The Effect of the Mixed Extract of Kalopanax pictus Nakai and Achyranthes japonica Nakai on the Improvement of Degenerative Osteoarthritis through Inflammation Inhibition in the Monosodium Iodoacetate-Induced Mouse Model.

Osteoarthritis is a chronic inflammatory disease, and, due to the lack of fundamental treatment, the main objective is to alleviate pain and prevent cartilage damage. Kalopanax pictus Nakai and Achyranthes japonica Nakai are herbal plants known for their excellent anti-inflammatory properties. The objective of this study is to confirm the potential of a mixture extract of Kalopanax pictus Nakai and Achyranthes japonica Nakai as a functional raw material for improving osteoarthritis through anti-inflammatory effects in macrophages and MIA-induced arthritis experimental animals. In macrophages inflamed by lipopolysaccharide (LPS), treatment of Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture inhibits NF-κB and mitogen-activated protein kinase (MAPK) activities, thereby inhibiting inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), inflammatory factors PGE2, MMP-2, and MMP-9, and nitric oxide (NO) was reduced. In addition, in an animal model of arthritis induced by MIA (monosodium iodoacetate), administration of Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture reduced blood levels of inflammatory cytokines TNF-α and IL-6, inflammatory factors prostaglandin E2(PGE2), matrix metalloproteinase-2(MMP-2), and NO. Through these anti-inflammatory effects, MIA-induced pain reduction (recovery of clinical index, increase in weight bearing, and increase in area and width of the foot), recovery of meniscus damage, loss of cartilage tissue or inflammatory cells in tissue infiltration reduction, and recovery of the proteglycan layer were confirmed. Therefore, it is considered that Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture has the potential as a functional raw material that promotes joint health.

Fructose malabsorption in ChREBP-deficient mice disrupts the small intestine immune microenvironment and leads to diarrhea-dominant bowel habit changes.

BACKGROUND: The mechanism by which incompletely absorbed fructose causes gastrointestinal symptoms is not fully understood. In this study, we investigated the immunological mechanisms of bowel habit changes associated with fructose malabsorption by examining Chrebp-knockout mice exhibiting defective fructose absorption. METHODS: Mice were fed a high-fructose diet (HFrD), and stool parameters were monitored. The gene expression in the small intestine was analyzed by RNA sequencing. Intestinal immune responses were assessed. The microbiota composition was determined by 16S rRNA profiling. Antibiotics were used to assess the relevance of microbes for HFrD-induced bowel habit changes. RESULTS: Chrebp-knockout (KO) mice fed HFrD showed diarrhea. Small-intestine samples from HFrD-fed Chrebp-KO mice revealed differentially expressed genes involved in the immune pathways, including IgA production. The number of IgA-producing cells in the small intestine decreased in HFrD-fed Chrebp-KO mice. These mice showed signs of increased intestinal permeability. Chrebp-KO mice fed a control diet showed intestinal bacterial imbalance, which the HFrD exaggerated. Bacterial reduction improved diarrhea-associated stool parameters and restored the decreased IgA synthesis induced in HFrD-fed Chrebp-KO mice. CONCLUSIONS: The collective data indicate that gut microbiome imbalance and disrupting homeostatic intestinal immune responses account for the development of gastrointestinal symptoms induced by fructose malabsorption.

Coarse-to-Fine Network-Based Intra Prediction in Versatile Video Coding.

After the development of the Versatile Video Coding (VVC) standard, research on neural network-based video coding technologies continues as a potential approach for future video coding standards. Particularly, neural network-based intra prediction is receiving attention as a solution to mitigate the limitations of traditional intra prediction performance in intricate images with limited spatial redundancy. This study presents an intra prediction method based on coarse-to-fine networks that employ both convolutional neural networks and fully connected layers to enhance VVC intra prediction performance. The coarse networks are designed to adjust the influence on prediction performance depending on the positions and conditions of reference samples. Moreover, the fine networks generate refined prediction samples by considering continuity with adjacent reference samples and facilitate prediction through upscaling at a block size unsupported by the coarse networks. The proposed networks are integrated into the VVC test model (VTM) as an additional intra prediction mode to evaluate the coding performance. The experimental results show that our coarse-to-fine network architecture provides an average gain of 1.31% Bjøntegaard delta-rate (BD-rate) saving for the luma component compared with VTM 11.0 and an average of 0.47% BD-rate saving compared with the previous related work.

