Background: Despite the high prevalence of seizure, epilepsy and abnormal electroencephalograms in individuals with autism spectrum disorder (ASD), there is little information regarding the relative effectiveness of treatments for seizures in the ASD population. In order to determine the effectiveness of traditional and non-traditional treatments for improving seizures and influencing other clinical factor relevant to ASD, we developed a comprehensive on-line seizure survey.

Methods: Announcements (by email and websites) by ASD support groups asked parents of children with ASD to complete the on-line surveys. Survey responders choose one of two surveys to complete: a survey about treatments for individuals with ASD and clinical or subclinical seizures or abnormal electroencephalograms, or a control survey for individuals with ASD without clinical or subclinical seizures or abnormal electroencephalograms. Survey responders rated the perceived effect of traditional antiepileptic drug (AED), non-AED seizure treatments and non-traditional ASD treatments on seizures and other clinical factors (sleep, communication, behavior, attention and mood), and listed up to three treatment side effects.

Results: Responses were obtained concerning 733 children with seizures and 290 controls. In general, AEDs were perceived to improve seizures but worsened other clinical factors for children with clinical seizure. Valproic acid, lamotrigine, levetiracetam and ethosuximide were perceived to improve seizures the most and worsen other clinical factors the least out of all AEDs in children with clinical seizures. Traditional non-AED seizure and non-traditional treatments, as a group, were perceived to improve other clinical factors and seizures but the perceived improvement in seizures was significantly less than that reported for AEDs. Certain traditional non-AED treatments, particularly the ketogenic diet, were perceived to improve both seizures and other clinical factors. For ASD individuals with reported subclinical seizures, other clinical factors were reported to be worsened by AEDs and improved by non-AED traditional seizure and non-traditional treatments. The rate of side effects was reportedly higher for AEDs compared to traditional non-AED treatments.

Conclusion: Although this survey-based method only provides information regarding parental perceptions of effectiveness, this information may be helpful for selecting seizure treatments in individuals with ASD.

This manuscript reviews biological abnormalities shared by autism spectrum disorder (ASD) and epilepsy. Two neuropathological findings are shared by ASD and epilepsy: abnormalities in minicolumn architecture and γ-aminobutyric acid (GABA) neurotransmission. The peripheral neuropil, which is the region that contains the inhibition circuits of the minicolumns, has been found to be decreased in the post-mortem ASD brain. ASD and epilepsy are associated with inhibitory GABA neurotransmission abnormalities including reduced GABA_A and GABA_B subunit expression. These abnormalities can elevate the excitation-to-inhibition balance, resulting in hyperexcitablity of the cortex and, in turn, increase the risk of seizures. Medical abnormalities associated with both epilepsy and ASD are discussed. These include specific genetic syndromes, specific metabolic disorders including disorders of energy metabolism and GABA and glutamate neurotransmission, mineral and vitamin deficiencies, heavy metal exposures and immune dysfunction. Many of these medical abnormalities can result in an elevation of the excitatory-to-inhibitory balance. Fragile X is linked to dysfunction of the mGluR5 receptor and Fragile X, Angelman and Rett syndromes are linked to a reduction in GABA[subscript A] receptor expression. Defects in energy metabolism can reduce GABA interneuron function. Both pyridoxine dependent seizures and succinic semialdehyde dehydrogenase deficiency cause GABA deficiencies while urea cycle defects and phenylketonuria cause abnormalities in glutamate neurotransmission. Mineral deficiencies can cause glutamate and GABA neurotransmission abnormalities and heavy metals can cause mitochondrial dysfunction which disrupts GABA metabolism. Thus, both ASD and epilepsy are associated with similar abnormalities that may alter the excitatory-to-inhibitory balance of the cortex. These parallels may explain the high prevalence of epilepsy in ASD and the elevated prevalence of ASD features in individuals with epilepsy.

Introduction: A number of previous studies examined a possible association of toxic metals and autism, and over half of those studies suggest that toxic metal levels are different in individuals with Autism Spectrum Disorders (ASD). Additionally, several studies found that those levels correlate with the severity of ASD.

