Effects of inaudible Binaural beats on visuospatial memory performance and hemodynamic responses.

This study aimed to observe the impact of pure Binaural Beats (BB) stimulation in the inaudible frequency range, excluding the influence of sound, on visuospatial memory. Additionally, we investigated whether the brainwave changes induced by BB stimulation directly affect brain activation. The experiment involved 17 participants (12 males with a mean age of 23.2 ± 1.7 and 5 females with a mean age of 21.0 ± 0.7) in their 20s. Each participant received 10 Hz BB stimulation by presenting frequencies of 18,000 Hz and 18,010 Hz to the left and right ears, respectively. The experiment consisted of Rest phase (5 min), Task phase (5 min), and Rest phase (5 min). The Task phase included conditions where participants performed the task either without BB stimulation "Task only" or with BB stimulation "Task + BB". Visuospatial memory was evaluated using the 3-back task. To observe brain activation, functional Near Infrared Spectroscopy (fNIRS) was employed to measure hemodynamic responses in all phases. The cognitive task performance (Accuracy, Reaction time) and oxyhemoglobin (HbO) concentration during the Task phase were compared between conditions with and without BB stimulation using paired t-tests. Results indicated a significantly shorter Reaction time in the Task + BB condition compared to the Task only condition. Moreover, an increase in HbO concentration was observed in the F1-F3, F2-F4, and P2-P4 regions during the Task + BB condition. In conclusion, the observed increase in HbO concentration suggests a positive influence on task performance. This study is meaningful in objectively demonstrating the impact of inaudible BB stimulation on visuospatial memory, utilizing both behavioral data and direct neural activation reflected in hemodynamic responses.

Optimized ultrasound neuromodulation for non-invasive control of behavior and physiology.

Focused ultrasound can non-invasively modulate neural activity, but whether effective stimulation parameters generalize across brain regions and cell types remains unknown. We used focused ultrasound coupled with fiber photometry to identify optimal neuromodulation parameters for four different arousal centers of the brain in an effort to yield overt changes in behavior. Applying coordinate descent, we found that optimal parameters for excitation or inhibition are highly distinct, the effects of which are generally conserved across brain regions and cell types. Optimized stimulations induced clear, target-specific behavioral effects, whereas non-optimized protocols of equivalent energy resulted in substantially less or no change in behavior. These outcomes were independent of auditory confounds and, contrary to expectation, accompanied by a cyclooxygenase-dependent and prolonged reduction in local blood flow and temperature with brain-region-specific scaling. These findings demonstrate that carefully tuned and targeted ultrasound can exhibit powerful effects on complex behavior and physiology.

Impact of Zinc Oxide on the Development of Aspergillus-Induced Maxillary Sinusitis Rabbit Model.

Aspergillus fumigatus is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal survival, growth, and proliferation. This study aimed to investigate the impact of ZO on A. fumigatus-induced fungal sinusitis in rabbits. Twenty-eight New Zealand white rabbits were divided into four groups for this study. Group 1 (6 sides) was treated with intramaxillary phosphate buffer saline (PBS) served as the negative control, Group 2 (6 sides) received intramaxillary PBS and ZO, Group 3 (8 sides) was treated with intramaxillary A. fumigatus alone, and Group 4 (8 sides) treated with intramaxillary A. fumigatus with ZO. After 4 and 12 weeks, sinus mucosal cytokine and transcription factor expressions were determined. A histological analysis was performed to determine inflammatory cell infiltration, number of secretory cells, and mucosal thickness. Fungal biofilm formation was determined using confocal laser microscopy. The intramaxillary instillation of A. fumigatus conidia led to an increase in protein and mRNA expression of interleukin (IL)-1ß and IL-8 in the maxillary sinus mucosa. They were associated with mitogen-activated protein kinase and activator protein-1. Furthermore, intramaxillary instillation of fungal conidia resulted in significant enhancement of inflammatory cell infiltration, epithelial thickening, and fungal biofilm formation. However, intramaxillary ZO did not have a significant impact on A. fumigatus-induced cytokine protein and mRNA expression, and inflammatory cell infiltration and epithelial thickness in sinonasal mucosa. While intramaxillary instillation of A. fumigatus increased mucosal inflammation, cytokine production, and biofilm formation, the intramaxillary application of ZO did not have a significant influence on inflammation in the maxillary sinus mucosa.

