Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy

Purpose To characterise longitudinal changes in the retinal microvasculature of type 2 diabetes mellitus (T2DM) as exemplified in a patient with proliferative diabetic retinopathy (PDR) using an adaptive optics scanning light ophthalmoscope (AOSLO). Methods A 35-year-old T2DM patient with PDR treated with scatter pan-retinal photocoagulation at the inferior retina 1 day prior to initial AOSLO imaging along with a 24-year-old healthy control were imaged in this study. AOSLO vascular structural and perfusion maps were acquired at four visits over a 20-week period. Capillary diameter and microaneurysm area changes were measured on the AOSLO structural maps. Imaging repeatability was established using longitudinal imaging of microvasculature in the healthy control. Results Capillary occlusion and recanalisation, capillary dilatation, resolution of local retinal haemorrhage, capillary hairpin formation, capillary bend formation, microaneurysm formation, progression and regression were documented over time in a region 2° superior to the fovea in the PDR patient. An identical microvascular network with same capillary diameter was observed in the control subject over time. Conclusions High-resolution serial AOSLO imaging enables in vivo observation of vasculopathic changes seen in diabetes mellitus. The implications of this methodology are significant, providing the opportunity for studying the dynamics of the pathological process, as well as the possibility of identifying highly sensitive and non-invasive biomarkers of end organ damage and response to treatment

PKA-activated ApAF–ApC/EBP heterodimer is a key downstream effector of ApCREB and is necessary and sufficient for the consolidation of long-term facilitation

Long-term memory requires transcriptional regulation by a combination of positive and negative transcription factors. Aplysia activating factor (ApAF) is known to be a positive transcription factor that forms heterodimers with ApC/EBP and ApCREB2. How these heterodimers are regulated and how they participate in the consolidation of long-term facilitation (LTF) has not, however, been characterized. We found that the functional activation of ApAF required phosphorylation of ApAF by PKA on Ser-266. In addition, ApAF lowered the threshold of LTF by forming a heterodimer with ApCREB2. Moreover, once activated by PKA, the ApAF–ApC/EBP heterodimer transactivates enhancer response element–containing genes and can induce LTF in the absence of CRE- and CREB-mediated gene expression. Collectively, these results suggest that PKA-activated ApAF–ApC/EBP heterodimer is a core downstream effector of ApCREB in the consolidation of LTF

Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib

Dual human epidermal growth factor receptor 2 (HER2) targeting can increase pathologic complete response rates (pCRs) to neoadjuvant therapy and improve progression-free survival in metastatic disease. CALGB 40601 examined the impact of dual HER2 blockade consisting of trastuzumab and lapatinib added to paclitaxel, considering tumor and microenvironment molecular features

Development of Mathematics Pedagogical Content Knowledge in Pre- service Teachers

Abstract: The objective of mathematics methodology courses in teacher preparation programmes is concerned about the development of MPCK in their pre-service teachers. As part of a research study on the development of MPCK in primary school beginning teachers, a 16-item instrument was developed to measure some aspects of the MPCK for teaching mathematics at primary level. The instrument was administered to the 2005 Intake of the Postgraduate Diploma in Education (Primary) student teachers at the National Institute of Education, Singapore just at the beginning of their programme. As they complete their methodology course in February 2006, the instrument was administered again. This paper discussed the findings concerning their performance in these two tests, with reference to the overall performance as well as topic-specific and MPCK construct-specific performance. The findings indicate that student teachers at the beginning of their programmes are generally quite weak in their mathematics pedagogical content knowledge, as might be expected. There was significant improvement in most aspects of their MPCK on completion of their mathematics pedagogy course

Investigation of Lithium Transference Number in PMMA Composite Polymer Electrolytes Using Monte Carlo (MC) Simulation and Recurrence Relation

In this study, Monte Carlo (MC) simulation is conducted with recurrence relation to study the effect of SiO2 with different particle size and their roles in enhancing the ionic conductivity and lithium transference number of PMMA composite polymer electrolytes (CPEs). The MC simulated ionic conductivity is verified with the measurements from Electrochemical Impedance Spectroscopy (EIS). Then, the lithium transference number of CPEs is calculated using recurrence relation with the MC simulated current density and the reference transference number obtained. Incorporation of micron-size SiO2 (≤10 μm) fillers into the mixture improves the ionic conductivity from 8.60×10−5 S/cm to 2.35×10−4 S/cm. The improvement is also observed on the lithium transference number, where it increases from 0.088 to 0.3757. Furthermore, the addition of nano-sized SiO2 (≤12 nm) fillers further increases the ionic conductivity up towards 3.79×10−4 S/cm and lithium transference number of 0.4105. The large effective surface area of SiO2 fillers is responsible for the improvement in ionic conductivity and the transference number in PMMA composite polymer electrolytes

FELLOW EYE CHANGES IN PATIENTS WITH NONISCHEMIC CENTRAL RETINAL VEIN OCCLUSION: Assessment of Perfused Foveal Microvascular Density and Identification of Nonperfused Capillaries.

International audienceEyes fellow to nonischemic central retinal vein occlusion (CRVO) were examined for abnormalities, which might explain their increased risk for future occlusion, using adaptive optics scanning light ophthalmoscope fluorescein angiography.Adaptive optics scanning light ophthalmoscope fluorescein angiography foveal microvascular densities were calculated. Nonperfused capillaries adjacent to the foveal avascular zone were identified. Spectral domain optical coherence tomography, ultrawide field fluorescein angiographies, and microperimetry were also performed.Ten fellow eyes of nine nonischemic CRVO and 1 nonischemic hemi-CRVO subjects and four affected eyes of three nonischemic CRVO and one nonischemic hemi-CRVO subjects were imaged. Ninety percent of fellow eyes and 100% of affected eyes demonstrated at least 1 nonperfused capillary compared with 31% of healthy eyes. Fellow eye microvascular density (35 ± 3.6 mm(-1)) was significantly higher than that of affected eyes (25 ± 5.2 mm(-1)) and significantly lower than that of healthy eyes (42 ± 4.2 mm(-1)). Compared with healthy controls, spectral domain optical coherence tomography thicknesses showed no significant difference, whereas microperimetry and 2/9 ultrawide field fluorescein angiography revealed abnormalities in fellow eyes.Fellow eye changes detectable on adaptive optics scanning light ophthalmoscope fluorescein angiography reflect subclinical pathology difficult to detect using conventional imaging technologies. These changes may help elucidate the pathogenesis of nonischemic CRVO and help identify eyes at increased risk of future occlusion