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Abstract Background Implicit learning was reported to be intact in schizophrenia using artificial grammar learning. However, emerging evidence indicates that artificial grammar learning is not a unitary process. The authors used dual coding stimuli and schizophrenia clinical symptom dimensions to re-evaluate the effect of schizophrenia on various components of artificial grammar learning. Methods Letter string and color pattern artificial grammar learning performances were compared between 63 schizophrenic patients and 27 comparison subjects. Four symptom dimensions derived from a Chinese Positive and Negative Symptom Scale ratings were correlated with patients' artificial grammar implicit learning performances along the two stimulus dimensions. Patients' explicit memory performances were assessed by verbal paired associates and visual reproduction subtests of the Wechsler Memory Scales Revised Version to provide a contrast to their implicit memory function. Results Schizophrenia severely hindered color pattern artificial grammar learning while the disease affected lexical string artificial grammar learning to a lesser degree after correcting the influences from age, education and the performance of explicit memory function of both verbal and visual modalities. Both learning performances correlated significantly with the severity of patients' schizophrenic clinical symptom dimensions that reflect poor abstract thinking, disorganized thinking, and stereotyped thinking. Conclusion The results of this study suggested that schizophrenia affects various mechanisms of artificial grammar learning differently. Implicit learning, knowledge acquisition in the absence of conscious awareness, is not entirely intact in patients with schizophrenia. Schizophrenia affects implicit learning through an impairment of the ability of making abstractions from rules and at least in part decreasing the capacity for perceptual learning.

Background: Despite guidelines from the American Academy of Pediatrics (AAP), many pediatric practices still do not have standardized screening processes in place to identify children with developmental delays. From April 2014 to April 2017, six federally qualified health center (FQHC) sites in Northern California implemented an intervention to increase (a) standardized developmental screening at recommended intervals and (b) follow-up care and support for early intervention services., Method: The intervention aimed to optimize each site's screening processes, supported by an automated electronic tablet-based system. To improve follow-up support, social workers were hired to conduct follow-up clinical assessments, provide psychosocial education and treatment, provide referrals and case management support, and collaborate with service partners. We analyze operational and implementation data to characterize site adoption, patient reach, implementation processes, and intervention effectiveness., Results: During the intervention's final year, when tablet-based screening was adopted, the sites screened an estimated 6,550 children ages 0-18 at 23 intervals in three domains (developmental, autism, and psychosocial/behavioral), compared to a baseline where they screened ages 0-3 at four intervals in one domain. Screening rates increased from 65.3% to 75.5% after automation was extended from the first to the second site, then to 91.8% after automation was expanded to the remaining sites. Follow-up visit rates ranged between 74% and 88%., Conclusions: Implementation of a multicomponent developmental and behavioral health screening and follow-up care intervention enabled FQHC sites to meet AAP recommendations and provide follow-up support. Disseminating the intervention may support population-level improvement in early detection and intervention for developmental delays and behavioral health concerns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: MicroRNAs (miRNAs) have been shown to be altered in both CVD and T2DM and can have an application as diagnostic and prognostic biomarkers. miRNAs are released into circulation when the cardiomyocyte is subjected to injury and damage., Objectives: Measuring circulating miRNA levels in human plasma may be of great potential use for measuring the extent of damage to cardiomyocytes and response to exercise. This review is aimed to highlight the potential application of miRNAs as biomarkers of CVD progression in T2DM, and the impact of exercise on recovery., Methods: The review aims to examine whether the health improvements following exercise in T2DM patients are reflective of changes in expression of plasma miRNAs. For this purpose, studies were identified from the literature that have established a correlation between diabetes, disease progression and plasma miRNA levels. We also reviewed studies which looked at the effect of exercise on plasma miRNA levels., Results: The review identified miRNA signatures that are affected by T2DM and DHD and a subset of these miRNAs that are also affected by different types of exercise. This approach helped us to identify those miRNAs whose expression and function can be altered by regular bouts of exercise., Conclusions: miRNAs identified as part of this review can serve as tools to monitor the cardio-protective, anti-inflammatory and metabolic effects of exercise in people suffering from T2DM. Future research should focus on regulation of these miRNAs in T2DM and how they can be altered by appropriate exercise interventions., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01066-4., Competing Interests: Conflict of interestThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2022.)

