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"Aung, Tin"
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The Regulation of JNK Signaling Pathways in Cell Death through the Interplay with Mitochondrial SAB and Upstream Post-Translational Effects
c-Jun-N-terminal kinase (JNK) activity plays a critical role in modulating cell death, which depends on the level and duration of JNK activation. The kinase cascade from MAPkinase kinase kinase (MAP3K) to MAPkinase kinase (MAP2K) to MAPKinase (MAPK) can be regulated by a number of direct and indirect post-transcriptional modifications, including acetylation, ubiquitination, phosphorylation, and their reversals. Recently, a JNK-mitochondrial SH3-domain binding protein 5 (SH3BP5/SAB)-ROS activation loop has been elucidated, which is required to sustain JNK activity. Importantly, the level of SAB expression in the outer membrane of mitochondria is a major determinant of the set-point for sustained JNK activation. SAB is a docking protein and substrate for JNK, leading to an intramitochondrial signal transduction pathway, which impairs electron transport and promotes reactive oxygen species (ROS) release to sustain the MAPK cascade.
Journal Article
Feeding practices and nutritional status of children age 6-23 months in Myanmar: A secondary analysis of the 2015-16 Demographic and Health Survey
Nutritional deficiencies are a major problem among developing countries including Myanmar. They can occur in all age groups, but the impact is more severe among children age 6-23 months as this period is critical for child development, and irreversible damages can occur due to nutritional deficiencies. Proper infant and young child feeding practices are pivotal to tackle nutritional problems and to prevent irreversible consequences among children. To assess the current feeding practices and associations with nutritional status, we conducted a secondary data analysis using the 2015-16 Myanmar Demographic and Health Survey. Multiple logistic regression analysis was done adjusting for covariates and the results were presented by adjusted odds ratios with 95% confidence intervals. A total of 1,222 children age 6-23 months were included in this analysis. Twenty percent were stunted and 43% were moderately anemic. Only 16% of children received a minimum acceptable diet, 25% received diverse food groups, 58% were fed with minimum meal frequency, 85% currently breastfed, and 59% consumed iron-rich foods. Breastfeeding reduced the odds of being stunted. Male sex, perceived small birth size, mother with short stature, and working mother were significant predictors of stunting. Iron-rich food consumption was inversely associated with moderate anemia. Male sex and maternal anemia were also significant predictors of moderate anemia. The study concluded that stunting and anemia among young children in Myanmar are major public health challenges that need urgent action. While further prospective research is needed to determine the effect of feeding practice on linear growth, interventions such as iron supplementation, and nutritional education programs according to the World Health Organization complementary feeding guidelines could help prevent stunting and childhood anemia and might reduce their prevalence in Myanmar.
Journal Article
In Vivo 3-Dimensional Strain Mapping of the Optic Nerve Head Following Intraocular Pressure Lowering by Trabeculectomy
Purpose: To map the 3-dimensional (3D) strain of the optic nerve head (ONH) in vivo after intraocular pressure (IOP) lowering by trabeculectomy (TE) and to establish associations between ONH strain and retinal sensitivity.Design: Observational case series.Participants: Nine patients with primary open-angle glaucoma (POAG) and 3 normal controls.Methods: The ONHs of 9 subjects with POAG (pre-TE IOP: 25.3 +/- 13.9 mmHg; post-TE IOP: 11.8 +/- 8.6 mmHg) were imaged (1 eye per subject) using optical coherence tomography (OCT) (Heidelberg Spectralis, Heidelberg Engineering GmbH, Heidelberg, Germany) before (< 21 days) and after (< 50 days) TE. The imaging protocol was repeated for 3 controls in whom IOP was not altered. In each post-TE OCT volume, 4 tissues were manually segmented (prelamina, choroid, sclera, and lamina cribrosa [LC]). For each ONH, a 3D tracking algorithm was applied to both post-and pre-TE OCT volumes to extract IOP-induced 3D displacements at segmented nodes. Displacements were filtered, smoothed, and processed to extract 3D strain relief (the amount of tissue deformation relieved after TE). Strain relief was compared with measures of retinal sensitivity from visual field testing.Main Outcome Measures: Three-dimensional ONH displacements and strain relief.Results: On average, strain relief (averaged or effective component) in the glaucoma ONHs (8.6%) due to TE was higher than that measured in the normal controls (1.07%). We found no associations between the magnitude of IOP decrease and the LC strain relief (P > 0.05), suggesting biomechanical variability across subjects. The LC displaced posteriorly, anteriorly, or not at all. Furthermore, we found linear associations between retinal sensitivity and LC effective strain relief (P < 0.001; high strain relief associated with low retinal sensitivity).Conclusions: We demonstrate that ONH displacements and strains can be measured in vivo and that TE can relieve ONH strains. Our data suggest a wide variability in ONH biomechanics in the subjects examined in this study. We further demonstrate associations between LC effective strain relief and retinal sensitivity.