Impaction of multiple dilacerated primary incisors: a case report.

Dental complications such as defective alveolar bone development, delayed eruption, and tooth impaction are related to neonatal oral intubation. This case report presents an example of potential complications that occur in children who have undergone oral intubation as neonates. A 20-month-old girl visited our pediatric clinic. We observed delayed, non-erupted teeth #51, #71, and #81 and determined a history of intubation during the neonatal period as a related factor. After 22 months of observation, tooth #71 erupted spontaneously. After 40 months of monitoring, teeth #51 and #81 were extracted surgically, and normal permanent teeth erupted six months later. This study is helpful for pediatric anesthesiologists, pediatricians, and dentists who diagnose and treat eruption disorders of the primary dentition.

Neuroprotective Effects of Sodium Butyrate through Suppressing Neuroinflammation and Modulating Antioxidant Enzymes.

The discovery of effective therapeutic agents against neurodegenerative diseases (NDDs) remains challenging. Neurotoxicity, inflammations, and oxidative stress are associating factors of NDDs. Sodium butyrate (NaB) is a short-chain fatty acid found in diet and produced in the gut that reportedly protects cancer, inflammation, obesity and so on. Previously, SH-SY5Y cells were studied as in vitro models of cerebral diseases. We have investigated the neuroprotective effects of NaB in SH-SY5Y cells stimulated with TNF-α. The expression of inflammatory mediators, including iNOS, COX-2, and mitogen-activated protein kinases (MAPK) and the apoptotic regulators, including P-53, Bcl-2 associated X (BAX) Protein, and caspase-3 were analyzed by western blot analysis. The anti-apoptotic gene Bcl-2 and the pro-apoptotic gene BAX translocation were also investigated. Our results showed that NaB attenuated cell death and inhibited the NO production and decreased the expression of iNOS and COX-2 in TNF-α-stimulated SH-SY5Y cells. NaB notably ameliorated apoptotic regulatory proteins p-53, Caspase-3 and caspase-1 level, and reversed phosphorylation of extracellular signal-regulated kinases and p-38 proteins. NaB ameliorated Glucocorticoid receptor and NLRP3 inflammasome expressions. NaB also suppressed the BAX nuclear translocation and modulated Nrf-2, HO-1 and MnSOD expression in neuroblastoma cells. In addition, NaB substantially reversed the reactive oxygen species in H2O2 induced SH-SY5Y cells. Altogether, our results suggest that sodium butyrate has potential therapeutic effects against NDDs.

Dental Management of Congenital Granular Cell Lesion and Neonatal Teeth: A Case Report.

Congenital granular cell lesion (CGCL) is a rare benign oral cavity tumor in infants. Neonatal teeth are also rare dental anomalies that appear during the first month of life. This report describes a case of eruption of neonatal teeth after surgical excision of CGCL. Surprisingly, residual neonatal teeth erupted after extraction of the neonatal teeth. If neonatal teeth are mobile, they should be carefully extracted with curettage of the underlying tissues of the dental papilla; failure to curette the socket might result in eruption of odontogenic remnants. If neonatal teeth were exfoliated, parents should be informed of the need for regular checkups with a dentist due to possibility of development of residual neonatal teeth.

Multiple Idiopathic Internal Root Resorption in an Adolescent: A Case R Multiple Idiopathic Internal Root Resorption in an Adolescent: A Case Report.

Internal root resorption (IRR) refers to a slow or rapid progressive resorption process that occurs in the pulp cavity of the tooth or the dentin of the root. IRR occurs as result of odontoclast action; in many cases, the pulp tissue exhibits chronic inflammation, and odontoblasts and predentin do not appear on the dentin wall near the pulp. Exact predisposing factors have not been clearly elucidated; therefore, it is difficult to identify reliable data on the prevalence of IRR because of its scarce occurrence and pathology. Reports have indicated that IRR is more common in the primary than in the permanent teeth. This case report discusses a 17-year-old girl with multiple idiopathic internal root resorptions of anterior permanent teeth in a short period of a time and its management.

Synthesis and Properties of Pentafluorosulfanyl Group (SF5)-Containing Meta-Diamide Insecticides.

