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Find video protocols related to scientific articles indexed in Pubmed.
Animal models of exfoliation syndrome, now and future.
J. Glaucoma
PUBLISHED: 10-03-2014
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At present, no animal models fully embody exfoliation syndrome or exfoliation glaucoma. Both genetic and environmental factors appear critical for disease manifestation, and both must be considered when generating animal models. Because mice provide a powerful mammalian platform for modeling complex disease, this paper focuses on mouse models of exfoliation syndrome and exfoliation glaucoma.
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Probing the Surface Calcium Binding Sites of Melanosomes Using Molecular Rulers.
J Phys Chem B
PUBLISHED: 09-25-2014
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Melanosomes have the capacity to bind significant concentrations of calcium, suggesting there are surface binding sites that enable cations to access the interior of fully pigmented melanosomes. The surface of melanosomes is known to contain significant concentrations of carboxylate groups which likely are the initial biding sites for calcium, but their arrangement on the surface of the melanosome is not known. In various calcium proteins, a bidentate coordination by two carboxylate groups is the most common structure. In this study, we determine the distance between neighboring surface carboxylic acid groups by examining the binding of a series of diamines (+)H3N(CH2)mNH3(+) (m = 1-5) to melanosomes isolated from the ink sacs of Sepia officinalis and bovine choroid tissue. Of these amines, ethylenediamine (m = 2) shows optimal bidentate binding, revealing a narrow distribution of distances between neighboring carboxylic acid groups, ?480 pm, similar to that found in proteins for calcium binding motifs involving two carboxylate groups.
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Parent-Teacher Agreement on ADHD Symptoms Across Development.
Psychol Assess
PUBLISHED: 09-16-2014
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Parent-teacher agreement on attention-deficit/hyperactivity disorder (ADHD) symptom ratings ranges from low to moderate. Most studies evaluating parent-teacher agreement have not assessed measurement invariance across raters. Hence, it is unclear whether discordance across raters is due to differing ADHD constructs across raters or other factors (e.g., subjective differences across raters). Additionally, the effect of development on parent-teacher agreement is relatively unknown. To address these limitations, the present study used parent and teacher ADHD ratings from a large (N = 6,659) developmentally diverse (ages 4-17) sample. Using exploratory structural equation modeling on half the sample, and then confirmatory factor analysis (CFA) on the other half of the sample, confirmed a 2-factor structure with significant cross-loadings for the 18 ADHD symptoms. CFA invariance analyses demonstrated that the 2-factor symptom structure was similar across raters and age groups. After confirming measurement invariance, the correlation between latent factors within and across raters was examined for each age group as well as across age groups. Parents reported greater severity of ADHD symptoms than did teachers, and both parents and teachers reported higher levels of hyperactivity/impulsivity in younger children than in older children and consistent levels of inattention across development. Finally, correlations between parent-teacher ratings of like factors were weak for inattention and moderate-strong for hyperactivity/impulsivity, and the magnitude of parent-teacher agreement did not vary across development. In conclusion, while parent and teacher ratings of ADHD behaviors are only weakly to moderately correlated, each reporter provides unique and valid clinical information as it relates to ADHD symptom presentation. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
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A Flexible Platform for Biofeedback-driven Control and Personalization of Electrical Nerve Stimulation Therapy.
IEEE Trans Neural Syst Rehabil Eng
PUBLISHED: 08-27-2014
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Electrical vagus nerve stimulation is a treatment alternative for many epileptic and depressed patients whose symptoms are not well managed with pharmaceutical therapy. However, the fixed stimulus, open loop dosing mechanism limits its efficacy and precludes major advances in the quality of therapy. A real-time, responsive form of vagus nerve stimulation is needed to control nerve activation according to therapeutic need. This personalized approach to therapy will improve efficacy and reduce the number and severity of side effects. We present autonomous neural control, a responsive, biofeedbackdriven approach that uses the degree of measured nerve activation to control stimulus delivery. We demonstrate autonomous neural control in rats, showing that it rapidly learns how to most efficiently activate any desired proportion of vagal A, B, and/or C fibers over time. This system will maximize efficacy by minimizing patient response variability and by minimizing therapeutic failures resulting from longitudinal decreases in nerve activation with increasing durations of treatment. The value of autonomous neural control equally applies to other applications of electrical nerve stimulation.
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Combinatorial targeting of early pathways profoundly inhibits neurodegeneration in a mouse model of glaucoma.
Neurobiol. Dis.
PUBLISHED: 08-15-2014
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The endothelin system is implicated in various human and animal glaucomas. Targeting the endothelin system has great promise as a treatment for human glaucoma, but the cell types involved and the exact mechanisms of action are not clearly elucidated. Here, we report a detailed characterization of the endothelin system in specific cell types of the optic nerve head (ONH) during glaucoma in DBA/2J mice. First, we show that key components of the endothelin system are expressed in multiple cell types. We discover that endothelin 2 (EDN2) is expressed in astrocytes as well as microglia/monocytes in the ONH. The endothelin receptor type A (Ednra) is expressed in vascular endothelial cells, while the endothelin receptor type B (Ednrb) receptor is expressed in ONH astrocytes. Second, we show that Macitentan treatment protects from glaucoma. Macitentan is a novel, orally administered, dual endothelin receptor antagonist with greater affinity, efficacy and safety than previous antagonists. Finally, we test the combinatorial effect of targeting both the endothelin and complement systems as a treatment for glaucoma. Similar to endothelin, the complement system is implicated in a variety of human and animal glaucomas, and has great promise as a treatment target. We discovered that combined targeting of the endothelin (Bosentan) and complement (C1qa mutation) systems is profoundly protective. Remarkably, 80% of DBA/2J eyes subjected to this combined inhibition developed no detectable glaucoma. This opens an exciting new avenue for neuroprotection in glaucoma.
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Does Sluggish Cognitive Tempo Fit Within a Bi-Factor Model of ADHD?
J Atten Disord
PUBLISHED: 07-10-2014
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Studies demonstrate sluggish cognitive tempo (SCT) symptoms to be distinct from inattentive and hyperactive-impulsive dimensions of ADHD. No study has examined SCT within a bi-factor model of ADHD, whereby SCT may form a specific factor distinct from inattention and hyperactivity/impulsivity while still fitting within a general ADHD factor, which was the purpose of the current study.
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Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.
PLoS Biol.
PUBLISHED: 07-01-2014
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Schlemm's canal (SC) plays central roles in ocular physiology. These roles depend on the molecular phenotypes of SC endothelial cells (SECs). Both the specific phenotype of SECs and development of SC remain poorly defined. To allow a modern and extensive analysis of SC and its origins, we developed a new whole-mount procedure to visualize its development in the context of surrounding tissues. We then applied genetic lineage tracing, specific-fluorescent reporter genes, immunofluorescence, high-resolution confocal microscopy, and three-dimensional (3D) rendering to study SC. Using these techniques, we show that SECs have a unique phenotype that is a blend of both blood and lymphatic endothelial cell phenotypes. By analyzing whole mounts of postnatal mouse eyes progressively to adulthood, we show that SC develops from blood vessels through a newly discovered process that we name "canalogenesis." Functional inhibition of KDR (VEGFR2), a critical receptor in initiating angiogenesis, shows that this receptor is required during canalogenesis. Unlike angiogenesis and similar to stages of vasculogenesis, during canalogenesis tip cells divide and form branched chains prior to vessel formation. Differing from both angiogenesis and vasculogenesis, during canalogenesis SECs express Prox1, a master regulator of lymphangiogenesis and lymphatic phenotypes. Thus, SC development resembles a blend of vascular developmental programs. These advances define SC as a unique vessel with a combination of blood vascular and lymphatic phenotypes. They are important for dissecting its functions that are essential for ocular health and normal vision.