New Findings: What is the central question of this study? This is the first study to assess the day-to-day reliability of passive leg movement-induced hyperaemia (PLM-H), an index of lower-limb microvascular function, in young, healthy women. What is the main finding and its importance? Passive leg movement-induced hyperaemia demonstrated good day-to-day reliability, comparable to other common indices of endothelial function, supporting the use of PLM-H to assess lower-limb microvascular function in women., Abstract: Passive leg movement-elicited hyperaemia (PLM-H) provides an index of lower-limb microvascular function. However, there is currently limited information regarding the reliability of PLM-H and no reliability information specific to women. The purpose of this study was to determine the reliability of PLM-H in women on two separate days. Seventeen young, healthy women [22 ± 3 years old (mean ± SD)] participated in two identical visits including three trials of PLM. Using duplex ultrasound, PLM-H was characterized by six indices: peak leg blood flow (LBF) and vascular conductance (LVC), peak change above baseline (Δpeak) for LBF and LVC, and area under the curve above baseline (AUC) during the first 60 s of PLM for LBF and LVC. The results demonstrated good day-to-day reliability of PLM-H characterized as peak LBF [r = 0.84, P < 0.001; intraclass correlation coefficient (ICC) = 0.84; coefficient of variation (CV) = 13.2%], peak LVC (r = 0.82, P < 0.001; ICC = 0.79; CV = 14.4%), Δpeak LBF (r = 0.83, P < 0.001; ICC = 0.82; CV = 17.8%) and Δpeak LVC (r = 0.83, P < 0.001; ICC = 0.80; CV = 16.5%). Characterization of PLM as AUC demonstrated moderate day-to-day reliability: AUC LBF (r = 0.71, P < 0.05; ICC = 0.70; CV = 31.2%) and AUC LVC (r = 0.78, P < 0.001; ICC = 0.74; CV = 27.1%). In conclusion, this study demonstrates that PLM-H has good reliability as an index of microvascular function; however, characterization of PLM-H as peak, Δpeak LBF and LVC is more reliable than AUC., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.)

Background Malignant gynecological tumors are the main cause of cancer-related deaths in women worldwide and include uterine carcinosarcomas, endometrial cancer, cervical cancer, ovarian cancer, and breast cancer. This study aims to determine the association between immune cell infiltration and malignant gynecological tumors and construct signatures for diagnosis and prognosis. Methods We acquired malignant gynecological tumor RNA-seq transcriptome data from the TCGA database. Next, the "CIBERSORT" algorithm calculated the infiltration of 22 immune cells in malignant gynecological tumors. To construct diagnosis and prognosis signatures, step-wise regression and LASSO analyses were applied, and nomogram and immune subtypes were further identified. Results Notably, Immune cell infiltration plays a significant role in tumorigenesis and development. There are obvious differences in the distribution of immune cells in normal, and tumor tissues. Resting NK cells, M0 Macrophages, and M1 Macrophages participated in the construction of the diagnostic model, with an AUC value of 0.898. LASSO analyses identified a risk signature including T cells CD8, activated NK cells, Monocytes, M2 Macrophages, resting Mast cells, and Neutrophils, proving the prognostic value for the risk signature. We identified two subtypes according to consensus clustering, where immune subtype 3 presented the highest risk. Conclusion We identified diagnostic and prognostic signatures based on immune cell infiltration. Thus, this study provided a strong basis for the early diagnosis and effective treatment of malignant gynecological tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Feng, Jiang, Xu, Li and Liu.)

New Findings: What is the central question of this study? The purpose of this study was to determine intra-individual reproducibility of follicular phase changes in endothelial function (flow-mediated dilatation) over two menstrual cycles in healthy, premenopausal women. What is the main finding and its importance? Phase changes in endothelial function were not consistent at the individual level across two menstrual cycles, which challenges the utility of interpreting individual responses over one cycle., Abstract: Evidence regarding the impact of menstrual phase on endothelial function is conflicting, and studies to date have examined responses only over a single cycle. It is unknown whether the observed inter-individual variability of phase changes in endothelial function reflects stable, inter-individual differences in responses to oestrogen (E 2 ; a primary female sex hormone). The purpose of this study was to examine changes in endothelial function from the early follicular (EF; low-E 2 ) phase to the late follicular (LF; high-E 2 ) phase over two consecutive cycles. Fourteen healthy, regularly menstruating women [22 ± 3 years of age (mean ± SD)] participated in four visits (EF Visit 1 , LF Visit 2 , EF Visit 3 and LF Visit 4 ) over two cycles. Ovulation testing was used to determine the time between the LF visit and ovulation. During each visit, endothelial function [brachial artery flow-mediated dilatation (FMD)], E 2 and progesterone were assessed. At the group level, there was no impact of phase or cycle on FMD (P = 0.48 and P = 0.65, respectively). The phase change in FMD in cycle 1 did not predict the phase change in cycle 2 (r = 0.03, P = 0.92). Using threshold-based classification (2 × typical error threshold), four of 14 participants (29%) exhibited directionally consistent phase changes in FMD across cycles. Oestrogen was not correlated between cycles, and this might have contributed to variability in the FMD response. The intra-individual variability in follicular fluctuation in FMD between menstrual cycles challenges the utility of interpreting individual responses to phase over a single menstrual cycle., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.)

Purpose: To evaluate the efficacy and adverse effects of using low-dose intravitreal triamcinolone acetonide (IVTA) to preserve vision in polypoidal choroidal vasculopathy (PCV) eyes., Methods: This retrospective chart review study examined 8 eyes of 7 PCV patients, for whom verteporfin photodynamic therapy (vPDT) or antivascular endothelial growth factor (VEGF) therapy was not affordable/available and also with intolerable risk because of underlying cardiovascular and/or cerebrovascular ischemia. Low-dose IVTA (1 mg/0.025 mL) monotherapy was administered and repeated every 4 weeks if intraretinal edema or subretinal fluid persisted., Results: The median follow-up time was 26.4 months. Three eyes (3/8) maintained their initial best-corrected visual acuity and 4 eyes (4/8) exhibited improvement, whereas 1 eye (1/8) sustained some loss. The mean injection number per month was 0.7 for the first 6 months, after which it decreased to 0.4. In regard to adverse effects, intraocular pressure (IOP) of more than 21 mmHg was noted as persisting for a few weeks in 4 eyes and that of more than 30 mmHg was noted once in 1 eye. The increased IOP was adequately controlled by using IOP-lowering agents. Two initially phakic eyes each underwent cataract surgery in the 12th and 14th months after treatment., Conclusions: Low-dose IVTA therapy may be valuable for preserving the vision of PCV patients, while vPDT or anti-VEGF is not affordable/available or of those with underlying diseases for whom anti-VEGF therapy is with intolerable risk.

