Preliminary study of a new online and equipment-free vision screening alternative for remote and isolated community.

INTRODUCTION: Vision screening has been initiated to detect potential vision problems, paving referral pathways towards a full eye examination. Time-cost-labour practicality challenges of equipment-based vision screening have lingered for decades. Going for the highest sensitivity and specificity or opting for a pragmatic and affordable vision screening program remains a dilemma in public eye health. We aimed to report the development of a new online and equipment-free vision screening called Eye: Questionnairebased Vision Screening (EyeQVS). We also analysed the visual profile of Orang Bateq resided in a remote locality, using findings from EyeQVS, single test vision screening and full eye examination. MATERIALS AND METHODS: Multi-perspective development strategies were employed in designing EyeQVS. The questionnaire items were constructed using the working backward technique, compiling common vision disorders from the literature and face validation using expert panels. Face validation and usability assessment were performed on EyeQVS. The vision screening was carried out using EyeQVS and single test visual acuity screening method. The full eye examination included visual acuity, refraction, binocular vision and ocular health assessment. The visual profile of indigenous people (Orang Bateq) at Kampung Bengoi and Kampung Atok, Jerantut, Pahang was analysed using EyeQVS, single test visual acuity screening method and full eye examination. RESULTS: The performance of EyeQVS was affirmative in both face validation and usability. About 95% of Orang Bateq failed full eye examination, while 55% failed EyeQVS screening. None of them failed single test vision screening. Binocular disorders and dry eye problems were commonly found in Orang Bateq. EyeQVS unearthed more various vision problems compared to the single test vision screening (visual acuity alone) as a screening tool in a remote location. CONCLUSION: EyeQVS can screen for binocular disorders and dry eyes problem commonly found among indigenous people, which might be missed using a single-test visual acuity screening approach. EyeQVS is a practical alternative for vision screening in places where financial or location hinders eye healthcare access.

Organotypic brain slice cultures to model neurodegenerative proteinopathies.

Organotypic slice cultures of brain or spinal cord have been a longstanding tool in neuroscience research but their utility for understanding Alzheimer's disease (AD) and other neurodegenerative proteinopathies has only recently begun to be evaluated. Organotypic brain slice cultures (BSCs) represent a physiologically relevant three-dimensional model of the brain. BSCs support all the central nervous system (CNS) cell types and can be produced from brain areas involved in neurodegenerative disease. BSCs can be used to better understand the induction and significance of proteinopathies underlying the development and progression of AD and other neurodegenerative disorders, and in the future may serve as bridging technologies between cell culture and in vivo experiments for the development and evaluation of novel therapeutic targets and strategies. We review the initial development and general use of BSCs in neuroscience research and highlight the advantages of these cultures as an ex vivo model. Subsequently we focus on i) BSC-based modeling of AD and other neurodegenerative proteinopathies ii) use of BSCs to understand mechanisms underlying these diseases and iii) how BSCs can serve as tools to screen for suitable therapeutics prior to in vivo investigations. Finally, we will examine i) open questions regarding the use of such cultures and ii) how emerging technologies such as recombinant adeno-associated viruses (rAAV) may be combined with these models to advance translational research relevant to neurodegenerative disorders.

Antibody-mediated protection against MERS-CoV in the murine model.

Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. The murine antisera induced were fully-neutralising in vitro for two separate clinical strains of the MERS coronavirus (MERS-CoV). To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. Subsequent challenge of the recipient transduced mice by the intra-nasal route with a clinical isolate of the MERS-CoV resulted in a significantly reduced viral load in their lungs, compared with transduced mice receiving a negative control antibody. The murine antisera used were derived from mice which had been primed sub-cutaneously with a recombinant fusion of RBD with a human IgG Fc tag (RBD-Fc), adsorbed to calcium phosphate microcrystals and then boosted by the oral route with the same fusion protein in reverse micelles. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV.

Dual route vaccination for plague with emergency use applications.