Case report: Unilateral papilledema in a dog with a large suprasellar mass and suspected intracranial hypertension: insights from funduscopy, optical coherence tomography, and magnetic resonance imaging.

A spayed, 8-year-old female Poodle, weighing 5.7 kg, was presented with the chief complaint of vision impairment. Vision assessment, including pupillary light reflexes, menace response, dazzle reflex, and maze navigation in photopic and scotopic circumstances, revealed a negative response in both eyes except for positive direct pupillary light reflex in the right eye and positive consensual pupillary light reflex from the right eye to the left eye. Systemic evaluation, including neurologic status, blood profile, and thoracic radiographs, did not reveal any abnormalities. Complete ophthalmic examinations, ocular ultrasonography, and electroretinography did not identify a cause of blindness. Upon funduscopy, the left eye exhibited an increased optic disk diameter, blurred optic disk borders, and loss of the physiologic pit, as well as an increase in vascular tortuosity. In the right eye, there were multifocal depigmented areas in the non-tapetal fundus and several pigmented spots surrounded by a region of dull tapetal reflection in the tapetal fundus. The optical coherence tomography revealed severe anterior deformation of the optic nerve head and Bruch's membrane in the peripapillary region of the left eye. Magnetic resonance imaging revealed an irregular, broad-based suprasellar mass, with features suggestive of intracranial hypertension, including dorsal displacement of third ventricles, a rightward shift of the falx cerebri, trans-tentorial herniation, perilesional edema, flattening/protrusion of the posterior sclera, and lager optic nerve sheath diameter in left side than right side. This is the first comprehensive report that describes unilateral papilledema in a dog with a brain tumor, using advanced ophthalmic and neuro-imaging modalities.

Isolated left hypoplasia of the pulmonary artery accompanied by lung hypoplasia and chronic bronchial disease in a cat.

A 2-year-old castrated Russian Blue cat presented with inappetence, depression, and labored respirations. Radiography findings suggested left lung atelectasis; however, the ultrasonography findings did not indicate lung atelectasis. The left pulmonary artery (PA) was abnormally small on echocardiography; further, there were no other cardiac anomalies. Computed tomography revealed an abnormally small left PA and left lung. Furthermore, bronchiectasis and tree-in-bud patterns were observed in the lung lobes. Based on these findings, the cat was diagnosed with isolated left PA hypoplasia, presumed left lung hypoplasia, and feline chronic bronchial disease. Early diagnosis of this disease is important because it can cause serious complications, including recurrent respiratory infection, bronchiectasis, massive hemoptysis, and pulmonary hypertension.

Visual Outcome and Fluid Changes Between Eyes With Polypoidal Choroidal Vasculopathy Receiving Biosimilar CKD-701 or Reference Ranibizumab Therapy: A Post Hoc Analysis of a Phase 3 Randomized Clinical Trial.

PURPOSE: To compare the visual outcome and fluid features of a proposed biosimilar, CKD-701, versus the reference ranibizumab in eyes with polypoidal choroidal vasculopathy (PCV). METHODS: This was a post hoc analysis of a phase 3 randomized clinical trial assessing the efficacy and safety of CKD-701 and ranibizumab. A total of 73 PCV eyes were assigned randomly to either CKD-701 (36 eyes) or ranibizumab (37 eyes). The mean changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), pigment epithelial detachment (PED) volume, and fluid features were compared. RESULTS: After three loading injections, the mean change in BCVA (letters) was +7.50 in the CKD-701 group and +6.32 in the ranibizumab group (p = .447). The changes in CRT and PED volume of the CKD-701 group (-107.25 ± 102.66 µm and -0.22 ± 0.46 mm3) were similar to those of the ranibizumab group (-96.78 ± 105.00 µm and -0.23 ± 0.54 mm3) (p = .668 and p = .943, respectively). Proportions of eyes with subretinal, intraretinal and sub-retinal pigment epithelium (RPE) fluids after three loading injections were not different between CKD-701 group (33.3%, 13.9% and 42.9%) and ranibizumab group (51.4%, 16.2% and 40.0%) (p = .071, p = 1.000 and p = .808). The visual and anatomical changes were similar between two groups at month 6 and 12 (all, p > .05). CONCLUSION: Biosimilar CKD-701 monotherapy resulted in comparable visual and anatomical changes to those achieved with reference ranibizumab in PCV eyes.

