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To characterize an Egyptian patient with glutaric acidemia type I (GA I) and to identify the causative mutation(s) that may be responsible for the disease phenotype. MRI was performed on the patient using the 1.5 T magnet, biochemical analysis was carried out using gas chromatography/mass spectrometry on the patient's dried blood spot, and the patient's organic acids were measured in dried blood and a urine sample using MS/MS and GC/MS, respectively. Total RNA was isolated from the patient's peripheral blood, and the synthesized cDNA was bi-directionally sequenced. The patient exhibited clinical features and MRI findings compatible with a diagnosis of GA I. The abnormal elevation of organic acids in the urine supported the presence of glutaryl-CoA dehydrogenase deficiency. Gene sequencing revealed a novel homozygous frameshift mutation, c.644_645insCTCG; p.(Pro217Leufs*14), in exon 8 of the GCDH gene. The present study revealed a novel frameshift mutation responsible for a severe GA I phenotype in an Egyptian patient. This novel mutation will ultimately contribute to a better understanding of the molecular pathology of the disease and shed light on the intricacies of the genotype-phenotype correlation of GA I disease. [ABSTRACT FROM AUTHOR]

Although the current treatment of schistosomiasis relies largely on praziquantel (PZQ), it has not been successful in significantly reducing the overall rate of disease cases, one of the suggested reasons being the inevitable resistance to PZQ. Previous studies showed that radiation-attenuated vaccine provides protection against Schistosoma mansoni in a host of various species. In the present study, we evaluated the effect of various vaccination strategies in C57BL/6 mice, including single or multiple vaccination strategy, subcurative dose (20 mg/kg) of PZQ, and a combination of single vaccination with subcurative dose of PZQ. Treatment either with subcurative dose of PZQ or with a single vaccination of attenuated cercariae (500 per mouse), caused significant reduction in total worm burden, hepatic, and intestinal ova counts of 43.03, 73.2, and 59.5 and 37.97, 52.02, and 26.3 %, respectively. Furthermore, tegumental changes were observed. In multiple vaccinated group, there was an extensive lysis in tegumental layers. High deformations in gastrodermis, testis cells, vitelline cells, and oocytes were recorded. Also, this study is to explore the role of humoral immunity using highly resistant rabbits that had been exposed to three immunizations with ultraviolet (UV)-irradiated cercariae (8000 per rabbit in each immunization), and their sera were tested for their ability to transfer protection. The reduction in challenge worm burden had reached 32.76-43.64 % when compared with recipients of normal serum or no serum. The reduction in hepatic and intestinal ova counts reached to 74.4 and 71.08 % in group immunized with vaccinated rabbit sera. Swelling and extensive lysis of tegumental layers, gastrodermis lumen, spermatocytes, and deformation of oocytes were recorded with more severity than that recorded in normal rabbit sera group. Our findings recorded that multiple vaccination strategy is the most effective strategy then passive transfer of vaccinated rabbit. This gives guiding in the design the appropriate therapeutic strategy. [ABSTRACT FROM AUTHOR]

A cross-sectional study was conducted to investigate whether caregiver's variations in socioeconomic status (SES) has direct bearing on challenges of nurturing children with autism spectrum disorder (ASD) in Oman. A cadre of caregivers (n = 150) from two types of SES (low-income and middle-high income) were compared based on four domains: (1) accessing and perception of remedial services, (2) utilization and perception of psychiatric services, (3) constraints for being a caregiver of children with ASD and (4) financial expenses of taking care of children with ASD. There is little indication that any particular SES fare well on these domains. Factors to mitigate such predicaments are therefore imperative in order to improve quality of life for caregivers among children with ASD. [ABSTRACT FROM AUTHOR]

Toxic levels of heavy metals and low levels of essential minerals have been suggested to play a critical role in the pathogenesis of autism spectrum disorders (ASD). This study documents the levels of heavy metals and essential minerals in hair samples of children with ASD in Muscat, the urbanized capital of Oman, Muscat. The study included 27 children with ASD and 27 matched non-ASD controls. Parental interviews were held and dietary intake questionnaires completed in conjunction with the collection of hair samples. Analysis of heavy metals and essential minerals was carried out by inductively coupled plasma mass spectrometry. Chi-square analysis and non-parametric Fisher's exact tests were used to assess statistical significance. Children with ASD had significantly higher levels of all 11 analyzed heavy metals in their hair samples ( P < 0.05), ranging from 150 to 365 % of control levels. ASD children also had significantly higher levels of essential minerals sulfur, sodium, magnesium, potassium, zinc, and iron, but lower levels of calcium and copper in their hair samples. This study corroborates data from previous studies in different parts of the world indicating the presence of elevated levels of heavy metals and selective depletion of essential minerals in the hair of children with ASD. [ABSTRACT FROM AUTHOR]

