Clinical characteristics, outcomes, and seasonality of acute respiratory infection associated with single and codetected rhinovirus species among hospitalized children in Amman, Jordan.

Rhinovirus (RV)-specific surveillance studies in the Middle East are limited. Therefore, we aimed to study the clinical characteristics, outcomes, and seasonality of RV-associated acute respiratory infection among hospitalized young children in Jordan. We conducted a prospective viral surveillance study and enrolled children <2 years old admitted to a large public hospital in Amman, Jordan (2010-2013). Demographic and clinical data were collected by structured interviews and chart abstractions. Nasal and/or throat swabs were collected and tested for a panel of respiratory viruses, and RV genotyping and speciation was performed. At least one virus was detected in 2641/3168 children (83.4%). RV was the second most common virus detected (n = 1238; 46.9%) and was codetected with another respiratory virus in 730 cases (59.0%). Children with RV codetection were more likely than those with RV-only detection to have respiratory distress but had similar outcomes. RV-A accounted for about half of RV-positive cases (54.7%), while children with RV-C had a higher frequency of wheezing and reactive airway disease. RV was detected year-round and peaked during winter. In conclusion, though children with RV codetection had worse clinical findings, neither codetection nor species affected most clinical outcomes.

APOE Gene polymorphism among Jordanian Alzheimer`s patients with relation to lipid profile.

OBJECTIVE: To investigate the frequencies of the apolipoprotein E (APOE) alleles and genotypes and study their relationship with the lipid profile in Jordanian patients with late-onset Alzheimer`s disease (AD). METHODS: This case-control study was carried out on 71 Jordanian individuals: 38 patients with late-onset AD (age >/=65 years) and 33 age-matched healthy controls. All participants were recruited from senior homes and Jordan University Hospital, Amman, Jordan between January 2010 and December 2013. Each sample was examined for APOE`s 3 major isoforms (e2, e3, e4) using the polymerase chain reaction technique (PCR) followed by the sequencing technique. In addition, samples were screened for lipid profiles (total cholesterol (TC), high-density lipoprotein (HDL), lower-density lipoprotein (LDL), and triglyceride (TG) levels. RESULTS: The e3/e4 genotype and e4 allele prevalence were higher in AD patients compared to healthy controls (26.3% vs. 3.0%, p=0.03 and 15.8% vs. 4.5%, p=0.03; respectively). In the AD group, the e2 carriers showed the lowest levels of total and LDL cholesterol, and the e4 carriers showed the highest levels of total and LDL cholesterol, although the difference was not statistically significant (p>0.05). CONCLUSION: APOE-e4 frequency was almost 4 times higher in the AD group compared to the control group, and this difference was statistically significant. A trend that was observed in the AD group regarding the lipid profile and e2 and e4 carriers requires further investigation using a larger sample size.

An intronic single-nucleotide polymorphism (rs13217795) in FOXO3 is associated with asthma and allergic rhinitis: a case-case-control study.

BACKGROUND: Asthma and allergic rhinitis are respiratory diseases with a significant global burden. Forkhead box O3 (FOXO3) is a gene involved in the etiology of a number of respiratory diseases. The objective of this study is to assess the association of rs13217795, an intronic FOXO3 single-nucleotide polymorphism, with asthma and allergic rhinitis. METHODS: In this case-case-control genetic association study, genotyping was conducted using the PCR-RFLP method. Genotype-based associations were investigated under the general, recessive, and dominant models of disease penetrance using binomial logistic regression; and, allele-based associations were tested using Pearson's chi-squared test. RESULTS: The final study population consisted of 94 controls, 124 asthmatics, and 110 allergic rhinitis patients. The general and recessive models of disease penetrance were statistically significant for both case-control comparisons. Under the general model, the odds of the asthma phenotype were 1.46 (0.64 to 3.34) and 3.42 (1.37 to 8.57) times higher in heterozygotes and derived allele homozygotes, respectively, compared to ancestral allele homozygotes. The corresponding odds ratios for the allergic rhinitis phenotype were 1.05 (0.46 to 2.40) and 2.35 (0.96 to 5.73), respectively. The dominant model of disease penetrance was not statistically significant. The minor allele in all study groups was the ancestral allele, with a frequency of 0.49 in controls. There was no deviation from Hardy-Weinberg equilibrium in controls. Both case-control allele-based associations were statistically significant. CONCLUSIONS: Herein we present the first report of the association between rs13217795 and allergic rhinitis, and the first independent verification of the association between rs13217795 and asthma. Marker selection in future genetic association studies of asthma and allergic rhinitis should include functional polymorphisms in linkage disequilibrium with rs13217795.