Here, we report a dual-route vaccination approach for plague, able to induce a rapid response involving systemic and mucosal immunity, whilst also providing ease of use in those resource-poor settings most vulnerable to disease outbreaks. This novel vaccine (VypVaxDuo) comprises the recombinant F1 and V proteins in free association. VypVaxDuo has been designed for administration via a sub-cutaneous priming dose followed by a single oral booster dose and has been demonstrated to induce early onset immunity 14 days after the primary immunisation; full protective efficacy against live organism challenge was achieved in Balb/c mice exposed to 2 × 104 median lethal doses of Yersinia pestis Co92, by the sub-cutaneous route at 25 days after the oral booster immunisation. This dual-route vaccination effectively induced serum IgG and serum and faecal IgA, specific for F1 and V, which constitute two key virulence factors in Y. pestis, and is therefore suitable for further development to prevent bubonic plague and for evaluation in models of pneumonic plague. This is an essential requirement for control of disease outbreaks in areas of the world endemic for plague and is supported further by the observed exceptional stability of the primary vaccine formulation in vialled form under thermostressed conditions (40 °C for 29 weeks, and 40 °C with 75% relative humidity for 6 weeks), meaning no cold chain for storage or distribution is needed. In clinical use, the injected priming dose would be administered on simple rehydration of the dry powder by means of a dual barrel syringe, with the subsequent single booster dose being provided in an enteric-coated capsule suitable for oral self-administration.

Enzymatic synthesis of beta-lactam antibiotics via direct condensation.

In this paper, the feasibility of precipitation driven synthesis of acidic and zwitterionic beta-lactam antibiotics is studied. As an example of the first type, penicillin G was produced in good yield (160 mmol kg(-1)) directly from the free acid and amine aqueous substrate suspension, where the synthesis product precipitated. Such a precipitation driven synthesis via direct reversal of the hydrolytic reaction is thermodynamically unfavourable for zwitterionic beta-lactam antibiotics, such as amoxicillin. In this paper, a novel method is suggested to help favour precipitation of (poorly soluble) product salts by deliberate addition of certain counter-ions. After screening a number of different counter-ions, it was found that the amoxicillin anion forms a poorly soluble salt with Zn(2+). Despite increased beta-lactam degradation due to the presence of zinc ions, in a synthetic reaction with 0.1 M ZnSO(4) present the synthetic yield could be increased at least 30-fold.

Cycloplegic refractions in healthy children aged 1 through 48 months.

OBJECTIVES: To provide a description of refractive errors in healthy, term-born children, aged 1 through 48 months, and to test the hypotheses that spherical equivalent becomes significantly less hyperopic and less variable with increasing age. METHODS: Following a prospective, cross-sectional design, cycloplegic retinoscopy was used to measure the refractive error in both eyes of 514 healthy, term-born children in 12 age groups. Three hundred were aged 12 months or younger. Spherical equivalent and cylindrical power and axis were analyzed as a function of age. Prediction limits for spherical equivalent were calculated. RESULTS: Spherical equivalents of right and left eyes did not differ at any age. Hyperopia declined significantly with increasing age. The variability in spherical equivalent also decreased significantly with age. Cylindrical error of 1 diopter or more was found in 25% of the children; the proportion with astigmatism was highest in infancy and then waned. Myopia and anisometropia were rare, occurring in 3% and 1% of the sample, respectively. CONCLUSIONS: Significant declines in hyperopia and variability of spherical equivalent appear to be features of emmetropization. The normal prediction limits provide guidelines against which data from individual patients can be compared.

Characterization of equine E-selectin.

Expression of E-selectin on activated endothelium is a critical initial step that leads to extravasation of leucocytes during inflammation, yet E-selectin is largely uncharacterized in several animal species including the horse. We have sequenced and compared E-selectin genes derived from activated cultures of purified equine (horse), cervid (black-tailed deer) and ovine (sheep) pulmonary artery endothelial cells (ECs). Phylogenetic and amino acid sequence comparisons indicate that bovine, cervid and ovine E-selectin are similar, whereas human and equine E-selectin are more closely related to each other than to the ruminant molecules. Human E- and P-selectin-specific monoclonal antibodies that also recognize equine E-selectin were identified and used to characterize its expression. Expression of E-selectin was more readily induced by lipopolysaccharide treatment in equine ECs than in human ECs and supported adhesion and activation of neutrophils, consistent with the extreme sensitivity of horses to endotoxaemia and septic shock.

