The Impact of Bone Marrow Stimulation on Arthroscopic Rotator Cuff Repair for Small to Large Rotator Cuff Tears: A Randomized Controlled Trial.

BACKGROUND: Bone marrow stimulation (BMS), a procedure involving the creation of multiple channels in the greater tuberosity, is often performed alongside arthroscopic rotator cuff repair (ARCR). This study evaluated the effect of BMS on clinical and structural outcomes following ARCR. METHOD: This study involved 204 patients with small, medium, and large full-thickness rotator cuff tears. In all, 103 patients who underwent BMS and ARCR made up the BMS group, while the 101 patients who only had ARCR made up the control group with randomization. Clinical and functional outcomes were assessed before and at 3 months, 6 months, 1 year, and 2 years after surgery, using parameters such as range of motion, functional scores (ASES and constant score), and clinical scores (VAS). Tendon integrity was also examined postoperatively via ultrasound at 6 months and 2 years. RESULTS: There were no significant differences between the two groups concerning range of motion, functional scores (ASES score and constant score), and clinical score (VAS) during the 2-year post-surgery period (all p>0.05). Similarly, the rotator cuff retear rate, as assessed using ultrasonographic tendon integrity checks over 2 years post-surgery, did not significantly vary between the groups (all p>0.05). CONCLUSION: There were no significant disparities in functional scores and clinical outcomes between the BMS and control groups. Further, no significant differences were observed in tendon integrity post-surgery. Therefore, the inclusion or exclusion of BMS is not anticipated to influence the postoperative outcome in ARCR for patients with small, medium, or large rotator cuff tears.

Dysfunction of NMDA receptors in neuronal models of an autism spectrum disorder patient with a DSCAM mutation and in Dscam-knockout mice.

Heterogeneity in the etiopathology of autism spectrum disorders (ASD) limits the development of generic remedies, requires individualistic and patient-specific research. Recent progress in human-induced pluripotent stem cell (iPSC) technology provides a novel platform for modeling ASDs for studying complex neuronal phenotypes. In this study, we generated telencephalic induced neuronal (iN) cells from iPSCs derived from an ASD patient with a heterozygous point mutation in the DSCAM gene. The mRNA of DSCAM and the density of DSCAM in dendrites were significantly decreased in ASD compared to control iN cells. RNA sequencing analysis revealed that several synaptic function-related genes including NMDA receptor subunits were downregulated in ASD iN cells. Moreover, NMDA receptor (R)-mediated currents were significantly reduced in ASD compared to control iN cells. Normal NMDA-R-mediated current levels were rescued by expressing wild-type DSCAM in ASD iN cells, and reduced currents were observed by truncated DSCAM expression in control iN cells. shRNA-mediated DSCAM knockdown in control iN cells resulted in the downregulation of an NMDA-R subunit, which was rescued by the overexpression of shRNA-resistant DSCAM. Furthermore, DSCAM was co-localized with NMDA-R components in the dendritic spines of iN cells whereas their co-localizations were significantly reduced in ASD iN cells. Levels of phospho-ERK1/2 were significantly lower in ASD iN cells, suggesting a potential mechanism. A neural stem cell-specific Dscam heterozygous knockout mouse model, showing deficits in social interaction and social memory with reduced NMDA-R currents. These data suggest that DSCAM mutation causes pathological symptoms of ASD by dysregulating NMDA-R function.

Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing.