Herein, we describe novel pentafluorosulfanyl (SF5) group-containing meta-diamide insecticides. For the facile preparation of the SF5-based compounds 4a-d, practical synthetic methods were applied. Among newly synthesized compounds, 3-benzamido-N-(2,6-dimethyl-4-(pentafluoro-λ6-sulfanyl)phenyl)-2-fluorobenzamide 4d showed (i) a high insecticidal activity, (ii) an excellent selectivity to insects, and (iii) good levels of water solubility and log P values. In this study, we demonstrated that the pentafluorosulfanyl moiety could serve as an attractive functionality for the discovery of a new scope of crop-protecting agents.

Decompression for Unerupted Primary Mandibular Second Molars Associated with Physical Barriers: Case Reports.

Primary impaction of primary teeth might be due to genetic predisposition or physical disturbance including odontoma, supernumerary tooth, and crowded tooth. Among them, calcific deposit or odontoma is commonly associated with primary dentition. Early diagnosis and treatment is the key to prevent complications. However, results of treatment may vary depending on the condition of unerupted tooth. Here we report two clinical cases of unerupted primary mandibular second molars with physical barriers such as compound odontoma and calcific deposit focusing on diagnostic means and the importance of early treatment of these lesions.

Caveolar remodeling is a critical mechanotransduction mechanism of the stretch-induced L-type Ca2+ channel activation in vascular myocytes.

Activation of L-type voltage-dependent Ca2+ channels (VDCCL) by membrane stretch contributes to many biological responses such as myogenic contraction of arteries. However, mechanism for the stretch-induced VDCCL activation is unclear. In this study, we examined the hypothesis that caveolar remodeling and its related signaling cascade contribute to the stretch-induced activation of VDCCL in rat mesenteric arterial smooth muscle cells. The VDCCL currents were recorded with nystatin-perforated or with conventional whole-cell patch-clamp technique. Hypotonic (~230 mOsm) swelling-induced membrane stretch reversibly increased the VDCCL currents. Electron microscope and confocal imaging analysis revealed that both hypotonic swelling and cholesterol depletion by methyl-ß-cychlodextrin (MßCD) similarly disrupted the caveolae structure and translocated caveolin-1 (Cav-1) from membrane to cytosolic space. Accordingly, MßCD also increased VDCCL currents. Moreover, subsequent hypotonic swelling after MßCD treatment failed to increase the VDCCL currents further. Western blotting experiments revealed that hypotonic swelling phosphorylated Cav-1 and JNK. Inhibitors of tyrosine kinases (genistein) and JNK (SP00125) prevented the swelling-induced facilitation of VDCCL currents. Knockdown of Cav-1 by small interfering RNA blocked both the VDCCL current facilitation by stretch and the related phosphorylation of JNK. Taken together, the results suggest that membrane stretch is transduced to the facilitation of VDCCL currents via caveolar structure-dependent tyrosine phosphorylation of Cav-1 and subsequent activation of JNK in rat mesenteric arterial myocytes.

The antibacterial activity of chlorhexidine digluconate against Streptococcus mutans biofilms follows sigmoidal patterns.

The aim of this study was to determine the pattern of the antibacterial activity of chlorhexidine digluconate (CHX) against mature Streptococcus mutans biofilms. Streptococcus mutans biofilms were formed on saliva-coated hydroxyapatite discs and then treated with 0-20% CHX, once, three times, or five times (1 min per treatment) during the period of mature biofilm formation (beyond 46 h). After the treatments, the colony-forming unit (CFU) counts of the treated biofilms were determined. The pH values of the spent culture medium were also determined to investigate the change in pH resulting from the antibacterial activity of CHX. The relationships between the concentration of CHX and the CFU counts and the concentration of CHX and culture medium pH, relative to the number of treatments performed, were evaluated using a sigmoidal curve-fitting procedure. The changes in CFU counts and culture medium pH followed sigmoidal curves and were dependent on the concentration of CHX (R2 = 0.99). The sigmoidal curves were left-shifted with increasing number of treatments. Furthermore, the culture-medium pH of the treated biofilms increased as their CFU counts decreased. The lowest CHX concentration to increase culture-medium pH above the critical pH also decreased as the number of treatments increased. These results may provide fundamental information for selecting the appropriate CHX concentrations to treat S. mutans biofilms.