Phage derived peptides for targeting of doxorubicin conjugates to solid tumours.

Barriers are frequently hampering targeting of drugs and toxins to solid tumours and their microenvironment. Nano-conjugates are low molecular weight conjugates of a small drug or toxin and a targeting ligand coupled through a cleavable linker group. They offer potential advantages for tumour specific delivery in diffusion-limited situations. We have exploited fd phage-derived peptides for the targeting of low molecular weight drug conjugates to solid tumours. As a model we have chosen doxorubicin conjugates targeted to the transferrin receptor (TfR). A library of phage expressing a cyclic nona-peptide was panned against TfR. The apparent affinity of phages determined by surface plasmon resonance (SPR) increased with each cycle of the panning procedure. After five rounds approximately 80% of phages expressed the same peptide, which mediated a 30-50-fold increased receptor specific cellular uptake of the phages. The corresponding peptide was synthesised using solid phase peptide chemistry on a sulfonamide based safety catch resin. Crude mixtures of the peptide, as well as transferrin itself, were able to inhibit the phage uptake significantly. The doxorubicin conjugate of the peptide containing a cleavable linker was prepared and endosomal uptake confirmed by fluorescence microscopy.

Predicting when precipitation-driven synthesis is feasible: application to biocatalysis.

Precipitation-driven synthesis offers the possibility of obtaining high reaction yields using very low volume reactors and is finding increasing applications in biocatalysis. Here, a model that allows straightforward prediction of when such a precipitation-driven reaction will be thermodynamically feasible is presented. This requires comparison of the equilibrium constant, Keq, with the saturated mass action ratio, Zsat, defined as the ratio of product solubilities to reactant solubilities. A hypothetical thermodynamic cycle that can be used to accurately predict Zsat, in water is described. The cycle involves three main processes: fusion of a solid to a supercooled liquid, ideal mixing of the liquid with octanol, and partitioning from octanol to water. To obtain the saturated mass action ratio using this cycle, only the melting points of the reactants and products, and in certain cases the pKa of ionisable groups, are required as input parameters. The model was tested on a range of enzyme-catalysed peptide syntheses from the literature and found to predict accurately when precipitation-driven reaction was possible. The methodology employed is quite general and the model is therefore expected to be applicable to a wide range of other (bio)-catalysed reactions.

The role of surgery in children with neurofibromatosis.

BACKGROUND/PURPOSE: Neurofibromatosis frequently is complicated by the development of symptomatic lesions such as optic gliomas and plexiform neurofibromas that require operative resection. Although characteristically benign, these neoplasms have often devastating functional and cosmetic effects and must be monitored for malignant transformation. The purpose of this study is to identify and describe the surgical considerations in the care of children with neurofibromatosis. METHODS: The authors reviewed the charts of all children (<21) at our institution with neurofibromatosis who underwent an operative procedure from 1979 to 1999. Patient demographics, symptomatic lesions, malignant transformation, form of surgical intervention, type of anesthesia, and outcome were collected. RESULTS: A total of 249 patients with either neurofibromatosis 1 or 2 were identified. Of these, 50 (20%) underwent a total of 93 operations. The average age at operation was 9.4 years (1.2 to 21 years). There were 40 soft tissue procedures, 21 intracranial, and 32 miscellaneous. The soft tissue masses typically were treated with wide local excision, and in 8 of these procedures multiple resections were performed. Fourteen of the 50 patients had malignancies. Five of the tumors were soft tissue sarcomas, and 9 were intracranial malignancies. Three patients died, 2 from malignancy and 1 from acute, obstructive hydrocephalus after operation. There were 3 patients alive with malignancy and 8 others living with varying levels of disability. CONCLUSIONS: Neurofibromatosis in the pediatric patient frequently requires surgical intervention, often because of symptoms such as pain or cosmetic deformity, or for malignancy. Children should be watched carefully for signs of malignant transformation and undergo biopsy for neurofibromas that exhibit rapid growth. Management of sarcomas should be aggressive with consideration given to re-excision, placement of brachytherapy catheters, metastectomy, and limb salvage with adjuvant therapy when possible. Preoperatively, children should receive clinical and radiographic (computed tomography or magnetic resonance imaging) evaluation for hydrocephalus.

