Correlation between a single nucleotide polymorphism (G/T at nt –88) in the Mx1 gene promoter and the response to interferon therapy for hepatitis C virus in Egyptian patients

Interferon used in the treatment of hepatitis C virus (HCV) patients stimulates the expression of a number of host genes encoding enzymes with antiviral activities, including myxovirus resistance gene- 1 (Mx1). Mx1 gene was found to have a single nucleotide polymorphism (SNP) at position -88 in the promotor region that affect the expression of Mx 1 protein and was suggested to be associated with the response of HCV. In this study, we assessed the relation between the SNP in the Mx1 gene and the responsiveness of Egyptian HCV patients to pegylated interferon and ribavirin treatment along with other host-related and virus-related predictors of treatment outcome. We genotyped the biallelic G/T SNP in the promoter region of Mx1 gene at position -88 from the transcription start site by restriction fragment length polymorphism (RFLP) in 42 interferon treatment-naïve Egyptian patients that were treated with pegylated interferon and ribavirin. We found that Mx1 nt-88 SNP is not significantly correlated to achieving sustained virological response (SVR) after pegylated interferon alpha and ribavirin combined treatment. We conclude that Mx1 gene polymorphism at codon nt-88 cannot be considered as biological marker to potentially identify responders and non-responders of HCV patients to achieve a sustained virological response to treatment with interferon (IFN) in combination with ribavirin.Key words: Hepatitis C virus (HCV), interferon (IFN), myxovirus resistance protein (Mx1 protein), myxovirus resistance gene-1 (Mx1 gene), single nucleotide polymorphism (SNP)

Genetic association between common beta-2 adrenoreceptor polymorphism and asthma severity in school-age children

Recent studies have suggested that polymorphism of the beta-2 adrenergic receptor (β2AR) gene at codon 16 affect an individual’s airway responsiveness. This study aimed to evaluate the association between beta-2 adrenoreceptor genotypes at position 16 and asthma severity among 59 school-aged children. They were divided into two groups: control group including 19 healthy children and 40 asthmatic children as the study group. The study group was also divided into 20 mild asthmatic children and the remaining 20 patients suffered from severe asthma. Blood samples were collected from Chest Department, Pediatrics Hospital, Ain Shams University, from February 2008 to March 2009. Molecular analysis was performed at Science Faculty, Ain Shams University, Cairo, Egypt. Venous blood sample were collected and genotyping of β2AR gene polymorphism at position 16 was identified by polymerase chain reaction– restriction fragment length polymorphism analysis, using the NcoI restriction enzyme. We found a highly statistically significant difference of polymorphisms’ distribution of β2AR gene at codon 16 among asthmatic patients and control subjects (χ2= 11.904; P = 0.0026), also among severe asthmatics and mild/moderate asthmatics(χ2 =10.108;P=0.0064). There was a strong association of heterozygous Arg16Gly of b2AR with severe asthmatics rather than that in control subjects (70% vs. 5.3%, P < 0.001), with odd ratio (OR) 42 (95% confidence interval (CI): 4.520–390.297), the highest OR in heterozygous Arg16Gly (42) suggests a dominant mode of action of the heterozygous Arg16Gly in development of asthma severity. So, we concluded that heterozygous Arg16Gly of b2AR gene appeared to be an important genetic factor in the expression of asthma severity. Keywords: Asthma; Beta-2 adrenoceptor gene polymorphisms; Arginine 16/Glycin

Purification and characterization of phenoloxidase from immunized haemolymph of Schistocerca gregaria

Phenoloxidase (PO) is a key factor in insect immunity. On invasion of microorganisms and pathogens, prophenoloxidase (PPO) changes to its active form, PO. The present study has been conducted to purify and characterize the PO from the haemolymph of desert locust, Schistocerca gregaria (Forskal) following activation of immune system by invasion of bacteria, Bacillus thuringiensis kurstaki (Bt). PO is purified by a combination of ammonium sulfate precipitation, blue sepharose CL-6B and phenyl sepharose CL-4B chromatography yielded a 209.97-fold purity and 54.75% recovery of activity. Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) reveals that the molecular weight of the purified PO is 70.154 kDa. The purified PO is characterized in terms of its biochemical and enzymatic properties by using L-DOPA as a specific substrate. Ca2+ and Cu2+ significantly stimulated PO activity when compared with other metals. The PO reaction was strongly inhibited by phenylthiourea and thiourea, moderately inhibited by ethylene diamine tetractic acid (EDTA) and poorly inhibited by ethylene glycol tetraacetic acid (EGTA) and diethyl dithiocarbamate (DTC). Inhibition of PO showed excellent recovery ability by addition of Ca2+ on EGTA-inhibited enzyme. Therefore, PO is most probably a kind of tyrosinase-type Ca2+-containing metalloenzyme. The content of Ca2+ is higher than other trace metal elements. The reactive intermediates yielded by PO with its specific substrate L-DOPA had a broad-spectrum bactericidal activity against Gram +ve bacteria (Bacillus cereus and Staphylococcus aureus) with a greater degree more than Gram-ve bacteria (Escherichia coli and Pseudomonas aeruginosa). From the present study, PO from S. gregaria is most probably a tyrosinasetype calcium-containing mono-phenoloxidase, which functions not only as a catalytic enzyme in melanin production in locusts, but perhaps also as a humoral factor in host defense via melaninization as in other insects.Key words: Schistocerca gregaria, phenoloxidase, purification