Incidence of bcr­abl fusion transcripts in healthy individuals.

Bcr­abl fusion transcripts, resulting from translocation t(9;22), are hallmarks of Philadelphia chromosome positive (Ph+) leukemias. This translocation is detected in >90% of patients with chronic myelogenous leukemia and ~20% of acute lymphoblastic leukemia patients, which predominantly express the p210 and p190 proteins, respectively. Although the occurrence of t(9;22) in healthy individuals has been previously demonstrated, the number of studies is limited and the results are inconsistent. The present study screened for the presence of bcr­abl transcripts in the blood of a group of healthy individuals using a sensitive­nested reverse transcription polymerase chain reaction (RT­PCR) assay. Samples were collected from 189 healthy volunteers (145 adults and 44 children). RNA was reverse transcribed and amplified by two rounds of PCR, amplifying the two common variants of bcr­abl transcripts, p190 and p210. While the bcr­abl p190 transcript was not detected, the p210 transcript was detected in ~10% of samples. Notably, the incidence of p210 translocation was higher in males (12.2%) compared with females (7.7%) and males were 2.4 times more likely to have the translocation. A significant incidence was also observed in adults compared with children, where adults were 6 times more likely to have the translocation. The presence of bcr­abl transcripts in the blood of a significant proportion of healthy individuals should be considered in long­term investigations to establish its exact association with the risk of developing leukemia. Furthermore, the current assays should be revised to consider the proportion of normal samples carrying the p210 transcripts when making a differential diagnosis.

Synthesis and biological activity assays of some new N1-(flavon-7-yl)amidrazone derivatives and related congeners.

A series of new N1-(flavon-7-yl)amidrazones incorporating N-piperazines and related congeners were synthesized by reacting the hydrazonoyl chloride derived from 7-aminoflavone and 7-amino-2-methylchromen-4-one with the appropriate piperazine. The chemical structures of the newly prepared compounds were confirmed by elemental analyses, (1)H NMR, (13)C NMR, and ESI-HRMS spectral data. The antitumor activity of these compounds was evaluated on breast cancer (MCF-7 and T47D) and Leukemic (K562) cell lines by a cell viability assay utilizing the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Although with varying degrees, a significant growth inhibitory and cytotoxic effect was observed on all three cancer cell lines. Among the compounds tested compounds, 5a, 15a, and 18b, were the most active against T47D cell line with IC(50) values of 1.42, 1.92, and 2.92 µM, respectively. By using other cancer cell lines and with further characterization of their biological mechanism of action, these compounds could prove to be useful candidates as anticancer drugs.

CYP1AI, glutathione S-transferase gene polymorphisms and risk of Polycythemia vera.

