Full field electroretinogram in autism spectrum disorder

Purpose To explore early findings that individuals with autism spectrum disorder (ASD) have reduced scotopic ERG b-wave amplitudes. Methods Dark adapted (DA) ERGs were acquired to a range of flash strengths, (-4.0 to 2.3 log phot cd.s.m-2), including and extending the ISCEV standard, from two subject groups: (ASD) N=11 and (Control) N=15 for DA and N=14 for light adapted (LA) ERGs who were matched for mean age and range. Naka-Rushton curves were fitted to DA b-wave amplitude growth over the first limb (-4.0 to -1.0 log phot cd.s.m-2). The derived parameters (Vmax, Km and n) were compared between groups. Scotopic 15 Hz flicker ERGs (14.93Hz) were recorded to 10 flash strengths presented in ascending order from -3.0 to 0.5 log Td.s to assess the slow and fast rod pathways respectively. LA ERGs were acquired to a range of flash strengths, (-0.5 to 1.0 log phot cd.s.m-2). Photopic 30 Hz, flicker ERGs, oscillatory potentials (OPs) and the responses to prolonged 120 ms ON- OFF stimuli were also recorded. Results For some individuals the DA b-wave amplitudes fell below the control 5th centile of the controls with up to four ASD participants (36%) at the 1.5 log phot cd.s.m-2 flash strength and two (18%) ASD participants at the lower -2 log phot cd.s.m-2 flash strength. However, across the thirteen flash strengths there were no significant group differences for b-wave amplitude’s growth (repeated measures ANOVA p=0.83). Nor were there any significant differences between the groups for the Naka-Rushton parameters (p>0.09). No group differences were observed in the 15Hz scotopic flicker phase or amplitude (p>0.1), DA ERG a- wave amplitude or time to peak (p>26). The DA b-wave time to peak at 0.5 log phot cd.s.m-2 were longer in the ASD group (corrected p=0.04). The single ISCEV LA 0.5 log phot cd.s.m-2 (p0.08) to the single flash stimuli although there was a significant interaction between group and flash strength for the b-wave amplitude (corrected p=0.006). The prolonged 120 ms ON-responses were smaller in the ASD group (corrected p=0.003), but the OFF response amplitude (p>0.6) and ON and OFF times to peaks (p>0.4) were similar between groups. The LA OPs showed an earlier bifurcation of OP2 in the younger ASD participants, however no other differences were apparent in the OPs or 30Hz flicker waveforms. Conclusion Some ASD individuals show subnormal DA ERG b-wave amplitudes. Under LA conditions the b-wave is reduced across the ASD group along with the ON response of the ERG. These exploratory findings, suggest there is altered cone-ON bipolar signalling in ASD

A new name for Agromyza flava Sousa & Couri (Diptera: Agromyzidae)

ABSTRACT A new name Agromyza pauciflava nom. nov. is proposed for Agromyza flava Sousa & Couri

Functional Screening of Lysosomal Storage Disorder Genes Identifies Modifiers of Alpha-Synuclein Neurotoxicity

Heterozygous variants in the glucocerebrosidase (GBA) gene are common and potent risk factors for Parkinson\u27s disease (PD). GBA also causes the autosomal recessive lysosomal storage disorder (LSD), Gaucher disease, and emerging evidence from human genetics implicates many other LSD genes in PD susceptibility. We have systemically tested 86 conserved fly homologs of 37 human LSD genes for requirements in the aging adult Drosophila brain and for potential genetic interactions with neurodegeneration caused by α-synuclein (αSyn), which forms Lewy body pathology in PD. Our screen identifies 15 genetic enhancers of αSyn-induced progressive locomotor dysfunction, including knockdown of fly homologs of GBA and other LSD genes with independent support as PD susceptibility factors from human genetics (SCARB2, SMPD1, CTSD, GNPTAB, SLC17A5). For several genes, results from multiple alleles suggest dose-sensitivity and context-dependent pleiotropy in the presence or absence of αSyn. Homologs of two genes causing cholesterol storage disorders, Npc1a / NPC1 and Lip4 / LIPA, were independently confirmed as loss-of-function enhancers of αSyn-induced retinal degeneration. The enzymes encoded by several modifier genes are upregulated in αSyn transgenic flies, based on unbiased proteomics, revealing a possible, albeit ineffective, compensatory response. Overall, our results reinforce the important role of lysosomal genes in brain health and PD pathogenesis, and implicate several metabolic pathways, including cholesterol homeostasis, in αSyn-mediated neurotoxicity

Reproducibility of the mfERG between instruments

Purpose First, to examine both the reproducibility of the multifocal electroretinogram (mfERG) recorded on different versions of the same instrument, and the repeatability of the mfERG recorded on a single instrument using two different amplifiers. Second, to demonstrate a means by which multicenter and longitudinal studies that use more than one recording instrument can compare and combine data effectively. Methods Three different amplifiers and two mfERG setups, one using VERIS™ 4.3 software (mfERG1) and another using VERIS™ Pro 5.2 software (mfERG2), were evaluated. A total of 73 subjects with normal vision were tested in three groups. Group 1 (n = 42) was recorded using two amplifiers in parallel on mfERG1. Group 2 (n = 52) was recorded on mfERG2 using a single amplifier. Group 3 was a subgroup of 21 subjects from groups 1 and 2 that were tested sequentially on both instruments. A fourth group of 26 subjects with diabetes were also recorded using the two parallel amplifiers on mfERG1. P1 implicit times and N1-P1 amplitudes of the 103 local first order mfERGs were measured, and the differences between the instruments and amplifiers were evaluated as raw scores and Z-scores based on normative data. Measurements of individual responses and measurements averaged over the 103 responses were analyzed. Results Simultaneous recordings made on mfERG1 with the two different amplifiers showed differences in implicit times but similar amplitudes. There was a mean implicit time difference of 2.5 ms between the amplifiers but conversion to Z-scores improved their agreement. Recordings made on different days with the two instruments produced similar but more variable results, with amplitudes differing between them more than implicit times. For local response implicit times, the 95% confidence interval of the difference between instruments was approximately ±1 Z-score (±0.9 ms) in either direction. For local response amplitude, it was approximately ±1.6 Z-scores (±0.3 μV). Conclusions Different amplifiers can yield quite different mfERG P1 implicit times, even with identical band-pass settings. However, the reproducibility of mfERG Z-scores across recording instrumentation is relatively high. Comparison of data across systems and laboratories, necessary for multicenter or longitudinal investigations, is facilitated if raw data are converted into Z-scores based on normative data