Detection and molecular characterization of vancomycin resistant Staphylococcus aureus from clinical isolates

Until now, few strains of vancomycin resistant Staphylococcus aureus (VRSA) have been reported worldwide. The disk diffusion method for determination of vancomycin sensitivity frequently misclassifies intermediately susceptible isolates to fully susceptible. However, non-automated minimum inhibitory concentration (MIC) detection methods are the gold standards. In the present study, 439 Gram positive clinical isolates were collected. Among them, 220 Staphylococcus aureus were identified. Multiplex polymerase chain reaction (PCR) detection method for vancomycin resistant S. aureus (VRSA) was developed for detection of both vanA gene (for vancomycin resistance) and nuc gene (specific for S. aureus) in a single step PCR compared to conventional non-automated disc diffusion and MIC detection methods. Molecular typing of VRSA isolates was performed using randomly amplified polymorphic (RAPD) DNA assay technique. The results show 10 VRSA isolates detected by disc diffusion method and MIC determination. Five out of them harbored vanA gene that were detected by multiplex PCR and most of them showed low clonal diversity.Key words: Molecular characterization, multiplex polymerase chain reaction (PCR), vancomycin resistant Staphylococcus aureus (VRSA), vanA gene, nuc gene, randomly amplified polymorphic DNA (RAPD) assay technique

The Determinant of Subjective Well-Being among the adult individuals in the UAE

Background: Enhancing individual wellbeing is a national priority in the United Arab Emirates. Up to date, wellbeing at the country level was measured through the national wellbeing survey that is sector specific comprising of 122 questions. The “World Health Organization 5 items (WHO-5) Well-being Index” is a reliable instrument to assess Subjective Well-Being, yet was never tested at national level in the UAE. Aim: This study examined the association of socio-economic determinants of health with the subjective well-being (SWB) using WHO-5 Well-being Index to inform public health policy in the UAE. Method: A cross-sectional survey from adults (aged 18+ and above) was conducted. About 10,000 individuals were randomly selected across all the seven Emirates. A total of 7367 adults (18 years and above) took part in the survey (response rate was 74%). The WHO-5 instrument is a valid screening measure as it includes only 5 items, is freely available in at least thirty-one languages, and is tremendously easy to complete, interpret and score. The social support of the respondents was evaluated by using the Multidimensional Scale of Perceived Social Support. Results: The results of the study demonstrate that majority of the participants (79.27%) reported moderate - high (≥50) well-being scores showing the good quality of life/well-being, whereas, only 20.72% of the individual reported ill-being/likely depression in the future. Respondent’s age, gender, marital status, monthly income (AED- UAE dirham), employment status and reporting at least one or more morbidity were found to be significantly associated with the SWB variables (p < 0.05). A significant association was found between the comprehensive/emotional and /mental well-being and perceived social support. Conclusion: The WHO-5 index can be used as a reliable screening tool to identify wellbeing inequalities among adult individuals based on socio-economic determinants of health in the UAE. Addressing the socio- Hira Abdul Razzak1, Dr. Alya Harbi2, Ms. Mubarkah Jaber AlKarbi3, Dr. Amin Mohamed ElShamy4 , Dr. Lubna Al Shaali5, Dr. Rasha E Salama6 , Ms. Malaz Bakri7, Dr. Ahmed Alosi8, Ms. Amna AlDhmanie9 1678 © 2021 JPPW. All rights reserved economic determinants of health in the UAE can enhance subjective well-being (SWB) and help the UAE to achieve its strategic aspiration to make the UAE among the world leaders in quality of life

Evaluation of midkine and anterior gradient 2 in a multimarker panel for the detection of ovarian cancer

The aims of this study were: to characterise and compare plasma concentrations of midkine (MDK) in normal healthy women with concentrations observed in women with ovarian cancer; and to establish and compare the performance of MDK with that of anterior gradient 2 protein (AGR2) and CA125 in the development of multi-analyte classification algorithms for ovarian cancer. Median plasma concentrations of immunoreactive MDK, AGR2 and CA125 were significantly greater in the case cohort (909 pg/ml, 765 pg/ml and 502 U/ml, respectively n = 46) than in the control cohort (383 pg/ml, 188 pg/ml and 13 U/ml, respectively n = 61) (p < 0.001). The area under the receiver operator characteristic curve (AUC) for MDK and AGR2 was not significantly different (0.734 ± 0.046 and 0.784 ± 0.049, respectively, mean ± SE) but were both significantly less than the AUC for CA125 (0.934 ± 0.030, p < 0.003). When subjected to stochastic gradient boosted logistic regression modelling, the AUC of the multi-analyte panel (MDK, AGR2 and CA125, 0.988 ± 0.010) was significantly greater than that of CA125 alone (0.934 ± 0.030, p = 0.035). The sensitivity and specificity of the multi-analyte algorithm were 95.2 and 97.7%, respectively. Within the study cohort, CA125 displayed a sensitivity and specificity of 87.0 and 94.6%, respectively. The data obtained in this study confirm that both MDK and AGR2 individually display utility as biomarkers for ovarian cancer and that in a multi-analyte panel significantly improve the diagnostic utility of CA125 in symptomatic women