Hydrogen peroxide induces vasorelaxation by enhancing 4-aminopyridine-sensitive Kv currents through S-glutathionylation.

Hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor. Since opposing vasoactive effects have been reported for H2O2 depending on the vascular bed and experimental conditions, this study was performed to assess whether H2O2 acts as a vasodilator in the rat mesenteric artery and, if so, to determine the underlying mechanisms. H2O2 elicited concentration-dependent relaxation in mesenteric arteries precontracted with norepinephrine. The vasodilatory effect of H2O2 was reversed by treatment with dithiothreitol. H2O2-elicited vasodilation was significantly reduced by blocking 4-aminopyridine (4-AP)-sensitive Kv channels, but it was resistant to blockers of big-conductance Ca(2+)-activated K(+) channels and inward rectifier K(+) channels. A patch-clamp study in mesenteric arterial smooth muscle cells (MASMCs) showed that H2O2 increased Kv currents in a concentration-dependent manner. H2O2 speeded up Kv channel activation and shifted steady state activation to hyperpolarizing potentials. Similar channel activation was seen with oxidized glutathione (GSSG). The H2O2-mediated channel activation was prevented by glutathione reductase. Consistent with S-glutathionylation, streptavidin pull-down assays with biotinylated glutathione ethyl ester showed incorporation of glutathione (GSH) in the Kv channel proteins in the presence of H2O2. Interestingly, conditions of increased oxidative stress within MASMCs impaired the capacity of H2O2 to stimulate Kv channels. Not only was the H2O2 stimulatory effect much weaker, but the inhibitory effect of H2O2 was unmasked. These data suggest that H2O2 activates 4-AP-sensitive Kv channels, possibly through S-glutathionylation, which elicits smooth muscle relaxation in rat mesenteric arteries. Furthermore, our results support the idea that the basal redox status of MASMCs determines the response of Kv currents to H2O2.

Blockade of voltage-gated K⁺ currents in rat mesenteric arterial smooth muscle cells by MK801.

MK801 (dizocilpine), a phencyclidine (PCP) derivative, is a potent noncompetitive antagonist of the N-Methyl-D-aspartate receptor (NMDAr). Another PCP derivative, ketamine, was reported to block voltage-gated K(+) (Kv) channels, which was independent of NMDAr function. Kv currents are major regulators of the membrane potential (Em) and excitability of muscles and neurons. Here, we investigated the effect of MK801 on the Kv channels and Em in rat mesenteric arterial smooth muscle cells (RMASMCs). We used the whole-cell patch clamp technique to analyze the effect of MK801 enantiomers on Kv channels and Em. (+)MK801 inhibited Kv channels in a concentration-dependent manner (IC50 of 89.1 ± 13.1 µM, Hill coefficient of 1.05 ± 0.08). The inhibition was voltage- and state- independent. (+)MK801 didn't influence steady-state activation and inactivation of Kv channels. (+)MK801 treatment depolarized Em in a concentration-dependent manner and concomitantly decreased membrane conductance. (-)MK801 also similarly inhibited the Kv channels (IC50 of 134.0 ± 17.5 µM, Hill coefficient of 0.87 ± 0.09). These results indicate that MK801 directly inhibits the Kv channel in a state-independent manner in RMASMCs. This MK801-mediated inhibition of Kv channels should be considered when assessing the various pharmacological effects produced by MK801, such as schizophrenia, neuroprotection, and hypertension.

Biodegradation of biphenyl and 2-chlorobiphenyl by a Pseudomonas sp. KM-04 isolated from PCBs-contaminated coal mine soil.

The biphenyl-degrading strain, Pseudomonas sp. KM-04, was isolated from polychlorinated biphenyls-contaminated soil sample obtained from the vicinity of a former coal mine. We herein report that strain KM-04 can use biphenyl as a sole carbon source, and resting cells convert biphenyl to its corresponding metabolic intermediates. Incubation of KM-04 with autoclaved mining-contaminated soil for 10 days in a slurry system reduced the levels of biphenyl and 2-chlorobiphenyl by 98.5 % and 82.3 %, respectively. Furthermore, treatment of a mine-soil microcosm with strain KM-04 for 15 days in a composting system under laboratory conditions reduced the levels of biphenyl and 2-chlorobiphenyl by 87.1 % and 68.7 %, respectively. These results suggest that KM-04 is a potential candidate for the biological removal of biphenyl and its chlorinated derivatives from polychlorinated biphenyl-contaminated mining areas.