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Enzyme-linked immunosorbent assay (ELISA) for the detection of use of the synthetic cannabinoid agonists UR-144 and XLR-11 in human urine.
J Anal Toxicol
PUBLISHED: 06-07-2014
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Ongoing changes in the synthetic cannabinoid drug market create the need for relevant targeted immunoassays for rapid screening of biological samples. We describe the validation and performance characteristics of an enzyme-linked immunosorbent assay designed to detect use of one of the most prevalent synthetic cannabinoids in urine, UR-144, by targeting its pentanoic acid metabolite. Fluorinated UR-144 (XLR-11) has been demonstrated to metabolize to this common product. The assay has significant cross-reactivity with UR-144-5-OH, UR-144-4-OH and XLR-11-4-OH metabolites, but <10% cross-reactivity with the parent compounds, and no measurable cross-reactivity with other synthetic cannabinoids and their metabolites at concentrations of <1,000 ng/mL. The assay's cutoff is 5 ng/mL relative to the pentanoic acid metabolite of UR-144, which is used as the calibrator. The method was validated with 90 positive and negative control urine samples for UR-144, XLR-11 and its metabolites tested versus liquid chromatography-tandem mass spectrometry. The accuracy, sensitivity and specificity were determined to be 100% for the assay at the specified cutoff.
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A dominant-negative mutation of mouse Lmx1b causes glaucoma and is semi-lethal via LBD1-mediated dimerisation.
PLoS Genet.
PUBLISHED: 05-01-2014
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Mutations in the LIM-homeodomain transcription factor LMX1B cause nail-patella syndrome, an autosomal dominant pleiotrophic human disorder in which nail, patella and elbow dysplasia is associated with other skeletal abnormalities and variably nephropathy and glaucoma. It is thought to be a haploinsufficient disorder. Studies in the mouse have shown that during development Lmx1b controls limb dorsal-ventral patterning and is also required for kidney and eye development, midbrain-hindbrain boundary establishment and the specification of specific neuronal subtypes. Mice completely deficient for Lmx1b die at birth. In contrast to the situation in humans, heterozygous null mice do not have a mutant phenotype. Here we report a novel mouse mutant Icst, an N-ethyl-N-nitrosourea-induced missense substitution, V265D, in the homeodomain of LMX1B that abolishes DNA binding and thereby the ability to transactivate other genes. Although the homozygous phenotypic consequences of Icst and the null allele of Lmx1b are the same, heterozygous Icst elicits a phenotype whilst the null allele does not. Heterozygous Icst causes glaucomatous eye defects and is semi-lethal, probably due to kidney failure. We show that the null phenotype is rescued more effectively by an Lmx1b transgene than is Icst. Co-immunoprecipitation experiments show that both wild-type and Icst LMX1B are found in complexes with LIM domain binding protein 1 (LDB1), resulting in lower levels of functional LMX1B in Icst heterozygotes than null heterozygotes. We conclude that Icst is a dominant-negative allele of Lmx1b. These findings indicate a reassessment of whether nail-patella syndrome is always haploinsufficient. Furthermore, Icst is a rare example of a model of human glaucoma caused by mutation of the same gene in humans and mice.
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DLK-dependent signaling is important for somal but not axonal degeneration of retinal ganglion cells following axonal injury.
Neurobiol. Dis.
PUBLISHED: 04-18-2014
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Injury to retinal ganglion cell (RGC) axons triggers rapid activation of Jun N-terminal kinase (JNK) signaling, a major prodeath pathway in injured RGCs. Of the multiple kinases that can activate JNK, dual leucine kinase (Dlk) is known to regulate both apoptosis and Wallerian degeneration triggered by axonal insult. Here we tested the importance of Dlk in regulating somal and axonal degeneration of RGCs following axonal injury. Removal of DLK from the developing optic cup did not grossly affect developmental RGC death or inner plexiform layer organization. In the adult, Dlk deficiency significantly delayed axonal-injury induced RGC death. The activation of JUN was also attenuated in Dlk deficient retinas. Dlk deficiency attenuated the activation of the somal pool of JNK but did not prevent activation of the axonal pool of JNK after axonal injury, indicating that JNK activation in different cellular compartments of an RGC following axonal injury is regulated by distinct upstream kinases. In contrast to its robust influence on somal degeneration, Dlk deficiency did not alter RGC axonal degeneration after axonal injury as assessed using physiological readouts of optic nerve function.
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The impact of different point-of-care testing lipid analysers on cardiovascular disease risk assessment.
J. Clin. Pathol.
PUBLISHED: 04-07-2014
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Lipid point-of-care testing (POCT) analysers are being used to screen target populations to identify individuals at high risk of developing cardiovascular disease (CVD) as part of the National Health Service (NHS) Health Checks programme. We evaluated the performance of the Cholestech LDX and CardioChek PA POCT analysers against laboratory methods in CVD risk assessment.
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ZnO nanodisk based UV detectors with printed electrodes.
Langmuir
PUBLISHED: 03-25-2014
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The fabrication of highly functional materials for practical devices requires a deep understanding of the association between morphological and structural properties and applications. A controlled hydrothermal method to produce single crystal ZnO hexagonal nanodisks, nanorings, and nanoroses using a mixed solution of zinc sulfate (ZnSO4) and hexamethylenetetramine (HMTA) without the need of catalysts, substrates, or templates at low temperature (75 °C) is introduced. Metal-semiconductor-metal (MSM) ultraviolet (UV) detectors were fabricated based on individual and multiple single-crystal zinc oxide (ZnO) hexagonal nanodisks. High quality single crystal individual nanodisk devices were fabricated with inkjet-printed silver electrodes. The detectors fabricated show record photoresponsivity (3300 A/W) and external quantum efficiency (1.2 × 10(4)), which we attribute to the absence of grain boundaries in the single crystal ZnO nanodisk and the polarity of its exposed surface.
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Headache and refractive errors in children.
J Pediatr Ophthalmol Strabismus
PUBLISHED: 03-13-2014
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To investigate the association between uncorrected or miscorrected refractive errors in children and headache, and to determine whether correction of refractive errors contributes to headache resolution.
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Determining immune components necessary for progression of pigment dispersing disease to glaucoma in DBA/2J mice.
BMC Genet.
PUBLISHED: 03-06-2014
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The molecular mechanisms causing pigment dispersion syndrome (PDS) and the pathway(s) by which it progresses to pigmentary glaucoma are not known. Mutations in two melanosomal protein genes (Tyrp1(b) and Gpnmb(R150X)) are responsible for pigment dispersing iris disease, which progresses to intraocular pressure (IOP) elevation and subsequent glaucoma in DBA/2J mice. Melanosomal defects along with ocular immune abnormalities play a role in the propagation of pigment dispersion and progression to IOP elevation. Here, we tested the role of specific immune components in the progression of the iris disease and high IOP.
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ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.
PLoS Genet.
PUBLISHED: 03-01-2014
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Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =? -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
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Aspects of the morphology of the juvenile life stages of Paradiplozoon ichthyoxanthon Avenant-Oldewage, 2013 (Monogenea: Diplozoidae).
