Glutathione S-transferase M1, T1 and P1 gene polymorphisms and the risk of developing type 2 diabetes mellitus in Egyptian diabetic patients with and without diabetic vascular complications

Background and aim of work: Persistent oxidative stress is one of several factors thatparticipate in the pathogenesis of type 2 diabetes mellitus (T2DM). Glutathione S-transferases (GSTs) are a family of antioxidant enzymes that exert important antioxidant roles in the elimination of reactive oxygen species. We aimed to assess the association of genetic polymorphisms in the GST isoenzymes M1, T1 and P1 with the risk of developing T2DM and its vascular related complications in Egyptian diabetic patients.Subjects and methods: Fifty-four T2DM patients of whom twenty-seven were suffering from vascular complications were compared to fifty-one healthy volunteers. Null genotypes in the GST M1 and T1 genes were screened using polymerase chain reaction (PCR). The A313G single nucleotide polymorphism in the GSTP1 gene was detected using PCR–restriction fragment length polymorphism.Results: No significant differences were noted between diabetic cases and control group regarding frequencies of null genotypes of GSTM1 and GSTT1 genes (χ2p=0.631 and χ2p= 0.832, respectively). Furthermore, both null genotypes were not associated with the risk of developing T2DM or its related vascular complications whether alone or in combination. The frequency of the heterozygous mutation (AG) in the A313G GSTP1 polymorphism among diabetic cases with and diabetic cases without vascular complications was significantly higher compared to the control group (p=0.023). The risk of developing T2DM was significantly higher in cases presenting with combined heterozygous GSTP1 and null GSTM1 genotypes (Odds ratio= 6.285, 95% confidence interval =1.184–33.347, p=0.021).Conclusion: Our results could point out to potential roles of GSTP1 polymorphism alone or combined with GSTM1 gene polymorphism in the pathogenesis of T2DM related oxidative stress. Screening for other functional GST gene polymorphisms is important to understand the impact of interaction of multiple genetic factors in the pathogenesis of T2DM

When is giving an impulse? An ERP investigation of intuitive prosocial behavior

Human prosociality is often assumed to emerge from exerting reflective control over initial, selfish impulses. However, recent findings suggest that prosocial actions can also stem from processes that are fast, automatic and intuitive. Here, we attempt to clarify when prosocial behavior may be intuitive by examining prosociality as a form of reward seeking. Using event-related potentials (ERPs), we explored whether a neural signature that rapidly encodes the motivational salience of an event\u2014the P300\u2014can predict intuitive prosocial motivation. Participants allocated varying amounts of money between themselves and charities they initially labelled as high- or low-empathy targets under conditions that promoted intuitive or reflective decision making. Consistent with our predictions, P300 amplitude over centroparietal regions was greater when giving involved high-empathy targets than low-empathy targets, but only when deciding under intuitive conditions. Reflective conditions, alternatively, elicited an earlier frontocentral positivity related to response inhibition, regardless of target. Our findings suggest that during prosocial decision making, larger P300 amplitude could (i) signal intuitive prosocial motivation and (ii) predict subsequent engagement in prosocial behavior. This work offers novel insight into when prosociality may be driven by intuitive processes and the roots of such behaviors

E. coli in tropical urban rivers : a case study of the Sungai Gombak basin

The primary study area is Sg. Gombak, a river that flows through the mostly urbanized state of Selangor and transcends the capital of Malaysia, Kuala Lumpur. The study aims to characterize E. coli, organics and nutrients on the main stem of the river and its tributaries of Sg. Batu and Sg. Kerayong. There were 28 identified spatial sampling stations throughout the basin. The results on the upper reaches of Sg. Gombak showed E. coli levels ranged between 100 – 400 cfu/100mL. The levels increased and remained between 11,000 cfu/100mL to 18,000 cfu/100 mL downstream upon receiving sewage effluent and other pollution sources. This was comparable to Sg. Batu. Conditions were even worse in Sg. Kerayong as E. coli levels were in excess of 140,000 cfu/100 mL. Ambient temperature increase in excess of 30°C with a ∆T rise of 3 to 4°C appeared to result in some decrement of E. coli; at 0.08/°C for Sg. Gombak and 0.20/°C for Sg. Batu, albeit this only occurred at single spatial points in both rivers. Variation in BOD5, NH3-N and NO3-N did not appear to significantly influence bacterial count in the basin. The study results also showed for the water to be deemed suitable for skin contact, a removal efficiency of at least 92% has to be achieved, which in turn, translated to a die-off period of at least two hours

