Objective To study the treatment patterns and visual outcome over one year in Asian patients with choroidal neovascular membrane secondary to age-related macular degeneration (AMD-CNV) and polypoidal choroidal vasculopathy (PCV). Design Prospective cohort, non-interventional study. Methods 132 treatment-naïve patients who received treatment for AMD-CNV and PCV were included. All patients underwent standardized examination procedures including retinal imaging at baseline and follow-up. AMD-CNV and PCV were defined on fundus fluorescein angiography and indocyanine green angiography at baseline. Patients were treated according to standard of care.We report the visual acuity (VA) and optical coherence tomography (OCT) measurements at baseline, month 3 and month 12 The factors influencing month 12 outcomes were analyzed. Main Outcome Measure Type of treatment, number of Anti-vascular endothelial growth factor (VEGF) treatments, visual outcome over one year. Results Anti-VEGF monotherapy was the initial treatment in 89.1% of AMD-CNV, but only 15.1% of PCV. The mean number of anti-VEGF injections up to month 12 was 3.97 (4.51 AMD-CNV, 3.43 PCV, p = 0.021). Baseline OCT, month 3 OCT and month 3 VA were significant in determining continuation of treatment after month 3. At month12, mean VA improved from 0.82 (∼20/132) at baseline to 0.68 (∼20/96) at month 12 (mean gain 6.5 ETDRS letters, p = 0.002). 34.2% of eyes (38/113 eyes) gained ≥15 ETDRS letters and 14.4% (16/113 eyes) lost ≥15 ETDRS letters. There were no significant differences in visual outcome between AMD-CNV and PCV (p = 0.51). Factors predictive of month 12 visual outcome were baseline VA, baseline OCT central macular thickness, month 3 VA and age. Conclusions There is significant variation in treatment patterns in Asian eyes with exudative maculopathy. There is significant visual improvement in all treatment groups at one year. These data highlight the need for high quality clinical trial data to provide evidence-based management of Asian AMD.
Abstract Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), impairs the beneficial effect of NO. The predictive value of ADMA for all-cause mortality remains controversial, though it is important in the development of cardiovascular disease (CVD) and progression to dialysis in renal disease. This systematic review and meta-analysis was conducted to investigate the association between circulating ADMA and all-cause mortality. Studies with data pertinent to the association between circulating ADMA and all-cause mortality were reviewed and OR, HR or RR with 95% CI derived from multivariate Cox’s proportional-hazards analysis were extracted. A total of 34 studies reporting 39137 participants were included in final analysis. The results demonstrated that circulating ADMA was independently associated with all-cause mortality (RR = 1.27, 95% CI: 1.20–1.34). The association was still statistically significant in patients with pre-existing renal disease (RR = 1.30, 95% CI: 1.19–1.43) and pre-existing CVD (RR = 1.26, 95% CI: 1.16–1.37). In those without pre-existing renal or CVD, ADMA also predicted all-cause mortality (RR = 1.31, 95% CI: 1.13–1.53). The present study suggests a positive association of circulating ADMA with all-cause mortality. Further studies are needed to investigate the effects of interventions on ADMA, and the value of ADMA as a biomarker.
Abstract Despite the fact that manganese (Mn) is known to be a neurotoxic element relevant to age-related disorders, the risk of oral exposure to Mn for age-related hearing loss remains unclear. In this study, we orally exposed wild-type young adult mice to Mn (Mn-exposed WT-mice) at 1.65 and 16.50 mg/L for 4 weeks. Mn-exposed WT-mice showed acceleration of age-related hearing loss. Mn-exposed WT-mice had neurodegeneration of spiral ganglion neurons (SGNs) with increased number of lipofuscin granules. Mn-exposed WT-mice also had increased hypoxia-inducible factor-1 alpha (Hif-1α) protein with less hydroxylation at proline 564 and decreased c-Ret protein in SGNs. Mn-mediated acceleration of age-related hearing loss involving neurodegeneration of SGNs was rescued in RET -transgenic mice carrying constitutively activated RET . Thus, oral exposure to Mn accelerates age-related hearing loss in mice with Ret-mediated neurodegeneration of SGNs.