Although the current treatment of schistosomiasis relies largely on praziquantel (PZQ), it has not significantly reduced the overall number of disease cases, perhaps due to inevitable resistance to PZQ. Previous studies showed that radiation-attenuated vaccine gives protection levels for Schistosoma mansoni in host various species. In the present study, we evaluated the effect of various vaccination strategies in C57BL/6 mice, including single or multiple vaccination strategy, subcurative dose (20 mg/kg) of PZQ, and a combination of single vaccination with subcurative dose of PZQ. Groups of five mice were sacrificed postinfection in 42 days and schistosomes were collected by perfusion and examined by scanning electron microscopy. Treatment either with subcurative dose of PZQ or with a single vaccination of attenuated cercariae (500 per mouse), caused significant reduction in total worm burden, hepatic and intestinal ova counts 43.03%, 73.2%, 59.5% and 37.97%, 52.02%, 26.3%, respectively. Furthermore, tegumental changes were observed, including severe swelling, fusion of tegumental folds, vesicle formation, and loss or shortening of the spines on the tubercles. However, multiple vaccination strategy resulted in much higher reduction in total worm burden, hepatic and intestinal ova count. However, multiple vaccination strategy resulted in high reduction of worm burden, hepatic and intestinal ova counts 72.5%, 90.7%, 65.79%, respectively, and further causing swollen, disruption of tubercles teguments and erosion, extensive peeling, fusion of tegumental folds. Our findings suggest that multiple vaccination strategy is the most effective strategy to clear schistosomal infection, indicating its potential in guiding the design of appropriate therapeutic strategy against schistosomes. [ABSTRACT FROM AUTHOR]

The purpose of the study is to explore the role of humoral immunity against Schistosoma mansoni infection in C57BL/6 mice using highly resistant rabbits that had been exposed to three separate immunizations with ultraviolet (UV)-irradiated cercariae (8,000 attenuated cercariae/rabbit in each immunization), and their sera were tested for their ability to transfer protection against S. mansoni challenge. The present study showed the reduction in challenge worm burden had reached 32.76-43.64% when compared with recipients of normal serum or no serum. The surface topography of the worms collected from immunized mice with either normal rabbit sera (NRS) or vaccinated rabbit sera (VRS) revealed severe tegumental alterations, especially in the VRS group. Worms collected from groups that were immunized by NRS or VRS postinfection (200 normal cercariae/mouse) by day 42. Worms from group immunized with NRS showed damage in the tegument, characterized by severe swelling or erosion of tegumental folds, accompanied by changes in tubercles, swelling, shortening, and loss of spines in male worms. The alteration in female tegument was characterized by swelling of tegumental folds, atrophy of ventral sucker, damage of sensory papillae along all the body, severe peeling in some regions, and appearance of few small blebs. VRS induced more severe tegumental damage than NRS in both male and female worms. Severe shrunken vesicles were protruded from the surface between the two suckers. The tegument of the male showed a collapse of tubercles followed by the appearance of vesicles on their surfaces, fusion, erosion, and superficial focal peeling of tegumental folds. In the female worms, severe damage to the oral sucker, the surface between the two suckers, extensive peeling, severe swelling of the tegument, and damage of sensory papillae. In conclusion, the present study support the hypothesis that high levels of antibodies were developed in rabbit sera after multiple exposures to attenuated cercariae of S. mansoni. Furthermore, immunization might have transferred protection against the infection, indicated by severe morphological alterations, a sign of elimination of the worms. Further investigation is being carried out to reveal the molecular mechanisms underlying the transfer of protection. [ABSTRACT FROM AUTHOR]

Like xeroderma pigmentosum (XP) patients, transgenic mice lacking nucleotide excision repair (NER) genes such as XPA and XPC are extremely susceptible to ultraviolet (UV)-induced skin cancer. Because the p53 gene is an important target for UV carcinogenesis and because the p53 protein modulates NER, we investigated the consequences of NER deficiency on UV-induced p53 mutations in XPC-/- mouse skin tumors. Thirty-eight (76%) of 50 UV-induced XPC-/- skin tumor analysed displayed C→T or CC→TT transitions at dipyrimidine sites on the untranscribed strand of the p53 gene. A major hot spot for p53 mutation occurred at codon 270, which is also a hot spot in UV-induced skin tumors from NER-proficient C3H and SKH-hr 1 mice. Interestingly, codon 270 mutations were induced in both XPC-/- and +/+ mouse skin after 1 week of UV irradiation, but the mutations persisted only in XPC-/- mouse skin after 3 – 4 weeks of chronic UV. The persistence of UV-induced p53 mutations in XPC-/- mouse skin was associated with decreased apoptosis and increased proliferation of keratinocytes, suggesting that these events may contribute to the accelerated development of UV-induced skin tumors in XPC-/- mice. [ABSTRACT FROM AUTHOR]