Ovarian cancer is characterized by a rapid intraperitoneal spread combination with ascites accumulation. However, the exact mechanisms for ovarian cancer intraperitoneal dissemination remain unknown. Visfatin has recently been established as a novel adipokine and its serum level is increased in various cancers. Here, we identified that the elevated level of visfatin in ascites was associated with ovarian cancer intraperitoneal dissemination. Using the transwell cell migration assay and the wound-healing assay, we found that ascites-derived visfatin could promote migration of Caov-3 cells. Meanwhile, visfatin could induce the aggregation of actin stress fibers and the formation of lamellipodia and filopodia in Caov-3 cells, concomitant with a shift of G-actin to F-actin. Inhibition of actin polymerization with cytochalasin D obviously abolished the effects of visfatin on the migration of Caov-3 cells. Further results showed that visfatin triggered Rho activation and its downstream cofilin phosphorylation in a time-dependent manner, which led to actin polymerization. More importantly, visfatin-induced Caov-3 cell migration was effectively blocked by C3 exoenzyme and Y27632, Rho, and ROCK inhibitor, respectively. Thus, our study showed that ascites-derived visfatin promoted migration of ovarian cancer cells through Rho/ROCK signaling-mediated actin polymerization, which was required for ovarian cancer intraperitoneal dissemination. These findings offered a novel molecular mechanism responsible for ovarian cancer intraperitoneal dissemination, which might be a potential target for ovarian cancer management.

This study aimed to induce malignant transformation of endometriosis in Sprague-Dawley rats by hyperestrogenemia and type II diabetes and evaluate its similarity with human disease in biological features. Rats with surgically induced endometriosis were randomized into two groups: those treated with estradiol (5 mg/kg three times/week after surgery), streptozotocin (25 mg/kg, 1 month after surgery), and high carbohydrate-and-fat feed (Es group); and those treated with placebo saline and standard feed (control group). All rats were randomly killed 2, 4, or 8 months after surgery. The endometriosis lesions and the corresponding eutopic endometria were subjected to morphological evaluation, TUNEL, and immunohistochemical analysis for the expressions of proliferating cell nuclear antigen, phosphatase and tensin homolog, phosphorylated protein kinase B, and phosphorylated mammalian target of rapamycin proteins. In the Es group, three cases (6.0%) of endometriosis showed atypical hyperplasia accompanied by simple hyperplastic eutopic endometria, and two cases (4.0%) of endometriosis showed endometrioid carcinoma accompanied by atypical hyperplastic eutopic endometria. In the Es group, the activity of organelles and the expressions of proliferating cell nuclear antigen, phosphorylated protein kinase B, and phosphorylated mammalian target of rapamycin increased, and the level of phosphatase and tensin homolog and TUNEL positivity decreased progressively in the order of endometriosis, atypical endometriosis, and malignant endometriosis. The same tendency was found in the corresponding eutopic endometria. The induced malignant endometriosis showed similarities with human disease in the pathological process and histomorphological and molecular biological features. The method is feasible. The malignant transformations of endometriosis and eutopic endometria may have correlations and similarities, but the former may suffer a higher risk of canceration., (© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

The aim of this study was to report the successful treatment of choroidal neovascularization (CNV) in pathologic myopia (PM) with a posterior sub-Tenon bevacizumab (PSTB; Avastin(®)) injection. The study was a prospective case series including nine eyes of eight patients with PM and CNV. All nine eyes were injected with PSTB (12.5 mg/0.5 ml). Treatment effectiveness was evaluated with optical coherence tomography (OCT). If intraretinal edema or subretinal fluid were detected, injections were repeated after 2 weeks. The main outcome measures were logMAR best-corrected visual acuity (BCVA) and central foveal thickness. The mean follow-up time was 77.56 weeks. BCVA improved by a mean of -0.38 logMAR (>3 lines). The average reduction in absolute central foveal thickness was 25.67 μm. OCT revealed marked CNV volume reduction and fluid-free status in seven eyes. The fluid-free status remained for ≥ 1 year in these eyes. Fluorescein angiography revealed CNV resolution in three eyes. Corneal stromal penetration of subconjunctival bevacizumab has been demonstrated in animal studies. PSTB may be an equally effective, yet less invasive alternative for the treatment of myopic CNV.