Tumor metastasis remains the major cause of cancer-related death, but its molecular basis is still not well understood. Here we uncovered a splicing-mediated pathway that is essential for breast cancer metastasis. We show that the RNA-binding protein heterogeneous nuclear ribonucleoprotein M (hnRNPM) promotes breast cancer metastasis by activating the switch of alternative splicing that occurs during epithelial-mesenchymal transition (EMT). Genome-wide deep sequencing analysis suggests that hnRNPM potentiates TGFß signaling and identifies CD44 as a key downstream target of hnRNPM. hnRNPM ablation prevents TGFß-induced EMT and inhibits breast cancer metastasis in mice, whereas enforced expression of the specific CD44 standard (CD44s) splice isoform overrides the loss of hnRNPM and permits EMT and metastasis. Mechanistically, we demonstrate that the ubiquitously expressed hnRNPM acts in a mesenchymal-specific manner to precisely control CD44 splice isoform switching during EMT. This restricted cell-type activity of hnRNPM is achieved by competition with ESRP1, an epithelial splicing regulator that binds to the same cis-regulatory RNA elements as hnRNPM and is repressed during EMT. Importantly, hnRNPM is associated with aggressive breast cancer and correlates with increased CD44s in patient specimens. These findings demonstrate a novel molecular mechanism through which tumor metastasis is endowed by the hnRNPM-mediated splicing program.

SIRT1 Promotes Host Protective Immunity against Toxoplasma gondii by Controlling the FoxO-Autophagy Axis via the AMPK and PI3K/AKT Signalling Pathways.

Sirtuin 1 (SIRT1) regulates cellular processes by deacetylating non-histone targets, including transcription factors and intracellular signalling mediators; thus, its abnormal activation is closely linked to the pathophysiology of several diseases. However, its function in Toxoplasma gondii infection is unclear. We found that SIRT1 contributes to autophagy activation via the AMP-activated protein kinase (AMPK) and PI3K/AKT signalling pathways, promoting anti-Toxoplasma responses. Myeloid-specific Sirt1-/- mice exhibited an increased cyst burden in brain tissue compared to wild-type mice following infection with the avirulent ME49 strain. Consistently, the intracellular survival of T. gondii was markedly increased in Sirt1-deficient bone-marrow-derived macrophages (BMDMs). In contrast, the activation of SIRT1 by resveratrol resulted in not only the induction of autophagy but also a significantly increased anti-Toxoplasma effect. Notably, SIRT1 regulates the FoxO-autophagy axis in several human diseases. Importantly, the T. gondii-induced phosphorylation, acetylation, and cytosolic translocation of FoxO1 was enhanced in Sirt1-deficient BMDMs and the pharmacological inhibition of PI3K/AKT signalling reduced the cytosolic translocation of FoxO1 in BMDMs infected with T. gondii. Further, the CaMKK2-dependent AMPK signalling pathway is responsible for the effect of SIRT1 on the FoxO3a-autophagy axis and for its anti-Toxoplasma activity. Collectively, our findings reveal a previously unappreciated role for SIRT1 in Toxoplasma infection.

The Anti-Inflammatory Effects of Glucagon-Like Peptide Receptor Agonist Lixisenatide on the Retinal Nuclear and Nerve Fiber Layers in an Animal Model of Early Type 2 Diabetes.

This study explored the anti-inflammatory effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA), known as lixisenatide, on the eyes of early type 2 diabetic mice. Diabetic (db/db) mice were divided into three groups: GLP-1RA [lixisenatide (LIX)], insulin (INS) with controlled hyperglycemia based on the glucose concentration of lixisenatide, and diabetic control (D-CON). Nondiabetic control mice (db/dm) were also characterized for comparison. After 8 weeks of treatment, mRNA levels of inflammatory markers, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, immunohistochemical staining; Western blot of glial fibrillary acidic protein (GFAP) and thioredoxin-interacting protein; and retinal thickness were assessed in the central and peripheral neurosensory retina. LIX showed decreased immunohistochemical staining for both thioredoxin-interacting protein and GFAP in the central and peripheral neurosensory retina compared with D-CON and INS, and decreased expression of these proteins in the neurosensory retina and immunohistochemical staining in the optic nerve head for GFAP compared with D-CON. The inner nuclear layer in the peripheral retina in LIX was only thinner than those of D-CON and INS. In an early type 2 diabetic mouse model, lixisenatide treatment showed superior anti-inflammatory effects on the retina and optic nerve head independent of hyperglycemia. Thus, the neuroprotective effects of lixisenatide treatment in the peripheral inner nuclear layer should be evaluated in early type 2 diabetic retinopathy.

