Purpose: To investigate the efficacy of aflibercept-bevacizumab alternate dosing (AD) in neovascular age-related macular degeneration (AMD) with a limited response to bimonthly aflibercept injections. Methods: This retrospective study included patients given aflibercept-bevacizumab AD to treat neovascular AMD with bevacizumab given every alternate month between bimonthly aflibercept injections when they had a limited response to bimonthly aflibercept alone. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were compared before AD and after the last AD. The incidence of subretinal fluid (SRF) and intraretinal fluid (IRF) before and after AD was also examined. Results: The study included 18 patients. The mean period between the diagnosis and AD was 37.9 ± 18.8 months and a mean of 3.1 ± 2.2 ADs were performed. The BCVA improved significantly from 0.45 ± 0.28 before AD to 0.36 ± 0.23 after AD (p = 0.036). The CRT decreased significantly from 440.3 ± 122.9 μm before AD to 317.7 ± 103.5 after AD (p = 0.001). The SRF was present in 94.4% and IRF in 55.6% before AD and in 22.2% and 11.1%, respectively, after AD. Conclusions Aflibercept–bevacizumab AD was effective at resolving SRF/IRF in neovascular AMD with a limited response to bimonthlyaflibercept injections and should be a useful treatment option.

Purpose: To evaluate the short-term outcomes of intravitreal injection therapy using the ranibizumab biosimilar CKD-701 in macular edema due to retinal vein occlusion. Methods: We conducted a retrospective analysis of medical records from patients diagnosed with macular edema secondary to retinal vein occlusion who received intravitreal injections of CKD-701. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) before and after a single injection were compared. Additionally, differences in these indicators were assessed between central and branch retinal vein occlusion (CRVO/BRVO). Results: The study included 22 subjects, with 17 cases of BRVO and 5 cases of CRVO. The efficacy was evaluated at 6.0 ± 2.2 weeks after injection. CRT decreased significantly from 534.8 ± 224.9 µm before injection to 367.8 ± 162.7 µm after injection (p < 0.001). The logarithm of the minimum angle of resolution BCVA improved significantly from 0.58 ± 0.41 to 0.48 ± 0.37 after injection (p = 0.002). The CRVO group showed a greater reduction in CRT compared to the BRVO group (p = 0.006). Conclusions A single injection of CKD-701 significantly improved both functional and anatomical outcomes in patients with macular edema secondary to retinal vein occlusion. Additional long-term studies are needed.

Purpose: To evaluate the short-term outcomes of intravitreal injection therapy using the ranibizumab biosimilar CKD-701 in macular edema due to retinal vein occlusion. Methods: We conducted a retrospective analysis of medical records from patients diagnosed with macular edema secondary to retinal vein occlusion who received intravitreal injections of CKD-701. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) before and after a single injection were compared. Additionally, differences in these indicators were assessed between central and branch retinal vein occlusion (CRVO/BRVO). Results: The study included 22 subjects, with 17 cases of BRVO and 5 cases of CRVO. The efficacy was evaluated at 6.0 ± 2.2 weeks after injection. CRT decreased significantly from 534.8 ± 224.9 µm before injection to 367.8 ± 162.7 µm after injection (p < 0.001). The logarithm of the minimum angle of resolution BCVA improved significantly from 0.58 ± 0.41 to 0.48 ± 0.37 after injection (p = 0.002). The CRVO group showed a greater reduction in CRT compared to the BRVO group (p = 0.006). Conclusions A single injection of CKD-701 significantly improved both functional and anatomical outcomes in patients with macular edema secondary to retinal vein occlusion. Additional long-term studies are needed.

Purpose: To evaluate the short-term outcomes of intravitreal injection therapy using the ranibizumab biosimilar CKD-701 in macular edema due to retinal vein occlusion. Methods: We conducted a retrospective analysis of medical records from patients diagnosed with macular edema secondary to retinal vein occlusion who received intravitreal injections of CKD-701. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) before and after a single injection were compared. Additionally, differences in these indicators were assessed between central and branch retinal vein occlusion (CRVO/BRVO). Results: The study included 22 subjects, with 17 cases of BRVO and 5 cases of CRVO. The efficacy was evaluated at 6.0 ± 2.2 weeks after injection. CRT decreased significantly from 534.8 ± 224.9 µm before injection to 367.8 ± 162.7 µm after injection (p < 0.001). The logarithm of the minimum angle of resolution BCVA improved significantly from 0.58 ± 0.41 to 0.48 ± 0.37 after injection (p = 0.002). The CRVO group showed a greater reduction in CRT compared to the BRVO group (p = 0.006). Conclusions A single injection of CKD-701 significantly improved both functional and anatomical outcomes in patients with macular edema secondary to retinal vein occlusion. Additional long-term studies are needed.