Objective: To evaluate the transvaginal approach for exogenous cesarean scar ectopic pregnancy (CSEP) lesion resection, according to our experience., Design: Retrospective study., Setting: University hospital., Patient(s): Twenty-three patients with confirmed exogenous CSEP treated with transvaginal resection of the lesions at the Shengjing Hospital of China Medical University., Intervention(s): Lesion resection by the transvaginal approach., Main Outcome Measure(s): Surgery time, intraoperative blood loss, postoperative drainage volume, and average days of postoperative hospitalization were compared between the transvaginal procedure group and the transabdominal procedure group., Result(s): Significant differences were found. No significant differences were found in the drop of serum hCG level after 48 hours and the postoperative recurrence rate between the two groups. The rate of successful treatment was 96%., Conclusion(s): The transvaginal approach for exogenous CSEP lesion resection possesses many advantages. In the hands of a skilled surgeon it can readily address the treatment problems posed by an exogenous CSEP without imposing an increase in surgical risk or technical difficulty., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Bevacizumab is a potent recombinant humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF). The purpose of this study was to evaluate the therapeutic effect of subconjunctival injection of bevacizumab on corneal neovascularization (NV) in different rabbit models., Methods: Several rabbit models of corneal NV were used, including (1) a corneal micropocket assay with VEGF pellet, (2) a corneal micropocket assay with basic fibroblast growth factor (b-FGF) pellets, (3) mechanical limbal injury-induced corneal NV, and (4) an alkali-induced model of corneal NV. Subconjunctival injections of bevacizumab (0.25-2.5 mg) were applied twice per week for 2 to 8 weeks. Digital photographs of the cornea were analyzed to determine the length of corneal NV and the area of cornea covered by NV as a percentage of the total corneal area. Immunohistochemical staining with anti-human IgG antibody labeled with Cy3 was used to determine the detection of intracorneal distribution of bevacizumab after injection., Results: Subconjunctival injection of bevacizumab caused significant inhibition of corneal NV formation as measured by length or surface area in all animal models (P<0.05). No significant ocular complications were found. Staining of bevacizumab was found in the corneal stroma for 3 to at least 14 days in the different rabbit models., Conclusions: Subconjunctival injection of bevacizumab is effective in inhibiting corneal NV in several rabbit models. Bevacizumab may diffuse into the corneal stroma and persist for a few days after injection. It may be useful in preventing corneal NV in the acute phase of various kinds of corneal inflammation.

Background and Objective: To evaluate the efficacy of intraocular gas tamponade and macular grid laser photocoagulation to manage recurrent macular hole retinal detachment after an initially successful reattachment by gas tamponade in highly myopic eyes., Patients and Methods: Five patients with high myopia and macular hole retinal detachment were treated by gas tamponade at the initial operation. Gas tamponade and macular grid laser photocoagulation were performed to treat recurrent retinal detachment at the second surgery. Demographic information, anatomic reattachment of the retina, and final visual acuity were studied., Results: Final successful retinal reattachment at the end of follow-up was obtained in all five eyes. Improvement of postoperative visual acuity with respect to preoperative visual acuity was observed in all patients., Conclusion: Intraocular gas tamponade and grid laser photocoagulation in the macula for the management of recurrent macular hole retinal detachment provides good long-term anatomic success and acceptable functional results.

Oxygenation changes in the left prefrontal cortex during language processing were assessed with near-infrared spectroscopy (NIRS). Oxyhemoglobin and deoxyhemoglobin concentrations at the Fp1 site during 5 min of resting with eyes closed (control), followed by 5 min of reading aloud, were monitored. A statistically significant change in the oxyhemoglobin concentration was observed by NIRS in all the subjects after execution of the experimental task. The observations of hyper-oxygenation as well as hypo-oxygenation in the present investigation extend past studies and suggest a complex phenomenon of activation that may be the result of a vascular steal mechanism, attenuated activation baselines, or active cortical deactivation.

Aims: To study the pattern of residual undetached cortical vitreous (RCV) after posterior vitreous detachment (PVD) in eyes with rhegmatogenous retinal detachment (RRD) and to examine the relationship between RCV and the development of epiretinal membrane (ERM)., Methods: A prospective study was conducted in 33 consecutive patients with clinically evident PVD who underwent pars plana vitrectomy for RRD. During vitrectomy, triamcinolone acetonide (0.2 cm(3), 10 mg/cm(3)) was applied to stain the RCV. The pattern of the staining were recorded. The formation of postoperative ERM was correlated with the staining pattern of RCV. Each case was followed for at least 6 months., Results: In all, 23 of the 33 patients had RCV of variable size, with a single stain patch observed in 13 patients and multiple patches in seven patients. Large circumferential areas of staining at the mid-periphery were noted in three patients. A total of 10 cases had staining over the fovea and five patients had staining over the disc. ERM developed in seven patients during follow-up. None corresponded to RCV., Conclusion: RCV is common in eyes with PVD and RRD. The macula and disc area are the most frequent locations for these vitreous islands. The relationship between RCV and ERM remains to be investigated.

Manipulation of perceptions is a remarkable human capability in a wide variety of physical and mental tasks under fuzzy or uncertain surroundings. Possibilistic reasoning can be treated as a mechanism that mimics human inference mechanisms with uncertain information. Petri nets are a graphical and mathematical modeling tool with powerful modeling and analytical ability. The focus of this paper is on the integration of Petri nets with possibilistic reasoning to reap the benefits of both formalisms. This integration leads to a possibilistic Petri nets model (PPN) with the following features. A possibilistic token carries information to describe an object and its corresponding possibility and necessity measures. Possibilistic transitions are classified into four types: inference transitions, duplication transitions, aggregation transitions, and aggregation-duplication transitions. A reasoning algorithm, based on possibilistic Petri nets, is also presented to improve the efficiency of possibilistic reasoning and an example related to diagnosis of cracks in reinforced concrete structures is used to illustrate the proposed approach.

