Zebrafish models to study drug abuse-related phenotypes.

Mounting evidence implicates the zebrafish (Danio rerio) as a promising model species for reward and addiction research. Modeling drug abuse-related behavior in both adult and larval zebrafish produced a wealth of clinically translatable data, also demonstrating their sensitivity to various drugs of abuse and the ability to develop tolerance. Several studies have also applied withdrawal paradigms to model the adverse effects of drug abuse in zebrafish. In this review, we summarize recent findings of a wide spectrum of zebrafish drug abuse-related behavioral and physiological phenotypes, discuss the existing challenges, and outline potential future directions of research in this field.

Inferior oblique belly transposition for V pattern strabismus.

Purpose: Monocular transposition of the inferior oblique muscle belly (IOMBT) effectively weakened mild to moderate inferior oblique overaction and corrected small primary position hypertropia. Now we aim to evaluate the efficacy of inferior oblique muscle belly transposition (IOMBT) in treating V pattern strabismus with upshoot in adduction.Methods: This is a retrospective review of 13 patients with V pattern who underwent IOMBT procedure from January 2017 to December 2018. The inclusion criteria were: the amount of V pattern from 15 to 25 pd; the degree of upshoot in adduction from +1 to +3; no or trace vertical deviation in primary gaze position. Bilateral IOMBT was performed to reduce the V pattern. Horizontal rectus muscle surgery was performed at the same stage to correct the horizontal deviation. The angle of deviation in upgaze and downgaze was measured pre- and postoperatively. The degree of elevation in adduction was graded. The amount of V pattern was the difference in horizontal angle between up- and downgaze. The change in the amount of V pattern was assessed postoperatively.Results: All 13 patients had complete resolution of the V pattern. The amount of V pattern changed from 18.92 ± 4.310 prism diopters to 3.462 ± 1.854 prism diopters postoperatively. The mean grade of upshoot in adduction changed from 1.92 to 0.12 postoperatively. No depression in adduction or consecutive A pattern were found after surgery.Conclusions: IOMBT can successfully eliminate the V pattern in patients with mild V pattern esotropia or exotropia with mild to moderate upshoot in adduction. This procedure appears to be a useful addition to our inferior oblique surgical armamentarium.

Inferior Oblique Belly Transposition for Small Angle Hypertropia With Inferior Oblique Overaction: A Pilot Study.

PURPOSE: To evaluate the efficacy of transposition of the belly of the inferior oblique muscle in treating inferior oblique overaction with small angle hypertropia. METHODS: The medical records of 10 patients who underwent inferior oblique belly transposition from March 2014 to July 2016 were reviewed. Transposition of the inferior oblique muscle belly consisted of suturing the entire body of the muscle to the sclera 5 mm posterior to the temporal insertion of the inferior rectus muscle. All patients had small hypertropias (< 5 prism diopters) in the primary gaze position with associated inferior oblique overaction. Deviations in both primary and lateral gazes, compensatory face turns or head tilts, and the degree of inferior oblique overaction were evaluated preoperatively and postoperatively. RESULTS: Nine of the 10 patients had a complete resolution of inferior oblique overaction. In the remaining patient, the inferior oblique overaction improved from +3 to +1. None of the patients had any residual vertical deviation. There was elimination of compensatory head tilting in 5 patients and correction of compensatory face turns in 4 patients. One patient with mild up drifting of the involved eye also improved after the procedure. All patients expressed subjective satisfaction with the surgical outcome. CONCLUSIONS: Transposition of the inferior oblique muscle belly effectively weakened mild to moderate inferior oblique overaction and corrected small primary position hypertropias. This procedure may be a useful addition to surgical treatment options in patients with small hypertropias associated with inferior oblique overaction. [J Pediatr Ophthalmol Strabismus. 2018;55(1):43-46.].

A symptom survey and quality of life questionnaire for nasolacrimal duct obstruction in children.

