Multiple Risk Factors: A Challenge in the Management of Autism.

Autism Spectrum Disorder (ASD) is an emerging health problem involving 1 out of every 68 children. The incidence rate of autism has increased 3 folds during the last 3 decades. Due to the illusive picture of aetiology, a considerable number of autistic children fail to receive proper behavioural and medicational treatment. The present study provides a cumulative account of autism risk factors. Several factors including the gene expression and gene mutations, environmental pollution, metal ion accumulation, exposure to pesticides, immune deficiencies, viral infections, mother's age, health, mental status, mother's interactions with the foetus, vaccination of mother and children, and modulations in gut microbiota have been debated. These risk factors may contribute to the development of autism either independently or synergistically leading to a broad spectrum of characteristics observed in autistic patients. The variable quantitative influence of a wide spectrum of risk factors may result in a unique set of features in each autistic individual. However, the exact mechanism behind the combined impact of various aetiological factors is poorly understood hindering the adaptation of specified and effective therapies.

LC-MS/MS-based metabolic profiling of Escherichia coli under heterologous gene expression stress.

Escherichia coli is frequently exploited for genetic manipulations and heterologous gene expression studies. We have evaluated the metabolic profile of E. coli strain BL21 (DE3) RIL CodonPlus after genetic modifications and subjecting to the production of recombinant protein. Three genetically variable E. coli cell types were studied, normal cells (susceptible to antibiotics) cultured in simple LB medium, cells harboring ampicillin-resistant plasmid pET21a (+), grown under antibiotic stress, and cells having recombinant plasmid pET21a (+) ligated with bacterial lactate dehydrogenase gene grown under ampicillin and standard isopropyl thiogalactoside (IPTG)-induced gene expression conditions. A total of 592 metabolites were identified through liquid chromatography-mass spectrometry/mass spectrometry analysis, feature and peak detection using XCMS and CAMERA followed by precursor identification by METLIN-based procedures. Overall, 107 metabolites were found differentially regulated among genetically modified cells. Quantitative analysis has shown a significant modulation in DHNA-CoA, p-aminobenzoic acid, and citrulline levels, indicating an alteration in vitamin K, folic acid biosynthesis, and urea cycle of E. coli cells during heterologous gene expression. Modulations in energy metabolites including NADH, AMP, ADP, ATP, carbohydrate, terpenoids, fatty acid metabolites, diadenosine tetraphosphate (Ap4A), and l-carnitine advocate major metabolic rearrangements. Our study provides a broader insight into the metabolic adaptations of bacterial cells during gene manipulation experiments that can be prolonged to improve the yield of heterologous gene products and concomitant production of valuable biomolecules.

Determination of hepatitis C virus genotypes circulating in different districts of Punjab (Pakistan).

INTRODUCTION: Hepatitis C virus (HCV) is a principal cause of severe liver diseases worldwide and a possible source of significant morbidity and fatality in the long term. Information on the genotype is more significant because it has prognostic value in the response to antiviral therapy. OBJECTIVES: This study aimed to determine the frequency of various HCV genotypes circulating in the different districts of Punjab and to show the pattern distribution of HCV genotypes in different age groups and sexes. MATERIALS AND METHODS: A total of 542 HCV-positive patients were selected from various districts of the province and were subjected to an HCV genotype-specific assay. Among 542 positive patients, 300 (55.35%) were men and 242 (44.65%) were women. There were 245 (45.20%), 61 (11.25%), 56 (10.33%), 56 (10.33%), 53 (9.77%), 27 (5%), 20 (3.69%), 16 (3%), and eight (1.47%) HCV-positive patients from Lahore, Sargodha, Multan, Toba Tek Singh, Faisalabad, Rawalpindi, Mandi Bahauddin Gujranwala, and Sahiwal districts, respectively. RESULTS: Of a total of 542 serum samples analyzed, 476 (88%) were successfully genotyped whereas 66 (12%) samples were undetermined genotypes. Among the typable genotypes, 1a was found in 37 (7%), 1b in 18 (3%), 3a in 386 (71%), and genotype 3b in five (1%) patients. Thirty patients (6%) were identified to be infected with mixed HCV genotypes. Genotypes 3a (P=0.0001), 1a (P=0.001), and untypable genotypes (P=0.03) were circulating significantly in all the studied districts. All the genotypes were distributed evenly in male and female patients. The most affected age range of patients was 21-40 years as compared with teenage and older age groups. CONCLUSION: The study found a significantly high prevalence of HCV among the patients of Punjab. In addition, genotype 1a was found to be a significantly and rapidly increasing genotype in the study area. It appears that HCV-3a (the most prevalent genotype) may be replaced by genotype 1a. If this occurs, it will make the present scenario more complex in terms of response to therapy and economic burden on the health sector of Pakistan. HCV infection is more common in the age group of 21-40 years. All the genotypes were distributed at the same frequency in men and women.