Quality of life and tumor control after short split-course chemoradiation for anal canal carcinoma

<p>Abstract</p> <p>Purpose</p> <p>To evaluate quality of life (QOL) and outcome of patients with anal carcinoma treated with short split-course chemoradiation (CRT).</p> <p>Methods</p> <p>From 1991 to 2005, 58 patients with anal cancer were curatively treated with CRT. External beam radiotherapy (52 Gy/26 fractions) with elective groin irradiation (24 Gy) was applied in 2 series divided by a median gap of 12 days. Chemotherapy including fluorouracil and Mitomycin-C was delivered in two sequences. Long-term QOL was assessed using the site-specific EORTC QLQ-CR29 and the global QLQ-C30 questionnaires.</p> <p>Results</p> <p>Five-year local control, colostomy-free survival, and overall survival were 78%, 94% and 80%, respectively. The global QOL score according to the QLQ-C30 was good with 70 out of 100. The QLQ-CR29 questionnaire revealed that 77% of patients were mostly satisfied with their body image. Significant anal pain or fecal incontinence was infrequently reported. Skin toxicity grade 3 or 4 was present in 76% of patients and erectile dysfunction was reported in 100% of male patients.</p> <p>Conclusions</p> <p>Short split-course CRT for anal carcinoma seems to be associated with good local control, survival and long-term global QOL. However, it is also associated with severe acute skin toxicity and sexual dysfunction. Implementation of modern techniques such as intensity-modulated radiation therapy (IMRT) might be considered to reduce toxicity.</p

Justified Concern or Exaggerated Fear: The Risk of Anaphylaxis in Percutaneous Treatment of Cystic Echinococcosis—A Systematic Literature Review

Percutaneous treatment (PT) emerged in the mid-1980s as an alternative to surgery for selected cases of abdominal cystic echinococcosis (CE). Despite its efficacy and widespread use, the puncture of echinococcal cysts is still far from being universally accepted. One of the main reasons for this reluctance is the perceived risk of anaphylaxis linked to PTs. To quantify the risk of anaphylactic reactions and lethal anaphylaxis with PT, we systematically searched MEDLINE for publications on PT of CE and reviewed the PT-related complications. After including 124 publications published between 1980 and 2010, we collected a total number of 5943 PT procedures on 5517 hepatic and non-hepatic echinococcal cysts. Overall, two cases of lethal anaphylaxis and 99 reversible anaphylactic reactions were reported. Lethal anaphylaxis occurred in 0.03% of PT procedures, corresponding to 0.04% of treated cysts, while reversible allergic reactions complicated 1.7% of PTs, corresponding to 1.8% of treated echinococcal cysts. Analysis of the literature shows that lethal anaphylaxis related to percutaneous treatment of CE is an extremely rare event and is observed no more frequently than drug-related anaphylactic side effects

Genes but Not Genomes Reveal Bacterial Domestication of Lactococcus Lactis

BACKGROUND: The population structure and diversity of Lactococcus lactis subsp. lactis, a major industrial bacterium involved in milk fermentation, was determined at both gene and genome level. Seventy-six lactococcal isolates of various origins were studied by different genotyping methods and thirty-six strains displaying unique macrorestriction fingerprints were analyzed by a new multilocus sequence typing (MLST) scheme. This gene-based analysis was compared to genomic characteristics determined by pulsed-field gel electrophoresis (PFGE). METHODOLOGY/PRINCIPAL FINDINGS: The MLST analysis revealed that L. lactis subsp. lactis is essentially clonal with infrequent intra- and intergenic recombination; also, despite its taxonomical classification as a subspecies, it displays a genetic diversity as substantial as that within several other bacterial species. Genome-based analysis revealed a genome size variability of 20%, a value typical of bacteria inhabiting different ecological niches, and that suggests a large pan-genome for this subspecies. However, the genomic characteristics (macrorestriction pattern, genome or chromosome size, plasmid content) did not correlate to the MLST-based phylogeny, with strains from the same sequence type (ST) differing by up to 230 kb in genome size. CONCLUSION/SIGNIFICANCE: The gene-based phylogeny was not fully consistent with the traditional classification into dairy and non-dairy strains but supported a new classification based on ecological separation between "environmental" strains, the main contributors to the genetic diversity within the subspecies, and "domesticated" strains, subject to recent genetic bottlenecks. Comparison between gene- and genome-based analyses revealed little relationship between core and dispensable genome phylogenies, indicating that clonal diversification and phenotypic variability of the "domesticated" strains essentially arose through substantial genomic flux within the dispensable genome