Changes in the BOLD signal of S1 and BA3 per finger/phalanx as a response to high-frequency vibratory stimulation.

PURPOSE AND METHOD: The purpose of this study was to determine the changes in the Blood Oxygen Level Dependent signal of Primary somatosensory area (S1) and Brodmann area 3 (BA3) per finger and phalanx in comparison to the activation voxel when 250 Hz vibratory stimulation with high sensitivity for the Pacinian corpuscle was given to the four fingers and three phalanges. RESULTS: The result of analyzing the activation voxel showed a significant difference for S1 per finger and phalanx, but for BA3, no significant difference was observed despite a similar trend to S1. In contrast, the activation intensity (BOLD) displayed a significant difference for S1 per finger and phalanx and for BA3, where the activation voxel had no significant variation. In addition, while the result of S1 did not indicate whether the index or the little fingers had the highest sensitivity based on the BOLD signal per finger, the result of BA3 marked the strongest BOLD signal for the little finger as a response to 250 Hz vibratory stimulation. The activation intensity per phalanx was the highest for the intermediate phalanx for S1 and BA3, which was in line with a previous study comparing the activation voxel. CONCLUSIONS: The method based on the intensity of the nerve activation is presumed to have high sensitivity as the signal intensity is monitored within a specific, defined area. Thus, for the extraction of brain activation patterns of micro-domains, such as BA3, monitoring the BOLD signal that reflects the nerve activation intensity more sensitively is likely to be advantageous.

Volume-rendering three-dimensional image analysis of macular neovascularization in age-related macular degeneration.

BACKGROUND: To visualize and investigate the three-dimensional (3D) images of macular neovascularization (MNV) in eyes with neovascular age-related macular degeneration using optical coherence tomography angiography (OCTA) according to the treatment response to intravitreal aflibercept injection (IVI). METHODS: OCTA images at baseline and 12 weeks (after three loading IVIs) were retrospectively reconstructed as 3D images for patients with type 1 and 2 MNV treated with the "pro-re-nata" regimen. The fluid-free and persistent fluid groups were divided according to the presence of subretinal and intraretinal fluid at 12 weeks after treatment. Using reconstructed 3D images of MNV, the volume, average volume per slice, and z-axis of the volumetric structure were evaluated. RESULTS: Twenty-three and nine were classified into the fluid-free and persistent fluid groups, respectively. The MNV volume decreased significantly from baseline to 12 weeks in the fluid-free group (p = 0.005), not in the persistent fluid group (p = 0.250). The average volume of MNV per slice at 12 weeks correlated with the persistent fluid group in both the univariate and multivariate analyses (p = 0.034, p = 0.039, Exp [B] = 14.005). CONCLUSIONS: This study may provide a perspective on vascular volumetric changes of MNV according to treatment response.