Acta Parasitol.
PUBLISHED: 02-24-2014
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There are eight life stages in the life-cycle of Diplozoon paradoxum and limited knowledge of the life-cycle for other diplozoid genera exists. The aim of this study was to record the number of life-stages of Paradiplozoon ichthyoxanthon obtained from, Labeobarbus aeneus and Labeobarbus kimberlyensis, in the Vaal Dam from 2005 to 2007. Six larval life stages and one adult stage of P. ichtyoxanthon were identified from specimens collected in vitro and in situ. In vitro, eggs hatched after 21 days at 18°C. Eggs collected during winter were significantly larger than those laid during spring or summer. Paradiplozoon ichthyoxanthon oncomiracidia have peripheral eyes with pink pigmentation, a tubular anterior bladder-like structure, bicuspid basal pharynx valve and a branched digestive caecum and residual shell material or vitellaria in the caecum. Immature reproductive tissue connected to the ventral sucker and dorsal papillae were noted for the first time in diporpa. Large nervous ganglia and innervation of muscle were observed around the ventral sucker.
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Treatment of consecutive exotropia: unilateral lateral rectus recession combined with medial rectus advancement or resection.
J Pediatr Ophthalmol Strabismus
PUBLISHED: 02-12-2014
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Consecutive exotropia presents a difficult clinical problem, especially when previously recessed medial recti are to be strengthened. Surgical options include advancement, typically with a small resection, and resection alone.
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Mediators of methylphenidate effects on math performance in children with attention-deficit hyperactivity disorder.
J Dev Behav Pediatr
PUBLISHED: 02-11-2014
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Stimulant medications, such as methylphenidate (MPH), improve the academic performance of children with attention-deficit hyperactivity disorder (ADHD). However, the mechanism by which MPH exerts an effect on academic performance is unclear. We examined MPH effects on math performance and investigated possible mediation of MPH effects by changes in time on-task, inhibitory control, selective attention, and reaction time variability.
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Near-infrared excited state dynamics of melanins: the effects of iron content, photo-damage, chemical oxidation, and aggregate size.
J Phys Chem A
PUBLISHED: 01-31-2014
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Ultrafast pump-probe measurements can discriminate the two forms of melanin found in biological tissue (eumelanin and pheomelanin), which may be useful for diagnosing and grading melanoma. However, recent work has shown that bound iron content changes eumelanin's pump-probe response, making it more similar to that of pheomelanin. Here we record the pump-probe response of these melanins at a wider range of wavelengths than previous work and show that with shorter pump wavelengths the response crosses over from being dominated by ground-state bleaching to being dominated by excited-state absorption. The crossover wavelength is different for each type of melanin. In our analysis, we found that the mechanism by which iron modifies eumelanin's pump-probe response cannot be attributed to Raman resonances or differences in melanin aggregation and is more likely caused by iron acting to broaden the unit spectra of individual chromophores in the heterogeneous melanin aggregate. We analyze the dependence on optical intensity, finding that iron-loaded eumelanin undergoes irreversible changes to the pump-probe response after intense laser exposure. Simultaneously acquired fluorescence data suggest that the previously reported "activation" of eumelanin fluorescence may be caused in part by the dissociation of metal ions or the selective degradation of iron-containing melanin.
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Phospholipid flippase ATP8A2 is required for normal visual and auditory function and photoreceptor and spiral ganglion cell survival.
J. Cell. Sci.
PUBLISHED: 01-10-2014
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ATP8A2 is a P4-ATPase that is highly expressed in the retina, brain, spinal cord and testes. In the retina, ATP8A2 is localized in photoreceptors where it uses ATP to transport phosphatidylserine (PS) and phosphatidylethanolamine (PE) from the exoplasmic to the cytoplasmic leaflet of membranes. Although mutations in ATP8A2 have been reported to cause mental retardation in humans and degeneration of spinal motor neurons in mice, the role of ATP8A2 in sensory systems has not been investigated. We have analyzed the retina and cochlea of ATP8A2-deficient mice to determine the role of ATP8A2 in visual and auditory systems. ATP8A2-deficient mice have shortened photoreceptor outer segments, a reduction in photoresponses and decreased photoreceptor viability. The ultrastructure and phagocytosis of the photoreceptor outer segment appeared normal, but the PS and PE compositions were altered and the rhodopsin content was decreased. The auditory brainstem response threshold was significantly higher and degeneration of spiral ganglion cells was apparent. Our studies indicate that ATP8A2 plays a crucial role in photoreceptor and spiral ganglion cell function and survival by maintaining phospholipid composition and contributing to vesicle trafficking.
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DBA/2J mice are susceptible to diabetic nephropathy and diabetic exacerbation of IOP elevation.
PLoS ONE
PUBLISHED: 01-01-2014
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Some pathological manifestations of diabetes in the eye include retinopathy, cataracts and elevated intraocular pressure (IOP). Loss of retinal ganglion cells (RGCs) in non-proliferative stages of diabetic retinopathy and small increases in IOP in diabetic patients has raised the possibility that diabetes affects the development and progression of ocular hypertension and glaucoma. The Ins2Akita mutation is known to cause diabetes and retinopathy on a C57BL/6J (B6) background by as early as 3 months of age. Here, the impact of the Akita mutation on glaucoma was assessed using DBA/2J (D2) mice, a widely used mouse model of ocular hypertension induced glaucoma. In D2.Ins2Akita/+ mice, the contribution of diabetes to vascular permeability, IOP elevation, RGC loss, and glaucoma development was assessed. D2.Ins2Akita/+ mice developed a severe diabetic nephropathy and early mortality between 6-8 months of age. This agrees with previous reports showing that the D2 background is more susceptible to diabetes than the B6 background. In addition, D2.Ins2Akita/+ mice had vascular leakage, astrocyte reactivity and a significant increase in IOP. However no RGC loss and no anterograde axonal transport dysfunction were found at 8.5 months of age. Therefore, our data show that despite severe diabetes and an increased IOP compared to controls, RGCs do not lose axon transport or degenerate. This may be due to a DBA/2J-specific genetic modifier(s) that could provide novel and important avenues for developing new therapies for diabetic retinopathy and possibly glaucoma.
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The myADHDportal.com Improvement Program: An innovative quality improvement intervention for improving the quality of ADHD care among community-based pediatricians.
Clin Pract Pediatr Psychol
PUBLISHED: 10-29-2013
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Though the American Academy of Pediatrics has developed and disseminated clear evidence-based guidelines for ADHD care, community-based pediatricians often have difficulty implementing these guidelines. New strategies are needed to improve the quality of care received by children with ADHD and to improve utilization of the AAP consensus guidelines by pediatricians. An evidence-based quality improvement intervention has been developed that effectively improves the quality of ADHD care delivered by community-based pediatricians. In order to facilitative widespread dissemination of this intervention model, the entire intervention has been modified for online delivery. The intervention is called the myADHDportal.com Improvement Program. The full functionality of this online intervention is described including the collection of online ADHD rating scales from parents and teachers and online communication between parents, teachers, and physicians. In addition, the web portal integrates several innovative quality improvement features including an online wizard for mapping ADHD patient flow, an online report card for monitoring quality of care, and an online wizard for guiding practices through the Plan-Do-Study-Act (PDSA) cycle process. The combination of clinical utility and quality improvement tools facilitates delivery of quality ADHD care and reduces several of the obstacles to implementing AAP-recommended practice behaviors. Initial results with this intervention model are reviewed and goals for dissemination are described.