Comparative Transcriptome Analysis of Human Adipose-Derived Stem Cells Undergoing Osteogenesis in 2D and 3D Culture Conditions.

Human adipose-derived stem cells (hADSCs) are types of mesenchymal stem cells (MSCs) that have been used as tissue engineering models for bone, cartilage, muscle, marrow stroma, tendon, fat and other connective tissues. Tissue regeneration materials composed of hADSCs have the potential to play an important role in reconstituting damaged tissue or diseased mesenchymal tissue. In this study, we assessed and investigated the osteogenesis of hADSCs in both two-dimensional (2D) and three-dimensional (3D) culture conditions. We confirmed that the hADSCs successfully differentiated into bone tissues by ARS staining and quantitative RT-PCR. To gain insight into the detailed biological difference between the two culture conditions, we profiled the overall gene expression by analyzing the whole transcriptome sequencing data using various bioinformatic methods. We profiled the overall gene expression through RNA-Seq and further analyzed this using various bioinformatic methods. During differential gene expression testing, significant differences in the gene expressions between hADSCs cultured in 2D and 3D conditions were observed. The genes related to skeletal development, bone development and bone remodeling processes were overexpressed in the 3D culture condition as compared to the 2D culture condition. In summary, our RNA-Seq-based study proves effective in providing new insights that contribute toward achieving a genome-wide understanding of gene regulation in mesenchymal stem cell osteogenic differentiation and bone tissue regeneration within the 3D culture system.

Light Inhibits COP1-Mediated Degradation of ICE Transcription Factors to Induce Stomatal Development in Arabidopsis.

Stomata are epidermal openings that facilitate plant-atmosphere gas exchange during photosynthesis, respiration, and water evaporation. Stomatal differentiation and patterning are spatially and temporally regulated by the master regulators SPEECHLESS (SPCH), MUTE, and FAMA, which constitute a central gene regulatory network along with Inducer of CBF Expression (ICE) transcription factors for this developmental process. Stomatal development is also profoundly influenced by environmental conditions, such as light, temperature, and humidity. Light induces stomatal development, and various photoreceptors modulate this response. However, it is unknown how light is functionally linked with the master regulatory network. Here, we demonstrate that, under dark conditions, the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) degrades ICE proteins through ubiquitination pathways in leaf abaxial epidermal cells in Arabidopsis thaliana Accordingly, the ICE proteins accumulate in the nuclei of leaf abaxial epidermal cells in COP1-defective mutants, which constitutively produce stomata. Notably, light in the blue, red, and far-red wavelength ranges suppresses the COP1-mediated degradation of the ICE proteins to induce stomatal development. These observations indicate that light is directly linked with the ICE-directed signaling module, via the COP1-mediated protein surveillance system, in the modulation of stomatal development.

Connective tissue growth factor (CTGF) regulates the fusion of osteoclast precursors by inhibiting Bcl6 in periodontitis.

Connective tissue growth factor (CTGF), an extracellular matrix protein with various biological functions, is known to be upregulated in multiple chronic diseases such as liver fibrosis and congestive heart failure, but the mechanism it undertakes to cause alveolar bone loss in periodontitis remains elusive. The present study therefore investigates the pathways involving CTGF in chronic periodontitis. RNA sequencing revealed a notable increase in the expression of CTGF in chronic periodontitis tissues. Also, TRAP staining, TRAP activity and bone resorption assays showed that osteoclast formation and function is significantly facilitated in CTGF-treated bone marrow-derived macrophages (BMMs). Interestingly, western blotting and immunofluorescence staining results displayed that CTGF had little effect on the osteoclastogenic differentiation mediated by the positive regulators of osteoclastogenesis such as nuclear factor of activated T cells 1 (NFATc1). However, following results showed that both the mRNA and protein expressions of B cell lymphoma 6 (Bcl6), a transcriptional repressor of "osteoclastic" genes, were significantly downregulated by CTGF treatment. Moreover, CTGF upregulated the expressions of v-ATPase V0 subunit d2 (ATP6v0d2) and Dendritic cell-specific transmembrane protein (DC-STAMP) which are osteoclastic genes specifically required for osteoclast cell-cell fusion in pre-osteoclasts. Findings from this study suggest that CTGF promotes the fusion of pre-osteoclasts by downregulating Bcl6 and subsequently increasing the expression of DC-STAMP in periodontitis. Understanding this novel mechanism that leads to increased osteoclastogenesis in periodontitis may be employed for the development of new therapeutic targets for preventing periodontitis-associated alveolar bone resorption.

