Transformation of polar nematic phases in the presence of an electric field.

Only a few years have passed since the discovery of polar nematics, and now they are becoming the most actively studied liquid-crystal materials. Despite numerous breakthrough findings made recently, a theoretical systematization is still lacking. In the present paper, we take a step toward systematization. The powerful technique of molecular-statistical physics has been applied to an assembly of polar molecules influenced by electric field. Three polar nematic phases were found to be stable at various conditions: the double-splay ferroelectric nematic N_{F}^{2D} (observed in the lower-temperature range in the absence of or at low electric field), the double-splay antiferroelectric nematic N_{AF} (observed at intermediate temperature in the absence of or at low electric field), and the single-splay ferroelectric nematic N_{F}^{1D} (observed at moderate electric field at any temperature below transition into paraelectric nematic N and in the higher-temperature range (also below N) at low electric field or without it. A paradoxical transition from N_{F}^{1D} to N induced by application of higher electric field has been found and explained. A transformation of the structure of polar nematic phases at the application of electric field has also been investigated by Monte Carlo simulations and experimentally by observation of polarizing optical microscope images. In particular, it has been realized that, at planar anchoring, N_{AF} in the presence of a moderate out-of-plane electric field exhibits twofold splay modulation: antiferroelectric in the plane of the substrate and ferroelectric in the plane normal to the substrate. Several additional subtransitions related to fitting the confined geometry of the cell by the structure of polar phases were detected.

Relationship between blood culture time to positivity, mortality rate, and severity of bacteremia.

OBJECTIVES: We investigated the association between patient severity or mortality and time to positivity in bacteremia caused by various pathogens. PATIENTS AND METHODS: This single-center retrospective study included patients with positive blood culture results. RESULTS: Longer time to positivity was associated with 30-day mortality for Staphylococcus aureus (221 cases, time to positivity: 17.4 h in the 30-day mortality group vs. 14.1 h in the survival group). Age, chronic kidney disease, cerebrovascular disease, hypertensive drug use, consciousness disorder, and minimal systolic blood pressure were significant predictors of 30-day mortality. For S. aureus, mortality within 30 days was significantly higher when time to positivity was > 24 h (p = 0.04). The time to positivity of Streptococcus pneumoniae, α, ß-hemolytic Streptococcus, Enterococcus sp., Enterobacteriaceae, glucose-nonfermenting Gram-negative rods, Candida sp., and anaerobe was not significantly associated with 30-day mortality. CONCLUSIONS: Among various pathogens, time to positivity > 24 h was associated with 30-day mortality for S. aureus.

Standardization of preoperative stoma site marking and its utility for preventing stoma leakage: a retrospective study of 519 patients who underwent laparoscopic/robotic rectal cancer surgery.

PURPOSE: Stoma site marking is an important preoperative intervention for preventing various stoma-associated complications. In our institution, standardized stoma site marking is routinely performed before rectal cancer surgery with stoma creation, and various stoma-associated factors are recorded in the ostomy-record template. The present study investigated risk factors for stoma leakage. METHODS: Our stoma site marking is standardized so that it can be performed by non-stoma specialists. To identify risk factors of stoma leakage at 3 months after surgery, various preoperative factors associated with stoma site marking in our ostomy-record template were retrospectively analyzed in 519 patients who underwent rectal cancer surgery with stoma creation from 2015 to 2020. RESULTS: Stoma leakage was seen in 35 of the 519 patients (6.7%). The distance between the stoma site marking and the umbilicus was less than 60 mm in 27 of the 35 patients (77%) who experienced stoma leakage, so a distance of less than 60 mm was identified as an independent risk factor for stoma leakage. Aside from preoperative factors, stoma leakage was also caused by postoperative skin wrinkles or surgical scars near the stoma site in 8 of 35 patients (23%). CONCLUSION: Preoperative standardized stoma site marking is necessary to achieve reliable marking that is easy to perform. To reduce the risk of stoma leakage, a distance of 60 mm or more between the stoma site marking and the umbilicus is ideal, and surgeons need to contrive ways to keep surgical scars away from the stoma site.

Emergence of paraelectric, improper antiferroelectric, and proper ferroelectric nematic phases in a liquid crystal composed of polar molecules.