Purpose: To investigate the long-term clinical course and prognostic factors of branch retinal artery occlusion (BRAO). Methods: The medical records of patients diagnosed with BRAO were reviewed retrospectively. Visual acuity (VA) and central retinal thickness (CRT) at diagnosis were compared with those measured at the final visit. Patients with a decimal VA ≥ 0.6 (good prognosis group) were compared with those with a decimal VA ≤ 0.5 (poor prognosis group) at the final visit. Results: Fifty-five patients were enrolled and the mean follow-up period was 45.8 ± 27.8 months. The mean logarithm of minimum angle of resolution improved from 0.53 ± 0.57 at diagnosis to 0.36 ± 0.61 at the final visit (p = 0.026). The decimal VA was ≤ 0.1 in 13 (23.6%) patients, ≥ 0.2 and ≤ 0.5 in 16 (29.1%) patients, and ≥ 0.6 in 26 (47.3%) patients at diagnosis; the respective values were 9 (16.4%), 8 (14.5%), and 38 (69.1%) at the final visit. The mean CRT significantly decreased from 273.9 ± 34.7 µm at diagnosis to 248.9 ± 27.0 µm at the final visit (p < 0.001). The poor prognosis group (n = 17) was older (p = 0.044) and had a higher incidence of papillomacular bundle involvement (p < 0.001) than the good prognosis group (n = 38). Conclusions Patients with BRAO generally showed relatively favorable long-term outcomes. However, the final VA was ≤ 0.1 in 16.4% of them, suggesting the need for further treatment modalities to improve the outcome of patients with a poor prognosis.

BACKGROUND: Beta-carotene (BC) is a carotenoid which exerts anti-cancer effects in several types of cancer, including colorectal cancer. Epigenetic modifications of genes, such as histone deacetylation and DNA hypermethylation, have also been detected in various types of cancer. To understand the molecular mechanism underlying cancer preventive and therapeutic effects of BC, microRNAs (miRNAs), histone acetylation, and global DNA methylation in colon cancer stem cells (CSCs) were investigated.METHODS: HCT116 colon cancer cells positive for expression of CD44 and CD133 were sorted by flow cytometry and used in subsequent experiments. Cell proliferation was examined by the MTT assay and self-renewal capacity was analyzed by the sphere formation assay. The miRNA sequencing array was used to detect miRNAs regulated by BC. Histone acetylation levels were measured by the Western blot analysis. mRNA expression of DNA methyltransferases (DNMTs) was examined by qPCR and global DNA methylation levels were determined by enzyme-linked immunosorbent assay.RESULTS: Treatment of CD44⁺CD133⁺ colon CSCs with BC caused a reduction in both cell proliferation and sphere formation. Analysis of the miRNA sequencing array showed that BC regulated expression of miRNAs associated with histone acetylation. Histone H3 and H4 acetylation levels were elevated by BC treatment. In addition, BC treatment down-regulated DNMT3A mRNA expression and global DNA methylation in colon CSCs.CONCLUSIONS: These results suggest that BC regulates epigenetic modifications for its anti-cancer effects in colon CSCs.
Acetylation ; beta Carotene ; Blotting, Western ; Cell Proliferation ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; DNA Methylation ; DNA ; Enzyme-Linked Immunosorbent Assay ; Epigenomics ; Flow Cytometry ; Histones ; Methyltransferases ; MicroRNAs ; RNA, Messenger ; Stem Cells ; Therapeutic Uses

Purpose: To explore and identify priorities of middle-aged couples’ educational needs for psychological well-being. Methods: Exploratory sequential mixed method design was used. Qualitative data were collected from 14 couples through couple interviews and analyzed using interpretative phenomenological analysis. Quantitative data were collected from 234 middle-aged adults using self-administered questionnaires and analyzed using paired t-test and Borichs’ needs assessment model. Finally, qualitative and quantitative data were integrated to describe mixed-method findings. Results: Three major themes were identified: (1) confronting vulnerability to mental health problem, (2) navigating lifes journey together, and (3) progressing toward self-transcendence. In quantitative results, “couple communication” had the highest need, followed by “mental health”, the “emotional awareness and expression”, and “improvement of marital relationships”. Integrated results indicated that couple-communication and mental health were priority needs. Conclusion Results of this study provided evidence for middle-aged couples educational needs for psychological well-being. Thus, healthcare professionals need to consider development of educational interventions to enhance couple communication and mental health for middle-aged couples psychological well-being.