Journal Article
A Deep Learning Approach to Denoise Optical Coherence Tomography Images of the Optic Nerve Head
Optical coherence tomography (OCT) has become an established clinical routine for the
in vivo
imaging of the optic nerve head (ONH) tissues, that is crucial in the diagnosis and management of various ocular and neuro-ocular pathologies. However, the presence of speckle noise affects the quality of OCT images and its interpretation. Although recent frame-averaging techniques have shown to enhance OCT image quality, they require longer scanning durations, resulting in patient discomfort. Using a custom deep learning network trained with 2,328 ‘clean B-scans’ (multi-frame B-scans; signal averaged), and their corresponding ‘noisy B-scans’ (clean B-scans + Gaussian noise), we were able to successfully denoise 1,552 unseen single-frame (without signal averaging) B-scans. The denoised B-scans were qualitatively similar to their corresponding multi-frame B-scans, with enhanced visibility of the ONH tissues. The mean signal to noise ratio (SNR) increased from 4.02 ± 0.68 dB (single-frame) to 8.14 ± 1.03 dB (denoised). For all the ONH tissues, the mean contrast to noise ratio (CNR) increased from 3.50 ± 0.56 (single-frame) to 7.63 ± 1.81 (denoised). The mean structural similarity index (MSSIM) increased from 0.13 ± 0.02 (single frame) to 0.65 ± 0.03 (denoised) when compared with the corresponding multi-frame B-scans. Our deep learning algorithm can denoise a single-frame OCT B-scan of the ONH in under 20 ms, thus offering a framework to obtain superior quality OCT B-scans with reduced scanning times and minimal patient discomfort.
Journal Article
Evaluation of changes of anterior segment parameters in patients with pseudoexfoliation syndrome after cataract surgery using anterior segment optical coherence tomography
The aim of the study was to compare the anterior segment parameters after cataract surgery in pseudoexfoliation syndrome (PEX) and control eyes. We conducted a prospective comparative study of 36 eyes (PEX group), 16 eyes (PEXG group) and 46 eyes (control group) of 98 patients after phacoemulsification with intraocular lens implantation. Before surgery, 1 week, 1 month and 3 months postoperatively, anterior chamber parameters were evaluated by swept source anterior segment optical coherence tomography (AS-OCT). Anterior chamber depth (ACD), angle opening distance (AOD500/750), trabecular-iris space area (TISA500/750), trabecular-iris angle (TIA500/750) and lens vault (LV) were assessed at each study visit. Preoperatively, ACD, AOD500/750 and TISA500/750 were significantly smaller, while LV was significantly greater in PEX and PEXG eyes than in controls. 3 months postoperatively all irido-corneal parameters and ACD were significantly greater in all study groups without intergroup differences. ACD and LV significantly increased in PEX group between 1 and 3 months after surgery while being stable in control group. Relative increases in ACD, AOD500, TISA750, TIA500/750 were significantly higher in PEX and PEXG groups than in controls. Our study finds that ACD and iridocorneal parameters in AS-OCT demonstrated significantly greater relative increases 3 months after phacoemulsification in PEX and PEXG groups than in control eyes. Significantly greater deepening of anterior chamber and opening of the irido-corneal angle may be a reason for different refractive outcomes and IOP control in patients with PEX and PEXG after routine cataract surgery.
Journal Article
Longitudinal assessment of optic nerve head changes using optical coherence tomography in a primate microbead model of ocular hypertension
In humans, the longitudinal characterisation of early optic nerve head (ONH) damage in ocular hypertension (OHT) is difficult as patients with glaucoma usually have structural ONH damage at the time of diagnosis. Previous studies assessed glaucomatous ONH cupping by measuring the anterior lamina cribrosa depth (LCD) and minimal rim width (MRW) using optical coherence tomography (OCT). In this study, we induced OHT by repeated intracameral microbead injections in 16 cynomolgus primates (10 unilateral; 6 bilateral) and assessed the structural changes of the ONH longitudinally to observe early changes. Elevated intraocular pressure (IOP) in OHT eyes was maintained for 7 months and serial OCT measurements were performed during this period. The mean IOP was significantly elevated in OHT eyes when compared to baseline and compared to the control eyes. Thinner MRW and deeper LCD values from baseline were observed in OHT eyes with the greatest changes seen between month 1 and month 2 of OHT. Both the mean and maximum IOP values were significant predictors of MRW and LCD changes, although the maximum IOP was a slightly better predictor. We believe that this model could be useful to study IOP-induced early ONH structural damage which is important for understanding glaucoma pathogenesis.
