near the surface of naturally oxidized rubrene

Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10

published_or_final_versio