CLINICAL OUTCOME OF POLYPOIDAL CHOROIDAL VASCULOPATHY/ANEURYSMAL TYPE 1 NEOVASCULARIZATION ACCORDING TO CHOROIDAL VASCULAR MORPHOLOGY.

PURPOSE: To determine the impact of choroidal vascular morphology on clinical outcomes in patients with polypoidal choroidal vasculopathy/aneurysmal Type 1 neovascularization. METHODS: Sixty-six eyes with polypoidal choroidal vasculopathy/aneurysmal Type 1 were included. Eyes were subdivided according to the choroidal vascular morphology of the large vessel layer on optical coherence tomography en face images: focal (n = 39) versus diffuse (n = 27) pachyvessels. All patients were treated with intravitreal ranibizumab pro re nata with or without rescue photodynamic therapy. RESULTS: Best-corrected visual acuity at baseline, 6, and 12 months did not differ between groups (P = 0.394, 0.142, and 0.292). At Month 3, best-corrected visual acuity was worse, and the proportion of eyes with fluid was higher in the focal group (P = 0.016 and 0.024). Among responders, the number of injections during 12-month follow-up was higher in the focal group (P = 0.033). During the total follow-up period, photodynamic therapy was required in 15 eyes (10 focal and 5 diffuse group, P = 0.497). The injection-free period after the photodynamic therapy was shorter in the focal group (P = 0.018). CONCLUSION: The polypoidal choroidal vasculopathy/aneurysmal Type 1 eyes with a diffuse pattern of pachyvessels required fewer injections during 12-month follow-up and showed a longer injection-free period after rescue photodynamic therapy.

Partial meniscectomy provides the favorable outcomes for symptomatic medial meniscus tear with an intact posterior root.

PURPOSE: This study aimed to investigate the long-term outcomes of arthroscopic partial meniscectomy for medial meniscus tear (with intact posterior root) and to analyze the risk factors for treatment failure. METHODS: The records of 165 patients who underwent partial meniscectomy for medial meniscus tear with intact posterior root with a minimum 5-year follow-up were included. Modified Lysholm score and radiologic outcomes were compared between preoperative and latest follow-up periods. The cumulative Outerbridge grade of the medial compartment was defined as follows: 0-4, low chondral wear; 5-6, intermediate wear; or 7-8, high wear. Kaplan-Meier survival and Cox hazard regression analyses were performed to assess the survivorship after partial meniscectomy. Conversion to total knee replacement arthroplasty, high tibial osteotomy or a Lysholm score of < 65 points indicated treatment failure. RESULTS: Mean Lysholm score improved from 66.3 ± 14.2 preoperatively to 81.8 ± 17.9 at the latest follow-up (p = 0.001). The postoperative 10-year survival rate of the low chondral wear group [97% (95% confidence interval (CI) 141.7-152.6 months)] was higher than that of the intermediate [83.1% (95% CI 129.6-147.9 months)] and high wear groups [76.1% (95% CI 115.2-135.0 months)]. A 1 mm joint space width narrowing led to a 37.7% increase in the failure rate [B = - 0.473; hazard ratio, 0.623 (95% CI 0.423-0.917); p = 0.016]. The high chondral wear group showed a higher failure rate compared to the low wear group [B = 1.870; hazard ratio, 6.488 (95% CI 0.853-49.333); p = 0.041]. CONCLUSION: Partial meniscectomy offers pain relief and functional improvement for medial meniscus tear with intact posterior root. Preoperative joint space narrowing and higher chondral wear at surgery were significant risk factors of treatment failure. Partial meniscectomy should be considered as an effective treatment for irreparable medial meniscus tear with intact posterior root without joint space narrowing and chondral wear. LEVEL OF EVIDENCE: Case series, Level IV.