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The relationship between ADHD symptom dimensions, clinical correlates, and functional impairments.
J Dev Behav Pediatr
PUBLISHED: 09-18-2013
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To better understand how heterogeneity in attention-deficit hyperactivity disorder (ADHD) symptoms relates to heterogeneity in functional impairment domains in children with ADHD after accounting for demographic variables and comorbidities, in particular oppositionality and internalizing symptoms.
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Fatal pediatric head injuries: a 20-year review of cases through the Auckland coroners office.
Am J Forensic Med Pathol
PUBLISHED: 08-17-2013
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Inflicted pediatric head injury is a significant issue in New Zealand, fatal cases receiving extensive media attention. The primary aims of this article were to analyze injury patterns and reported mechanisms against both age and cause (accidental or inflicted). The secondary aims were to quantify these deaths and identify trends over time. We retrospectively reviewed pediatric deaths due to head injury in children younger than 15 years referred to the Coronial Service of Auckland, New Zealand, from January 1, 1991, to December 31, 2010. One hundred sixty-seven cases were identified. Overall incidence was stable over time; however, the rate of inflicted head injury increased significantly (from 0.1 to 0.4/100,000 per year). Evidence of impact was seen in 90% of cases. In children younger than 2 years, in the absence of motor vehicle or pedestrian trauma, subdural hemorrhage and diffuse axonal injury were both highly suggestive of inflicted injury. The absence of a history of trauma or a history of a fall less than 1 m was also highly suggestive of inflicted injury. Retinal hemorrhages in these fatal head injuries were severe in 77% of cases and moderate in the remainder.
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Pump-Probe Microscopic Imaging of Jurassic-Aged Eumelanin.
J Phys Chem Lett
PUBLISHED: 07-13-2013
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Melanins are biological pigments found throughout the animal kingdom that have many diverse functions. Pump-probe imaging can differentiate the two kinds of melanins found in human skin, eumelanin and pheomelanin, the distributions of which are relevant to the diagnosis of melanoma. The long-term stability of the melanin pump-probe signal is central to using this technology to analyze melanin distributions in archived tissue samples to improve diagnostic procedures. This report shows that most of the pump-probe signal from eumelanin derived from a Jurassic cephalopod is essentially identical to that of eumelanin extracted from its modern counterpart, Sepia officinalis. However, additional classes of eumelanin signals found in the fossil reveal that the pump-probe signature is sensitive to iron content, which could be a valuable tool for pathologists who cannot otherwise know the microscopic distributions of iron in melanins.
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Deficiency of complement component 5 ameliorates glaucoma in DBA/2J mice.
J Neuroinflammation
PUBLISHED: 05-03-2013
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Glaucoma is an age-related neurodegenerative disorder involving the loss of retinal ganglion cells (RGCs), which results in blindness. Studies in animal models have shown that activation of inflammatory processes occurs early in the disease. In particular, the complement cascade is activated very early in DBA/2J mice, a widely used mouse model of glaucoma. A comprehensive analysis of the role of the complement cascade in DBA/2J glaucoma has not been possible because DBA/2J mice are naturally deficient in complement component 5 (C5, also known as hemolytic complement, Hc), a key mediator of the downstream processes of the complement cascade, including the formation of the membrane attack complex.
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Validation of a novel immunoassay for the detection of synthetic cannabinoids and metabolites in urine specimens.
J Anal Toxicol
PUBLISHED: 04-26-2013
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Synthetic cannabinoid drugs do not cross react on traditional marijuana immunoassay tests, preventing their use in large scale drug screening programs. This paper describes the validation and performance characteristics of two enzyme linked immunosorbent assays designed to detect the use of two common synthetic cannabinoids in urine, JWH-018 and JWH-250. The JWH-018 assay has significant cross-reactivity with several synthetic cannabinoids and their metabolites, whereas the JWH-250 assay has limited cross-reactivity. The assays are calibrated at 5 ng/mL with the 5-OH metabolite of JWH-018 and the 4-OH metabolite of JWH-250. The method was validated with 114 urine samples for JHW-018 and 84 urine samples for JWH-250 and confirmed by using liquid chromatography tandem mass spectrometry, which tests for metabolites of JWH-018, JWH-019, JWH-073, JWH-250 and AM-2201. The accuracy was determined to be 98% with greater than 95% sensitivity and specificity for both assays.
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Echinocandins in invasive candidiasis.
Mycoses
PUBLISHED: 04-04-2013
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We summarise a recent meeting, sponsored by Pfizer Inc., where experts in Asia shared their clinical experience in managing IC. The echinocandins have demonstrated good activity against non-albicans infections and also azole-resistant strains, both preclinically and in recent clinical trials. As well as proving efficacious, echinocandins have a favourable safety profile and are well tolerated, including among inpatient subpopulations, such as transplant recipients and those with renal or hepatic dysfunction. In addition the echinocandins generally have minimal drug-drug interactions, unlike the oral azoles, which have multiple effects on cytochrome P450-mediated drug metabolism. Echinocandins are characterised by a good safety profile, few drug-drug interactions and good susceptibilities. With the increase in potentially azole-resistant non-albicans infections, echinocandins may become the first-line treatment of choice for many patients.
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Patterns of structural head injury in children younger than 3 years: a ten-year review of 519 patients.
J Trauma Acute Care Surg
PUBLISHED: 03-22-2013
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Abusive head injury is a major contributor to morbidity and mortality in infants and toddlers, but data comparing patterns of injury in corroborated accidental trauma and confessed child abuse are scarce.
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The effectiveness of policy changes designed to increase the attendance rate for outpatient retinopathy of prematurity (ROP) screening examinations.
J AAPOS
PUBLISHED: 03-04-2013
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To determine the effectiveness of a series of policy changes designed to increase the attendance rate for outpatient retinopathy of prematurity (ROP) screening examinations.
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Melanins and melanogenesis: methods, standards, protocols.
Pigment Cell Melanoma Res
PUBLISHED: 03-02-2013
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Despite considerable advances in the past decade, melanin research still suffers from the lack of universally accepted and shared nomenclature, methodologies, and structural models. This paper stems from the joint efforts of chemists, biochemists, physicists, biologists, and physicians with recognized and consolidated expertise in the field of melanins and melanogenesis, who critically reviewed and experimentally revisited methods, standards, and protocols to provide for the first time a consensus set of recommended procedures to be adopted and shared by researchers involved in pigment cell research. The aim of the paper was to define an unprecedented frame of reference built on cutting-edge knowledge and state-of-the-art methodology, to enable reliable comparison of results among laboratories and new progress in the field based on standardized methods and shared information.
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Quantifying the association constant and stoichiometry of the complexation between colloidal polyacrylate-coated gold nanoparticles and chymotrypsin.
J Phys Chem B
PUBLISHED: 02-07-2013
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Qualitative and quantitative insights into the capacity and association constant for the binding of chymotrypsin to polyacrylate-coated gold nanoparticles is determined using fluorescence quenching, optical absorption and circular dichroism spectroscopy, isothermal calorimetry, and gel electrophoresis. The collective data reveal a binding capacity and constant for this particular system of ~7 and ~2 × 10(6) M(-1), respectively. These values vary among the individual techniques, and not all techniques are able to provide quantitative information. The present study demonstrates that accurately quantifying the association between nanoparticles and biological materials requires using multiple approaches to ensure consistency among the binding parameters determined.