BACKGROUND: Associations between polymorphisms for gene encoding enzymes involved in biotransformation of xenobiotics and susceptibility to several cancers have been shown in several studies. The aim of the present study was to evaluate the association of polymorphisms of cytochrome P450 (CYP1A1) and GST deletions with the incidence of Polycythemia vera (PV) among the Jordanian population. METHODS: The study included 61 PV patients and 70 cancer-free healthy controls. CYP1A1 (m1, m2, m3, m4) and GST (T1, M1) genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. The risk of cancer associated with gene polymorphisms was estimated by calculations of odds ratio (ORs) and confidence intervals (95% CIs) using Mantel-Haenszel statistics. RESULTS: A statistically significant difference between the PV group and the control group was observed in the case of GSTM1 null genotype with 3.38 fold increase in risk of developing PV (95% CI=1.63-7.01, p=0.001) while GSTT1 null genotype showed no significance (OR=1.11; 95% CI=0.50-2.44, p=0.38). No significant association was found between the CYP1A1 mutant genotypes (m1, m2, m4) and PV. The m3 genotype was absent in both patients and controls. Interestingly, a substantial significant increase of PV risk for the combination of GSTM1 null genotype and CYP1A1 m1 (T6235C) genotype was observed (OR=4.38; 95% CI=1.15-16.73, p=.02). Furthermore, the present case-control study showed that the studied Jordanian population generally resembles Caucasian populations with respect to the frequencies of CYP1A1 polymorphisms. CONCLUSION: Our data suggests that GSTM1 null genotype alone and in combination with CYP1A1 m1 genotype may be predisposing risk factors for PV in the Jordanian population.

Synthesis and biological activity of some 3-(4-(substituted)-piperazin-1-yl)cinnolines.

A new series of 6-substituted-4-methyl-3-(4-arylpiperazin-1-yl)cinnolines 8-10 were synthesized as potential antifungal agents via intramolecular cyclization of the respective 1-(2-arylhydrazono)-1-(4-arylpiperazin-1-yl)propan-2-ones 5-7, mediated by polyphosphoric acid (PPA). The amidrazones themselves were synthesized via direct interaction of the appropriate hydrazonoyl chlorides 4a-d with the corresponding N-substituted piperazine in the presence of triethylamine. The structures of the new prepared compounds were confirmed by elemental analyses, (1)H-NMR, (13)C-NMR, and ESI-HRMS spectral data. The antitumor, antibacterial, and antifungal activity of the newly synthesized compounds was evaluated.

Synthesis, and antitumor activity of some N1-(coumarin-7-yl) amidrazones and related congeners.

A series of new N1-(coumarin-7-yl)amidrazones incorporating N-piperazines and related congeners were synthesized by reacting the hydrazonoyl chloride derived from 7-amino-4-methylcoumarin with the appropriate piperazines. The chemical structures of the newly prepared compounds were supported by elemental analyses, ¹H-NMR, ¹³C-NMR, and ESI-HRMS spectral data. The antitumor activity of the newly synthesized compounds was evaluated. Among all the compounds tested, 7-{2-[1-(4-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)piperazin-1-yl)-2-oxopropylidene]hydrazinyl}-4-methyl-2H-chromen-2-one (3n) was the most potent against MCF-7 and K562 cells, with IC50 values of 20.2 and 9.3 µM, respectively.

Persistent bacteraemia due to methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in a patient with erythrodermic psoriasis.

A 49-y-old male with erythrodermic psoriasis developed persistent bacteraemia for 3 months due to methicillin-resistant Staphylococcus aureus despite antimicrobial therapy. The skin was the likely focus. Three consecutive isolates from the blood and 1 from the nose were identical and had vancomycin MIC of 4 mg/l.

Enterotoxicity and genetic variation among clinical Staphylococcus aureus isolates in Jordan.

A total of 100 Jordanian clinical Staphylococcus aureus isolates was analysed for the presence of the enterotoxin genes sea, seb, sec, sed and see using multiplex PCR. Twenty-three isolates (23 %) were potentially enterotoxigenic. The prevalence of sea, sec and sea plus sec among the total clinical isolates was 15, 4 and 4 %, respectively. None of the isolates harboured sed, seb or see genes. S. aureus isolates were subjected to DNA fingerprinting by randomly amplified polymorphic DNA (RAPD) analysis to test whether isolates harbouring the toxin genes were genetically clustered. A total of 13 genotypes was identified at a 47 % similarity level. Genotypes I and V accounted for the largest number of enterotoxigenic isolates (19 %). This study has demonstrated the genetic diversity of Jordanian clinical S. aureus isolates and shown that the presence of the toxin genes is not genotype specific.