We have elaborated a theoretical approach for the description of polar nematic phases observed by Nishikawa et al. [Adv. Mater. 29, 1702354 (2017)0935-964810.1002/adma.201702354], their structures, and transitions between them. Specific symmetry contributions to the pair molecular potentials provide the molecular mechanisms responsible for the formation of proper and improper polarity on the macroscopic level. An improper antiferroelectric nematic M2 phase can arise between paraelectric nematic M1 and proper ferroelectric nematic MP in the temperature scale. The local polarization in M2 arises mostly due to the local splay deformation. The director distribution in M2 represents the conjugation of cylindrical waves with opposite splay and polarization signs. The director and polarization are parallel to the cylindrical domain axes in the middle of each cylinder but exhibit considerable (mostly radial) deformation on the periphery of each cylinder. Polarization vectors are mostly stacked antiparallel on the borders between the domains without the director disruption. The domain size decreases with the decreasing temperature, the percentage of the antiferroelectric decouplings increases, and M2 exhibits the first-order phase transition into proper ferroelectric MP. With the increasing temperature the domain size in the M2 phase increases, the domination of particular polar orientation of molecules reduces, and finally, the domain size diverges at particular temperature corresponding to the second-order phase transition from M2 to paraelectric M1. Variations of the polar and nonpolar orientational order parameters are estimated within each phase and between the phases. Our experimental and computer simulation results (also presented in the paper) fully support our theoretical findings.

The effects of wheel-running using the upper limbs following immobilization after inducing arthritis in the knees of rats.

This study investigated the effects of wheel-running using the upper limbs following immobilization after inducing arthritis in the knees of rats. Forty male Wistar rats (aged 8 weeks) divided into four groups randomly: arthritis (AR), immobilization after arthritis (Im), wheel-running exercise with the upper limbs following immobilization after arthritis induction (Im+Ex) and sham arthritis induction (Con). The knee joints of the Im and Im+Ex groups were immobilized with a cast for 4 weeks. In the Im+Ex group, wheel-running exercise was administered for 60 min/day (5 times/week). The swelling and the pressure pain threshold (PPT) of the knee joint were evaluated for observing the condition of inflammatory symptoms in affected area, and the paw withdraw response (PWR) was evaluated for observing the condition of secondary hyperalgesia in distant area. Especially, in order to evaluate histological inflammation in the knee joint, the number of macrophage (CD68-positive cells) in the synovium was examined. The expression of calcitonin gene-related peptide (CGRP) in the spinal dorsal horn (L2-3 and L4-5) was examined to evaluate central sensitization. The Im+Ex group showed a significantly better recovery than the Im group in the swelling, PPTs, and PWRs. Additionally, CGRP expression of the spinal dorsal horn (L2-3 and L4-5) in the Im+Ex group was significantly decreased compared with the Im group. According to the results, upper limb exercise can decrease pain in the affected area, reduce hyperalgesia in distant areas, and suppress the central sensitization in the spinal dorsal horn by triggering exercise-induced hypoalgesia (EIH).

Long-term outcomes and recurrence-free interval after the treatment of keloids with a standardized protocol.

BACKGROUND: Recurrence rates of keloids have generally been reported at one time point. However, the longer the duration after treatment, the greater the likelihood that such lesions will recur. In this study, we analysed the time to recurrence during long-term follow-up. MATERIAL AND METHODS: We retrospectively reviewed recurrence-free interval in 52 patients with keloid (age 8-79 years) who had been treated between June 2006 and January 2011 using a standardised protocol developed by our group. RESULTS: Mean duration of follow-up was 37.5 (range, 7-120) months in patients with keloid. Kaplan-Meier survival curves revealed a statistically significant difference in recurrence-free interval between ear keloids and keloids excluding ear keloids. Recurrence rate for keloids was high in the first 2 years after treatment. CONCLUSIONS: Kaplan-Meier analysis was useful for understanding the tendency of recurrence of keloids after treatment using a standardised protocol.

Serum immunoglobulin G antibody titer to Fusobacterium nucleatum is associated with unfavorable outcome after stroke.