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Combined optical and atropine treatment of children with residual amblyopia after atropine penalization.
J Pediatr Ophthalmol Strabismus
PUBLISHED: 01-11-2013
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The authors studied 5 cases in which combined optical and atropine treatment (COAT) was instituted in children with residual amblyopia after atropine penalization. All 5 amblyopic eyes improved without lasting decrease in the visual acuity of the dominant eyes. Appropriately administered, COAT may rescue atropine failures.
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The relationship between thermoregulation and REM sleep behaviour disorder in Parkinsons disease.
PLoS ONE
PUBLISHED: 01-01-2013
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This study explored the relationship between symptoms of rapid eye movement sleep behaviour disorder, thermoregulation and sleep in Parkinsons Disease.
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Retinal ganglion cell dendritic atrophy in DBA/2J glaucoma.
PLoS ONE
PUBLISHED: 01-01-2013
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Glaucoma is a complex disease affecting an estimated 70 million people worldwide, characterised by the progressive degeneration of retinal ganglion cells and accompanying visual field loss. The common site of damage to retinal ganglion cells is thought to be at the optic nerve head, however evidence from other optic neuropathies and neurodegenerative disorders suggests that dendritic structures undergo a prolonged period of atrophy that may accompany or even precede soma loss and neuronal cell death. Using the DBA/2J mouse model of glaucoma this investigation aims to elucidate the impact of increasing intraocular pressure on retinal ganglion cell dendrites using DBA/2J mice that express YFP throughout the retinal ganglion cells driven by Thy1 (DBA/2J.Thy1(YFP)) and DiOlistically labelled retinal ganglion cells in DBA/2J mice. Here we show retinal ganglion cell dendritic degeneration in DiOlistically labelled DBA/2J retinal ganglion cells but not in the DBA/2J.Thy1(YFP) retinal ganglion cells suggesting that a potential downregulation of Thy1 allows only healthy retinal ganglion cells to express YFP. These data may highlight alternative pathways to retinal ganglion cell loss in DBA/2J glaucoma.
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Use of an Internet portal to improve community-based pediatric ADHD care: a cluster randomized trial.
Pediatrics
PUBLISHED: 10-17-2011
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To determine the effectiveness of a quality improvement program to improve pediatricians adherence to existing, evidence-based, attention-deficit/hyperactivity disorder (ADHD) practice guidelines.
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UV-absorption spectra of melanosomes containing varying 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid content.
J Phys Chem B
PUBLISHED: 10-10-2011
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Central to understanding the photochemical properties of melanosomes is a direct measurement of their absorption coefficients. Herein, the absorption spectra of intact melanosomes of varying molecular compositions and embryonic origins were measured and compared over the spectral range from 245 to 310 nm. The absorption spectra of melanosomes predominately comprised of the eumelanin pigment were found to differ significantly from their constituent precursor molecules, 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA). This difference was most notable in the UV-A region and indicates that the electronic structures of the monomeric building blocks, DHICA in particular, are significantly modified upon polymerization to the melanin pigment. Furthermore, in comparing embryonic differences, the absorption coefficients of melanosomes isolated from bovine retinal pigment epithelial (RPE) cells (originating from the primitive forebrain) were greater than those for bovine choroid or iris melanosomes (originating from the neural crest). This difference suggests that either the pigment is present in greater density in RPE melanosomes or that there is an underlying difference in molecular structure.
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A generic miniature multi-feature programmable wireless powering headstage ASIC for implantable biomedical systems.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 08-29-2011
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Wireless powering holds immense promise to enable a variety of implantable biomedical measurement systems with different power supply and current budget requirements. Effective power management demands more functionality in the headstage design like power level detection for range estimation and power save modes for sleep-wake operation. This paper proposes a single chip ASIC solution that addresses these problems by incorporating digitally programmable features and thus has the potential to enable wireless powering for many implantable systems. The ASIC includes an RF rectifier which has a peak efficiency of 17.9% at 900 MHz and 11.0% at 2.4 GHz, a robust 1 V bandgap reference and LDO voltage regulator whose output can be programmed in the range of 1 V-1.5 V, and can drive upto 4 mA of load current. The input RF power level detector has a threshold of 1.6 V and the power management block can be programmed to give a 6%, 12.5% or 25% duty cycle power line to the transmitter resulting in upto 60% reduction in average power. The ASIC was fabricated using the TSMC 65 nm process, occupies 1mm(2) die area and the headstage consumes ~300 ?A at 1.2V regulated supply.
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The association of refractive error, strabismus, and amblyopia with congenital ptosis.
J AAPOS
PUBLISHED: 06-09-2011
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To determine the frequency of amblyopia and its associations among children with congenital ptosis.
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Datgan, a reusable software system for facile interrogation and visualization of complex transcription profiling data.
BMC Genomics
PUBLISHED: 06-09-2011
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We introduce Glaucoma Discovery Platform (GDP), an online environment for facile visualization and interrogation of complex transcription profiling datasets for glaucoma. We also report the availability of Datgan, the suite of scripts that was developed to construct GDP. This reusable software system complements existing repositories such as NCBI GEO or EBI ArrayExpress as it allows the construction of searchable databases to maximize understanding of user-selected transcription profiling datasets.
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Sleep-wake disturbances in common neurodegenerative diseases: a closer look at selected aspects of the neural circuitry.
J. Neurol. Sci.
PUBLISHED: 04-07-2011
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There is a growing appreciation regarding the relationship between common neurodegenerative diseases, such as Alzheimers and Parkinsons and sleep-wake disturbances. These clinical features often herald the onset of such conditions and certainly appear to influence disease phenotype and progression. This article reviews some of the pathophysiological processes underlying specific disruptions within the neural circuitry underlying sleep-wake disturbances and explores how clinicopathological relationships commonly manifest. It is proposed that a greater understanding of these relationships should allow insights in to the efficacy of currently available treatments and help in the development of future therapies targeting disruptions within the sleep-wake neural circuitry.
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Evidence for higher reaction time variability for children with ADHD on a range of cognitive tasks including reward and event rate manipulations.
Neuropsychology
PUBLISHED: 04-06-2011
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The purpose of the research study was to examine the manifestation of variability in reaction times (RT) in children with attention deficit hyperactivity disorder (ADHD) and to examine whether RT variability presented differently across a variety of neuropsychological tasks, was present across the two most common ADHD subtypes, and whether it was affected by reward and event rate (ER) manipulations.
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Mutations in the RNA granule component TDRD7 cause cataract and glaucoma.
Science
PUBLISHED: 03-26-2011
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The precise transcriptional regulation of gene expression is essential for vertebrate development, but the role of posttranscriptional regulatory mechanisms is less clear. Cytoplasmic RNA granules (RGs) function in the posttranscriptional control of gene expression, but the extent of RG involvement in organogenesis is unknown. We describe two human cases of pediatric cataract with loss-of-function mutations in TDRD7 and demonstrate that Tdrd7 nullizygosity in mouse causes cataracts, as well as glaucoma and an arrest in spermatogenesis. TDRD7 is a Tudor domain RNA binding protein that is expressed in lens fiber cells in distinct TDRD7-RGs that interact with STAU1-ribonucleoproteins (RNPs). TDRD7 coimmunoprecipitates with specific lens messenger RNAs (mRNAs) and is required for the posttranscriptional control of mRNAs that are critical to normal lens development and to RG function. These findings demonstrate a role for RGs in vertebrate organogenesis.
