PURPOSE: To develop a profiling tool which accurately assigns a patient to the appropriate attitudinal cluster for the management of asthma. METHODS: Attitudinal data from an online survey of 2,467 patients with asthma from 8 Asian countries/region, aged 18-50 years, having had ≥2 prescriptions in the previous 2 years and access to social media was used in a discriminant function analysis to identify a minimal set of questions for the Profiling Tool. A split-sample procedure based on 100 sets of randomly selected estimation and validation sub-samples from the original sample was used to cross-validate the Tool and assess the robustness of its predictive accuracy. RESULTS: Our Profiling Tool contained 10 attitudinal questions for the patient and 1 GINA-based level of asthma control question for the physician. It achieved a predictive accuracy of 76.2%. The estimation and validation sub-sample accuracies of 76.7% and 75.3%, respectively, were consistent with the tool's predictive accuracy at 95% confidence level; and their 1.4 percentage-points difference set upper-bound estimate for the degree of over-fitting. CONCLUSIONS: The Profiling Tool is highly predictive (>75%) of the attitudinal clusters that best describe patients with asthma in the Asian population. By identifying the attitudinal profile of the patient, the physician can make the appropriate asthma management decisions in practice. The challenge is to integrate its use into the consultation workflow and apply to areas where Internet resources are not available or patients who are not comfortable with the use of such technology.
Asia ; Asian Continental Ancestry Group ; Asthma* ; Discriminant Analysis ; Disease Management ; Humans ; Internet ; Prescriptions ; Social Media

OBJECTIVETo review the functions of these intracellular signals in their regulation of retinal ganglion cell (RGC) axon regeneration.

DATA SOURCESRelevant articles published in English or Chinese from 1970 to present were selected from PubMed. Searches were made using the terms "intrinsic determinants, axon regeneration, RGC, optic nerve regeneration, and central nervous system axon regeneration."

STUDY SELECTIONArticles studying the mechanisms controlling RGC and central nervous system (CNS) axon regeneration were reviewed. Articles focusing on the intrinsic determinants of axon regeneration were selected.

RESULTSLike other CNS neurons of mammals, RGCs undergo a developmental loss in their ability to grow axons as they mature, which is a critical contributing factor to the failure of nerve regeneration and repair after injury. This growth failure can be attributed, at least in part, by the induction of molecular programs preventing cellular overgrowth and termination of axonal growth upon maturation. Key intracellular signals and transcription factors, including B cell lymphoma/leukemia 2, cyclic adenine monophosphate, mammalian target of rapamycin, and Krüppel-like transcription factors, have been identified to play central roles in this process.

CONCLUSIONSIntense effort and substantial progress have been made to identify the various intrinsic growth pathways that regulate RGC axon regeneration. More work is needed to elucidate the mechanisms of and the interrelationship between the actions of these factors and to successfully achieve regeneration and repair of the severed RGC axons.

Animals ; Cyclic AMP ; physiology ; Humans ; Kruppel-Like Transcription Factors ; physiology ; Nerve Regeneration ; Optic Nerve ; physiology ; PTEN Phosphohydrolase ; physiology ; Proto-Oncogene Proteins c-bcl-2 ; physiology ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; physiology ; TOR Serine-Threonine Kinases ; physiology

BACKGROUNDIn a previous study, we demonstrated that ephrin-A2 and -A3 negatively regulate the growth of neural progenitor cells in the central nervous system. Adult mice deficient in ephrin-A2 and -A3 (A2(-/-)A3(-/-)) displayed active ongoing neurogenesis throughout the brain, and mice deficient in ephrin-A3 alone showed increased proliferation of ciliary epithelium derived retinal stem cells. This study aimed to detect that the increase in proliferation and neurogenic potential of Müller cells is influenced by the absence of ephrin-A2 and -A3.

METHODSWe assessed the retinal and Müller cell expression of ephrin-As and their receptor and neural progenitor cell markers by immunostaining and real-time PCR. We cultured purified primary Müller cells derived from wild-type and A2(-/-)A3(-/-) mice in a defined culture medium that enables trans-differentiation of Müller cells into retinal neurons. To evaluate proliferating Müller cells in vivo, we injected 5'-ethylnyl-2'-deoxiuridine (EdU) intraperitoneally to adult mice.

RESULTSExpression of ephrin-A2/A3 and their receptor EphA4 were detected in the retinas of adult mice, with EphA4 expression particularly enriched in Müller cells. Müller cells of A2(-/-)A3(-/-) mice exhibited significantly elevated expression of retinal progenitor cell markers, Pax6 and Chx10, when compared with those from wild-type mice. Moreover, a higher percentage of Müller cells of A2(-/-)A3(-/-) mice trans-differentiated and became recoverin+ and β-III-tublin+ in the culture than those from wild type mice. Strikingly, an increased number of EdU+ retinal cells was detected in the retinas of adult A2(-/-)A3(-/-) mice as compared with wild-type mice.

CONCLUSIONSEphrin-A2 and -A3 are negative regulators of the proliferative and neurogenic potentials of Müller cells. Manipulating ephrin-A signaling may thus represent a novel strategy for stimulating neuroregeneration from endogenous progenitors to participate in retinal repair in case of disease or damage.

Animals ; Cell Differentiation ; genetics ; physiology ; Ephrin-A2 ; genetics ; metabolism ; Ephrin-A3 ; genetics ; metabolism ; Fluorescent Antibody Technique ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Real-Time Polymerase Chain Reaction ; Receptor, EphA4 ; genetics ; metabolism ; Retina ; cytology ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells ; cytology ; metabolism