In this paper, a fuzzy Petri net approach to modeling fuzzy rule-based reasoning is proposed to bring together the possibilistic entailment and the fuzzy reasoning to handle uncertain and imprecise information. The three key components in our fuzzy rule-based reasoning-fuzzy propositions, truth-qualified fuzzy rules, and truth-qualified fuzzy facts-can be formulated as fuzzy places, uncertain transitions, and uncertain fuzzy tokens, respectively. Four types of uncertain transitions-inference, aggregation, duplication, and aggregation-duplication transitions-are introduced to fulfil the mechanism of fuzzy rule-based reasoning. A framework of integrated expert systems based on our fuzzy Petri net, called fuzzy Petri net-based expert system (FPNES), is implemented in Java. Major features of FPNES include knowledge representation through the use of hierarchical fuzzy Petri nets, a reasoning mechanism based on fuzzy Petri nets, and transformation of modularized fuzzy rule bases into hierarchical fuzzy Petri nets. An application to the damage assessment of the Da-Shi bridge in Taiwan is used as an illustrative example of FPNES.

We propose novel discrete cosine transform (DCT) pseudophase techniques to estimate shift/delay between two one-dimensional(1-D) signals directly from their DCT coefficients by computing the pseudophase shift hidden in DCT and then employing the sinusoidal orthogonal principles, applicable to signal delay estimation remote sensing. Under the two-dimensional (2-D) translational motion model, we further extend the pseudophase techniques to the DCT-based motion estimation (DXT-ME) algorithm for 2-D signals/images. The DXT-ME algorithm has certain advantages over the commonly used full search block-matching approach (BKM-ME) for application to video coding despite certain limitations. In addition to its robustness in a noisy environment and low computational complexity, O(M(2)) for an MxM search range in comparison to the O(N(2) . M(2)) complexity of BKM-ME for an NxN block, its ability to estimate motion completely in DCT domain makes possible the fully DCT-based motion-compensated video coder structure, which has only one major component in the feedback loop instead of three as in the conventional hybrid video coder design, and thus results in a higher system throughput. Furthermore, combination of the DCT and motion estimation units can provide space for further optimization of the overall coder. In addition, the DXT-ME algorithm has solely highly parallel local operations and this property makes feasible parallel implementation suitable for very large scale integration (VLSI) design. Simulation on a number of video sequences is presented with comparison to BKM-ME and other fast block search algorithms for video coding applications even though DXT-ME is completely different from any block search algorithms.

We develop an algorithm to reconstruct the wavelet coefficients of an image from the Radon transform data. The proposed method uses the properties of wavelets to localize the Radon transform and can be used to reconstruct a local region of the cross section of a body, using almost completely local data that significantly reduces the amount of exposure and computations in X-ray tomography. The property that distinguishes our algorithm from the previous algorithms is based on the observation that for some wavelet bases with sufficiently many vanishing moments, the ramp-filtered version of the scaling function as well as the wavelet function has extremely rapid decay. We show that the variance of the elements of the null-space is negligible in the locally reconstructed image. Also, we find an upper bound for the reconstruction error in terms of the amount of data used in the algorithm. To reconstruct a local region 16 pixels in radius in a 256x256 image, we require 22% of full exposure data.

Cell-mediated tractional retinal detachment (TRD) is the end result of various intraocular proliferative disorders. Interactions between cells and extracellular matrix via cellular surface receptors, integrins, play an important role. Anti-adhesion therapy has been suggested as a promising way to treat the integrin-dependent pathological events. We tested three synthetic peptides, Gly-Arg-Gly-Asp-Ser (GRGDS), derived from the fibronectin receptor binding domain; Try-Ile-Gly-Ser-Arg (YIGSR), from the laminin receptor binding domain, and Ala-Asp-Gly-Glu-Ala (ADGEA), from the collagen receptor binding domain, to evaluate their inhibitory effect on cell-mediated matrix attachment and vitreous contraction in vitro, and on cell-induced TRD in rabbit eyes in vivo. Indirect immunofluorescent stain demonstrated both bovine retinal pigment epithelial (RPE) cells and rabbit dermal fibroblasts expressed the alpha 2 beta 1, alpha 5 beta 1 and alpha 6 beta 1 integrins, the collagen, fibronectin, and laminin receptors, respectively. GRGDS exhibited a broad spectrum of inhibitory activity on RPE cell attachment to extracellular matrices. YIGSR specifically inhibited RPE cell attachment to laminin, whereas ADGEA inhibited RPE cell attachment to collagen type I and IV. ADGEA inhibited RPE cell-induced vitreous contraction in a dose-dependent manner, whereas GRGDS and YIGSR had no effect. ADGEA (1250 micrograms/mL) delayed the development of TRD but did not prevent it. ADGEA was nontoxic to cells and retina, as demonstrated by cytotoxicity tests and histological examination. The synthetic peptide, ADGEA, and its analogs may be potential candidates for the treatment of cell-mediated collagenous contraction in the ocular tissues.