Cyclosporin A (CsA) does not only exert a toxic effect on kidney parenchymal cells, but also protects them against necrotic cell death by inhibiting opening of mitochondrial permeability transition pore. However, whether CsA plays a role in hydrogen peroxide-induced kidney proximal tubular cell death is currently unclear. In the present study, treatment with CsA further increased apoptosis and necrosis in HK-2 human kidney proximal tubule epithelial cells during exposure to hydrogen peroxide. In addition, hydrogen peroxide-induced p53 activation and BH3 interacting-domain death agonist (BID) expression were higher in CsA-treated cells than those in non-treated cells, whereas hydrogen peroxide-induced activation of mitogen-activated protein kinases including p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase and activation of protein kinase B were not significantly altered by treatment with CsA. In oxidant-antioxidant system, reactive oxygen species (ROS) production induced by hydrogen peroxide was further enhanced by treatment with CsA. However, expression levels of antioxidant enzymes including manganese superoxide dismutase, copper/zinc superoxide dismutase, and catalase were not altered by treatment with hydrogen peroxide or CsA. Treatment with CsA further enhanced mitochondrial membrane potential induced by exposure to hydrogen peroxide, although it did not alter endoplasmic reticulum stress based on expression of glucose-regulated protein 78 and 94. Taken together, these data suggest that CsA can aggravate hydrogen peroxide-induced cell death through p53 activation, BID expression, and ROS production.
Apoptosis ; Catalase ; Cell Death ; Cyclosporine ; Endoplasmic Reticulum Stress ; Epithelial Cells ; Humans ; Hydrogen Peroxide ; Hydrogen ; JNK Mitogen-Activated Protein Kinases ; Kidney ; Membrane Potential, Mitochondrial ; Mitogen-Activated Protein Kinases ; Necrosis ; Permeability ; Phosphotransferases ; Proto-Oncogene Proteins c-akt ; Reactive Oxygen Species ; Superoxide Dismutase

The μ-opioid receptor (MOR) is a class of opioid receptors characterized by a high affinity for β-endorphin and morphine. MOR is a G proteincoupled receptor (GPCR) that plays a role in reward and analgesic effects. While expression of MOR has been well established in neurons and microglia, astrocytic MOR expression has been less clear. Recently, we have reported that MOR is expressed in hippocampal astrocytes, and its activation has a critical role in the establishment of conditioned place preference. Despite this critical role, the expression and function of astrocytic MOR from other brain regions are still unknown. Here, we report that MOR is significantly expressed in astrocytes and GABAergic neurons from various brain regions including the hippocampus, nucleus accumbens, periaqueductal gray, amygdala, and arcuate nucleus. Using the MORmCherry reporter mice and Imaris analysis, we demonstrate that astrocytic MOR expression exceeded 60% in all tested regions. Also, we observed similar MOR expression of GABAergic neurons as shown in the previous distribution studies and it is noteworthy that MOR expression is particularly in parvalbumin (PV)-positive neurons. Furthermore, consistent with the normal MOR function observed in the MOR-mCherry mouse, our study also demonstrates intact MOR functionality in astrocytes through iGluSnFr-mediated glutamate imaging. Finally, we show the sex-difference in the expression pattern of MOR in PV-positive neurons, but not in the GABAergic neurons and astrocytes. Taken together, our findings highlight a substantial astrocytic MOR presence across various brain regions.

Incongruous visual field defects, such as sectoranopia, can result from lateral geniculate nucleus infarction. We present a rare case of right lateral geniculate nucleus infarction that manifests as a left inferior homonymous paracentral scotoma. According to the retinotopic organization of the visual tract, central vision from the macula is delivered to the occipital pole via the posterior portion of the lateral geniculate nucleus. Consequently, not only can occipital pole infarction lead to central visual loss, but partial lateral geniculate nucleus infarction can also produce similar manifestations of central visual loss.