Stroke can be a cause of death, while in non-fatal cases it is a common cause of various disabilities resulting from associated brain damage. However, whether a specific periodontal pathogen is associated with increased risk of unfavorable outcome after stroke remains unknown. We examined risk factors for unfavorable outcome following stroke occurrence, including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset (favorable = score 0 or 1; unfavorable = score 2-6). The associations of risk factors with unfavorable outcome, including serum titers of IgG antibodies to 16 periodontal pathogens, were examined. Logistic regression analysis showed that the initial National Institutes of Health stroke scale score [odds ratio (OR) = 1·24, 95% confidence interval (CI) = 1·18-1·31, P < 0·001] and C-reactive protein (OR = 1·29, 95% CI = 1·10-1·51, P = 0·002) were independently associated with unfavorable outcome after stroke. Following adjustment with those, detection of the antibody for Fusobacterium nucleatum ATCC 10953 in serum remained an independent predictor of unfavorable outcome (OR = 3·12, 95% CI = 1·55-6·29, P = 0·002). Determination of the antibody titer to F. nucleatum ATCC 10953 in serum may be useful as a predictor of unfavorable outcome after stroke.

Honeycomb blocks composed of carbonate apatite, ß-tricalcium phosphate, and hydroxyapatite for bone regeneration: effects of composition on biological responses.

Synthetic scaffolds exhibiting bone repair ability equal to that of autogenous bone are required in the fields of orthopedics and dentistry. A suitable synthetic bone graft substitute should induce osteogenic differentiation of mesenchymal stem cells, osteogenesis, and angiogenesis. In this study, three types of honeycomb blocks (HCBs), composed of hydroxyapatite (HAp), ß-tricalcium phosphate (TCP), and carbonate apatite (CO3Ap), were fabricated, and the effects of HCB composition on bone formation and maturation were investigated. The HC structure was selected to promote cell penetration and tissue ingrowth. HAp and ß-TCP HCBs were fabricated by extrusion molding followed by sintering. The CO3Ap HCBs were fabricated by extrusion molding followed by sintering and dissolution-precipitation reactions. These HCBs had similar macroporous structures: all harbored uniformly distributed macropores (∼160 â€‹µm) that were regularly arrayed and penetrated the blocks unidirectionally. Moreover, the volumes of macropores were nearly equal (∼0.15 â€‹cm3/g). The compressive strengths of CO3Ap, HAp, and ß-TCP HCBs were 22.8 â€‹± â€‹3.5, 34.2 â€‹± â€‹3.3, and 24.4 â€‹± â€‹2.4 â€‹MPa, respectively. Owing to the honeycomb-type macroporous structure, the compressive strengths of these HCBs were higher than those of commercial scaffolds with intricate three-dimensional or unidirectional macroporous structure. Notably, bone maturation was markedly faster in CO3Ap HCB grafting than in ß-TCP and HAp HCB grafting, and the mature bone area percentages for CO3Ap HCBs at postsurgery weeks 4 and 12 were 14.3- and 4.3-fold higher and 7.5- and 1.4-fold higher than those for HAp and ß-TCP HCBs, respectively. The differences in bone maturation and formation were probably caused by the disparity in concentrations of calcium ions surrounding the HCBs, which were dictated by the inherent material resorption behavior and mechanism; generally, CO3Ap is resorbed only by osteoclastic resorption, HAp is not resorbed, and ß-TCP is rapidly dissolved even in the absence of osteoclasts. Besides the composition, the microporous structure of HC struts, inevitably generated during the formation of HCBs of various compositions, may contribute to the differences in bone maturation and formation.

Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study.