PURPOSE: To develop and validate a new parental questionnaire addressing symptoms and health-related quality of life (HRQL) in childhood nasolacrimal duct obstruction (NLDO). DESIGN: Cross-sectional study. PARTICIPANTS: Children ages 6 to younger than 48 months with and without clinical signs of NLDO. METHODS: A new questionnaire was developed using semistructured interviews with parents of children with NLDO and through discussions with expert clinicians. Questionnaires were completed by parents of children with and without NLDO. Cronbach's alpha was calculated as a measure of internal-consistency reliability. Factor analysis was used to evaluate a priori subscales: symptoms and HRQL. Discriminant construct validity was assessed by comparing questionnaire scores between children with and without NLDO and between affected and unaffected eyes of children with unilateral NLDO. Instrument responsiveness was determined by comparing presurgical and postsurgical intervention scores in a subset of NLDO patients who underwent surgical treatment. MAIN OUTCOME MEASURE: The NLDO questionnaire score. RESULTS: Eighty-seven children were enrolled, 56 with and 31 without NLDO. All but 2 questions on the questionnaire showed a good distribution of responses, a high correlation with the rest of the questionnaire, and excellent discrimination between patients with and without NLDO. Cronbach's alpha values were good for the overall questionnaire (0.95), and for 2 predetermined subscales: symptoms (0.95) and HRQL (0.85). On a 0 to 4 scale, NLDO patients had worse scores compared with non-NLDO patients for both symptoms (mean difference, 2.1; 95% confidence interval [CI], 1.9-2.3) and HRQL (mean difference, 1.2; 95% CI, 0.9-1.5) subscales. The NLDO patients had worse scores before intervention compared with after intervention for both the symptoms (mean difference, 2.2; 95% CI, 1.6-2.9) and HRQL (mean difference, 1.4; 95% CI, 0.8-2.1) subscales. Finally, NLDO patients had worse symptom scores for affected eyes compared with unaffected eyes (mean difference, 2.3; 95% CI, 1.9-2.6). CONCLUSIONS: This novel NLDO questionnaire is useful in quantifying parental perception of symptoms and HRQL in childhood NLDO. The questionnaire may have a role in future clinical studies of NLDO.

Bilateral congenital lacrimal sac fistulae in a patient with ectrodactyly-ectodermal dysplasia-clefting syndrome.

We describe a case of bilateral congenital lacrimal sac fistulas, associated with ectrodactyly-ectodermal dysplasia-clefting syndrome. The embryologic basis for this condition is discussed, as well as the epidemiology, typical presentation, and possible treatment modalities. After we excised the fistulas and intubated the nasolacrimal ducts in this patient, he experienced improvement in symptoms by report.

Tensor LRR and Sparse Coding-Based Subspace Clustering.

Subspace clustering groups a set of samples from a union of several linear subspaces into clusters, so that the samples in the same cluster are drawn from the same linear subspace. In the majority of the existing work on subspace clustering, clusters are built based on feature information, while sample correlations in their original spatial structure are simply ignored. Besides, original high-dimensional feature vector contains noisy/redundant information, and the time complexity grows exponentially with the number of dimensions. To address these issues, we propose a tensor low-rank representation (TLRR) and sparse coding-based (TLRRSC) subspace clustering method by simultaneously considering feature information and spatial structures. TLRR seeks the lowest rank representation over original spatial structures along all spatial directions. Sparse coding learns a dictionary along feature spaces, so that each sample can be represented by a few atoms of the learned dictionary. The affinity matrix used for spectral clustering is built from the joint similarities in both spatial and feature spaces. TLRRSC can well capture the global structure and inherent feature information of data and provide a robust subspace segmentation from corrupted data. Experimental results on both synthetic and real-world data sets show that TLRRSC outperforms several established stateof- the-art methods.

Balloon dilation of the nasolacrimal duct.

PURPOSE: Our purpose is to report our experience with balloon catheter dilation of the nasolacrimal duct after failed probing for congenital nasolacrimal duct obstruction. METHODS: We undertook a retrospective chart review. Patients who were enrolled had symptoms of persistent nasolacrimal duct obstruction after simple probing and irrigation. Balloon nasolacrimal ductoplasty was performed using the LacriCATH system (Quest Medical, Inc. An Atrion Company, Allen, TX). Outcomes were determined by postoperative examination and telephone follow-up. RESULTS: Thirty-nine lacrimal systems of 26 patients (age range, 10 months to 84 months) were treated. Of the obstructed ducts treated, 82% (32/39) showed resolution of epiphora. There were 9 children older than the age of 2, with 15 nasolacrimal systems studied. These had 11 of 15 successes for a success rate of 73%. There were 17 children between the ages of 10 months and 2 years with 24 nasolacrimal systems studied. These had 21 of 24 successes for a success rate of approximately 88%. The difference was not statistically significant (P = 0.28). CONCLUSION: Balloon dilation of the nasolacrimal duct is an alternative to silicone intubation in the treatment of congenital nasolacrimal duct obstruction after failed simple probing. Although our success rate was slightly lower than some published reports of nasolacrimal system intubation, this simple and atraumatic procedure was successful in 82% of cases for this specific situation.