Purpose: Integrin-mediated extracellular matrix (ECM) attachment plays an important role in vitreous contraction of retinal pigment epithelial (RPE) cells. Disintegrins, a group of Arg-Gly-Asp (RGD)-containing peptides from viper venom, are potential anti-adhesion agents that interfere with integrin-ECM binding. This study was performed to determine whether disintegrins were effective in inhibiting RPE cell-induced matrix attachment in vitro and tractional retinal detachment in a rabbit model in vivo., Methods: Two disintegrins, echistatin from viper Echis carinatus and flavoridin from Trimeresurus flavoviridis, were used. The expression of integrins on the surface of bovine and rabbit RPE cells was examined by indirect immunofluorescent stain with specific anti-integrin monoclonal antibodies. The inhibitory effect of disintegrins on RPE cell-mediated ECM attachment and vitreous contraction was evaluated with cell adhesion and vitreous contraction assays. In the in vivo model, rabbit eyes were injected intravitreously with either homologous rabbit RPE cells alone or together with disintegrins to induce tractional retinal detachment. The cytotoxic effect of disintegrins was examined with a cell proliferation assay using the alamar blue method. Retinal toxicity of disintegrins was evaluated with electroretinograms and histologic examination of the rabbit eyes., Results: Bovine and rabbit RPE cells showed the positive staining for the integrins alpha 2 beta 1 and alpha 5 beta 1 on cell surface. Disintegrins, echistatin, and flavoridin inhibited RPE cell attachment to the ECM. The potency of disintegrins was 150 to 300 times higher than that of Gly-Arg-Gly-Asp-Ser (GRGDS) peptide. The disintegrins also inhibited RPE cell-induced vitreous contraction in a dose-dependent manner, whereas the GRGDS peptide had no effect. In the in vivo experiment, echistatin (50 microgram/ml) or flavoridin (80 microgram/ml) significantly inhibited RPE cell-induced tractional retinal detachment compared with the control group at week 2 (P< 0.05) and week 4 (P< 0.01) after surgery. Disintegrins were nontoxic to RPE cells and rabbit retina as evaluated by cytotoxicity tests, electroretinograms, and histologic examinations., Conclusions: The disintegrins were effective in inhibiting RPE cell attachment to the ECM and vitreous contraction in vitro. They also were effective in suppressing RPE cell-induced tractional retinal detachment in the rabbit eyes. They were nontoxic. Disintegrins and their analogs might be potential anti-adhesion therapeutic agents in the treatment of proliferative vitreoretinopathy.

Patients with various stages of crystalline retinopathy were examined with vitreous fluorophotometry and the results were compared with those of normal subjects. Two patients with glistening crystals without pigment clumps, together with atrophy of the retinal pigment epithelium in the posterior pole, showed a normal inward permeability of fluorescein. Three patients with a large area of choriocapillaris atrophy in the posterior pole, in addition to atrophy of retinal pigment epithelium, demonstrated an increase in the rate of inward fluorescein penetration. Three patients with extensive areas of choriocapillaris atrophy throughout the fundus also revealed an increased posterior vitreous penetration ratio.

To evaluate the magnitude of parental upset associated with (1) the features of induction most upsetting to parents; (2) the characteristics of parents most likely to become upset; and (3) the accuracy of the anaesthetist's perception of the magnitude of parental upset. The parents (101 mothers and 43 fathers) of 103 children scheduled for elective outpatient surgery requiring general anaesthesia with induction by mask were asked on admission to participate in this study. Parents and children were educated about anaesthesia and surgery according to unit protocols. Immediately after induction of anaesthesia, the parents were asked to complete a demographic information sheet and the Parental Reactions to Anesthesia Induction Questionnaire. Responses were analyzed using descriptive statistics and content analysis. The most upsetting factors for both mothers and fathers in order of significance were: (1) separation from the child after induction of anaesthesia; (2) watching/feeling the child go limp during induction; and (3) seeing the child upset before induction. Characteristics of parents most likely to become upset revealed positive correlations between the amount of upset between mothers and fathers, mothers of an only child, and mothers or fathers who were health care workers (P < 0.05). The anaesthetist's perception of upset correlated with maternal (P < 0.05), but not parental, self-assessment of upset. We conclude that selected factors of parental participation are upsetting for the parents and that recognizing the factors associated with parental upset may enable operating room personnel to minimize these negative consequences.

Fluorescein angiography is the traditional tool for the detection of choroidal neovascularization of age-related macular degeneration. However, some limitations exist which impede its efficacy in the detection of subretinal neovascularization. Indocyanine green videoangiography is a recently developed technique which differs from fluorescein angiography in many ways. We performed indocyanine green videoangiography in 18 eyes with occult choroidal neovascularization, demonstrated by fluorescein angiography. Sixteen of the 18 eyes showed an abnormal vessel loop in the early phase of indocyanine green videoangiography. In the late phase, all 18 eyes had abnormal dye retention around the suspected neovascular area; however, only 12 eyes revealed a distinct border of neovascularization. No side effects, such as nausea, vomiting, or allergic reactions, were noted in our patients. Advantages and drawbacks of indocyanine green videoangiography in comparison with fluorescein angiography are discussed.

