Maged El-Setouhy

Genotoxic effects of waterpipe smoking on the buccal mucosa cells

Waterpipe smoking is popular in many parts of the world. Micronuclei (MN) evaluation in the exfoliated oral cells of smokers is a non-invasive technique for evaluation of possible tobacco harm. We aimed to assess whether MN levels are higher in waterpipe smokers than in never smokers. We examined oral smears of 128 adult male waterpipe smokers and 78 males who never smoked tobacco in rural Egypt. The total number of MN per 1000 cells per subject, and the number of MN-containing cells per individual were compared. We observed a higher level of total MN in waterpipe smokers (10 +/- 4) than in never smokers (4 +/- 2, p < 0.001). A similar difference was found for the mean number of affected cells per individual (8 +/- 3 vs. 4 +/- 1.62, p < 0.001). MN levels were not significantly dose related. This study is among the first to assess the association between waterpipe smoking and a cytogenetic measure of tobacco harm. The twofold increase in MN level is consistent with previous reports of MN in cigarette smokers. More research is needed to determine if such MN levels are predictive of future health consequences.

Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration: a multicenter evaluation.

Background Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS) to determine if MDA can be stopped within an LF evaluation unit (EU) after at least five effective rounds of annual treatment. To test the value and practicality of these guidelines, a multicenter operational research trial was undertaken in 11 countries covering various geographic and epidemiological settings. Methodology The TAS was conducted twice in each EU with TAS-1 and TAS-2 approximately 24 months apart. Lot quality assurance sampling (LQAS) formed the basis of the TAS survey design but specific EU characteristics defined the survey site (school or community), eligible population (6–7 year olds or 1st–2nd graders), survey type (systematic or cluster-sampling), target sample size, and critical cutoff (a statistically powered threshold below which transmission is expected to be no longer sustainable). The primary diagnostic tools were the immunochromatographic (ICT) test for W. bancrofti EUs and the BmR1 test (Brugia Rapid or PanLF) for Brugia spp. EUs. Principal Findings/Conclusions In 10 of 11 EUs, the number of TAS-1 positive cases was below the critical cutoff, indicating that MDA could be stopped. The same results were found in the follow-up TAS-2, therefore, confirming the previous decision outcome. Sample sizes were highly sex and age-representative and closely matched the target value after factoring in estimates of non-participation. The TAS was determined to be a practical and effective evaluation tool for stopping MDA although its validity for longer-term post-MDA surveillance requires further investigation.

DRD2/ANKK1 TaqI polymorphism and smoking behavior of Egyptian male cigarette smokers.

Little is known about the genetic contribution to cigarette smoking and nicotine addiction in Egypt. The dopamine D2 receptor gene contains a TaqI repeat fragment length polymorphism creating two alleles with functional significance, DRD2*A1 and DRD2*A2. We investigated the relationship between these alleles and tobacco use in a study of 389 Egyptian male current smokers (mean age = 40 years; SD = 12). Participants were interviewed in 2004 on their smoking behaviors and quit attempts, and were given the Fagerström Test for Nicotine Dependence (FTND). Blood samples were obtained and genotyped for DRD2 A1and A2 alleles. The frequencies of A1/A2, A1/A2, and A2/A2 genotypes were 6%, 29%, and 65%, respectively. We found no statistically significant association between genotype and age at onset of smoking, years of smoking, FTND score, or average number of cigarettes smoked per day. DRD2 genotype was associated with the number of cigarettes smoked in the past 48 hr (42.2 in A1 carriers vs. 37.6 in A2, p = .03), the previous quit duration (28% in A1 vs. 40% in A2 quit for more than 1 month, p = .05), and the depth of inhalation (82% in A1 vs. 72% in A2 inhaled the smoke deeply, p = .03). Logistic regression analysis including DRD2 genotype, FTND score, age at smoking initiation, marital status, and education as predictors showed that maximum duration of quit time was associated with FTND score (p = .003), DRD2 genotype (p = .01), marital status (p = .03), and age at smoking initiation (p = .04). These findings suggest a modest association between DRD2 genotype and quitting behavior in male cigarette smokers in Egypt.