Atropine vs patching for treatment of moderate amblyopia: follow-up at 15 years of age of a randomized clinical trial.

IMPORTANCE: Initial treatment for amblyopia of the fellow eye with patching and atropine sulfate eyedrops improves visual acuity. Long-term data on the durability of treatment benefit are needed. OBJECTIVE: To report visual acuity at 15 years of age among patients who were younger than 7 years when enrolled in a treatment trial for moderate amblyopia. DESIGN, SETTING, AND PARTICIPANTS: In a multicenter clinical trial, 419 children with amblyopia (visual acuity, 20/40 to 20/100) were randomly assigned to patching (minimum of 6 h/d) or atropine sulfate eyedrops, 1% (1 drop daily), for 6 months. Treatment after 6 months was at the discretion of the investigator. Two years after enrollment, an unselected subgroup of 188 children were enrolled into long-term follow-up. INTERVENTION: Initial treatment with patching or atropine with subsequent treatment at investigator discretion. MAIN OUTCOMES AND MEASURES: Visual acuity at 15 years of age with the electronic Early Treatment Diabetic Retinopathy Study test in amblyopic and fellow eyes. RESULTS: Mean visual acuity in the amblyopic eye measured in 147 participants at 15 years of age was 0.14 logMAR (approximately 20/25); 59.9% of amblyopic eyes had visual acuity of 20/25 or better and 33.3%, 20/20 or better. Mean interocular acuity difference (IOD) at 15 years of age was 0.21 logMAR (2.1 lines); 48.3% had an IOD of 2 or more lines and 71.4%, 1 or more lines. Treatment (other than spectacles) was prescribed for 9 participants (6.1%) aged 10 to 15 years. Mean IOD was similar at examinations at 10 and 15 years of age (2.0 and 2.1 logMAR lines, respectively; P = .39). Better visual acuity at the 15-year examination was achieved in those who were younger than 5 years at the time of entry into the randomized clinical trial (mean logMAR, 0.09) compared with those aged 5 to 6 years (mean logMAR, 0.18; P < .001). When we compared subgroups based on original treatment with atropine or patching, no significant differences were observed in visual acuity of amblyopic and fellow eyes at 15 years of age (P = .44 and P = .43, respectively). CONCLUSIONS AND RELEVANCE: At 15 years of age, most children treated for moderate amblyopia when younger than 7 years have good visual acuity, although mild residual amblyopia is common. The outcome is similar regardless of initial treatment with atropine or patching. The results indicate that improvement occurring with amblyopia treatment is maintained until at least 15 years of age. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000170.

Relevance units latent variable model and nonlinear dimensionality reduction.

A new dimensionality reduction method, called relevance units latent variable model (RULVM), is proposed in this paper. RULVM has a close link with the framework of Gaussian process latent variable model (GPLVM) and it originates from a recently developed sparse kernel model called relevance units machine (RUM). RUM follows the idea of relevance vector machine (RVM) under the Bayesian framework but releases the constraint that relevance vectors (RVs) have to be selected from the input vectors. RUM treats relevance units (RUs) as part of the parameters to be learned from the data. As a result, a RUM maintains all the advantages of RVM and offers superior sparsity. RULVM inherits the advantages of sparseness offered by the RUM and the experimental result shows that RULVM algorithm possesses considerable computational advantages over GPLVM algorithm.

The effects of chronic social defeat stress on mouse self-grooming behavior and its patterning.

Stress induced by social defeat is a strong modifier of animal anxiety and depression-like phenotypes. Self-grooming is a common rodent behavior, and has an ordered cephalo-caudal progression from licking of the paws to head, body, genitals and tail. Acute stress is known to alter grooming activity levels and disrupt its patterning. Following 15-17 days of chronic social defeat stress, grooming behavior was analyzed in adult male C57BL/6J mice exhibiting either dominant or subordinate behavior. Our study showed that subordinate mice experience higher levels of anxiety and display disorganized patterning of their grooming behaviors, which emerges as a behavioral marker of chronic social stress. These findings indicate that chronic social stress modulates grooming behavior in mice, thus illustrating the importance of grooming phenotypes for neurobehavioral stress research.

Analyzing habituation responses to novelty in zebrafish (Danio rerio).