OBJECTIVES: To evaluate the efficacy, safety, and tolerability of perampanel, a selective, non-competitive, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, as an adjunctive treatment for patients with refractory partial-onset seizures (POS) from Asia-Pacific. MATERIALS & METHODS: This multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT01618695) involved patients aged ≥12 years with refractory POS (receiving 1-3 antiepileptic drugs). Patients were randomized (1:1:1:1) to receive once-daily placebo or perampanel 4, 8, or 12 mg over a 6-week titration and 13-week maintenance double-blind period. Enzyme-inducing antiepileptic drugs were equally stratified between groups. The primary efficacy endpoint was percent change in POS frequency per 28 days (double-blind phase vs baseline). Other efficacy endpoints included ≥50% responder rate and seizure freedom. Treatment-emergent adverse events (TEAEs) were also monitored. RESULTS: Of 710 randomized patients, seizure frequency data were available for 704 patients. Median percent changes in POS frequency per 28 days indicated dose-proportional reductions in seizure frequency: -10.8% with placebo and -17.3% (P = .2330), -29.0% (P = .0003), and -38.0% (P < .0001) with perampanel 4, 8, and 12 mg, respectively. In total, 108 (15.3%) patients discontinued treatment; 44 (6.2%) due to TEAEs. TEAEs occurring in ≥5% of patients, and reported at least twice as frequently with perampanel vs placebo, included dizziness and irritability. CONCLUSIONS: Adjunctive perampanel (8 and 12 mg/d) significantly improved seizure control in patients with refractory POS. Safety and tolerability were acceptable at daily doses of perampanel 4-12 mg.

Observation and Control of Laser-Enabled Auger Decay.

Single-photon laser-enabled Auger decay (spLEAD) is predicted theoretically [B. Cooper and V. Averbukh, Phys. Rev. Lett. 111, 083004 (2013)PRLTAO0031-900710.1103/PhysRevLett.111.083004] and here we report its first experimental observation in neon. Using coherent, bichromatic free-electron laser pulses, we detect the process and coherently control the angular distribution of the emitted electrons by varying the phase difference between the two laser fields. Since spLEAD is highly sensitive to electron correlation, this is a promising method for probing both correlation and ultrafast hole migration in more complex systems.

Cheese supplemented with probiotics reduced the Candida levels in denture wearers-RCT.

OBJECTIVES: The access to probiotics should be facilitated in order to encourage their usage. We evaluated the effect of consumption of two experimental probiotic-containing cheeses on the oral colonization of Candida in denture wearers. METHODS: Sixty denture wearers harboring oral Candida were randomly allocated in groups who received cheese supplemented with Lactobacillus acidophilus NCFM (T1) or Lactobacillus rhamnosus Lr-32 (T2), daily for 8 weeks, and a control group (C) who received a control cheese. Oral samples were obtained through a mouthwash, and Candida levels were determined (CFU/mL) at baseline and after the 8-week experimental period. RESULTS: At baseline, the mean levels of Candida spp. (log CFU/mL) were similar among the groups. However, the mean levels of Candida were significantly reduced in groups T1 and T2 but not in C (Tukey, p<.05). The reduction in Candida oral levels occurred independently on the colonizing Candida species, participant age, and use of bi- or unimaxillary dentures. CONCLUSIONS: Daily consumption of cheese supplemented with probiotics, with either L. acidophilus NCFM or L. rhamnosus Lr-32, was able to reduce the colonization of oral Candida in complete denture wearers, suggesting its potential in reducing the risk of oral candidiasis in this highly susceptible population.

An in vivo screening system to identify tumorigenic genes.

Screening for oncogenes has mostly been performed by in vitro transformation assays. However, some oncogenes might not exhibit their transforming activities in vitro unless putative essential factors from in vivo microenvironments are adequately supplied. Here, we have developed an in vivo screening system that evaluates the tumorigenicity of target genes. This system uses a retroviral high-efficiency gene transfer technique, a large collection of human cDNA clones corresponding to ~70% of human genes and a luciferase-expressing immortalized mouse mammary epithelial cell line (NMuMG-luc). From 845 genes that were highly expressed in human breast cancer cell lines, we focused on 205 genes encoding membrane proteins and/or kinases as that had the greater possibility of being oncogenes or drug targets. The 205 genes were divided into five subgroups, each containing 34-43 genes, and then introduced them into NMuMG-luc cells. These cells were subcutaneously injected into nude mice and monitored for tumor development by in vivo imaging. Tumors were observed in three subgroups. Using DNA microarray analyses and individual tumorigenic assays, we found that three genes, ADORA2B, PRKACB and LPAR3, were tumorigenic. ADORA2B and LPAR3 encode G-protein-coupled receptors and PRKACB encodes a protein kinase A catalytic subunit. Cells overexpressing ADORA2B, LPAR3 or PRKACB did not show transforming phenotypes in vitro, suggesting that transformation by these genes requires in vivo microenvironments. In addition, several clinical data sets, including one for breast cancer, showed that the expression of these genes correlated with lower overall survival rate.