Two-Year Follow-Up Study of Patients with Neovascular Age-Related Macular Degeneration Undergoing Anti-VEGF Treatment during the COVID-19 Pandemic.

BACKGROUND: regular intravitreal anti-vascular endothelial growth factor (VEGF) treatment is crucial for patients with neovascular age-related macular degeneration (nAMD), and delayed treatment can exacerbate disease progression. METHODS: we compared the outcomes of on-time versus delayed intravitreal anti-VEGF treatment for patients with nAMD. This study was conducted during the coronavirus disease 2019 (COVID-19) pandemic with a 2-year follow-up period. The best-corrected visual acuity (BCVA) and anatomical findings were evaluated before the pandemic, during the pandemic, and at 6-, 12-, 18-, and 24-months post-pandemic. RESULTS: The delayed and on-time groups comprised 54 and 72 patients, respectively. After the pandemic, the injection interval increased by 0.65 ± 1.51 months (p = 0.003), with 22.2% of the patients in the delayed group switching to the treat-and-extended regimen (p < 0.001). The delayed group showed greater mean BCVA deterioration (p = 0.027) and central subfield thickness (p = 0.037) at 6 months and worse maximum subretinal fluid height (p = 0.022) at 18 months than the on-time group. No difference was observed between the groups in the second year. CONCLUSION: the negative effects of delaying anti-VEGF treatment because of the COVID-19 pandemic can be ameliorated by changing the treatment regimen and shortening treatment intervals.

Gochujang, a traditional Korean fermented food, protects through suppressed inflammatory pathways and histological structure disruption in dextran sodium sulfate (DSS)-induced colitis mice.

The mechanisms underlying chronic inflammatory diseases remain unclear. Therefore, researchers have explored the mechanisms underlying colitis using diverse materials. Recently, there has been an increasing interest in fermented products and bioconversion materials, their potential efficacy is being actively studied. Gochujang, a traditional Korean fermented product, is crafted by blending fermented Meju powder, gochu (Korean chili) powder, glutinous rice, and salt. In our study, we explored the effectiveness of Gochujang (500 mg/kg; Cheongju and Hongcheon, Korea) in dextran sulfate sodium (DSS)-induced colitis mice model. Gochujang was orally administered for 2 weeks, followed by the induction of colitis using 3% DSS in the previous week. During our investigation, Gochujang variants (TCG22-25, Cheongju and TCG22-48, Hongcheon) did not exhibit significant inhibition of weight reduction (p = 0.061) but notably (p = 0.001) suppressed the reduction in large intestine length in DSS-induced colitis mice. In the serum from colitis mice, TCG22-48 demonstrated reduced levels of the inflammatory cytokines interleukin (IL)-6 (p = 0.001) and tumor necrosis factor (TNF)-α (p = 0.001). Additionally, it inhibited the phosphorylation of Erk (p = 0.028), p38, and NF-κB (p = 0.001) the inflammatory mechanism. In our study, TCG22-25 demonstrated a reduction in the IL-6 level (p = 0.001) in serum and inhibited the phosphorylation of p38 and NF-κB (p = 0.001). Histological analysis revealed a significant (p = 0.001) reduction in the pathological score of the large intestine from TCG22-25 and TCG22-48. In conclusion, the intake of Gochujang demonstrates potent anti-inflammatory effects, mitigating colitis by preventing the large intestine length reduction of animals with colitis, lowering serum levels of TNF-α and IL-6 cytokines, and inhibiting histological disruption and inflammatory mechanism phosphorylation.

Comparison of Retinal and Choroidal Microvasculature Changes in Monocular Amblyopic and Non-amblyopic Eyes following Short-term Patch Occlusion Treatment.

