Alexander's disease and the story of Louise.

We describe the rare condition known as Alexander's disease or Alexander's leukodystrophy, which is essentially a childhood dementia. We then present the case of Louise Davies (we are using Louise's real name with the permission and special request of her mother), a woman who was diagnosed with this disease at the age of 5 years and is still alive at the age of 38, making her the longest known survivor of this condition. Although now severely impaired, both physically and mentally, and able to do very little, she has lived far longer than expected. We present some neuropsychological results from her childhood before measuring her decline over the past four years. We conclude by considering whether or not the diagnosis was correct and why she has lived so long

Alexander's disease and the story of Louise.

We describe the rare condition known as Alexander's disease or Alexander's leukodystrophy, which is essentially a childhood dementia. We then present the case of Louise Davies (we are using Louise's real name with the permission and special request of her mother), a woman who was diagnosed with this disease at the age of 5 years and is still alive at the age of 38, making her the longest known survivor of this condition. Although now severely impaired, both physically and mentally, and able to do very little, she has lived far longer than expected. We present some neuropsychological results from her childhood before measuring her decline over the past four years. We conclude by considering whether or not the diagnosis was correct and why she has lived so long

Studying effects of gold nanoparticle on dose enhancement in megavoltage radiation

Background: Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. Objective: The aim of this study is to understand characteristics of secondary electrons generated from interaction of gold nanoparticles GNPs with x-rays as a function of nanoparticle size and beam energy and thereby further understanding of GNPenhanced radiotherapy. Methods: Effective range, defection angle, dose deposition, energy, and interaction processes of electrons produced from the interaction of x-rays with a GNP were calculated by Monte Carlo simulations. The MCNPX code was used to simulate and track electrons generated from 30 and 50 nm diameter GNP when it is irradiated with a cobalt-60 and 6MV photon and electron beam in water. Results: When a GNP was present, depending on beam types used, secondary electron production increased by 10- to 2000-fold compared to absence of a GNP. Conclusion: GNPs with larger diameters also contributed to more doses. © 2015, Shiraz University of Medical Sciences. All rights reserved

Association of single nucleotide polymorphisms in IGFI, IGF-II and IGFBP-II with production traits in breeder hens of Mazandaran native fowls breeding station

The purpose of this study was to detect the polymorphism in IGF-I, IGF-II and IGFBP-II marker loci and their association with body weight at 8 weeks, average egg weight and total number of eggs laid during first 12 weeks after flocks maturity in breeder hens of native fowls. Blood samples were collected randomly from 160 individuals and genomic DNA was extracted using modified salting out method. A set of specific primer pairs were used for amplification of target genomic DNA at each marker loci and polymorphisms were detected using PCR-RFLP method. For IGF-I and IGFBP-II marker loci, allele B was the most frequent allele and ranged from 0.61 to 0.63 while, allele A was identified as a dominant allele in IGF-I marker site due to the highest frequency (0.57). The frequency of AA homozygous genotype was the lowest among all marker loci (0.08), whereas, AB genotype showed the highest frequency (0.61). Analysis of phenotypic data showed that the average egg weight and total number of eggs laid during first 12 weeks after flocks maturity were significantly affected by IGF-II and IGF-I marker loci respectively. No significant associations were observed between IGFBP-II genotypes and production traits. Comparison between detected alleles in the present study with reported allele by other research groups revealed a new allelic pattern for the analyzed marker loci in breeder hens of Mazandaran native fowls breeding station

Mitigation of Humic Acid Inhibition in Anaerobic Digestion of Cellulose by Addition of Various Salts

Humic compounds are inhibitory to the anaerobic hydrolysis of cellulosic biomass. In this study, the impact of salt addition to mitigate the inhibitory effects of humic compounds was investigated. The experiment was conducted using batch tests to monitor the anaerobic hydrolysis of cellulose in the presence of humic acid. Sodium, potassium, calcium, magnesium and iron salts were tested separately for their efficiency to mitigate humic acid inhibition. All experiments were done under mesophilic conditions (30 °C) and at pH 7. Methane production was monitored online, using the Automatic Methane Potential Test System. Methane production, soluble chemical oxygen demand and volatile fatty acid content of the samples were measured to calculate the hydrolysis efficiencies. Addition of magnesium, calcium and iron salts clearly mitigated the inhibitory effects of humic acid and hydrolysis efficiencies reached up to 75%, 65% and 72%, respectively, which were similar to control experiments. Conversely, potassium and sodium salts addition did not mitigate the inhibition and hydrolysis efficiencies were found to be less than 40%. Mitigation of humic acid inhibition via salt addition was also validated by inductively coupled plasma atomic emission spectroscopy analyses, which showed the binding capacity of different cations to humic aci

Volume reduction of caudate nucleus is associated with movement coordination deficits in patients with hippocampal atrophy due to perinatal hypoxia-ischaemia

Acute sentinel hypoxia-ischaemia in neonates can target the hippocampus, mammillary bodies, thalamus, and the basal ganglia. Our previous work with paediatric patients with a history of hypoxia-ischaemia has revealed hippocampal and diencephalic damage that impacts cognitive memory. However, the structural and functional status of other brain regions vulnerable to hypoxia-ischaemia, such as the basal ganglia, has not been investigated in these patients. Furthermore, it is not known whether there are any behavioural sequelae of such damage, especially in patients with no diagnosis of neurological disorder. Based on the established role of the basal ganglia and the thalamus in movement coordination, we studied manual motor function in 20 participants exposed to neonatal hypoxia-ischaemia, and a group of 17 healthy controls of comparable age. The patients’ handwriting speed and accuracy was within the normal range (Detailed Assessment of Speed of Handwriting), and their movement adaptation learning (Rotary Pursuit task) was comparable to the control group’s performance. However, as a group, patients showed an impairment in the Grooved Pegboard task and a trend for impairment in speed of movement while performing the Rotary Pursuit task, suggesting that some patients have subtle deficits in fine, complex hand movements. Voxel-based morphometry and volumetry showed bilateral reduction in grey matter volume of the thalamus and caudate nucleus. Reduced volumes in the caudate nucleus correlated across patients with performance on the Grooved Pegboard task. In summary, the fine movement coordination deficit affecting the hand and the wrist in patients exposed to early hypoxic-ischaemic brain injury may be related to reduced volumes of the caudate nucleus, and consistent with anecdotal parental reports of clumsiness and coordination difficulties in this cohort

Mutations in thyroid hormone receptor α1 cause premature neurogenesis and progenitor cell depletion in human cortical development

Mutations in the thyroid hormone receptor α 1 gene (THRA) have recently been identified as a cause of intellectual deficit in humans. Patients present with structural abnormalities including microencephaly, reduced cerebellar volume and decreased axonal density. Here, we show that directed differentiation of THRA mutant patient-derived induced pluripotent stem cells to forebrain neural progenitors is markedly reduced, but mutant progenitor cells can generate deep and upper cortical layer neurons and form functional neuronal networks. Quantitative lineage tracing shows that THRA mutation-containing progenitor cells exit the cell cycle prematurely, resulting in reduced clonal output. Using a micropatterned chip assay, we find that spatial self-organization of mutation-containing progenitor cells in vitro is impaired, consistent with down-regulated expression of cell–cell adhesion genes. These results reveal that thyroid hormone receptor α1 is required for normal neural progenitor cell proliferation in human cerebral cortical development. They also exemplify quantitative approaches for studying neurodevelopmental disorders using patient-derived cells in vitro