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Alteration of the serine protease PRSS56 causes angle-closure glaucoma in mice and posterior microphthalmia in humans and mice.
Nat. Genet.
PUBLISHED: 03-18-2011
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Angle-closure glaucoma (ACG) is a subset of glaucoma affecting 16 million people. Although 4 million people are bilaterally blind from ACG, the causative molecular mechanisms of ACG remain to be defined. High intraocular pressure induces glaucoma in ACG. High intraocular pressure traditionally was suggested to result from the iris blocking or closing the angle of the eye, thereby limiting aqueous humor drainage. Eyes from individuals with ACG often have a modestly decreased axial length, shallow anterior chamber and relatively large lens, features that predispose to angle closure. Here we show that genetic alteration of a previously unidentified serine protease (PRSS56) alters axial length and causes a mouse phenotype resembling ACG. Mutations affecting this protease also cause a severe decrease of axial length in individuals with posterior microphthalmia. Together, these data suggest that alterations of this serine protease may contribute to a spectrum of human ocular conditions including reduced ocular size and ACG.
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1-[6-(6-Acetyl-pyridin-2-yl)pyridin-2-yl]ethanone.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 03-08-2011
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In the title compound, C(14)H(12)N(2)O(2), the asymmetric unit comprises one half-mol-ecule with an inversion center between the pyridine rings. The rings are trans coplanar with the acetyl groups deviating slightly from the mean planes, making a dihedral angle of 4.63?(4)°. In the crystal, mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds, forming a supra-molecular sheet parallel to (100).
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Varying difficulty of Snellen letters and common errors in amblyopic and fellow eyes.
Arch. Ophthalmol.
PUBLISHED: 02-16-2011
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To investigate the varying difficulty of Snellen letters in children with amblyopia.
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Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death.
PLoS ONE
PUBLISHED: 02-07-2011
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Glaucoma, the most frequent optic neuropathy, is a leading cause of blindness worldwide. Death of retinal ganglion cells (RGCs) occurs in all forms of glaucoma and accounts for the loss of vision, however the molecular mechanisms that cause RGC loss remain unclear. The pro-apoptotic molecule, Fas ligand, is a transmembrane protein that can be cleaved from the cell surface by metalloproteinases to release a soluble protein with antagonistic activity. Previous studies documented that constitutive ocular expression of FasL maintained immune privilege and prevented neoangeogenesis. We now show that FasL also plays a major role in retinal neurotoxicity. Importantly, in both TNF? triggered RGC death and a spontaneous model of glaucoma, gene-targeted mice that express only full-length FasL exhibit accelerated RGC death. By contrast, FasL-deficiency, or administration of soluble FasL, protected RGCs from cell death. These data identify membrane-bound FasL as a critical effector molecule and potential therapeutic target in glaucoma.
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Effects of stimulant medication, incentives, and event rate on reaction time variability in children with ADHD.
Neuropsychopharmacology
PUBLISHED: 01-19-2011
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This study examined the effects of methylphenidate (MPH) on reaction time (RT) variability in children with attention deficit hyperactivity disorder (ADHD). Using a broad battery of computerized tasks, and both conventional and ex-Gaussian indicators of RT variability, in addition to within-task manipulations of incentive and event rate (ER), this study comprehensively examined the breadth, specificity, and possible moderators of effects of MPH on RT variability. A total of 93 children with ADHD completed a 4-week within-subject, randomized, double-blind, placebo-controlled crossover trial of MPH to identify an optimal dosage. Children were then randomly assigned to receive either their optimal MPH dose or placebo after which they completed five neuropsychological tasks, each allowing trial-by-trial assessment of RTs. Stimulant effects on RT variability were observed on both measures of the total RT distribution (ie, coefficient of variation) as well as on an ex-Gaussian measure examining the exponential portion of the RT distribution (ie, ?). There was minimal, if any, effect of MPH on performance accuracy or RT speed. Within-task incentive and ER manipulations did not appreciably affect stimulant effects across the tasks. The pattern of significant and pervasive effects of MPH on RT variability, and few effects of MPH on accuracy and RT speed suggest that MPH primarily affects RT variability. Given the magnitude and breadth of effects of MPH on RT variability as well as the apparent specificity of these effects of MPH on RT variability indicators, future research should focus on neurophysiological correlates of effects of MPH on RT variability in an effort to better define MPH pharmacodynamics.
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Pharmacological activity of novel 2-hydroxyacetophenone isatin derivatives on cardiac and vascular smooth muscles in rats.
J. Cardiovasc. Pharmacol.
PUBLISHED: 01-15-2011
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Isatin (1H-indole-2,3 dione) is an endogenous compound with biological activities. Many of its derivatives have pharmacological effects, including inhibition of cyclic guanosine monophosphate levels in cardiac tissue; sedative-hypnotic profiles; anticonvulsant, analgesic, antithermic, and anti-inflammatory activities; and anxiolytic, antimicrobial, and proapoptotic effects. Carbamates derived from isatin have a vasorelaxant profile. This study investigated the activity of 2 novel 2-hydroxyacetophenone derivatives of isatin (named MB101 and MB130) on the contractility of rat aorta and papillary muscles. Both compounds induced a concentration-dependent relaxation (5-100 ?M) in the endothelium-intact aorta that was abolished by N-nitro-L-arginine methyl ester. Atropine, a muscarinic receptor antagonist, significantly prevented vasodilatation of 100 ?M MB101. In contrast, atropine caused no significant alteration in MB130-induced vasorelaxation. Naloxone, a nonselective opioid receptor antagonist, completely prevented the relaxing effect of MB101 and MB130 at all concentrations. In papillary muscles, only MB130 induced a significant depression, and this contractile response was not altered by propranolol and atropine. Both the compounds reduced systolic and diastolic pressures in a dose-dependent manner in anesthetized rats. The 2-hydroxyacetophenones produced direct effects on vascular tonus through either muscarinic or opioid pathways. MB130 produced cardiac depression by opioid receptors and bradykinin because pretreatment HOE140 or with naloxone, an antagonist of type-2, bradykinin were able to partially block the decrease in twitch amplitude in papillary muscles induced by MB130. These findings provide information for designing new strategies for the treatment of cardiovascular disorders.
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Mutations in zebrafish lrp2 result in adult-onset ocular pathogenesis that models myopia and other risk factors for glaucoma.
PLoS Genet.
PUBLISHED: 01-13-2011
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The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2) underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individuals--but not all--develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease.
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Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma.
J. Clin. Invest.
PUBLISHED: 01-05-2011
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Glaucoma is one of the most common neurodegenerative diseases. Despite this, the earliest stages of this complex disease are still unclear. This study was specifically designed to identify early stages of glaucoma in DBA/2J mice. To do this, we used genome-wide expression profiling of optic nerve head and retina and a series of computational methods. Eyes with no detectable glaucoma by conventional assays were grouped into molecularly defined stages of disease using unbiased hierarchical clustering. These stages represent a temporally ordered sequence of glaucoma states. We then determined networks and biological processes that were altered at these early stages. Early-stage expression changes included upregulation of both the complement cascade and the endothelin system, and so we tested the therapeutic value of separately inhibiting them. Mice with a mutation in complement component 1a (C1qa) were protected from glaucoma. Similarly, inhibition of the endothelin system with bosentan, an endothelin receptor antagonist, was strongly protective against glaucomatous damage. Since endothelin 2 is potently vasoconstrictive and was produced by microglia/macrophages, our data provide what we believe to be a novel link between these cell types and vascular dysfunction in glaucoma. Targeting early molecular events, such as complement and endothelin induction, may provide effective new treatments for human glaucoma.