APOBEC3A associates with human papillomavirus genome integration in oropharyngeal cancers.

The prevalence of human papillomavirus (HPV)-related oropharyngeal cancers has been increasing in developed countries. We recently demonstrated that members of the apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3, A3) family, which are antiviral factors, can induce hypermutation of HPV DNA in vitro. In the present study, we found numerous C-to-T and G-to-A hypermutations in the HPV16 genome in oropharyngeal cancer (OPC) biopsy samples using differential DNA denaturation PCR and next-generation sequencing. A3s were more abundantly expressed in HPV16-positive OPCs than in HPV-negative, as assessed using immunohistochemistry and reverse transcription quantitative PCR. In addition, interferons upregulated A3s in an HPV16-positive OPC cell line. Furthermore, quantitative PCR analysis of HPV DNA suggests that APOBEC3A (A3A) expression is strongly correlated with the integration of HPV DNA. These results suggest that HPV16 infection may upregulate A3A expression, thereby increasing the chance of viral DNA integration. The role of A3A in HPV-induced carcinogenesis is discussed.

The kinetics of VEGF and MCP-1 in the second vitrectomy cases with proliferative diabetic retinopathy.

PurposeTo determine whether the concentrations of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP)-1 in the vitreous changed after vitrectomy in patients with proliferative diabetic retinopathy (PDR).ParticipantsTwenty-one eyes of 21 patients who needed a second surgery for PDR were included. The reasons for the second surgery were tractional retinal detachment (TRD), neovascular glaucoma, persistent vitreous hemorrhage, macular pucker, and secondary intraocular lens (IOL) implant.MethodsWe measured the VEGF and MCP-1 levels using sandwich enzyme-linked immunosorbent assays in vitreous samples collected from patients with PDR before pars plana vitrectomy (without IOL implantation), and from the same patients during the second surgery.ResultsThere was not significant change in mean VEGF concentrations when comparing first (0.81±0.88 ng/ml) and second surgeries (1.09±1.51 ng/ml). The MCP-1 level was significantly elevated at the time of second surgery (2.20±2.21 ng/ml) compared with the first vitrectomy (0.72±0.57 ng/ml). The MCP-1 levels of the second surgery cases with TRD (3.18±2.27 ng/ml) increased significantly compared with those with other complications (1.72±2.10 ng/ml).ConclusionsAt the second vitrectomy, VEGF did not change significantly in the vitreous of the patients examined. The MCP-1 concentration was markedly elevated at the second vitrectomy, implying an association between the prolonged inflammation after vitrectomy and complications, especially TRD.

Comparison between Monte Carlo simulation and measurement with a 3D polymer gel dosimeter for dose distributions in biological samples.

In this research, we used a 135 MeV/nucleon carbon-ion beam to irradiate a biological sample composed of fresh chicken meat and bones, which was placed in front of a PAGAT gel dosimeter, and compared the measured and simulated transverse-relaxation-rate (R2) distributions in the gel dosimeter. We experimentally measured the three-dimensional R2 distribution, which records the dose induced by particles penetrating the sample, by using magnetic resonance imaging. The obtained R2 distribution reflected the heterogeneity of the biological sample. We also conducted Monte Carlo simulations using the PHITS code by reconstructing the elemental composition of the biological sample from its computed tomography images while taking into account the dependence of the gel response on the linear energy transfer. The simulation reproduced the experimental distal edge structure of the R2 distribution with an accuracy under about 2 mm, which is approximately the same as the voxel size currently used in treatment planning.

[OPTIMIZATION OF THE METHOD OF SUPRAPANCREATIC LYMPH NODE DISSECTION IN LAPAROSCOPY-ASSISTED GASTRECTOMY (IN THE FINAL ANALYSIS OF INTERNATIONAL CONFERENCES <>)].

The article analyzed the methods of suprapancretic lymph node dissection in laparoscopic gastrectomy which were devel- oped and applied in Japan. The authors described the details of operation technique. There were noted the advantages of medial approach for suprapancreatic lymph node dissection.