Methods: In order to further investigate these points, this paper performs the most detailed statistical analysis to date of a data set in this field. First morning urine samples were collected from 67 children and adults with ASD and 50 neurotypical controls of similar age and gender. The samples were analyzed to determine the levels of 10 urinary toxic metals (UTM). Autism-related symptoms were assessed with eleven behavioral measures. Statistical analysis was used to distinguish participants on the ASD spectrum and neurotypical participants based upon the UTM data alone. The analysis also included examining the association of autism severity with toxic metal excretion data using linear and nonlinear analysis. “Leave-one-out” cross-validation was used to ensure statistical independence of results.

Results and Discussion: Average excretion levels of several toxic metals (lead, tin, thallium, antimony) were significantly higher in the ASD group. However, ASD classification using univariate statistics proved difficult due to large variability, but nonlinear multivariate statistical analysis significantly improved ASD classification with Type I/II errors of 15% and 18%, respectively. These results clearly indicate that the urinary toxic metal excretion profiles of participants in the ASD group were significantly different from those of the neurotypical participants. Similarly, nonlinear methods determined a significantly stronger association between the behavioral measures and toxic metal excretion. The association was strongest for the Aberrant Behavior Checklist (including subscales on Irritability, Stereotypy, Hyperactivity, and Inappropriate Speech), but significant associations were found for UTM with all eleven autism-related assessments with cross-validation R² values ranging from 0.12–0.48.

Background: The relationship between relative metabolic disturbances and developmental disorders is an emerging research focus. This study compares the nutritional and metabolic status of children with autism with that of neurotypical children and investigates the possible association of autism severity with biomarkers.

Method:Participants were children ages 5-16 years in Arizona with Autistic Spectrum Disorder (n = 55) compared with non-sibling, neurotypical controls (n = 44) of similar age, gender and geographical distribution. Neither group had taken any vitamin/mineral supplements in the two months prior to sample collection. Autism severity was assessed using the Pervasive Development Disorder Behavior Inventory (PDD-BI), Autism Treatment Evaluation Checklist (ATEC), and Severity of Autism Scale (SAS). Study measurements included: vitamins, biomarkers of vitamin status, minerals, plasma amino acids, plasma glutathione, and biomarkers of oxidative stress, methylation, sulfation and energy production.

Results: Biomarkers of children with autism compared to those of controls using a t-test or Wilcoxon test found the following statistically significant differences (p < 0.001): Low levels of biotin, plasma glutathione, RBC SAM, plasma uridine, plasma ATP, RBC NADH, RBC NADPH, plasma sulfate (free and total), and plasma tryptophan; also high levels of oxidative stress markers and plasma glutamate. Levels of biomarkers for the neurotypical controls were in good agreement with accessed published reference ranges. In the Autism group, mean levels of vitamins, minerals, and most amino acids commonly measured in clinical care were within published reference ranges. A stepwise, multiple linear regression analysis demonstrated significant associations between several groups of biomarkers with all three autism severity scales, including vitamins (adjusted R[superscript 2] of 0.25-0.57), minerals (adj. R[superscript 2] of 0.22-0.38), and plasma amino acids (adj. R[superscript 2] of 0.22-0.39).

Conclusion: The autism group had many statistically significant differences in their nutritional and metabolic status, including biomarkers indicative of vitamin insufficiency, increased oxidative stress, reduced capacity for energy transport, sulfation and detoxification. Several of the biomarker groups were significantly associated with variations in the severity of autism. These nutritional and metabolic differences are generally in agreement with other published results and are likely amenable to nutritional supplementation. Research investigating treatment and its relationship to the co-morbidities and etiology of autism is warranted.

Background: Children with autism have often been reported to have gastrointestinal problems that are more frequent and more severe than in children from the general population.

Methods: Gastrointestinal flora and gastrointestinal status were assessed from stool samples of 58 children with Autism Spectrum Disorders (ASD) and 39 healthy typical children of similar ages. Stool testing included bacterial and yeast culture tests, lysozyme, lactoferrin, secretory IgA, elastase, digestion markers, short chain fatty acids (SCFA's), pH, and blood presence. Gastrointestinal symptoms were assessed with a modified six-item GI Severity Index (6-GSI) questionnaire, and autistic symptoms were assessed with the Autism Treatment Evaluation Checklist (ATEC).