We successfully used high-density vitreous substitutes to remove four dislocated crystalline lenses and three dislocated intraocular lenses (IOLs) from the vitreous cavity. Fluorosilicone oil (300 cs) was used to remove the four lenses and one of the IOLs. Perfluorophenanthrene (Vitreon) was used to remove the other two dislocated IOLs. The dislocated lenses or IOLs were floated by the high-density vitreous substitutes and removed safely without damaging the retina; there were no intraoperative complications. Postoperative residual fluorosilicone oil droplets were found in one case.

In order to better acknowledge the ocular fundus picture in premature infants and to determine the incidence and clinical course of retinopathy of prematurity (ROP), from October 1987 to April 1989, 187 cases with a gestational age of less than 38 weeks or a birth weight of less than 2,500 g were enrolled for examination and follow-up study with indirect ophthalmoscope. One hundred and fifty cases (80.21%) were free from ROP bilaterally. Thirty-seven cases (19.79%) had ROP. Except for one case that showed unilateral regressed ROP, all were bilaterally affected. The mean birth weight and gestational age in the nonROP group were 1,824 +/- 426 g and 33.6 +/- 2.9 weeks, respectively, and in the ROP group were 1,395 +/- 490 g and 30.7 +/- 3.9 weeks, respectively. The difference for both factors between the two groups were statistically significant (p less than 0.05). Several specific fundus features were noticed in a high percentage of the nonROP group, these included a small cup to disc (C/D) ratio, pigmented ring around the disc, hypopigmented fundus and a greenish-gray color in the peripheral vascularized retina. In addition, 8.2% of this group had persistent primary vitreous remnant, and 5.6% had retinal hemorrhage. The macular development was subdivided into three stages. In both the ROP and nonROP groups, the difference of gestational age at each advancing stage was statistically significant by the Student t-test. No delay in macular development was noticed in the ROP group.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated the use of a heavier-than-water fluorinated silicone oil in the treatment of 30 selected cases of complicated retinal detachment from January 1988 to July 1989. Proliferative vitreoretinopathy grade C-2 or greater accounted for 19 cases, proliferative diabetic retinopathy with traction detachment for two cases, giant retinal tears five, ruptured globe with retinal detachment two, massive choroidal effusion with retinal detachment one, and acute retinal necrosis with retinal detachment one. Initial retinal reattachment was achieved in all cases. Complications included redetachment seven (23%), cataract six (75% of phakic patients), raised intraocular pressure four (13%), hypotony four (13%), keratopathy three (10%), uveitis-synechia formation three (10%), phthisis two (3%), choroidal haemorrhage one (3%), and vitreous haemorrhage one (3%). Postoperative visual acuities with at least six months' follow-up range from no light perception to 20/50, with seven patients (23%) 20/400 or better.

The concentration of cyclosporine in the vitreous after intravitreal injection of 100 micrograms of either free or liposome-bound cyclosporine was studied in albino rabbits. We found that the half-life of free cyclosporine was about 6 hours and that of liposome-bound cyclosporine was about 3 days. The finding indicates that liposome-bound cyclosporine prolongs the availability of the drug.

The effect of both regular silicone and fluorosilicone in preventing retinal detachment caused by experimental proliferative vitreoretinopathy was studied in rabbit eyes which received 250,000 fibroblasts after vitrectomy and lensectomy. In the control group, 14 out of 20 eyes which received fibroblasts had retinal detachments with disorganization of internal structures. In eyes receiving fibroblast and regular silicone, 4 out of 20 eyes had shallow retinal detachment. In the eyes receiving fibroblasts and fluorosilicone, 5 of 28 eyes had shallow retinal detachment. Our findings indicate that both regular silicone and fluorosilicone were effective in preventing retinal detachments caused by experimental proliferative vitreoretinopathy. There was no statistical difference between the two silicone oils.

The efficacy of intravitreally administered amphotericin B was evaluated. Experimental fungal infections were produced by inoculation of Candida albicans organisms into the vitreous cavities of 46 rabbit eyes. After 72 hr, eight eyes received intravitreal injections of 10 micrograms of free amphotericin B; and ten eyes each received 10 micrograms, 20 micrograms, and 40 micrograms of liposome-bound amphotericin B. The remaining eight eyes served as controls: four eyes received dextrose solution and four eyes received empty liposomes. Histopathologic examination 8 weeks after inoculation showed clear vitreous without retinal damage in groups treated with either 10 micrograms free amphotericin B or 20 micrograms of liposome-bound drug. All eyes in the control group and six eyes (60%) in the group treated with 10 micrograms of liposome-bound amphotericin B developed vitreous abscesses with evidence of fungal infection. In eyes treated with 40 micrograms of liposome-bound amphotericin B, fungal infection was successfully eradicated, but retinal damage was detected in all eyes by light microscopy. It is proposed that a reduced toxicity of intravitreally injected liposome-bound drugs is accompanied by reduced efficacy. In the treatment of fungal endophthalmitis, an increased dosage of liposome-bound amphotericin B (above that dosage of free drug which would be required) is suggested.

A 68-year-old white male had a pigmented choroidal tumor associated with progressive loss of vision. Clinical studies with fluorescein angiography and magnetic resonance imaging suggested a diagnosis of choroidal melanoma. Specimens obtained by internal eye wall resection revealed a choroidal nevus.