Measuring enzyme motility in organic media using novel H-D exchange methodology.

A novel deuterium ((2)H) NMR technique as developed for measuring the total number of deuterons exchanged by lyophilised protein samples following hydrogen-deuterium (H-D) exchange. Using this methodology differences in the H-D exchange behaviour of the proteolytic enzyme subtilisin Carlsberg hydrated either in air or an organic solvent were probed as a function of hydration. At low thermodynamic water activity (a(w)), the degree of H-D exchange increased rapidly with hydration (from anhydrous to a(w) 0.22). At a(w) 0.22, subtilisin powders hydrated in air were found to have reached an H-D exchange level comparable to that found upon aqueous dissolution and in agreement with previous studies using lysozyme. Lyophilised subtilisin hydrated in either dichloromethane (DCM) or diisopropyl ether (DIPE) showed a pattern of exchange (vs. a(w)) comparable to that found for powders hydrated in air. However, subtilisin hydrated in n-hexane showed a significant reduction in H-D exchange at all a(w) studied. Control experiments demonstrated that the reduction in H-D exchange observed for subtilisin in n-hexane was not a kinetic effect. This lower level of exchange in n-hexane implies that hydrated subtilisin Carlsberg has a lower conformational motility and more rigid protein matrix.

Behavioral phenotype of neurofibromatosis, type 1.

Neurofibromatosis, type 1 (NF1) is a very common inherited disorder that was first described in the late 19th century. NF1 is associated with a myriad of behavioral manifestations in addition to its frequent and often severe medical and physical complications. Learning disability, cognitive impairment, emotional and psychosocial difficulties have been reported so frequently in neurofibromatosis that these are often considered hallmarks. This report briefly introduces the medical and physical characteristics of NF1. We then detail the behavioral manifestations of NF1 with additional discussion of possible etiologies for the high incidence of these behavioral difficulties. MRDD Research Reviews 2000;6:117-124.

Quantitative morphology of the corpus callosum in children with neurofibromatosis and attention-deficit hyperactivity disorder.

Neurofibromatosis-1 is a common autosomal-dominant genetic disorder associated with numerous physical anomalies and an increased incidence of attention-deficit hyperactivity disorder (ADHD). Studies of children with idiopathic ADHD have suggested a link between corpus callosum size and symptom severity. This study examines the contribution of corpus callosum morphology to symptoms of ADHD in children with neurofibromatosis. Eighteen control subjects and 36 children with neurofibromatosis underwent magnetic resonance imaging of the brain. Twelve subjects with neurofibromatosis had evidence of ADHD and 24 did not. Subjects with neurofibromatosis had significantly larger total corpus callosum area and significantly larger regional measurements in three of seven areas. However, there were no differences between the neurofibromatosis alone and neurofibromatosis plus ADHD groups. Increased severity of attention problems was associated with smaller total callosal areas. These results suggest that some features of ADHD in children with neurofibromatosis could be linked to quantifiable differences in brain morphology, but the nature of the genetic mutation in neurofibromatosis suggests that neurochemical effects also could be important.

Brain volume in children with neurofibromatosis type 1: relation to neuropsychological status.

OBJECTIVE: To determine characteristics of brain morphology in children and adolescents with neurofibromatosis type 1 and relate these characteristics to neuropsychological functioning. BACKGROUND: Neurofibromatosis type 1 is associated with numerous CNS abnormalities and cognitive impairment. Abnormal high signal intensity visible on brain MRI, brain tumors, and macrocephaly are common. Research into links between neuroanatomic and cognitive features has been inconclusive. METHODS: Fifty-two children and adolescents with neurofibromatosis type 1 were compared with 19 control subjects on several quantitative neuroanatomic and neuropsychological measures. RESULTS: Total brain volume, especially gray matter, was significantly greater for neurofibromatosis type 1 subjects than the control subjects. Group differences in the ratio of gray matter to white matter were more prominent in younger than in older subjects. Volume of gray matter in the subjects with neurofibromatosis type 1 was related to their degree of learning disability. Corpus callosum size was significantly larger for subjects in the neurofibromatosis type 1 group, and diminished performance on measures of academic achievement and visual-spatial and motor skills were associated with greater regional corpus callosum size. CONCLUSIONS: Neuroanatomic morphology and the developmental pattern of gray matter and white matter in subjects with neurofibromatosis type 1 differed from in control subjects. Some of these differences are related to the neuropsychological status of the neurofibromatosis type 1 group. We propose that delayed developmental apoptosis results in macrocephaly and a delay in the development of appropriate neuronal connections in children with neurofibromatosis type 1. We further propose that these morphologic delays are related to the cognitive profile of neurofibromatosis type 1.