In recent years, concerns have escalated regarding eye health problems arising from Light-emitting diode (LED), which emits high-energy blue light (BL), potentially causing corneal epithelial dysfunctions (CEpD). Nevertheless, the mechanisms underlying this damage remain poorly comprehended. This study endeavors to explore the specific mechanisms through which BL exposure induces CEpD. The study carried out diverse assays and treatments to investigate the toxicological effects of BL exposure. 48 hours (h) of 440 nm of BL exposure decreased the migration of human corneal epithelial cells (hCEpCs) while augmenting reactive oxygen species (ROS) production and apoptosis. RNA-Sequencing and bioinformatic analysis indicated that cellular oxidation and reduction equilibrium, wound healing, the positive regulation of the apoptotic process, and the Phosphoinositide 3-kinase (PI3K)/AKT pathway were significantly influenced by BL exposure. Treatment with N-acetylcysteine (NAC), a ROS scavenger, restored cell viability and AKT/S6 kinase (S6K) activation, suggesting the involvement of ROS in BL-induced damage. NAC also reversed BL-induced apoptosis and migration. Blocking AKT/S6K replicated detrimental effects, while pre-treatment with SC79 (SC), an AKT activator, alleviated the changes caused by BL exposure in hCEpCs. Furthermore, in mice, the combination of AKT inhibition and BL exposure led to CEpD. However, treatment with SC and NAC restored CEpD caused by BL exposure. These results imply that the regulation of the ROS/PI3K/AKT/S6K axis is implicated in BL-induced CEpD. Collectively, this study offers insights into the molecular mechanisms of BL-induced CEpD and proposes targeting the ROS/PI3K/AKT/S6K cascade as a potential therapeutic approach. The findings contribute to ocular health knowledge and establish the basis for developing interventions to safeguard the cornea from the detrimental effects of excessive BL exposure.
This study aims to develop and validate nomogram models utilizing clinical and thoracic aorta imaging factors to assess the risk of hypertension for lung cancer screening cohorts. We included 804 patients and collected baseline clinical data, biochemical indicators, coexisting conditions, and thoracic aorta factors. Patients were randomly divided into a training set (70%) and a validation set (30%). In the training set, variance, t-test/Mann-Whitney U-test and standard least absolute shrinkage and selection operator were used to select thoracic aorta imaging features for constructing the AIScore. Multivariate logistic backward stepwise regression was utilized to analyze the influencing factors of hypertension. Five prediction models (named AIMeasure model, BasicClinical model, TotalClinical model, AIBasicClinical model, AITotalClinical model) were constructed for practical clinical use, tailored to different data scenarios. Additionally, the performance of the models was evaluated using receiver operating characteristic (ROC) curves, calibration curves and decision curve analyses (DCA). The areas under the ROC curve for the five models were 0.73, 0.77, 0.83, 0.78, 0.84 in the training set, and 0.77, 0.78, 0.81, 0.78, 0.82 in the validation set, respectively. Furthermore, the calibration curves and DCAs of both sets performed well on accuracy and clinical practicality. The nomogram models for hypertension risk prediction demonstrate good predictive capability and clinical utility. These models can serve as effective tools for assessing hypertension risk, enabling timely non-pharmacological interventions to preempt or delay the future onset of hypertension.
Polycomb repressive complex 2 (PRC2)-mediated histone H3 lysine 27 (H3K27) methylation is vital for Polycomb gene silencing, a classic epigenetic phenomenon that maintains transcriptional silencing throughout cell divisions. We report that PRC2 activity is regulated by the density of its substrate nucleosome arrays. Neighboring nucleosomes activate the PRC2 complex with a fragment of their H3 histones (Ala(31) to Arg(42)). We also identified mutations on PRC2 subunit Su(z)12, which impair its binding and response to the activating peptide and its ability in establishing H3K27 trimethylation levels in vivo. In mouse embryonic stem cells, local chromatin compaction occurs before the formation of trimethylated H3K27 upon transcription cessation of the retinoic acid-regulated gene CYP26a1. We propose that PRC2 can sense the chromatin environment to exert its role in the maintenance of transcriptional states.
The American Heart Association has updated the cardiovascular health (CVH) assessment tool, referred to as the Life's Essential 8 (LE8). Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease worldwide and is linked to an elevated risk of mortality. We aimed to explore the association of LE8 with all cause and cause-specific mortality in MASLD in a prospective cohort study. A total of 10,050 participants with MASLD from the NHANES 2005–2018 dataset were included in the study. LE8 was evaluated by combining four health behaviors and four health factors, with scores of 0–49 categorized as low CVH, 50–79 as moderate CVH, and 80–100 as high CVH. In the fully adjusted model, each one-point increase in the LE8 score corresponded to a 2.7, 2.7, and 1.6% decrease in all-cause, CVD, and cancer mortality risk, respectively, in people with MASLD. Compared to low CVH, being in moderate/high CVH was negatively associated with most mortality outcomes, while health factors lost significant association with cancer mortality.
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