Aspergillus Enhances Eosinophil and Neutrophil Extracellular DNA Trap Formation in Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is characterized by inflammatory cell infiltration in the sinonasal mucosa. Eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) are prominently found in CRS. This study aimed to investigate the effect of airborne fungi, Alternaria alternata and Aspergillus fumigatus, on EET and NET formation. Nasal epithelial cells, eosinophils, and neutrophils were isolated from eosinophilic CRS (ECRS), non-ECRS (NECRS), and healthy control. We determined eosinophil and neutrophil transepithelial migration after fungal treatment. We then determined the release of EETs and NETs by fungi using Sytox Green staining and determined the role of reactive oxygen species (ROS) using ROS inhibitors. We identified more abundant EETs and NETs in ECRS than in NECRS. A. alternata and A. fumigatus enhanced eosinophil and neutrophil transepithelial migration. A. fumigatus strongly induced EET and NET formation in CRS and, simultaneously, suppressed fungal metabolic activity. EET formation in CRS is associated with nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and NET formation with NADPH-oxidase and mitochondrial ROS. A. fumigatus, but not A. alternata, induced EET and NET formation, and peripheral blood eosinophils and neutrophils exhibited different immune responses against A. fumigatus following the inflammatory status of the host. Aspergillus-fumigatus-induced EET and NET formation plays a crucial role in CRS pathogenesis.

Clinical Factors, Treatment Selection, and Outcomes in Postcataract Fungal Endophthalmitis from Contaminated Viscoelastics.

PURPOSE: To investigate the factors associated with treatment outcomes of postcataract surgery fungal endophthalmitis outbreaks related to contaminated viscoelastics. DESIGN: Retrospective analysis of clinical data from multiple institutions. SUBJECTS: This study included 228 eyes of 210 patients who were diagnosed with postcataract surgery fungal endophthalmitis related to the use of viscoelastic material (Unial, Unimed Pharmaceutical Inc); they were followed up for 6 months after the diagnosis. METHODS: Clinical features and causative species were identified and treatment outcomes were analyzed in patients who underwent 6 months of follow-up. Propensity score matching was conducted to elucidate the impact of vitrectomy timing and intraocular lens (IOL) removal on treatment outcomes. MAIN OUTCOME MEASURES: Clinical factors and selection of treatment modalities associated with treatment outcomes at 6 months. RESULTS: Baseline visual acuity (P < 0.01), age (P = 0.05), and the presence of corneal edema (P < 0.01) were closely associated with poor best-corrected visual acuity (BCVA) at 6 months. Patients who underwent immediate vitrectomy after diagnosis showed significantly better BCVA at 6 months (mean logarithm of minimum angle of resolution 0.26 ± 0.43 vs. 0.52 ± 0.52, P = 0.03) and greater degree of visual improvement (mean -0.17 ± 0.37 improvement vs. 0.10 ± 0.57 deterioration, P = 0.03) than those who underwent deferred vitrectomy. Patients who underwent IOL removal during vitrectomy required a lower number of intravitreal antifungal agent injections (mean 8.9 ± 9.1 vs. 16.7 ± 12.2, P < 0.01) and showed a lower incidence of repeated vitrectomy (20% vs. 82%, P < 0.01) than in those without IOL removal. CONCLUSIONS: In postcataract fungal endophthalmitis, prompt vitrectomy at the time of diagnosis resulted in better treatment outcomes, and IOL removal reduced the treatment burden. Prompt and aggressive surgical intervention should be considered for postcataract fungal endophthalmitis.

Effects of inaudible binaural beats on visuospatial memory.

OBJECTIVES: Binaural beats are auditory beat stimulation that produces sounds and induces a specific state of brain wave based on the difference in the frequency of stimulation. This study aimed to investigate the effects of inaudible binaural beats on visuospatial memory at 18 000 Hz reference and 10 Hz difference frequencies. METHODS: Eighteen adult subjects in their twenties were enrolled, including 12 males (mean age: 23.8 ±â€…1.2) and 6 females (mean age: 22.8 ±â€…0.8). An auditory stimulator providing 10 Hz binaural beats stimulation via 18 000 Hz to the left and 18 010 Hz to the right ears was used. The experiment consisted of two 5-min phases, including a rest phase and a task phase involving task performance without (Task-only) and with binaural beats stimulation (Task+BB). A 3-back task was used to measure visuospatial memory. Cognitive ability measured by task performance (accuracy and reaction time) with and without binaural beats, as well as variations in alpha power across different brain domains, were compared using paired t-tests. RESULTS: Compared to the Task-only condition, the Task+BB condition had significantly higher accuracy and significantly shorter reaction time. The electroencephalogram analysis showed that the reduction level in alpha power for the task performance under the Task+BB condition was significantly lower in all brain areas except the frontal, compared to that under the Task-only condition. CONCLUSION: The significance of this study lies in having verified the independent effects of binaural beats stimulation without any auditory influence, based on visuospatial memory.