Neurocognitive development of children after a cerebellar tumor in infancy: A longitudinal study.

PURPOSE: To assess the long-term neuropsychologic effects experienced by children who have tumors in the cerebellum that are diagnosed and treated during infancy. PATIENTS AND METHODS: Twenty-seven children with posterior fossa tumors diagnosed at less than 36 months of age were assessed prospectively with a comprehensive set of age-appropriate tests. Group means and SDs are reported for assessments conducted at diagnosis (analysis 1) and at the most recent follow-up appointment (analysis 2). Cognitive developmental growth curves were derived from the prospective data (analysis 3) using mixed model regression analyses and controlling for age at diagnosis and socioeconomic status. RESULTS: In the first analysis, eight of 11 infants at diagnosis scored within normal limits on all neuropsychologic domains, except for motor skills, which were impaired. In the second analysis, mean scores at the most recent follow-up of 21 of 27 patients were mostly in the normal range; however, group comparisons between those who had (n = 7) and had not (n = 14) been treated with cranial radiation therapy (CRT) showed that patients in the irradiated (CRT) group scored significantly lower than those in the nonirradiated (No-CRT) group on verbal intelligence quotient (IQ) and in the motor domain. In the third analysis (growth curves of CRT and No-CRT groups), statistically significant differences in slope were found on verbal IQ, performance IQ, perceptual-motor skills, language, and attention/executive skills. Slopes on the fine-motor domain were similar; both groups declined at approximately the same rate. CONCLUSION: Neurocognitive development and outcome of children with cerebellar tumors diagnosed in infancy is very positive among those who were treated with surgery and chemotherapy. Declines in performance across time were minimal, and scores tended to remain within normal limits. By itself, a cerebellar tumor in infancy does not seem to have a significant impact on children. However, those who received CRT as part of their treatment are likely to have neurocognitive and psychosocial deficits that require remediational interventions.

Brain tumors in children with neurofibromatosis: additional neuropsychological morbidity?

Neurofibromatosis type 1 is a common autosomal dominant genetic disorder associated with numerous physical anomalies and an increased incidence of neuropsychological impairment. Tumors of the CNS occur in approximately 15% of children with neurofibromatosis, presenting additional risk for cognitive impairment. This study examines the impact of an additional diagnosis of brain tumor on the cognitive profile of children with neurofibromatosis. A comprehensive battery of neuropsychological tests was administered to 149 children with neurofibromatosis. Thirty-six of these children had a codiagnosis of brain tumor. A subset of 36 children with neurofibromatosis alone was matched with the group of children diagnosed with neurofibromatosis and brain tumor. Although mean scores of the neurofibromatosis plus brain tumor group were, in general, lower than those of the neurofibromatosis alone group, these differences were not statistically significant. Children in the neurofibromatosis plus brain tumor group who received cranial irradiation (n = 9) demonstrated weaker academic abilities than did children with brain tumor who had not received that treatment. These results suggest that neurofibromatosis is associated with impairments in cognitive functioning, but the severity of the problems is not significantly exacerbated by the codiagnosis of a brain tumor unless treatment includes cranial irradiation.

Activity and mobility of subtilisin in low water organic media: hydration is more important than solvent dielectric.

