Three different p53 DNA polymorphisms (a 16-bp duplication in intron 3 and BstUland MsplRFLPs in exon 4 and intron 6, respectively) and haplotype combinations were studied in some major ethnic groups: Caucasians (Swedes), Chinese, Dravidian Indians and African Blacks. Significant ethnic differences in single polymorphisms were found between all groups except for African Blacks-Dravidian Indians, who differed only in their MspI7-16-bp duplication haplotype distribution. Since previous results have shown that p53 alleles are correlated with latitude (degree of insolation), the similarity between these two groups, who are genetically quite distinct, may be due to ecological adaptation to similar climatic conditions. All other major ethnic groups differed significantly from each other with respect to their haplotype distributions; thus, p53 alleles and haplotypes should be very useful as anthropological markers. Asiatic Mongoloid groups appear to be characterized by very low frequencies of the 16-bp duplication and the MspIA1 allele. These mutations have probably been introduced by migration to east Asia from either Europe or Africa, where the highest frequencies were found. The results of this study indicate that p53, besides its role as a tumor suppressor, shows distinct ethnic heterogeneity and may be involved in ecological (climatic) adaptation.

The study aimed to examine for the first time the spectra of viral and bacterial pathogens along with the antibiotic susceptibility of the isolated bacteria in under-5 children with acute respiratory infections (ARIs) in hospital settings of Dhaka, Bangladesh. Nasal swabs were collected from 200 under-five children hospitalized with clinical signs of ARIs. Nasal swabs from 30 asymptomatic children were also collected. Screening of viral pathogens targeted ten respiratory viruses using RT-qPCR. Bacterial pathogens were identified by bacteriological culture methods and antimicrobial susceptibility of the isolates was determined following CLSI guidelines. About 82.5% (n = 165) of specimens were positive for pathogens. Of 165 infected cases, 3% (n = 6) had only single bacterial pathogens, whereas 43.5% (n = 87) cases had only single viral pathogens. The remaining 36% (n = 72) cases had coinfections. In symptomatic cases, human rhinovirus was detected as the predominant virus (31.5%), followed by RSV (31%), HMPV (13%), HBoV (11%), HPIV-3 (10.5%), and adenovirus (7%). Streptococcus pneumoniae was the most frequently isolated bacterial pathogen (9%), whereas Klebsiella pneumaniae, Streptococcus spp., Enterobacter agglomerans, and Haemophilus influenzae were 5.5%, 5%, 2%, and 1.5%, respectively. Of 15 multidrug-resistant bacteria, a Klebsiella pneumoniae isolate and an Enterobacter agglomerans isolate exhibited resistance against more than 10 different antibiotics. Both ARI incidence and predominant pathogen detection rates were higher during post-monsoon and winter, peaking in September. Pathogen detection rates and coinfection incidence in less than 1-year group were significantly higher (P = 0.0034 and 0.049, respectively) than in 1–5 years age group. Pathogen detection rate (43%) in asymptomatic cases was significantly lower compared to symptomatic group (P<0.0001). Human rhinovirus, HPIV-3, adenovirus, Streptococcus pneumonia, and Klebsiella pneumaniae had significant involvement in coinfections with P values of 0.0001, 0.009 and 0.0001, 0.0001 and 0.001 respectively. Further investigations are required to better understand the clinical roles of the isolated pathogens and their seasonality.

Serum and CSF-Zn simultaneously decreased in FS children in comparison to their matched NSF peers. Further prospectively designed multicentral studies are recommended to conduct in geographically diverse regions involving larger sample to confirm or refute our findings. It remains crucial in standardizing/strengthening national seizure prevention protocol with adequate Zn supplementation.