Serum amino acid abnormalities in pediatric patients with chronic renal failure with and without history of thromboembolic manifestations

Background: Plasma amino acid concentrations have been reported to be abnormal in patients with chronic renal failure. L-Arginine has been used to improve endothelial function by increasing nitric oxide (NO) bioavailability. The present study aim at investigating the status of plasma amino acids in pediatric patients with chronic renal failure (CRF) on regular hemodialysis (HD) with and without history of thromboembolic manifestations.Methods: The study included 21 hemodialysis patients subdivided into two groups (those with no history of thromboembolic manifestations and those with positive history of thromboembolic manifestations) The control group included 13 age and sex matched apparently healthy subjects, After careful history taking, clinical examination, the following laboratory investigations were performed: serum calcium, phosphate, albumin, and creatinine (for controls only), complete blood count (CBC) and serum amino acid analysis.Results: HD patients had a significantly lower concentration of threonine, valine, methionine, leucine, tyrosine, phenylalanine and tryptophane than the control group (p= 0.032, 0.020, 0.046, 0.011, 0.000, 0.022, and 0.004 respectively). There was no significant difference between HD patients and the control group as regard aspartic acid, serine, asparagine, glutamic acid, proline, glycine, alanine, cystine, isoleucine, lysine, histidine, and arginine. The mean serum L-arginine level was lower in 61.9% of HD patients than the mean of the controls with no significant difference. L-Arginine concentration was not significantly different between HD patients with and without history of thromboembolic manifestations.Conclusion: Several abnormalities in amino acids were present in HD patients compared to controls. The mean serum L-arginine level was lower in 61.9% of HD patients than the mean of the controls with no significant difference. L-Arginine concentration was not significantly different between HD patients with and without history of thromboembolic manifestations. HD patients without history of thromboembolic manifestations had significantly lower glutamic acid concentrations and significantly higher phenylalanine concentrations than HD patients with history of thromboembolic manifestations.Keywords: Serum amino acid; Chronic renal failure; L-Arginin

Molecular epidemiology of antibiotic-associated diarrhoea due to Clostridium difficile and clostridium perfringens in Ain Shams University Hospitals

Background: As we are living in the era of antibiotic overuse, antibiotic associated diarrhea (AAD) is considered now a distinct health problem with a need for more attention. Aim of the Study: was to perform a highly specific detection and definition of pathogenic Clostridium perfringens and Clostridium difficile related AAD in children compared to adults and geriatircs. Patients and Methods: One hundred and fifty patients diagnosed for AAD were included in this study (50 children, 50 adults and 50 geriatric patients). All of them were subjected to full medical history including complete therapeutic history of antibiotics and collection of stool sample during the attack for detection of Clostridium perfringenes enterotoxin (CPEnt) and Clostridium difficile cytotoxin by (EIA) kit. PCR detection of Clostridium perfringenes cpe gene (Coding gene for CPEnt) was performed as well. Results: Results showed that prevalence of Clostridium difficile cytotoxin was 24% while Clostridium perfringenes enterotoxin was 12% as detected by EIA in faecal specimens as a whole. Detection of cpe gene by PCR was positive in 16% of all cases. Children (OR: 4.2, 95% CI: 1.3-14.8, P_0.01) and geriatric patients (OR: 3.4, 95% CI: 1.2-13.5, P_0.02) were significantly more prone to Clostridium difficile AAD compared to adults. Also, childhood was a significant risk for Clostridium perfringens AAD (OR: 2.1, 95% CI: 0.54-7.4, P_0.04). In Conclusion: children and geriatric patients are more vulnerable to develop AAD with antibiotic abuse compared to adults. Abbreviations: AAD=Antibiotic associated diarrhea, CI=Confidence interval, ELISA=Enzyme-linked immunosorbent assay, OR=Odd ratio, PCR=Polymerase chain reaction. Keywords: Antibiotic-associated diarrhea, children, Clostridium perfringens, Clostridium difficile. Egypt. J. Hum. Genet Vol. 8 (2) 2007: pp. 121-13