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Missing optomotor head-turning reflex in the DBA/2J mouse.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-01-2011
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The optomotor reflex of DBA/2J (D2), DBA/2J-Gpnmb+ (D2-Gpnmb+), and C57BL/6J (B6) mouse strains was assayed, and the retinal ganglion cell (RGC) firing patterns, direction selectivity, vestibulomotor function and central vision was compared between the D2 and B6 mouse lines.
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Structural correlation between the nerve fiber layer and retinal ganglion cell loss in mice with targeted disruption of the Brn3b gene.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-01-2011
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Mice with a targeted disruption of Brn3b (knockout Brn3b(-/-)) undergo the loss of a majority of retinal ganglion cells (RGCs) before birth. Spectral domain optical coherence tomography (SD-OCT) allows for the noninvasive examination of Brn3b(-/-) cellular loss in vivo.
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Anterior segment dysgenesis and early-onset glaucoma in nee mice with mutation of Sh3pxd2b.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-01-2011
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Mutations in SH3PXD2B cause Frank-Ter Haar syndrome, a rare condition characterized by congenital glaucoma, as well as craniofacial, skeletal, and cardiac anomalies. The nee strain of mice carries a spontaneously arising mutation in Sh3pxd2b. The purpose of this study was to test whether nee mice develop glaucoma.
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The fabrication of large-area, free-standing GaN by a novel nanoetching process.
Nanotechnology
PUBLISHED: 12-20-2010
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A simple yet versatile nanoetching process in porosifying and machining GaN is reported in this work. By combining different porosifying conditions through potentiostatic modulation or embedding doping design, we are able to separate and lift off GaN layers over a macroscopic area (?cm(2)). Strain relaxation and single crystallinity are confirmed by Raman and transmission electron microscopy, respectively. This method is expected to open up a new dimension in epitaxy, design and manufacture of GaN heterostructures and devices.
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Insights into the thermodynamics of copper association with amyloid-?, ?-synuclein and prion proteins.
Metallomics
PUBLISHED: 11-29-2010
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This review examines recent studies on the thermodynamics of copper association with amyloid-?, ?-synuclein and prion protein, with an eye towards using this information to understand the etiology of associated neurodegenerative diseases. A variety of binding affinities and binding sites, which are essential to understand the function and consequence of copper-protein interaction, have been reported for copper to these three neurobiologic systems. This current review reconciles the disparate models presented in the literature.
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Sub-cubic millimeter intraocular pressure monitoring implant to enable genetic studies on pressure-induced neurodegeneration.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 11-25-2010
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There is often a strong correlation between elevated levels of intraocular pressure (IOP) and glaucoma; however, the underlying mechanisms that lead to blindness are not well understood. The key may lie in the study of genetic factors which determine IOP and lead to glaucoma-related blindness. Mice are typically used for genetic research due to their short generation time and accelerated lifespan, manageability, the availability of established and pure lines, and the ability to manipulate the genome. Post genetic manipulation, IOP monitoring at regular intervals is needed and for large scale testing, on the order of thousands of mice, it is crucial to have at least a partially automated data collection scheme. This work presents a fully wireless system on a chip that measures 300 µm in its widest dimension, has a wireless microwave-based data and power link, and is capable of relaying digitized pressure recordings to a nearby base-station.
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Blunting the negative impact of healthcare reform.
Healthc Financ Manage
PUBLISHED: 09-14-2010
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To prepare for reform, organizations should take the following preventive measures: Create an integrated plan to evaluate the changes under health reform and implement actions for long-term financial success. Plan for lower Medicare payments by negotiating with commercial insurance carriers for contract renewals and implementing cost containment measures. Assess the effectiveness of the charge structure. Improve or establish new procedures to identify and report all charity care services provided.
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Ptosis and ophthalmoplegia associated with epidermolysis bullosa simplex-muscular dystrophy.
Ophthal Plast Reconstr Surg
PUBLISHED: 09-11-2010
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The association of epidermolysis bullosa simplex and muscular dystrophy (EBS-MD) has rarely been discussed in ophthalmology literature. This case report offers a brief summary of epidermolysis bullosa and describes what is known about EBS-MD. The case involves a patient with EBS-MD who presented with ptosis and ophthalmoplegia, suggesting that these may be complications of EBS-MD.
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The red and the black.
Acc. Chem. Res.
PUBLISHED: 08-24-2010
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"Pigmentation, which is primarily determined by the amount, the type, and the distribution of melanin, shows a remarkable diversity in human populations, and in this sense, it is an atypical trait."--E. J. Parra. Melanin is found throughout the human body, skin, eye, brain, hair, and inner ear, yet its molecular structure remains elusive. Researchers have characterized the molecular building blocks of melanin but have not been able to describe how those components fit together in the overall architecture of the pigment. Melanin is categorized into two distinct classes, pheomelanin (red) and eumelanin (black). Although these classes share a common biosynthetic origin, specific molecular reactions occurring early in pigment production differentiate these two types. Pure eumelanin is found throughout nature, which has allowed researchers to characterize and quantify its chemical properties. However, pure pheomelanin is not observed in nature and rarely makes up more than ~25% of the total melanin present. In this Account, we explore our current understanding of the structure and reactivity of the red and black pigments. Epidemiological studies of skin and ocular cancers suggest that increasing relative proportions of pheomelanin correlate with increased risk factors for these diseases. Therefore, understanding the factors that control the relative abundance of the two pigments has become increasingly important. Consequently, researchers have worked to elucidate the chemistry of pheomelanin to determine whether the pigment could cause these cancers and, if so, by what mechanisms. The photoactivation of oxygen by pheomelanin in the UV-A range could contribute to the development of UV-induced cancers: recent measurement of the surface photoionization threshold of intact melanosomes reveals a lower photoionization potential for pheomelanin than eumelanin. A complementary study of intact human melanosomes isolated from different colored irides reveals that the absorption coefficient of the melanosome decreases with increasing pheomelanin content. These results suggest that the epidemiological data may simply result from an increased exposure of the underlying tissues to UV light.
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Quantification of the binding properties of Cu2+ to the amyloid beta peptide: coordination spheres for human and rat peptides and implication on Cu2+-induced aggregation.
J Phys Chem B
PUBLISHED: 08-10-2010
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There is no consensus on the coordinating ligands for Cu(2+) by Abeta. However, the differences in peptide sequence between human and rat have been hypothesized to alter metal ion binding in a manner that alters Cu(2+)-induced aggregation of Abeta. Herein, we employ isothermal titration calorimetry (ITC), circular dichroism (CD), and electron paramagnetic resonance (EPR) spectroscopy to examine the Cu(2+) coordination spheres to human and rat Abeta and an extensive set of Abeta(16) mutants. EPR of the mutant peptides is consistent with a 3N1O binding geometry, like the native human peptide at pH 7.4. The thermodynamic data reveal an equilibrium between three coordination spheres, {NH(2), O, N(Im)(His6), N(-)}, {NH(2), O, N(Im)(His6), N(Im)(His13)}, and {NH(2), O, N(Im)(His6), N(Im)(His14)}, for human Abeta(16) but one dominant coordination for rat Abeta(16), {NH(2), O, N(Im)(His6), N(-)}, at pH 7.4-6.5. ITC and CD data establish that the mutation R5G is sufficient for reproducing this difference in Cu(2+) binding properties at pH 7.4. The substitution of bulky and positively charged Arg by Gly is proposed to stabilize the coordination {NH(2), O-, N(Im)(His6), N(-)} that then results in one dominating coordination sphere for the case of the rat peptide. The differences in the coordination geometries for Cu(2+) by the human and rat Abeta are proposed to contribute to the variation in the ability of Cu(2+) to induce aggregation of Abeta peptides.