A Multicenter Study of the Awareness and Attitudes of Egyptian Faculty towards Research Ethics: A Pilot Study

The awareness and attitudes of faculty towards research ethics committees (RECs) and research ethics practices are largely unknown. Accordingly, we conducted a cross-sectional survey study involving various faculties (Medicine, Nursing, Pharmacy, and Dentistry) from four universities in Egypt. A large majority (> 85%) held positive attitudes towards RECs, but almost a third thought that RECs would delay research. More than half had not received prior training in research or medical ethics, but more than 90% thought that this subject matter should be taught to postgraduates. A large majority recognized the need for informed consent and confidentiality protections in research, but some held attitudes regarding certain research ethics practices that were questionable. We conclude that a curriculum in research ethics should be developed for university faculty and that further qualitative studies should explore the basis of several of the attitudes regarding practices in research ethics.

Exome sequencing of oral squamous cell carcinoma in users of Arabian snuff reveals novel candidates for driver genes.

The study sought to identify genetic aberrations driving oral squamous cell carcinoma (OSCC) development among users of shammah, an Arabian preparation of smokeless tobacco. Twenty archival OSCC samples, 15 of which with a history of shammah exposure, were whole‐exome sequenced at an average depth of 127×. Somatic mutations were identified using a novel, matched controls‐independent filtration algorithm. CODEX and Exomedepth coupled with a novel, Database of Genomic Variant‐based filter were employed to call somatic gene‐copy number variations. Significantly mutated genes were identified with Oncodrive FM and the Youn and Simons method. Candidate driver genes were nominated based on Gene Set Enrichment Analysis. The observed mutational spectrum was similar to that reported by the TCGA project. In addition to confirming known genes of OSCC (TP53, CDKNA2, CASP8, PIK3CA, HRAS, FAT1, TP63, CCND1 and FADD) the analysis identified several candidate novel driver events including mutations of NOTCH3, CSMD3, CRB1, CLTCL1, OSMR and TRPM2, amplification of the proto‐oncogenes FOSL1, RELA, TRAF6, MDM2, FRS2 and BAG1, and deletion of the recently described tumor suppressor SMARCC1. Analysis also revealed significantly altered pathways not previously implicated in OSCC including Oncostatin‐M signalling pathway, AP‐1 and C‐MYB transcription networks and endocytosis. There was a trend for higher number of mutations, amplifications and driver events in samples with history of shammah exposure particularly those that tested EBV positive, suggesting an interaction between tobacco exposure and EBV. The work provides further evidence for the genetic heterogeneity of oral cancer and suggests shammah‐associated OSCC is characterized by extensive amplification of oncogenes.

Albendazole and its metabolites in the breast milk of lactating women following a single oral dose of albendazole

AIMS Albendazole (ABZ) is used in several anthelminthic drug programs. ABZ side-effects are generally mild, but ABZ-induced pancytopenia may be serious. In filariasis programmes, it may be necessary to administer ABZ to breastfeeding women. Few data are available on safety of ABZ for breastfed infants. In addition, the pharmacokinetics of ABZ and its metabolites in human milk is insufficiently investigated. The aim was to study pharmacokinetics of ABZ and its metabolites [ABZ sulphoxide (ABSX) and ABZ sulphone] in the breast milk lactating women after one single oral dose of ABZ. METHODS Thirty-three lactating women (age 18-40 years) participated in the study. They received a single oral 400-mg dose of ABZ. Five milk samples were taken at 0, 6, 12, 24 and 36 h. One serum sample was taken after 6 h. Samples were analysed using high-performance liquid chromatography and pharmacokinetic analysis was performed. RESULTS ABZ was detectable in milk samples 6 h after the oral dose. The mean concentration of serum ABZ was 63.7 +/- 11.9 ng ml(-1). The pharmacokinetic parameters for ABSX were calculated as follows: 351.9 +/- 32.4 ng ml(-1), 6.9 +/- 0.5 h, 12.4 +/- 2.2 h and 5190.3 +/- 482.8 ng*h ml(-1) for C(max), T(max), t((1/2)) and AUC(0-36), respectively. The milk-to-serum ratios (range) for ABZ and ABSX were 0.9 (0.2-6.5) and 0.6 (0.1-1.5), respectively. CONCLUSIONS After an oral dose of 400 mg, ABZ and ABSX attain low concentrations in breast milk that are unlikely to be considered harmful for the breastfed infant.

Why would khat chewers quit? An in-depth, qualitative study on Saudi Khat quitters.