Valgus stress ultrasound for medial ulnar collateral ligament injuries in athletes: is ultrasound alone enough for diagnosis?

BACKGROUND: We hypothesized that valgus stress ultrasound would be useful for both identifying medial ulnar collateral ligament (MUCL) tears and assessing the severity of the tears. Hence, we performed valgus stress ultrasound of the elbow in athletes with MUCL injuries, confirmed by magnetic resonance imaging (MRI), to determine whether ultrasound can be used as a diagnostic tool. METHODS: Stress ultrasound and MRI data from 146 athletes with medial elbow pain were compared prospectively. MRI findings for MUCL injuries were classified into 3 levels as follows: low-grade partial tear (≤50%), high-grade partial tear (>50%), and complete tear. The degree of joint laxity on stress ultrasound was evaluated by measuring joint gapping after applying a 2.5-kg load to the wrist. Joint gapping was measured at 30° and 90° of elbow flexion for the dominant arm and nondominant arm, and the differences between the dominant and nondominant arms were determined. RESULTS: A higher degree of MUCL injury on MRI was associated with greater joint gapping in the medial elbow on stress ultrasound. At 30° of elbow flexion, the cutoff value for complete MUCL rupture was 0.5 mm (P < .001), with a sensitivity and specificity of 88.1% and 61.5%, respectively. At 90° of elbow flexion, the cutoff value for complete MUCL rupture was 1.0 mm (P < .001), with a sensitivity and specificity of 81.0% and 66.4%, respectively. CONCLUSION: Stress ultrasound can be used to diagnose complete MUCL tears in athletes when joint gapping is greater than 0.5 mm at 30° of elbow flexion and greater than 1 mm at 90° of elbow flexion.

Does anchor insertion angle or placement of the suture anchor affect glenoid rim fracture occurrence after arthroscopic Bankart repair?

BACKGROUND: The purposes were to compare the characteristics of 2 groups of patients who underwent revision Bankart repair with and without glenoid rim fractures and to examine risk factors for glenoid rim fractures. METHODS: We retrospectively analyzed 39 patients who needed revision surgery after arthroscopic Bankart repair and identified 19 patients with and 20 patients without glenoid rim fractures. The insertion angle of the suture anchor, anchor position on the glenoid, and demographic data were compared between the groups. RESULTS: The mean anchor insertion angles in the glenoid fracture group (group F) at the 2-, 3-, 4-, and 5-o'clock positions were 64°, 58°, 55°, and 55°, respectively; those in the no-fracture group (group R) were 60°, 63°, 60°, and 55°, respectively (P = .630, P = .207, P = .166, and P = .976, respectively). At the 5-o'clock position, anchors were fixed to the glenoid face in 13 cases in group F and in 3 cases in group R (P = .040). Although age (P = .529) and sex (P = 1.0) did not differ between the groups, elite and professional athletes had a significantly higher incidence of glenoid rim fractures (P = .009). CONCLUSION: The anchor insertion angle did not affect glenoid rim fracture occurrence after arthroscopic Bankart repair. However, the placement of the suture anchor at the 5-o'clock position on the glenoid face could increase the risk of glenoid rim fracture after trauma. Athletes were more likely to have glenoid rim fractures owing to major trauma after arthroscopic Bankart repair.

Evaluation of Salmon, Tuna, and Beef Freshness Using a Portable Spectrometer.