Biallelic variants in ADARB1, encoding a dsRNA-specific adenosine deaminase, cause a severe developmental and epileptic encephalopathy

Background: Adenosine-to-inosine RNA editing is a co-transcriptional/post-transcriptional modification of double-stranded RNA, catalysed by one of two active adenosine deaminases acting on RNA (ADARs), ADAR1 and ADAR2. ADARB1 encodes the enzyme ADAR2 that is highly expressed in the brain and essential to modulate the function of glutamate and serotonin receptors. Impaired ADAR2 editing causes early onset progressive epilepsy and premature death in mice. In humans, ADAR2 dysfunction has been very recently linked to a neurodevelopmental disorder with microcephaly and epilepsy in four unrelated subjects. / Methods: We studied three children from two consanguineous families with severe developmental and epileptic encephalopathy (DEE) through detailed physical and instrumental examinations. Exome sequencing (ES) was used to identify ADARB1 mutations as the underlying genetic cause and in vitro assays with transiently transfected cells were performed to ascertain the impact on ADAR2 enzymatic activity and splicing. / Results: All patients showed global developmental delay, intractable early infantile-onset seizures, microcephaly, severe-to-profound intellectual disability, axial hypotonia and progressive appendicular spasticity. ES revealed the novel missense c.1889G>A, p.(Arg630Gln) and deletion c.1245_1247+1 del, p.(Leu415PhefsTer14) variants in ADARB1 (NM_015833.4). The p.(Leu415PhefsTer14) variant leads to incorrect splicing resulting in frameshift with a premature stop codon and loss of enzyme function. In vitro RNA editing assays showed that the p.(Arg630Gln) variant resulted in a severe impairment of ADAR2 enzymatic activity. / Conclusion: In conclusion, these data support the pathogenic role of biallelic ADARB1 variants as the cause of a distinctive form of DEE, reinforcing the importance of RNA editing in brain function and development

Biallelic variants in ADARB1, encoding a dsRNA-specific adenosine deaminase, cause a severe developmental and epileptic encephalopathy.

BACKGROUND: Adenosine-to-inosine RNA editing is a co-transcriptional/post-transcriptional modification of double-stranded RNA, catalysed by one of two active adenosine deaminases acting on RNA (ADARs), ADAR1 and ADAR2. ADARB1 encodes the enzyme ADAR2 that is highly expressed in the brain and essential to modulate the function of glutamate and serotonin receptors. Impaired ADAR2 editing causes early onset progressive epilepsy and premature death in mice. In humans, ADAR2 dysfunction has been very recently linked to a neurodevelopmental disorder with microcephaly and epilepsy in four unrelated subjects. METHODS: We studied three children from two consanguineous families with severe developmental and epileptic encephalopathy (DEE) through detailed physical and instrumental examinations. Exome sequencing (ES) was used to identify ADARB1 mutations as the underlying genetic cause and in vitro assays with transiently transfected cells were performed to ascertain the impact on ADAR2 enzymatic activity and splicing. RESULTS: All patients showed global developmental delay, intractable early infantile-onset seizures, microcephaly, severe-to-profound intellectual disability, axial hypotonia and progressive appendicular spasticity. ES revealed the novel missense c.1889G>A, p.(Arg630Gln) and deletion c.1245_1247+1 del, p.(Leu415PhefsTer14) variants in ADARB1 (NM_015833.4). The p.(Leu415PhefsTer14) variant leads to incorrect splicing resulting in frameshift with a premature stop codon and loss of enzyme function. In vitro RNA editing assays showed that the p.(Arg630Gln) variant resulted in a severe impairment of ADAR2 enzymatic activity. CONCLUSION: In conclusion, these data support the pathogenic role of biallelic ADARB1 variants as the cause of a distinctive form of DEE, reinforcing the importance of RNA editing in brain function and development