Mutation in insulin receptor attenuates oxidative stress and apoptosis in pancreatic beta-cells induced by nutrition excess: reduced insulin signaling and ROS.

Type 2 diabetes results from the failure of beta-cells to adequately compensate for insulin resistance. Although the reduction of beta-cell mass is because of increased cell death and/or inadequate replication or neogenesis, the mechanism underlying beta-cell mass reduction is not fully understood. Here, we clarify the role of insulin signaling pathway in the beta-cell apoptosis using insulin resistant model mice. Wild-type mice and those carrying a mutation in the insulin receptor (mIR) were fed either regular chow or a high-fat diet for 6 weeks and subsequently investigated for beta-cell apoptosis, endoplasmic reticulum stress, and oxidative stress. Insulin tolerance tests revealed that mIR mice fed a high-fat diet (mIRHF) had higher insulin resistance. Beta-cell apoptosis was increased 2-fold in the wild-type mice fed a high-fat diet (wHF) compared with control mice, whereas beta-cell apoptosis in mIRHF mice did not increase compared with that in mIR mice. The expression of endoplasmic reticulum stress markers in isolated islets did not differ between the groups. Staining of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal in islets of wHF mice significantly increased, but the staining in mIRHF mice was not different from that in control group. Gene expression of the antioxidant enzyme MnSOD was significantly higher in mIRHF mice than those in the other 3 groups. A mutation in the insulin receptor attenuated the oxidative stress and apoptosis in beta-cells even though high caloric nutrient was loaded. Our results suggest that reduced insulin signaling protects beta-cells thorough decline of oxidative stress.

Modulation of the osteoconductive property and immune response of poly(ether ether ketone) by modification with calcium ions.

Both bone-forming cells and immune cells have pivotal roles in bone tissue repair. In this work, we prepared a Ca-modified poly(ether ether ketone) (PEEK) to enhance the osteoconductivity but mitigate immune response of cells. To modify Ca ions onto a chemically inert PEEK, PEEK was first coated with poly(norepinephrine) followed by soaking in Ca(OH)2 aqueous solution. Modification of Ca ions onto PEEK enhanced the proliferation and differentiation of MC3T3-E1 preosteoblast cells and human mesenchymal stem cells, but had no apparent effect on MLC-6 osteoclast-like cells. Naïve RAW264.7 macrophages cultured on pristine PEEK produced proinflammatory cytokines, but not on Ca-modified PEEK. Lipopolysaccharide-stimulated RAW264.7 macrophages on Ca-modified PEEK produced lower levels of proinflammatory cytokines but higher levels of anti-inflammatory cytokines compared with those on pristine PEEK. Lower levels of proinflammatory cytokines on Ca-modified PEEK were partially owing to higher interleukin-10 production mediated by Ca-activated pathways. Simple Ca modification of PEEK was shown to activate osteoblastic cell proliferation and differentiation, and shift macrophages towards an anti-inflammatory/wound healing type, which would be useful not only for bone tissue implants but also other implanted biomaterials.

Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin.

Age-related macular degeneration (AMD) is a vision-threatening disease characterized by choroidal fibrovascular membrane (FVM) formation, choroidal neovascularization (CNV) and choroidal fibrosis. No safe and effective therapeutic method has been developed for the choroidal fibrosis, although anti-vascular endothelial growth factor therapy can partially shrink the CNV. We recently reported that periostin (POSTN), which is produced by retinal pigment epithelial cells, has an important role in the formation of preretinal FVMs, but its role in choroidal FVMs has not been determined. In this study, we used Postn knockout mice to investigate the role played by POSTN in choroidal FVM formation. In addition, we used a new class of RNA interference (RNAi) agent (NK0144) that targets POSTN and determined its effect on choroidal FVM development. Genetic ablation of Postn had an inhibitory effect not only on CNV formation but also on choroidal fibrosis in a mouse CNV model. NK0144 also had a greater inhibitory effect on both the CNV and choroidal fibrosis than control RNAi with no apparent adverse effects. These findings suggest a causal relationship between POSTN and choroidal FVM formation, and also a potential therapeutic role of intravitreal NK0144 for AMD.