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Description

Background: Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited.

Method: This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism

Background: Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited.

Method: This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism were assessed. None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study. For a subset of the participants (53 children ages 5-16) pre and post measurements of nutritional and metabolic status were also conducted.

Results: The vitamin/mineral supplement was generally well-tolerated, and individually titrated to optimum benefit. Levels of many vitamins, minerals, and biomarkers improved/increased showing good compliance and absorption. Statistically significant improvements in metabolic status were many including: total sulfate (+17%, p = 0.001), S-adenosylmethionine (SAM; +6%, p = 0.003), reduced glutathione (+17%, p = 0.0008), ratio of oxidized glutathione to reduced glutathione (GSSG:GSH; -27%, p = 0.002), nitrotyrosine (-29%, p = 0.004), ATP (+25%, p = 0.000001), NADH (+28%, p = 0.0002), and NADPH (+30%, p = 0.001). Most of these metabolic biomarkers improved to normal or near-normal levels. The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised (PGI-R, Average Change, p = 0.008), and on the subscores for Hyperactivity (p = 0.003), Tantrumming (p = 0.009), Overall (p = 0.02), and Receptive Language (p = 0.03). For the other three assessment tools the difference between treatment group and placebo group was not statistically significant. Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers (adj. R[superscript 2] = 0.61, p < 0.0005) with the initial levels of biotin and vitamin K being the most significant (p < 0.05); both biotin and vitamin K are made by beneficial intestinal flora.

Conclusions: Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism.

ContributorsAdams, James (Author) / Audhya, Tapan (Author) / McDonough-Means, Sharon (Author) / Rubin, Robert A. (Author) / Quig, David (Author) / Geis, Elizabeth (Author) / Gehn, Eva (Author) / Loresto, Melissa (Author) / Mitchell, Jessica (Author) / Atwood, Sharon (Author) / Barnhouse, Suzanne (Author) / Lee, Wondra (Author) / Autism/Asperger's Research Program (Contributor)
Created2011-12-12
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Description

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

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 D4h symmetry at ground state, a C4v 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.

ContributorsTheisen, Rebekah (Author) / Huang, Liang (Author) / Fleetham, Tyler (Author) / Adams, James (Author) / Li, Jian (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-03-07
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Description

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.

ContributorsKang, Dae Wook (Author) / Park, Jin (Author) / Ilhan, Zehra (Author) / Wallstrom, Garrick (Author) / LaBaer, Joshua (Author) / Adams, James (Author) / Krajmalnik-Brown, Rosa (Author) / Biodesign Institute (Contributor)
Created2013-06-03
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Description
Current culturing methods allow for human neural progenitor cells to be differentiated into neurons for use in diagnostic tools and disease modeling. An issue arises in the relatively low number of cells that can be successfully expanded and differentiated using these current methods, making the progress of research dependent on

Current culturing methods allow for human neural progenitor cells to be differentiated into neurons for use in diagnostic tools and disease modeling. An issue arises in the relatively low number of cells that can be successfully expanded and differentiated using these current methods, making the progress of research dependent on these cultures as a large number of cells are needed to conduct relevant assays. This project focuses on the expansion and differentiation of human neural progenitor cells cultured on microcarriers and within a rotating bioreactor system as a way to increase the total number of cells generated. Additionally, cryopreservation and the characteristics of these neurons post thaw is being investigated to create a way for long term storage, as well as, a method for standardizing cell lines between multiple experiments at different time points. The experiments covered in this study are aimed to compare the characteristics of differentiated human neurons, both demented and non-demented cell lines between pre-cryopreservation, freshly differentiated neurons and post-cryopreservation neurons. The assays conducted include immunofluorescence, calcium imaging, quantitative polymerase chain reaction, flow cytometry and ELISA data looking at Alzheimer’s disease traits. With the data collected within this study, the use of bioreactors, in addition to, cryopreservation of human neurons for long term storage can be better implemented into human neural progenitor cell research. Both of these aspects will increase the output of these cultures and potentially remove the bottleneck currently found within human neural disease modeling.
ContributorsHenson, Tanner Jay (Author) / Brafman, David (Thesis director) / Kodibagkar, Vikram (Committee member) / School of Life Sciences (Contributor) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description
The story of graphene truly began in what was simply a stub in the journal Physical Review not two years after the end of World War II. In 1947, McGill University physicist P.R. Wallace authored “The Band Theory of Graphite” and attempted to develop a foundation on which the structure-property

The story of graphene truly began in what was simply a stub in the journal Physical Review not two years after the end of World War II. In 1947, McGill University physicist P.R. Wallace authored “The Band Theory of Graphite” and attempted to develop a foundation on which the structure-property relationship of graphite could be explored; he calculates the number of free electrons and conductivity of what he describes as “a single hexagonal layer” and “suppos[es] that conduction takes place only in layers” in bulk graphite to predict wave functions, energies at specific atomic sites in the hexagonal lattice, and energy contours using a tight binding approximation for a hypothesized version of what we now call ‘armchair-style’ graphene. While Wallace was the first to explore the band structure and Brillouin Zones of single-layer graphite, the concept of two-dimensional materials was not new. In fact, for years, it was dismissed as a thermodynamic impossibility.

Everything seemed poised against any proposed physical and experimental stability of a structure like graphene. “Thermodynamically impossible”– a not uncommon shutdown to proposed novel physical or chemical concepts– was once used to describe the entire field of proposed two-dimensional crystals functioning separately from a three-dimensional base or crystalline structure. Rudolf Peierls and Lev Davoidovich Landau, both very accomplished physicists respectively known for the Manhattan Project and for developing a mathematical theory of helium superfluidity, rejected the possibility of isolated monolayer to few-layered crystal lattices. Their reasoning was that diverging thermodynamic-based crystal lattice fluctuations would render the material unstable regardless of controlled temperature. This logic is flawed, but not necessarily inaccurate– diamond, for instance, is thermodynamically metastable at room temperature and pressure in that there exists a slow (i.e. slow on the scale of millions of years) but continuous transformation to graphite. However, this logic was used to support an explanation of thermodynamic impossibility that was provided for graphene’s lack of isolation as late as 1979 by Cornell solid-state physicist Nathaniel David Mermin. These physicists’ claims had clear and consistent grounding in experimental data: as thin films become thinner, there exists a trend of a decreasing melting temperature and increasing instability that renders the films into islands at somewhere around ten to twenty atomic layers. This is driven by the thermodynamically-favorable minimization of surface energy.
ContributorsShulman, Neal Arthur (Author) / Adams, James (Thesis director) / Islam, Rafiqul (Committee member) / Materials Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05