INKILN is a Novel Long Noncoding RNA Promoting Vascular Smooth Muscle Inflammation via Scaffolding MKL1 and USP10.

BACKGROUND: Activation of vascular smooth muscle cell (VSMC) inflammation is vital to initiate vascular disease. The role of human-specific long noncoding RNAs in VSMC inflammation is poorly understood. METHODS: Bulk RNA sequencing in differentiated human VSMCs revealed a novel human-specific long noncoding RNA called inflammatory MKL1 (megakaryoblastic leukemia 1) interacting long noncoding RNA (INKILN). INKILN expression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation as well as human atherosclerosis and abdominal aortic aneurysm. The transcriptional regulation of INKILN was verified through luciferase reporter and chromatin immunoprecipitation assays. Loss-of-function and gain-of-function studies and multiple RNA-protein and protein-protein interaction assays were used to uncover a mechanistic role of INKILN in the VSMC proinflammatory gene program. Bacterial artificial chromosome transgenic mice were used to study INKILN expression and function in ligation injury-induced neointimal formation. RESULTS: INKILN expression is downregulated in contractile VSMCs and induced in human atherosclerosis and abdominal aortic aneurysm. INKILN is transcriptionally activated by the p65 pathway, partially through a predicted NF-κB (nuclear factor kappa B) site within its proximal promoter. INKILN activates proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. INKILN physically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway. INKILN depletion blocks interleukin-1ß-induced nuclear localization of both p65 and MKL1. Knockdown of INKILN abolishes the physical interaction between p65 and MKL1 and the luciferase activity of an NF-κB reporter. Furthermore, INKILN knockdown enhances MKL1 ubiquitination through reduced physical interaction with the deubiquitinating enzyme USP10 (ubiquitin-specific peptidase 10). INKILN is induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in bacterial artificial chromosome transgenic mice. CONCLUSIONS: These findings elucidate an important pathway of VSMC inflammation involving an INKILN/MKL1/USP10 regulatory axis. Human bacterial artificial chromosome transgenic mice offer a novel and physiologically relevant approach for investigating human-specific long noncoding RNAs under vascular disease conditions.

Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans.

This study aimed to investigate the clinical characteristics of Korean patients with retinal dystrophy associated with pathogenic variants of cone rod homeobox-containing gene (CRX). We retrospectively enrolled Korean patients with CRX-associated retinal dystrophy (CRX-RD) who visited two tertiary referral hospitals. Pathogenic variants were identified using targeted panel sequencing or whole-exome sequencing. We analyzed clinical features and phenotypic spectra according to genotype. Eleven patients with CRX-RD were included in this study. Six patients with cone-rod dystrophy (CORD), two with macular dystrophy (MD), two with Leber congenital amaurosis (LCA), and one with retinitis pigmentosa (RP) were included. One patient (9.1%) had autosomal recessive inheritance, and the other ten patients (90.9%) had autosomal dominant inheritance. Six patients (54.5%) were male, and the mean age of symptom onset was 27.0 ± 17.9 years. At the first presentation, the mean age was 39.4 ± 20.6 years, and best-corrected visual acuity (BCVA) (logMAR) was 0.76 ± 0.90 in the better eye. Negative electroretinography (ERG) was observed in seven (63.6%) patients. Nine pathogenic variants were identified, including two novel variants, c.101-1G>A and c.898T>C:p.(*300Glnext*118). Taken together with the variants reported in prior studies, all variants within the homeodomain are missense variants, whereas most variants downstream of the homeodomain are truncating variants (88%). The clinical features of pathogenic variants within the homeodomain are either CORD or MD with bull's eye maculopathy, whereas variants downstream of the homeodomain cause more diverse phenotypes, with CORD and MD in 36%, LCA in 40%, and RP in 24%. This is the first case series in Korea to investigate the CRX-RD genotype-phenotype correlation. Pathogenic variants downstream of the homeodomain of the CRX gene are present as RP, LCA, and CORD, whereas pathogenic variants within the homeodomain are mainly present as CORD or MD with bull's eye maculopathy. This trend was similar to previous genotype-phenotype analyses of CRX-RD. Further molecular biologic research on this correlation is required.