The relationship between hydration, catalytic activity and protein dynamics was investigated for subtilisin Carlsberg in organic solvents with low water content. The organic media were cyclohexane, dichloromethane or acetonitrile, with controlled thermodynamic water activity (aw). Catalytic rate profiles showed the same dependence on aw for the three different solvents. The structural mobility of the enzyme in air and organic media was probed by proton solid-state NMR relaxation measurements. Both spin-lattice relaxation time (T1 ) and line width at half height (apparent spin-spin relaxation time (T2)) were determined for protein which was exchanged and hydrated with D2O. We found NMR relaxation was much more dependent on aw than medium identity (despite very different dielectrics) showing that enzyme hydration is the primary determinant of mobility. Results suggest that initial hydration up to aw 0.22 causes rigidification of part of the protein structure. As aw is increased further, enzyme mobility is found to increase. Above aw 0.44, a large increase in the proportion of more mobile protons coincides with a steep rise in catalytic activity for the enzyme in each of the solvents studied.

Learning disability subtypes in children with neurofibromatosis.

A high incidence of learning disabilities (LD) has been reported in children with neurofibromatosis Type 1 (NF-1), and many children affected with this disease are thought to have a form of LD that is characterized by selective visuospatial and motor deficits. However, the evidence is subject to sampling biases and is limited by the clinical-inferential methods used to classify children into LD subtypes. In the present study, objective statistical methods were used to categorize LD in 105 children with NF-1 between the ages of 6 and 18 years. A cluster analysis of achievement test scores yielded 10 groups; 6 of which met our criterion for academic deficiency. An analysis of neuropsychological data for 72 children with academic deficiencies with complete neuropsychological data yielded three groups: a neuropsychologically normal group (n = 28), a group with general academic deficiencies (n = 34), and a group with visuospatial-construction deficiencies (n = 10). The low incidence of visuospatial-constructional deficits and the absence of cases involving pure linguistic deficits is notable.

Functionalized dendritic polybenzylethers as acid/base buffers for biocatalysis in nonpolar solvents.

A carboxylic acid functionalized dendritic polybenzyl ether has been synthesized and used with its sodium salt to generate a novel acid/base buffer soluble in nonpolar organic solvents. The effect of different ratios of the two buffer forms on the catalytic activity of subtilisin Carlsberg and chymotrypsin was investigated in toluene. It was found that reproducible transesterification rates were obtained at each molar ratio consistent with a buffering effect. As the molar ratio of the sodium salt to acid was increased there was a corresponding increase in the catalytic activity of both enzymes although their profiles were not identical. This is consistent with a requirement for deprotonation of a residue at active site of the enzyme as observed in aqueous solution. The ability to alter and precisely control the ionization state of biocatalysts in nonpolar solvents may find useful applications for both fundamental studies and in syntheses where reactants or products have acid/base properties. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 278-282, 1997.

Visual anomalies in young children exposed to cocaine.

PURPOSE: The number of children exposed to cocaine in utero each year is increasing. Recent reports suggest significant visual anomalies in infants prenatally exposed to cocaine. The purpose of this retrospective study was to determine if children exposed prenatally to cocaine were at a greater risk for visual abnormalities, such as strabismus and significant refractive errors. METHODS: This pilot study was conducted at two sites, an outpatient clinic and a hospital-based practice. Consecutive files from January to July, 1993, of 79 children (aged 4 months to 94 months); who were identified by case history or meconium analysis information as being exposed to cocaine in utero, were reviewed. Fifty-five children met the inclusion criteria for the study. In addition, a control group of 100 pediatric patients were randomly selected from the pediatric patients seen at the outpatient clinical site. RESULTS: Of the 30 children from the Illinois Eye Institute (IEI) and the 25 children from The Children's Hospital (TCH), spherical refractive errors in the right eye ranged from +6.50 to -12.50 D. The median refractive errors were +0.75 and +0.50 D, respectively. No statistical difference was found in spherical refractive error, astigmatism, or anisometropia between the cocaine-exposed cohorts and the control group (N = 100). Strabismus was found in 15/55 (27%) of the children in the cocaine-exposed group. There was a statistically significant difference in the prevalence of strabismus between the cocaine-exposed group and the control group. Further analysis revealed that full birthweight (> 2500 g) children prenatally exposed to cocaine were at a greater risk for strabismus as compared to the full birthweight control group. Ocular abnormalities were rare, but included optic nerve atrophy and retinopathy of prematurity. CONCLUSIONS: These data suggest cocaine exposure during pregnancy may place a child at risk for conditions that may negatively impact the visual system, specifically strabismus.