Results: Gastrointestinal symptoms (assessed by the 6-GSI) were strongly correlated with the severity of autism (assessed by the ATEC), (r = 0.59, p < 0.001). Children with 6-GSI scores above 3 had much higher ATEC Total scores than those with 6-GSI-scores of 3 or lower (81.5 +/- 28 vs. 49.0 +/- 21, p = 0.00002).
Children with autism had much lower levels of total short chain fatty acids (-27%, p = 0.00002), including lower levels of acetate, proprionate, and valerate; this difference was greater in the children with autism taking probiotics, but also significant in those not taking probiotics. Children with autism had lower levels of species of Bifidobacter (-43%, p = 0.002) and higher levels of species of Lactobacillus (+100%, p = 0.00002), but similar levels of other bacteria and yeast using standard culture growth-based techniques. Lysozyme was somewhat lower in children with autism (-27%, p = 0.04), possibly associated with probiotic usage. Other markers of digestive function were similar in both groups.

Conclusions: The strong correlation of gastrointestinal symptoms with autism severity indicates that children with more severe autism are likely to have more severe gastrointestinal symptoms and vice versa. It is possible that autism symptoms are exacerbated or even partially due to the underlying gastrointestinal problems. The low level of SCFA's was partly associated with increased probiotic use, and probably partly due to either lower production (less sacchrolytic fermentation by beneficial bacteria and/or lower intake of soluble fiber) and/or greater absorption into the body (due to longer transit time and/or increased gut permeability).

The electronic structure of eight zinc-centered porphyrin macrocyclic molecules are investigated using density functional theory for ground-state properties, time-dependent density functional theory (TDDFT) for excited states, and Franck-Condon (FC) analysis for further characterization of the UV-vis spectrum. Symmetry breaking was utilized to find the lowest energy of the excited states for many states in the spectra. To confirm the theoretical modeling, the spectroscopic result from zinc phthalocyanine (ZnPc) is used to compare to the TDDFT and FC result. After confirmation of the modeling, five more planar molecules are investigated: zinc tetrabenzoporphyrin (ZnTBP), zinc tetrabenzomonoazaporphyrin (ZnTBMAP), zinc tetrabenzocisdiazaporphyrin (ZnTBcisDAP), zinc tetrabenzotransdiazaporphyrin (ZnTBtransDAP), and zinc tetrabenzotriazaporphyrin (ZnTBTrAP). The two latter molecules are then compared to their phenylated sister molecules: zinc monophenyltetrabenzotriazaporphyrin (ZnMPTBTrAP) and zinc diphenyltetrabenzotransdiazaporphyrin (ZnDPTBtransDAP). The spectroscopic results from the synthesis of ZnMPTBTrAP and ZnDPTBtransDAP are then compared to their theoretical models and non-phenylated pairs. While the Franck-Condon results were not as illuminating for every B-band, the Q-band results were successful in all eight molecules, with a considerable amount of spectral analysis in the range of interest between 300 and 750 nm. The π-π^* transitions are evident in the results for all of the Q bands, while satellite vibrations are also visible in the spectra. In particular, this investigation finds that, while ZnPc has a D_4h symmetry at ground state, a C_4v symmetry is predicted in the excited-state Q band region. The theoretical results for ZnPc found an excitation energy at the Q-band 0-0 transition of 1.88 eV in vacuum, which is in remarkable agreement with published gas-phase spectroscopy, as well as our own results of ZnPc in solution with Tetrahydrofuran that are provided in this paper.