Hyperreflective foci distribution in eyes with dry age-related macular degeneration with subretinal drusenoid deposits.

PURPOSE: To investigate the distribution of hyperreflective foci (HRF) in eyes with dry age-related macular degeneration (AMD). METHODS: We retrospectively reviewed optical coherence tomography (OCT) images of 58 dry AMD eyes presenting HRF. The distribution of HRF according to the early treatment diabetic retinopathy study area was analyzed according to the presence of subretinal drusenoid deposits (SDDs). RESULTS: We classified 32 eyes and 26 eyes into the dry AMD with SDD group (SDD group) and dry AMD without SDD group (non-SDD group), respectively. The non-SDD group had higher prevalence and density of HRF at the fovea (65.4% and 1.71 ± 1.48) than the SDD group (37.5% and 0.48 ± 0.63, P = 0.035 and P < 0.001, respectively). However, the prevalence and density of HRF in the outer circle area of the SDD group (81.3% and 0.11 ± 0.09) were greater than those of the non-SDD group (53.8% and 0.05 ± 0.06, p = 0.025 and p = 0.004, respectively). The SDD group showed higher prevalence and mean densities of HRF in the superior and temporal area than in the non-SDD group (all, p < 0.05). CONCLUSION: HRF distributions in dry AMD varied according to the presence of SDDs. This might support that the degenerative features may be different between dry AMD eyes with and without SDDs.

Study on the Cognitive Characteristics Induced by Changes in the Intensity, Frequency and Duration of Vibratory Stimuli.

The purpose of this study is to analyze the cognitive characteristics that can be induced by vibration stimuli at two intensities, three frequencies, and five presentation periods. The experiment was conducted on 20 right-handed adult males, and a subjective evaluation was performed using a questionnaire. Regression analysis was performed to observe the parameters affecting cognitive characteristics according to changes in intensity, frequency, and stimulation duration. The regression analysis results showed that the cognitive characteristics affected by changes in intensity, frequency, and stimulation duration were "heavy", "bold", "thick", and "light". The cognitive characteristics affected by two-variable combinations were "deep", "clear", "vibrating", "dense", "numb", "blunt", "shallow", "fuzzy", and "soft". Cognitive characteristics affected by either intensity, frequency, or stimulation duration were "fast", "pungent", "skinny", "thin", "slow", "ticklish", "tingling", "prickling", "tap", and "rugged". By observing the cognitive characteristics that can be induced by the combination of intensity, frequency, and stimulation duration, we confirmed that in addition to intensity and frequency, the stimulation duration is an important factor that influences the induction of various cognitive characteristics. The results presented in the study can be used to enhance the utility of haptic surfaces for extended reality applications.

Frequency-following response effect according to gender using a 10-Hz binaural beat stimulation.

BACKGROUND: Several studies have continuously investigated FFRs using binaural beat (BB) stimulations and their related effects. However, only a few studies have investigated the differences in BB stimulation effects according to basic demographic characteristics, such as gender and age. OBJECTIVE: This study aimed to determine the alpha wave activity after a 10-Hz BB stimulation and subsequently identify differences according to gender across all brain areas (frontal, central, parietal, temporal, and occipital areas). METHODS: A total of 23 healthy adults (11 male and 12 female), aged 20-29, participated in the study. For the 10-Hz BB stimulation, pure tone auditory stimuli of 250 and 260 Hz were given to the left and right ear, respectively. Through a power spectrum analysis of the phase-excluding BBs (non-BBs) and phase-including 10-Hz BBs (α-BBs), the alpha power at each brain area was estimated. These values were compared using a mixed-design ANOVA. RESULTS: With the exception of the temporal area, all other brain areas showed a significant increase in alpha power for α-BBs compared to those of non-BBs. However, the difference according to gender was not significant. CONCLUSION: The results indicated the lack of gender effects in alpha wave generation through a 10-Hz BB stimulation.