The concentration of cyclosporine in the aqueous and vitreous humors of albino rabbits was measured, using HPLC at intervals of 24, 48, 96, and 192 hours after subconjunctival injections of 2.5 mg of free or liposome-bound cyclosporine. The aqueous concentration was reasonably high in both groups until day 4: 1050 nanograms per milliliter in the group receiving free cyclosporine, and 1438 nanograms per milliliter in the group receiving liposome-bound cyclosporine. The vitreous concentration was very low in both groups.

Two groups of albino rabbits received an intravitreal injection of liposome-encapsulated trifluorothymidine. One group underwent a clearance study using high-performance liquid chromatography. The results of this study demonstrated a prolonged vitreal drug level within the range of ID50 for many strains of herpesvirus and human cytomegalovirus (CMV) at 28 days after injection. The eyes of another group were evaluated with preoperative and postoperative indirect ophthalmoscopy, electroretinography, and histologic examination. No retinal toxicity was found.

Intravitreal liposome-encapsulated antibiotics and antiviral drugs were used in patients with acute toxoplasmosis retinochoroiditis, presumed propionibacterium acne endophthalmitis after cataract surgery, and presumed cytomegalovirus retinitis associated with AIDS. A single intravitreal dose was effective in the treatment of all the conditions. Intravitreal liposomes may prove to be an advantageous drug delivery system for the treatment of chronic intraocular inflammatory disorders.

Two pulsed neodimium yittrium aluminum garnet (Nd:YAG) laser systems were evaluated for contact surgery through a fiberoptic system with a sapphire tip. Pulsed Nd:YAG laser at 1060 nm was as effective as continuous-wave Nd:YAG laser in producing tissue incisions. A combination of 1060-nm and 530-nm wavelengths achieved smooth cutting at lower energy levels. Corneal endothelial cell damage occurred at the high power level (7 watts) required for smooth underwater incisions with both continuous wave and pulsed lasers.

Fluorosilicone oil, a high specific gravity fluorinated silicone oil, has been recently reevaluated for temporary use in surgery to repair complicated retinal detachments. We evaluated the toxicity of a low-viscosity (300 centistokes) fluorosilicone oil as a vitreous substitute in vitrectomized eyes of albino rabbits. No toxicities could be demonstrated by histopathologic and electroretinographic examinations 6 weeks following surgery. In vitro experiments also showed no toxic effects on cultured retinoblastoma cells. When fluorosilicone oil was injected into the anterior chamber, endothelial cell damage could be seen 2 weeks following injection. Low-viscosity fluorosilicone oil appears to be a safe vitreous substitute for temporary use; it is easily injected and removed, and it maintains adequate surface tension for intraocular tamponade. Because of its relative low viscosity, 300-cst fluorosilicone oil (FS) may be a better vitreous substitute than perfluorocarbon liquids for both intraoperative manipulation of the retina and short-term intraocular tamponade for complicated retinal detachments.

Cytarabine has been demonstrated to be a more potent inhibitor of fibroblast proliferation than fluorouracil. It is, however, more toxic to the retina. We evaluated the ocular toxicity of liposome-encapsulated cytarabine in vitrectomized and nonvitrectomized rabbit eyes by ophthalmic and histopathologic examination. In the vitrectomized group, doses of up to 26 micrograms were nontoxic to the retina. In nonvitrectomized eyes, doses of up to 55 micrograms were nontoxic. Doses of 85 micrograms resulted in loss of ganglion cells and disorganization of photoreceptor cells. The results obtained in this study demonstrated a substantial reduction in ocular toxicity of liposome-encapsulated cytarabine, as compared with a previous study which employed free drug. By virtue of its reduced toxicity, cytarabine in a liposomal vehicle may be of value in the treatment of ocular proliferative disorders.

Perfluorophenanthrene, a liquid fluorocarbon with a specific gravity approximately twice that of water, potentially offers certain advantages as a vitreous substitute in vitreoretinal surgery. To determine its efficacy and safety we first purified it by chemical methods used in the preparation of experimental blood substitutes to a level at which it was not at all or only minimally toxic to culture-grown retinoblastoma cells. Nineteen of 22 vitrectomized eyes of white New Zealand rabbits injected with this purified perfluorophenanthrene showed satisfactory clinical tolerance. Light and electron microscopy showed minimal or no toxic effects in the 19 eyes, although uptake of perfluorophenanthrene by some preretinal cells was observed 28 days after implantation. Postoperative light-adapted electroretinography recordings of eight of the injected eyes showed no significant change. Perfluorophenanthrene injected into the anterior chamber of the rabbit eyes had toxic effects on the cornea. If further experimentations confirm our findings, perfluorophenanthrene may be a suitable transparent high-density liquid for temporary use in surgery to repair retinal detachments.

Gore-Tex (polytetrafluoroethylene) grafts have been used in a variety of surgical procedures, particularly vascular, plastic, and reconstructive surgery. As suggested by previous animal studies, Gore-Tex soft tissue patches (expanded polytetrafluoroethylene) may have application in ocular surgery for scleral buckling and support procedures. We buckled the scleras of 14 rabbit eyes using strips of polytetrafluoroethylene soft tissue patches and monitored ocular tissue reaction and histologic changes in response to this material.

The retinal toxicity of intraocular liposome-bound cyclosporine was studied in albino rabbits by means of electrophysiology and histopathology. During a followup period of one month, no histopathological or electroretinographic changes were noted using concentrations of 100, 200 and 500 micrograms injected intravitreally.