Many upper limb amputees experience an incessant, post-amputation “phantom limb pain” and report that their missing limbs feel paralyzed in an uncomfortable posture. One hypothesis is that efferent commands no longer generate expected afferent signals, such as proprioceptive feedback from changes in limb configuration, and that the mismatch of motor commands and visual feedback is interpreted as pain. Non-invasive therapeutic techniques for treating phantom limb pain, such as mirror visual feedback (MVF), rely on visualizations of postural changes. Advances in neural interfaces for artificial sensory feedback now make it possible to combine MVF with a high-tech “rubber hand” illusion, in which subjects develop a sense of embodiment with a fake hand when subjected to congruent visual and somatosensory feedback. We discuss clinical benefits that could arise from the confluence of known concepts such as MVF and the rubber hand illusion, and new technologies such as neural interfaces for sensory feedback and highly sensorized robot hand testbeds, such as the “BairClaw” presented here. Our multi-articulating, anthropomorphic robot testbed can be used to study proprioceptive and tactile sensory stimuli during physical finger–object interactions. Conceived for artificial grasp, manipulation, and haptic exploration, the BairClaw could also be used for future studies on the neurorehabilitation of somatosensory disorders due to upper limb impairment or loss. A remote actuation system enables the modular control of tendon-driven hands. The artificial proprioception system enables direct measurement of joint angles and tendon tensions while temperature, vibration, and skin deformation are provided by a multimodal tactile sensor. The provision of multimodal sensory feedback that is spatiotemporally consistent with commanded actions could lead to benefits such as reduced phantom limb pain, and increased prosthesis use due to improved functionality and reduced cognitive burden.

Flow diverting devices and stents can be used to treat cerebral aneurysms too difficult to treat with coiling or craniotomy and clipping. However, the hemodynamic effects of these devices have not been studied in depth. The objective of this study was to quantify and understand the fluid dynamic changes that occur within bifurcating aneurysms when treated with different devices and configurations. Two physical models of bifurcating cerebral aneurysms were constructed: an idealized model and a patient-specific model. The models were treated with four device configurations: a single low-porosity Pipeline embolization device (PED) and one, two, and three high-porosity Enterprise stents deployed in a telescoping fashion. Particle image velocimetry was used to measure the fluid dynamics within the aneurysms; pressure was measured within the patient-specific model. The PED resulted in the greatest reductions in fluid dynamic activity within the aneurysm for both models. However, a configuration of three telescoping stents reduced the fluid dynamic activity within the aneurysm similarly to the PED treatment. Pressure within the patient-specific aneurysm did not show significant changes among the treatment configurations; however, the pressure difference across the untreated vessel side of the model was greatest with the PED. Treatment with stents and a flow diverter led to reductions in aneurysmal fluid dynamic activity for both idealized and patient-specific models. While the PED resulted in the greatest flow reductions, telescoping high-porosity stents performed similarly and may represent a viable treatment alternative in situations where the use of a PED is not an option.

Background: Styrene is an important building-block petrochemical and monomer used to produce numerous plastics. Whereas styrene bioproduction by Escherichia coli was previously reported, the long-term potential of this approach will ultimately rely on the use of hosts with improved industrial phenotypes, such as the yeast Saccharomyces cerevisiae.

Results: Classical metabolic evolution was first applied to isolate a mutant capable of phenylalanine over-production to 357 mg/L. Transcription analysis revealed up-regulation of several phenylalanine biosynthesis pathway genes including ARO3, encoding the bottleneck enzyme DAHP synthase. To catalyze the first pathway step, phenylalanine ammonia lyase encoded by PAL2 from A. thaliana was constitutively expressed from a high copy plasmid. The final pathway step, phenylacrylate decarboxylase, was catalyzed by the native FDC1. Expression of FDC1 was naturally induced by trans-cinnamate, the pathway intermediate and its substrate, at levels sufficient for ensuring flux through the pathway. Deletion of ARO10 to eliminate the competing Ehrlich pathway and expression of a feedback-resistant DAHP synthase encoded by ARO4[subscript K229L] preserved and promoted the endogenous availability precursor phenylalanine, leading to improved pathway flux and styrene production. These systematic improvements allowed styrene titers to ultimately reach 29 mg/L at a glucose yield of 1.44 mg/g, a 60% improvement over the initial strain.

Conclusions: The potential of S. cerevisiae as a host for renewable styrene production has been demonstrated. Significant strain improvements, however, will ultimately be needed to achieve economical production levels.