A Pilot Study: Extraction of a Neural Network and Feature Extraction of Generation and Reduction Mechanisms Due to Acute Stress.

This study aimed to compare the functional connectivity (FC) assessed during acute stress and recovery after stress using the Montreal imaging stress task (MIST) in adults in their 20s and 30s with Korean Perceived Stress Scale (PSS) scores between 15 and 19 points inclusive. Four seed networks, including the salience network, default mode network, frontoparietal network, and dorsal attention network, were specified to extract the results. Healthy male and female adults who were required to make an effort to relieve stress were exposed to acute stress tasks, and the most common FCs were observed in the salience network, default mode network, and frontoparietal network during the stress and recovery phases. Compared to the stress phase, the increased effect size was significantly different in the recovery phase. In the stress phase, characteristically common FCs were observed in the dorsal attention network. During the recovery period, Salience network (Anterior Insula, R) and Salience network (anterior cingulate cortex, ACC)/Salience network (rostral prefrontal cortex, RPFC), Salience network (AInsula) and Salience network (RPFC), and Default Mode network (posterior cingulate) cortex, PCC) and fronto-parietal network (lateral prefrontal cortex, LPFC) FC were characteristically observed.

An Outbreak of Fungal Endophthalmitis After Cataract Surgery in South Korea.

Importance: Fungal endophthalmitis caused by contaminated medical products is extremely rare; it follows an intractable clinical course with a poor visual prognosis. Objective: To report the epidemiologic and clinical features and treatment outcomes of a nationwide fungal endophthalmitis outbreak after cataract surgery as a result of contaminated viscoelastic agents in South Korea. Design, Setting, and Participants: This was a retrospective case series analysis of clinical data from multiple institutions in South Korea conducted from September 1, 2020, to October 31, 2021. Data were collected through nationwide surveys in May and October 2021 from the 100 members of the Korean Retinal Society. Patients were diagnosed with fungal endophthalmitis resulting from the use of the viscoelastic material sodium hyaluronate (Unial [Unimed Pharmaceutical Inc]). Data were analyzed from November 1, 2021, to May 30, 2022. Main Outcomes and Measures: The clinical features and causative species were identified, and treatment outcomes were analyzed for patients who underwent 6 months of follow-up. Results: The fungal endophthalmitis outbreak developed between September 1, 2020, and June 30, 2021, and peaked in November 2020. An official investigation by the Korea Disease Control and Prevention Agency confirmed contamination of viscoelastic material. All 281 eyes of 265 patients (mean [SD] age, 65.4 [10.8] years; 153 female individuals [57.7%]) were diagnosed with fungal endophthalmitis, based on clinical examinations and supportive culture results. The mean (SD) time period between cataract surgery and diagnosis was 24.7 (17.3) days. Patients exhibited characteristic clinical features of fungal endophthalmitis, including vitreous opacity (212 of 281 [75.4%]), infiltration into the intraocular lens (143 of 281 [50.9%]), and ciliary infiltration (55 of 281 [19.6%]). Cultures were performed in 260 eyes, and fungal presence was confirmed in 103 eyes (39.6%). Among them, Fusarium species were identified in 89 eyes (86.4%). Among the 228 eyes included in the treatment outcome analysis, the mean (SD) best-corrected visual acuity improved from 0.78 (0.74) logMAR (Snellen equivalent, 20/120 [7.3 lines]) to 0.36 (0.49) logMAR (Snellen equivalent, 20/45 [4.9 lines]) at 6 months. Furthermore, disease remission with no signs of fungal endophthalmitis (or cells in the anterior chamber milder than grade 1) was noted in 214 eyes (93.9%). Conclusions and Relevance: This was a retrospectively reviewed case series of a fungal endophthalmitis outbreak resulting from contaminated viscoelastic material. Findings of this case series study support the potential benefit of prompt, aggressive surgical intervention that may reduce treatment burden and improve prognosis of fungal endophthalmitis caused by contaminated medical products.