PURPOSE: Our objective was to investigate whether there were differences in the short-term changes of retinal and choroidal microvasculature between amblyopic and non-amblyopic eyes after patch occlusion treatment in patients with monocular amblyopia. Additionally, we aimed to determine if these changes were associated with improvements in clinical parameters. METHODS: We conducted a retrospective, longitudinal paired-eye case-control study by analyzing the medical records of patients under the age of 12 who had monocular amblyopia and underwent patch occlusion treatment for a duration of 2 to 12 months. Using optical coherence tomography angiography images, we compared the foveal avascular zone width, retinal blood vessel density (VD), choroidal thickness (CT), and choroidal vascularity index (CVI) in amblyopic and non-amblyopic eyes before and after patch occlusion treatment. We analyzed the correlations between the aforementioned parameters and changes in best-corrected visual acuity (BCVA) and stereopsis. RESULTS: Overall, 114 eyes from 57 patients were enrolled. At baseline, parafoveal superficial plexus VD, foveal and parafoveal deep capillary plexus VD (DCPD) were lower by 0.994 ± 3.312% (p = .026), 2.403 ± 8.273% (p = .033), and 2.469 ± 4.095% (p < .001), respectively; CT was thicker by 30.6 ± 90.7 µm (p = .014); and CVI was higher by 1.920 ± 3.432% (p < 001) in the amblyopic eyes than in the non-amblyopic eyes. Following short-term patch occlusion treatment, foveal and parafoveal DCPD increased by 1.264 ± 3.829% (p = .017) and 1.028 ± 3.662% (p = .036), respectively, CT thinned by 15.5 ± 51.5 µm (p = .019), and CVI decreased by 1.296 ± 3.997% (p = .018) in the amblyopic eyes. Following patch occlusion treatment, as the foveal DCPD decreased and CVI increased, the BCVA improved (p = .017 and .035, respectively). CONCLUSION: Following patch occlusion treatment, increased foveal DCPD and decreased CVI were associated with improved BCVA.

Orexinergic neurons modulate stress coping responses in mice.

Stress is a critical precipitating factor for major depression. However, individual responses to the same stressor vary widely, possibly owing to individual variations in stress resilience. Nevertheless, the factors that determine stress susceptibility and resilience remain poorly understood. Orexin neurons have been implicated in the control of stress-induced arousal. Therefore, we investigated whether orexin-expressing neurons are involved in the regulation of stress resilience in male mice. We found that the level of c-fos expression was significantly different in susceptible versus resilient mice in the learned helplessness test (LHT). Furthermore, activating orexinergic neurons induced resilience in the susceptible group, and this resilience was also consistently observed in other behavioral tests. However, activating orexinergic neurons during the induction period (during inescapable stress exposure) did not affect stress resilience in the escape test. In addition, analyses using pathway-specific optic stimulation revealed that activating orexinergic projections to the medial part of the nucleus accumbens (NAc) alone mediated a decrease in anxiety but was not sufficient to induce resilience in the LHT. Collectively, our data suggest that orexinergic projections to multiple targets control diverse and flexible stress-related behaviors in response to various stressors.

Short-term effects of occlusion therapy and optical correction on microvasculature in monocular amblyopia: a retrospective case-control study.

This retrospective longitudinal case-control study investigated the short-term effects of patch occlusion treatment compared with optical correction on the microvasculature in monocular amblyopia. We included patients with monocular amblyopia treated for 2-12 months; they were classified into two groups according to the treatment regimen: patch occlusion or optical correction. Children aged < 12 years who presented to our clinic for examination without amblyopia diagnosis were enrolled as the control group. Changes in retinal and choroid microvasculature according to treatment were examined, and the correlation between changes in microvasculature and improvement in best-corrected visual acuity (BCVA) was evaluated. There were 57, 35, and 41 patients in the patch occlusion, optical correction, and control groups, respectively (mean age, 6.4 ± 2.0 years). Both amblyopic groups showed changes in the foveal and parafoveal deep capillary plexus vessel density (DCPD), choroidal thickness, and choroidal vascularity index (CVI) following short-term treatment (mean, 4.5 months). In the patch occlusion group, BCVA improved as the foveal DCPD increased (P = 0.013) and the CVI decreased (P = 0.037). In the optical correction group, BCVA improved as the foveal and parafoveal DCPD increased (P = 0.009). Increased foveal DCPD following amblyopia treatment and decreased CVI by patch occlusion were associated with improved BCVA.