Journal Article
Association of peripheral anterior synechiae with anterior segment parameters in eyes with primary angle closure glaucoma
To investigate the association of peripheral anterior synechiae (PAS) with intraocular pressure (IOP) and anterior-segment parameters in subjects with primary angle-closure glaucoma (PACG). A total of 267 subjects with PACG were recruited and underwent gonioscopy and anterior-segment optical coherence tomography (ASOCT). Customized software was used to measure ASOCT parameters, including angle opening distance (AOD750) and trabecular-iris-space-area (TISA750) at 750 µm from the scleral spur, anterior chamber depth, width, area and volume (ACD, ACW, ACA, ACV), iris thickness (IT750), iris area (IAREA), and lens vault (LV). Presenting IOP was defined as the first IOP reading before the initiation of IOP-lowering treatment. The mean age of the 267 subjects was 67.0 ± 8.9 years, 140 (52.4%) were male, and 246 (92.1%) were of Chinese ethnicity. PAS was present in 122 (45.7%) subjects, and was most frequently found in the superior quadrant (79.5%). Subjects with PAS had greater presenting IOP (28.7 ± 12.9 vs 22.4 ± 9.7 mmHg, p < 0.001), narrower AOD750 (p < 0.001), smaller TISA750 (p < 0.001), ACD (p = 0.04), ACA (p = 0.02), ACV (p = 0.01) and larger LV (p = 0.01) compared to PACG eyes without PAS. No significant differences were noted for iris parameters. A multivariate logistic regression analysis showed that higher presenting IOP (β = 0.20, p < 0.001), worse visual field mean deviation (β = − 0.20, p = 0.01) and narrower AOD750 (β = − 0.25, p = 0.03) were the only parameters that significantly correlated with the extent of PAS in clock hours. Almost one-half of the subjects with PACG demonstrated PAS; these eyes were associated with higher presenting IOP, smaller anterior segment dimensions and more severe disease.
Journal Article
Serum CCDC25 Levels as a Potential Marker for Metabolic Syndrome
Metabolic syndrome (MetS) stands as a significant risk for developing various severe health problems. Therefore, the discovery of biomarkers capable of predicting the progression of metabolic conditions is crucial for improving overall health outcomes. Recently, we reported that coiled-coil domain containing 25 (CCDC25) might be associated with key proteins involved in metabolic pathways, by bioinformatics analysis. Thus, we assumed that serum CCDC25 levels might have an association with MetS status.
In this study, based on the modified National Cholesterol Education Program-Adult Treatment Panel III (modified NCEP-ATP III) criteria, the participants who had three or more of abnormal criteria were defined as MetS, and those who had 1 or 2 abnormal criteria as pre-MetS groups; those who had no abnormal criteria were classified as the healthy control (HC) group. Serum CCDC25 levels were measured using the dot blot assay.
The results showed that serum CCDC25 levels of the MetS group (0.072±0.026 ng/μl) were significantly higher (p<0.001) than that of pre-MetS (0.031±0.011 ng/μl) or HC groups (0.018±0.007 ng/μl). We can discern a consistent trend indicating that serum CCDC25 level is well correlated with the number of abnormal criteria of MetS of each participant. Although serum CCDC25 levels correlated with the distribution of all 5 MetS criteria, the highest correlation was seen in serum CCDC25 levels and triglyceride (TG) levels, with r=0.563, followed by systolic blood pressure (SBP) levels (r=0.557) and high-density lipoprotein-cholesterol (HDL-C) levels (r=-0.545).
CCDC25 showed correlations with all MetS parameters, particularly with TG, SBP, and HDL-C. This prompts speculation that heightened CCDC25 levels may indicate the development and/or progression of those MetS-associated diseases.
Journal Article
Ophthalmic primary care in Singapore: Considerations for review
Ophthalmic primary care (OPC) of Singapore residents is mainly provided for by trained specialists. This is due both to the current nature of the public healthcare system as well as societal perceptions and preferences, and it imposes a heavy burden on the country’s ophthalmologist resource. Changing population demographics, escalating costs as well limitations to medical manpower growth have necessitated a shift in Singapore’s healthcare strategy to focus on primary and preventive care. This national policy change further emphasizes the need to invest in OPC as a more structured service. Revisiting the principles of primary care and how they apply to ophthalmology will be an important first step in a timely review of the country’s OPC system.
Journal Article