There has been strong demand for the development of an accurate but simple method to assess the freshness of food. In this study, we demonstrated a system to determine food freshness by analyzing the spectral response from a portable visible/near-infrared (VIS/NIR) spectrometer using the Convolutional Neural Network (CNN)-based machine learning algorithm. Spectral response data from salmon, tuna, and beef incubated at 25 °C were obtained every minute for 30 h and then categorized into three states of "fresh", "likely spoiled", and "spoiled" based on time and pH. Using the obtained spectral data, a CNN-based machine learning algorithm was built to evaluate the freshness of experimental objects. In addition, a CNN-based machine learning algorithm with a shift-invariant feature can minimize the effect of the variation caused using multiple devices in a real environment. The accuracy of the obtained machine learning model based on the spectral data in predicting the freshness was approximately 85% for salmon, 88% for tuna, and 92% for beef. Therefore, our study demonstrates the practicality of a portable spectrometer in food freshness assessment.

Differential gene expression profiles of human periodontal ligament cells preserved in Hank's balanced salt solution and milk.

BACKGROUND/AIM: Various types of storage media have been investigated to preserve avulsed teeth. However, the efficacies of storage media mainly focus on the aspect of cell viability. The aim of this study was to evaluate and compare the gene expression profiles of human periodontal ligament cells preserved in Hank's balanced salt solution (HBSS) and milk over different storage durations. MATERIAL AND METHODS: Human periodontal ligament cells were cultured and preserved in HBSS and milk for 3 and 6 hours. Next, total RNA was isolated. QuantSeq 3' mRNA-Sequencing was used to examine differences in gene expression in HBSS- and milk-grown periodontal ligament cells. Bioinformatics analysis was also performed to predict the function of the differentially expressed genes. RESULTS: The number of differentially expressed genes shared among all groups was 101. In gene set enrichment analysis, the shared differentially expressed genes in HBSS and milk were associated with the TNF-α signaling pathway (P = 1.07E-7 ). Seven hallmark gene sets were also identified in HBSS. Moreover, hallmark gene sets associated with hypoxia (P = 7.26E-5 ) and apoptosis (P = 4.06E-4 ) were identified in HBSS. In milk, 10 hallmark gene sets along with gene sets for inflammatory response (P = 6.87E-3 ) were identified. CONCLUSIONS: Compared to those in milk, genes in HBSS were differentially expressed with increasing storage duration, suggesting that diverse and different gene expression may be involved in HBSS and milk. However, a more detailed functional analysis of these differentially expressed genes in storage solutions should be performed in the future.

Three-Dimensional Analysis of Scapular Kinematics During Arm Elevation in Baseball Players With Scapular Dyskinesis: Comparison of Dominant and Nondominant Arms.

BACKGROUND: The knowledge of 3-dimensional scapular kinematics is essential for understanding the pathological lesions of the shoulder and elbow in throwing athletes. Many studies about alterations of the resting scapular position, dynamic scapular motion, or scapular dyskinesis (SD) have been conducted, yet none of them have identified a consistent pattern of altered scapular kinematics in throwing athletes. Hypothesis/Purpose: To analyze the 3-dimensional scapular kinematics of dominant and nondominant arms in baseball players with a pathological condition of the shoulder or elbow. STUDY DESIGN: Cross-sectional study. METHODS: Bilateral scapular positions, consisting of upward rotation (UR), superior translation (ST), internal rotation (IR), protraction (PRO), and anterior tilting (AT) with an arm at rest and at 150° forward elevation, were measured among 319 baseball players with SD using 3-dimensional computed tomography. Angular values of scapula were compared between dominant and nondominant arms with statistical analysis. LEVEL OF EVIDENCE: Level III, diagnostic study. RESULTS: The scapular position of dominant arms showed significantly more AT, less ST at rest and more UR and IR and less ST, PRO, and AT at 150° full forward elevation compared with the nondominant arms. The magnitude of mean change of UR, IR, PRO, and AT during arm elevation increased significantly between the paired arms (P value: UR, ST, PRO, and AT: <.001 and IR: .001). CONCLUSION: When compared with the nondominant arms, UR, AT, and PRO with the arm at 150° forward elevation of dominant symptomatic arms in baseball players tilted toward positive compensation, whereas IR altered toward negative decompensation. In addition, the angular increment of the scapula increased significantly in dominant symptomatic arms compared with the nondominant arms.