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Complications of strabismus surgery.
Curr Opin Ophthalmol
PUBLISHED: 07-24-2010
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To examine the common and serious complications of strabismus surgery, emphasizing prevention, identification, and treatment.
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The ultraviolet absorption coefficient of melanosomes decreases with increasing pheomelanin content.
J Phys Chem B
PUBLISHED: 07-10-2010
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Uveal melanosomes from the iridal stroma contain both eumelanin and pheomelanin, the ratio of which varies with iris color. Herein, we report the absorption coefficient at lambda = 244 nm for individual human iridal stroma melanosomes from dark brown and blue-green irides. The melanosomes are nearly identical in size, but differ in the relative concentration composition, ranging from a eumelanin/pheomelanin ratio of 14.8:1 (dark brown) to 1.3:1 (blue-green or hazel). The absorption coefficient of the melanosome decreases as its pheomelanin content increases. The origin of this decrease is attributed to a corresponding decrease in the number of UV-absorbing chromophores, reflecting the different molecular volumes of the monomeric building blocks of the two pigments. In agreement with reported data on synthetic pigments, the absorption coefficient of pheomelanin is found to be slightly larger than that for eumelanin at lambda = 244 nm (by a factor of 1.2). On the basis of the reported optical properties of synthetic models, this result suggests that the absorption of pheomelanin is less than eumelanin at wavelengths of biological relevance ( approximately 315-400 nm).
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Anisometropic amblyopia: axial length versus corneal curvature in children with severe refractive imbalance.
J AAPOS
PUBLISHED: 05-05-2010
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To define the ocular parameters associated with anisometropic ambylopia in children with severe hyperopia, myopia, or astigmatism in 1 eye.
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Eye pain in preschool children: diagnostic and prognostic significance.
J AAPOS
PUBLISHED: 03-21-2010
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Preschool children often present for ophthalmologic examination because of eye pain. Although the differential diagnosis includes serious conditions, the diagnostic and prognostic importance of apparently isolated eye pain are unknown.
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Imaging, chemical and spectroscopic studies of the methylation-induced decomposition of melanosomes.
Photochem. Photobiol.
PUBLISHED: 03-17-2010
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The morphological and chemical changes associated with the exposure of melanosomes to methyl iodide are assessed by a variety of analytical, imaging and spectroscopic methods. Scanning electron microscopy, light scattering and N(2) adsorption measurements all indicate significant changes in the morphology of the pigment following methylation. Solid-state nuclear magnetic resonance (SS-NMR) spectroscopy and chemical degradation analysis reveals the methylation results in the introduction of ester groups into the pigment structures. Amino acid analysis further reveals that Arg, Cys, His, Ser and Tyr undergo methylation; the SS-NMR data provide additional evidence for the methylation of the sulfur of Cys. Methylation results in increased solubility of the melanosome; the absorption properties of the dissolved material are characterized by an absorption maximum at 225 nm, with a long tail throughout the UV-A and UV-B, indicating that the solubilized material is a combination of protein and pigment. The methylation-induced decomposition of the melanosomes provides new insights into both the observed increase in O-methyl derivatives of the indolic precursor to eumelanin in the urine of melanoma patients and how increased levels of biologic methylating agents in the brain induce symptoms that resemble Parkinsons disease.
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Parental Agreement on ADHD Symptom-Specific and Broadband Externalizing Ratings of Child Behavior.
J Emot Behav Disord
PUBLISHED: 03-01-2010
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Mothers and fathers often disagree in their ratings of child behavior as evidenced clinically and supported by a substantial literature examining parental agreement on broadband rating scales. The present study examined mother-father agreement on DSM-based, ADHD symptom-specific ratings, as compared to agreement on broadband ratings of externalizing behavior. Using mother and father ratings from 324 children who participated in the Multimodal Treatment Study of Children with ADHD, parental agreement was computed and patterns of disagreement were examined. Mother-father ratings were significantly correlated. However, a clear pattern of higher ratings by mothers compared to fathers was present across ratings. Agreement on ADHD symptom-specific ratings was significantly lower than agreement for broadband externalizing behaviors or ODD symptoms. Of several moderator variables tested, parental stress was the only variable that predicted the discrepancy in ratings. Disagreement between parents is clinically significant and may pose complications to the diagnostic process.
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Review of vector-borne diseases in Hong Kong.
Travel Med Infect Dis
PUBLISHED: 01-21-2010
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The epidemiology of vector-borne diseases in Hong Kong has changed over the past decade but still poses a significant public health risk. We provided a comprehensive review of the epidemiological information and analysed the trends of major vector-borne diseases, including the vector situation in Hong Kong. The incidence of malaria has dropped dramatically in the past few decades and is now mainly an imported disease acquired from malaria endemic countries. Locally acquired dengue fever occurred in 2002 and 2003, and thereafter all cases were imported, mainly from Southeast Asia areas. Only a few local cases of Japanese encephalitis were reported in the past decade. In contrast, there is a notable increase in scrub typhus and spotted fever cases. The emergence of chikungunya fever in Asia and Indian Ocean countries also resulted in importation of human cases. Given the heavy traffic between this international city and other parts of the world, as well as the presence of vectors in this densely populated area, vigilance should be maintained against these infections. Comprehensive public health measures encompassing disease surveillance, vector surveillance and control measures with support from all sectors of the community are required to combat the old and newly emerging vector-borne diseases in Hong Kong.
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Pathological considerations in the treatment of Parkinsons disease: more than just a wiring diagram.
Clin Neurol Neurosurg
PUBLISHED: 01-21-2010
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Parkinsons disease (PD) represents a common but challenging condition in which an increasing number of therapeutic options have evolved over the course of the last 50 years. The introduction of dopaminergic therapies has dramatically improved outcomes but life expectancies remain significantly curtailed. Currently, all available treatment options are directed towards the amelioration of symptoms. However, it is hoped that a greater understanding of the distinctive pathology underlying PD might offer some novel therapeutic approaches. The identification of degeneration within the nigrostriatal tract as the most prominent pathological process in PD has led to the development of a number of therapies. However, despite initially good symptomatic control it has become clear that the longer-term use of these medications is associated with a number of debilitating motor complications. The management of these drug-related issues has necessitated a further tier of therapeutic options based largely on a greater understanding of the basal ganglia circuitry involved. Indeed, surgical interventions targeting these neural circuits have provided increased control of motor symptoms in patients with advanced disease, however, such techniques still fail to slow or reverse the disease. To this end, a number of novel approaches focussed on restoration or repair of the diseased brain have received increasing attention. Nevertheless, there are multiple symptoms that are unresponsive to any of these therapies, highlighting the involvement of other neurotransmitter systems and the complexities of the disease beyond the basal ganglia circuitry. An appreciation of the ongoing neurodegenerative processes at the core of PD and the burden of disease associated with them, emphasises the need for increased research into more effective and comprehensive treatment methodologies.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.