Analysis of habituation is widely used to characterize animal cognitive phenotypes and their modulation. Although zebrafish (Danio rerio) are increasingly utilized in neurobehavioral research, their habituation responses have not been extensively investigated. Utilizing the novel tank test, we examine intra- and inter-session habituation and demonstrate robust habituation responses in adult zebrafish. Analyzing the intra-session habituation to novelty further, we also show that selected anxiogenic drugs (caffeine, pentylenetetrazole), as well as stress-inducing alarm pheromone, attenuated zebrafish habituation. Some acute anxiolytic agents, such as morphine and ethanol, while predictably reducing zebrafish anxiety, had no effects on habituation. Chronic ethanol and fluoxetine treatments improved intra-session habituation in zebrafish. In general, our study parallels literature on rodent habituation responses to novelty, and reconfirms zebrafish as a promising model for cognitive neurobehavioral research.

Modeling withdrawal syndrome in zebrafish.

The zebrafish (Danio rerio) is rapidly becoming a popular model species in behavioral neuroscience research. Zebrafish behavior is robustly affected by environmental and pharmacological manipulations, and can be examined using exploration-based paradigms, paralleled by analysis of endocrine (cortisol) stress responses. Discontinuation of various psychotropic drugs evokes withdrawal in both humans and rodents, characterized by increased anxiety. Sensitivity of zebrafish to drugs of abuse has been recently reported in the literature. Here we examine the effects of ethanol, diazepam, morphine and caffeine withdrawal on zebrafish behavior. Overall, discontinuation of ethanol, diazepam and morphine produced anxiogenic-like behavioral or endocrine responses, demonstrating the utility of zebrafish in translational research of withdrawal syndrome.

Measuring behavioral and endocrine responses to novelty stress in adult zebrafish.

Several behavioral assays are currently used for high-throughput neurophenotyping and screening of genetic mutations and psychotropic drugs in zebrafish (Danio rerio). In this protocol, we describe a battery of two assays to characterize anxiety-related behavioral and endocrine phenotypes in adult zebrafish. Here, we detail how to use the 'novel tank' test to assess behavioral indices of anxiety (including reduced exploration, increased freezing behavior and erratic movement), which are quantifiable using manual registration and computer-aided video-tracking analyses. In addition, we describe how to analyze whole-body zebrafish cortisol concentrations that correspond to their behavior in the novel tank test. This protocol is an easy, inexpensive and effective alternative to other methods of measuring stress responses in zebrafish, thus enabling the rapid acquisition and analysis of large amounts of data. As will be shown here, fish anxiety-like behavior can be either attenuated or exaggerated depending on stress or drug exposure, with cortisol levels generally expected to parallel anxiety behaviors. This protocol can be completed over the course of 2 d, with a variable testing duration depending on the number of fish used.

Orbital Dermoid Cyst Presenting with a Discharging Sinus Tract.

This report describes a case of orbital dermoid cyst presenting with a discharging sinus tract. The embryologic basis for orbital dermoids in general is discussed, as well as their typical presentation and management. In the current case, patient presentation and management were somewhat different because of signs of infection and a communicating sinus tract, both highly unusual for orbital dermoids. However, after complete excision of the dermoid and sinus tract, the patient showed complete recovery.

Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish.

The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of stress and anxiety. Here we further validate zebrafish models of stress by analyzing how environmental and pharmacological manipulations affect their behavioral and physiological phenotypes. Experimental manipulations included exposure to alarm pheromone, chronic exposure to fluoxetine, acute exposure to caffeine, as well as acute and chronic exposure to ethanol. Acute (but not chronic) alarm pheromone and acute caffeine produced robust anxiogenic effects, including reduced exploration, increased erratic movements and freezing behavior in zebrafish tested in the novel tank diving test. In contrast, ethanol and fluoxetine had robust anxiolytic effects, including increased exploration and reduced erratic movements. The behavior of several zebrafish strains was also quantified to ascertain differences in their behavioral profiles, revealing high-anxiety (leopard, albino) and low-anxiety (wild type) strains. We also used LocoScan (CleverSys Inc.) video-tracking tool to quantify anxiety-related behaviors in zebrafish, and dissect anxiety-related phenotypes from locomotor activity. Finally, we developed a simple and effective method of measuring zebrafish physiological stress responses (based on a human salivary cortisol assay), and showed that alterations in whole-body cortisol levels in zebrafish parallel behavioral indices of anxiety. Collectively, our results confirm zebrafish as a valid, reliable, and high-throughput model of stress and affective disorders.