Liquid Chromatography tandem mass spectrometry (LC-MS/MS) is used for the diagnosis of more than 30 inborn errors of metabolisms (IEMs). Accurate and reliable diagnosis of IEMs by quantifying amino acids (AAs) and acylcarnitines (ACs) using LC-MS/MS systems depend on the establishment of age-specific cut-offs of the analytes. This study aimed to (1) determine the age-specific cut-off values of AAs and ACs in Bangladesh and (2) validate the LC-MS/MS method for diagnosis of the patients with IEMs. A total of 570 enrolled healthy participants were divided into 3 age groups, namely, (1) newborns (1-7 days), (2) 8 days–7 years, and (3) 8–17 years, to establish the age-specific cut-offs for AAs and ACs. Also, 273 suspected patients with IEMs were enrolled to evaluate the reliability of the established cut-off values. Quantitation of AAs and ACs was performed on an automated LC-MS/MS system using dried blood spot (DBS) cards. Then the specimens of the enrolled clinically suspected patients were analyzed by the established method. Nine patients came out as screening positive for different IEMs, including two borderline positive cases of medium-chain acyl-CoA dehydrogenase deficiency (MCAD). A second-tier test for confirmation of the screening positive cases was conducted by urinary metabolic profiling using gas chromatography- mass spectrometry (GC-MS). Out of 9 cases that came out as screening positive by LC-MS/MS, seven cases were confirmed by urinary GC-MS analysis including 3 cases with phenylketonuria, 1 with citrullinemia type II, 1 with methylmalonic acidemia, 1 with isovaleric acidemia and 1 with carnitine uptake defect. Two borderline positive cases with MCAD were found negative by urinary GC-MS analysis. In conclusion, along with establishment of a validated LC-MS/MS method for quantitation of AAs and ACs from the DBS cards, the study also demonstrates the presence of predominantly available IEMs in Bangladesh.

Clobazam was observed to be an effective broad-spectrum antiepileptic with 'mild' side effects in Indian children.

A total of 543 random samples of blood collected from unrelated male blood donors of Amman, Jordan, were analysed for ABO and Rh(D) blood groups, serum haptoglobin, transferrin and albumin; glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, lactate dehydrogenase; and haemoglobin phenotypes. The results of the study establish the Arab characteristics of the population with no or minimal presence of African genes.

In a study of transferrin receptor (TFR) polymorphism in different ethnic groups using PCR and restriction cleavage we found a new Hin6I polymorphism in intron 7 and confirmed a tentative BanI polymorphism in exon 4 reported by Evans and Kemp [Gene 1997;199:123–131]. In all ethnic groups there was a complete and highly significant (p < 10^–10) linkage disequilibrium where all BanI 1 alleles were linked to Hin6I 1 alleles. Furthermore in the European populations, but not in the Chinese, there was a close correlation between the three BanI-Hin6I haplotypes and the alleles of a previously described three-allelic RsaI polymorphism in the TFR gene studied by Southern blotting. There were distinct ethnic differences in TFR allele and haplotype frequencies. Thus the Saamis were significantly different from the other European ethnic groups, and the Lithuanians had a significantly increased frequency of the BanI 2-Hin6I 1 haplotype, suggesting that this marker may be informative in tracing prehistoric migrations and admixture by Baltic peoples. The new TFR polymorphisms and haplotypes may also be useful markers in studies of interactions with the transferrin and hemochromatosis genes, the genetic influence on body iron stores and disease associations.

Although thyroid dyshormonogenesis (TDH) accounts for 10-20% of congenital hypothyroidism (CH), the molecular etiology of TDH is unknown in Bangladesh. Thyroid peroxidase (TPO) is most frequently associated with TDH and the present study investigated the spectrum of TPO mutations in Bangladeshi patients and analyzed the effects of mutations on TPO protein structure through in silico approach. Sequencing-based analysis of TPO gene revealed four mutations in 36 diagnosed patients with TDH including three nonsynonymous mutations, namely, p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro, and one synonymous mutation p.Pro715Pro. Homology modelling-based analysis of predicted structures of MPO-like domain (TPO142-738) and the full-length TPO protein (TPO1-933) revealed differences between mutant and wild type structures. Molecular docking studies were performed between predicted structures and heme. TPO1-933 predicted structure showed more reliable results in terms of interactions with the heme prosthetic group as the binding energies were -11.5 kcal/mol, -3.2 kcal/mol, -11.5 kcal/mol, and -7.9 kcal/mol for WT, p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro, respectively, implying that p.Ala373Ser and p.Thr725Pro mutations were more damaging than p.Ser398Thr. However, for the TPO142-738 predicted structures, the binding energies were -11.9 kcal/mol, -10.8 kcal/mol, -2.5 kcal/mol, and -5.3 kcal/mol for the wild type protein, mutant proteins with p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro substitutions, respectively. However, when the interactions between the crucial residues including residues His239, Arg396, Glu399, and His494 of TPO protein and heme were taken into consideration using both TPO1-933 and TPO142-738 predicted structures, it appeared that p.Ala373Ser and p.Thr725Pro could affect the interactions more severely than the p.Ser398Thr. Validation of the molecular docking results was performed by computer simulation in terms of quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics (MD) simulation. In conclusion, the substitutions mutations, namely, p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro, had been involved in Bangladeshi patients with TDH and molecular docking-based study revealed that these mutations had damaging effect on the TPO protein activity.