Remote Memory and Cortical Synaptic Plasticity Require Neuronal CCCTC-Binding Factor (CTCF).

The molecular mechanism of long-term memory has been extensively studied in the context of the hippocampus-dependent recent memory examined within several days. However, months-old remote memory maintained in the cortex for long-term has not been investigated much at the molecular level yet. Various epigenetic mechanisms are known to be important for long-term memory, but how the 3D chromatin architecture and its regulator molecules contribute to neuronal plasticity and systems consolidation is still largely unknown. CCCTC-binding factor (CTCF) is an 11-zinc finger protein well known for its role as a genome architecture molecule. Male conditional knock-out mice in which CTCF is lost in excitatory neurons during adulthood showed normal recent memory in the contextual fear conditioning and spatial water maze tasks. However, they showed remarkable impairments in remote memory in both tasks. Underlying the remote memory-specific phenotypes, we observed that female CTCF conditional knock-out mice exhibit disrupted cortical LTP, but not hippocampal LTP. Similarly, we observed that CTCF deletion in inhibitory neurons caused partial impairment of remote memory. Through RNA sequencing, we observed that CTCF knockdown in cortical neuron culture caused altered expression of genes that are highly involved in cell adhesion, synaptic plasticity, and memory. These results suggest that remote memory storage in the cortex requires CTCF-mediated gene regulation in neurons, whereas recent memory formation in the hippocampus does not.SIGNIFICANCE STATEMENT CCCTC-binding factor (CTCF) is a well-known 3D genome architectural protein that regulates gene expression. Here, we use two different CTCF conditional knock-out mouse lines and reveal, for the first time, that CTCF is critically involved in the regulation of remote memory. We also show that CTCF is necessary for appropriate expression of genes, many of which we found to be involved in the learning- and memory-related processes. Our study provides behavioral and physiological evidence for the involvement of CTCF-mediated gene regulation in the remote long-term memory and elucidates our understanding of systems consolidation mechanisms.

Retinoschisis in eyes with pachychoroid and retinal pigment epithelial atrophy.

PURPOSE: To describe the clinical characteristics and courses for eyes with retinoschisis associated with pachychoroid. METHODS: A retrospective interventional case series study. Twenty-one eyes (18 patients) with pachychoroid that showed retinoschisis without evidence of neovascularization that had been followed for 1 year were included. Multimodal imaging, including fundus photography, spectral-domain optical coherence tomography (OCT) with an enhanced depth protocol, fluorescein angiography (FA), and indocyanine green angiography (ICGA), was provided and treatment outcomes were analyzed. RESULTS: Focal RPE atrophy was present below or adjacent to the schisis in all eyes, and the mean atrophy area was 1.38 ± 1.37 mm2. Intraretinal fluids of the schisis originated from the atrophy area and involved the retinal layer which was correlated with the extent of outer retinal defect. Dilated Haller layer vessel and choroidal vascular hyperpermeability were observed under the area with atrophy in all eyes. After 1 year of treatment, 11 eyes (52%) still had fluid and 7 of them had fluid at the macula. Nonetheless, the mean central macular thickness decreased (144.4 to 121.8, P < 0.001), visual acuity improved (0.65 to 0.47, P = 0.026), and subfoveal choroidal thickness decreased (442.2 µm to 394.9 µm, P < 0.001). CONCLUSION: Atrophy of RPE can cause retinoschisis in eyes with pachychoroid. The intraretinal fluid that originated from underlying choroid and choroidal thickness decreased as intraretinal fluid diminished.