Individual, family and environmental factors associated with pediatric excess weight in Spain: a cross-sectional study

Background: There is a growing worldwide trend of obesity in children. Identifying the causes and modifiable factors associated with child obesity is important in order to design effective public health strategies. Our objective was to provide empirical evidence of the association that some individual and environmental factors may have with child excess weight.Method: A cross-sectional study was performed using multi-stage probability sampling of 978 Spanish children aged between 8 and 17 years, with objectively measured height and weight, along with other individual, family and neighborhood variables. Crude and adjusted odds ratios were calculated.Results: In 2012, 4 in 10 children were either overweight or obese with a higher prevalence amongst males and in the 8–12 year age group. Child obesity was associated negatively with the socio-economic status of the adult responsible for the child’s diet, OR 0.78 (CI95% 0.59–1.00), girls OR 0.75 (CI95% 0.57–0.99), older age of the child (0.41; CI95% 0.31–0.55), daily breakfast (OR 0.59; p = 0.028) and half an hour or more of physical activity every day. No association was found for neighborhood variables relating to perceived neighborhood quality and safety.Conclusion: This study identifies potential modifiable factors such as physical activity, daily breakfast and caregiver education as areas for public health policies. To be successful, an intervention should take into account both individual and family factors when designing prevention strategies to combat the worldwide epidemic of child excess weight.This study was funded by grant number PI10/02018, Ministerio de Economía y Competitividad del Reino de España (Ministry of Economy and Competitiveness, Spain), Instituto de Salud Carlos III-FEDER

The effect of nutritional supplementation on the multifocal electroretinogram in healthy eyes

BACKGROUND: Previous studies have demonstrated an increase in macular pigment optical density (MPOD) with lutein (L)-based supplementation in healthy eyes. However, not all studies have assessed whether this increase in MPOD is associated with changes to other measures of retinal function such as the multifocal ERG (mfERG). Some studies also fail to report dietary levels of L and zeaxanthin (Z). Because of the associations between increased levels of L and Z, and reduced risk of AMD, this study was designed to assess the effects of L-based supplementation on mfERG amplitudes and latencies in healthy eyes. METHODS: Multifocal ERG amplitudes, visual acuity, contrast sensitivity, MPOD and dietary levels of L and Z were assessed in this longitudinal, randomized clinical trial. Fifty-two healthy eyes from 52 participants were randomly allocated to receive a L-based supplement (treated group), or no supplement (non-treated group). RESULTS: There were 25 subjects aged 18-77 (mean age ± SD; 48 ± 17) in the treated group and 27 subjects aged 21-69 (mean age ± SD; 43 ± 16) in the non-treated group. All participants attended for three visits: visit one at baseline, visit two at 20 weeks and visit three at 40 weeks. A statistically significant increase in MPOD (F = 17.0, p ≤ 0.001) and shortening of mfERG ring 2 P1 latency (F = 3.69, p = 0.04) was seen in the treated group. CONCLUSIONS: Although the results were not clinically significant, the reported trend for improvement in MPOD and mfERG outcomes warrants further investigation

Task-Dependence of Texture-Segregation-Specific VEP Components

Recently, texture-segregation-specific components have been isolated in the human visual evoked potential (tsVEPs). As tsVEPs are characterised by a negative peak near 200 ms they occur between luminance-contrast responses (P100) and cognitive responses (P300). The aim of this study was to estimate the temporal overlap of tsVEPs and cognitive VEP components by directing a task to either visual or auditory stimuli. Eight visually normal subjects participated in the experiment. Horizontal and vertical line segments were arranged to yield either an ‘orientation chequerboard’ stimulus or two fields with homogeneous orientations. As auditory stimuli, two tones with different pitches were presented through headphones. Auditory and visual stimuli were temporally uncorrelated, which allowed off-line isolation of VEPs and AEPs by appropriate averaging from the same raw data. VEPs and AEPs were recorded from an array of 13 electrodes ranging from frontal to occipital positions. tsVEPs were isolated under two conditions, where the subjects detected the presence of (a) the orientation chequerboard, or (b) the higher pitch by pressing a button. It was found that (1) tsVEPs could be isolated under both tasks; (2) tsVEPs were strongly modulated by the task; (3) the task-specific modulation occurred in the same time domain as the tsVEP itself, but showed a different topography; (4) AEPs were less modulated by the task. The data suggest that an additional task concerning the gradient content of texture stimuli may modulate the resulting tsVEPs. This may partially account for the interindividual variability in recent tsVEP data, as a comparable task may be introduced tacitly by the subjects. </jats:p