INKILN is a novel long noncoding RNA promoting vascular smooth muscle inflammation via scaffolding MKL1 and USP10.

Background: Activation of vascular smooth muscle cells (VSMCs) inflammation is vital to initiate vascular disease. However, the role of human-specific long noncoding RNAs (lncRNAs) in VSMC inflammation is poorly understood. Methods: Bulk RNA-seq in differentiated human VSMCs revealed a novel human-specific lncRNA called IN flammatory M K L1 I nteracting L ong N oncoding RNA ( INKILN ). INKILN expression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation and human atherosclerosis and abdominal aortic aneurysm (AAA) samples. The transcriptional regulation of INKILN was determined through luciferase reporter system and chromatin immunoprecipitation assay. Both loss- and gain-of-function approaches and multiple RNA-protein and protein-protein interaction assays were utilized to uncover the role of INKILN in VSMC proinflammatory gene program and underlying mechanisms. Bacterial Artificial Chromosome (BAC) transgenic (Tg) mice were utilized to study INKLIN expression and function in ligation injury-induced neointimal formation. Results: INKILN expression is downregulated in contractile VSMCs and induced by human atherosclerosis and abdominal aortic aneurysm. INKILN is transcriptionally activated by the p65 pathway, partially through a predicted NF-κB site within its proximal promoter. INKILN activates the proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. Mechanistically, INKILN physically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway. INKILN depletion blocks ILIß-induced nuclear localization of both p65 and MKL1. Knockdown of INKILN abolishes the physical interaction between p65 and MKL1, and the luciferase activity of an NF-κB reporter. Further, INKILN knockdown enhances MKL1 ubiquitination, likely through the reduced physical interaction with the deubiquitinating enzyme, USP10. INKILN is induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in BAC Tg mice. Conclusions: These findings elucidate an important pathway of VSMC inflammation involving an INKILN /MKL1/USP10 regulatory axis. Human BAC Tg mice offer a novel and physiologically relevant approach for investigating human-specific lncRNAs under vascular disease conditions.

Predictive role of optical coherence tomography angiography for exudation recurrence in patients with type 1 neovascular age-related macular degeneration treated with pro-re-nata protocol.

OBJECTIVES: We sought to identify the consecutive changes and predictive features for exudation recurrence in macular neovascularization (MNV) using optical coherence tomography angiography (OCTA) in type 1 neovascular age-related macular degeneration (NVAMD). METHODS: A total of 291 OCTA images in consecutive visit of 45 patients newly diagnosed with type 1 NMV and treated with three loading intravitreal anti-vascular endothelial growth factor injections (IVIs) and a pro-re-nata (PRN) therapy regimen were analysed. Quantitative features of OCTA included the MNV area, MNV length, total number of endpoints (open-ended vessels) and junctions (internal branching) using AngioTool. Two subgroups were divided according to exudation recurrence time from the third IVI (group 1: ≤3 months vs. group 2: >3 months). RESULTS: The area, length, number of total junctions, and endpoints decreased during three loading IVIs and increased at exudation recurrence (all p < 0.05). In a subgroup analysis of consecutive OCTA images, the number of total endpoints increased at two months prior to exudate recurrence in group 2 (the late recurrence group, p = 0.020). A higher total number of endpoints of MNV at baseline were found to be related with group 1 (early recurrence, p = 0.020 and 0.012 in univariate and multivariate regression analyses). CONCLUSIONS: The MNV with higher open-ended vessels at the lesion periphery at baseline might be expected to show earlier recurrence of exudation after loading IVIs. By observing the number of open-ended vessels in consecutive OCTA images, exudation recurrence could be predicted.