CHOROIDAL MORPHOLOGY IN EYES WITH PERIPAPILLARY POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: This study analyzes a subset of patients with peripapillary polypoidal choroidal vasculopathy (PCV) to determine whether quantifiable pachychoroid features colocalize with disease foci. METHODS: Patients with PCV diagnosed by indocyanine green angiography were identified for the analysis of medical records and multimodal imaging and classified as having peripapillary or macular PCV. The ratio of Haller layer thickness to total choroidal thickness was calculated at the fovea and at the site of dilated Haller vessels that showed spatial correlation with the origin of neovascularization. Choroidal thickness was measured horizontally across the fovea and circumferentially around the temporal side of the disk to study its relationship to neovascularization. RESULTS: Three hundred and fourteen eyes of 299 patients with PCV were identified, of which 17 eyes (5%) had peripapillary disease. Although eyes with peripapillary PCV exhibited thinner subfoveal choroids than those with macular PCV, at the extrafoveal disease foci, choroidal thickness, Haller's layer thickness, and its ratio to total choroidal thickness were relatively high. CONCLUSION: Quantitative indices of choroidal structure previously identified in macular PCV performed consistently when applied to a peripapillary PCV cohort, thus supporting the hypothesis that inner choroidal thinning and Haller vessel enlargement are mechanistically relevant to these related entities.

FOCAL DISRUPTIONS IN ELLIPSOID ZONE AND INTERDIGITATION ZONE ON SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN PACHYCHOROID PIGMENT EPITHELIOPATHY.

PURPOSE: To describe a distinctive focal disruption of the ellipsoid zone (EZ)/interdigitation zone (IZ) determined by spectral-domain optical coherence tomography in eyes with pachychoroid pigment epitheliopathy. METHODS: Twenty patients with focal EZ/IZ disruptions associated with pachychoroid without history or findings indicative of subretinal fluid were evaluated. Detailed clinical/imaging characteristics and their longitudinal changes were evaluated. RESULTS: A total of 27 lesions from 21 eyes were included. The mean subfoveal choroidal thickness was 450 µm. In six of seven eyes with previous imaging data to compare, characteristic drusenoid lesions associated with thick choroid preceded focal EZ/IZ disruptions at the corresponding sites. Dilated outer choroidal vessels were noted beneath the focal EZ/IZ disruption in 24 lesions (88.9%), with attenuation of choriocapillaris in 18 lesions (66.7%). The external limiting membrane was intact in all lesions. All except three eyes did not show morphologic changes, and mean visual acuity was maintained (Snellen equivalent, 20/25) during a mean follow-up period of 20 months. CONCLUSION: Focal disruptions of the EZ/IZ band can develop in pachychoroid eyes in the absence of subretinal fluid, with a stable clinical course, and possibly as a result of regression of drusenoid lesions. This may represent an atrophic form of pachychoroid manifestation.

Rapid progression of cataract to mature stage after intravitreal dexamethasone implant injection: a case report.

BACKGROUND: This study aims to report a case of rapid progression of cataract to mature stage after intravitreal dexamethasone implantation for macular edema due to branch retinal vein occlusion. CASE PRESENTATION: A 59-year-old Korean male with complaints of sudden metamorphopsia and reduced visual acuity for three days in the left eye was referred to our clinic. Ophthalmological investigations included fundus photography, fluorescein angiography, and optical coherence tomography. In the left eye, branch retinal vein occlusion with macular edema was observed. We performed intravitreal dexamethasone implantation in the left eye three times within a period of one year. One week after the third intravitreal dexamethasone implantation, grade 1 posterior subcapsular opacity and raised intraocular pressure were observed in the left eye. Three weeks later, mature cataract was observed in the left eye. We performed cataract surgery along with intravitreal ranibizumab injection in the left eye. The procedure was uneventful, and the visual acuity improved postoperatively. CONCLUSIONS: Posterior subcapsular cataract developed due to intravitreal dexamethasone implantation can progress rapidly to mature stage. Therefore, short-term follow-up examinations may be necessary for early diagnosis and treatment of this complication.