ABSTRACT Background: Khat chewing, which has many adverse health and social consequences, is highly prevalent and socially accepted in the Jazan region of the Kingdom of Saudi Arabia. Methods: A qualitative study was conducted with 47 adult male former khat users regarding their khat initiation, continuance, and cessation, the amounts of khat they had used, and the health and social consequences of their use and cessation of use. Results: Participants noted a desire to show maturity, ease of availability of khat, and peer pressure as reasons for initiating khat chewing. Many noted long leisure times with little to do as a reason for continuing use. Negative consequences of khat use were seen in economic, health, familial, and sexual areas of their lives. After quitting khat use, participants saw improvements in all of these areas. Conclusions: A comprehensive community development program (CCDP) tackling, among other issues, the normalization of khat use, substantial leisure times with few positive activities, and misinformation about the “benefits” of khat use, as well as developing peer and family training programs to help prevent or stop khat use, would be useful to reduce khat chewing in this community.

Neuropsychological Functioning Among Chronic Khat Users in Jazan Region, Saudi Arabia

BACKGROUND Khat chewing effects in the central nervous system are attributed to cathinone and cathine, which are structurally related to amphetamine. However, studies on neuropsychological problems arising from khat use in humans are not extensive and have only included observational and single-case studies. The aims of this study were to (1) to examine neuropsychological functions among khat chewers, and (2) to determine factors affecting neuropsychological outcomes among khat chewers. METHODS A sample of 70 adult male khat chewers and a control group of 72 nonchewers were recruited from the Jazan region in southwest Saudi Arabia. A questionnaire examining socioeconomic background, medical and occupational history, education, and khat chewing behaviors was administered. Neuropsychological performance was assessed using computerized tests from the Behavioral Assessment and Research System (BARS) that assessed learning, episodic and working memory, motor speed/coordination, attention/information processing speed, sustained attention, set-shifting/response inhibition, and perceptual functions; noncomputerized tests, Trail Making A and B, Block Design, and Benton Visual Retention tests were also administered. RESULTS Khat chewers performed significantly worse on 3 out of 14 neuropsychological subtests compared with the control group, representing learning, motor speed/coordination, and set-shifting/response inhibition functions. Age and educational level were identified as predictors of neuropsychological outcomes of khat chewers. CONCLUSIONS The chronic chewing of khat leaves is associated with deficits in some neuropsychological functions, which may affect the mental and neurological health of communities in which khat chewing is a common habit.

Knowledge and Practice Related to Compliance with Mass Drug Administration during the Egyptian National Filariasis Elimination Program

Lymphatic filariasis (LF) has been targeted for global elimination by 2020. The primary tool for the program is mass drug administration (MDA) with antifilarial medications to reduce the source of microfilariae required for mosquito transmission of the parasite. This strategy requires high MDA compliance rates. Egypt initiated a national filariasis elimination program in 2000 that targeted approximately 2.7 million persons in 181 disease-endemic localities. This study assessed factors associated with MDA compliance in year three of the Egyptian LF elimination program. 2,859 subjects were interviewed in six villages. The surveyed compliance rate for MDA in these villages was 85.3% (95% confidence interval = 83.9-86.5%). Compliance with MDA was positively associated with LF knowledge scores, male sex, and older age. Adverse events reported by 18.4% of participants were mild and more common in females. This study has provided new information on factors associated with MDA compliance during Egypts successful LF elimination program.

Health-related quality of life after serious occupational injury in Egyptian workers: a cross-sectional study

Objectives Occupational injuries can have severe socioeconomic consequences; however, little research has examined the health-related quality of life (HRQoL) of workers following occupational injuries, especially in developing countries. This study was to employ the European Quality of Life Five Dimensions (EQ-5D) tool to measure HRQoL 6 months following serious occupational injury sustained by insured workers in the East Delta Region of Egypt. Design This cross-sectional study was conducted from July to December 2008 among workers injured severely enough to be off work for at least 6 months after an occupational injury. Setting The Nile Insurance Hospital in Qalyubia, Egypt. Participants Adult workers returning for follow-up evaluation after being given 6 months off work by a physician for an occupational injury. Outcomes The workers described their health and quality of life using the EQ-5D instrument. Results Most study participants were male (n=118 (90%)), with mean age of 41.5 years. Fractures were the most common type of injury (n=96 (73%)), mostly involving the lower limbs (n=70 (53%)). Participants identified persistent problems related to mobility (n=78 (60%)), self-care (n=69 (53%)), performing usual activities (n=109 (83%)), pain/discomfort (n=119 (91%)) and anxiety/depression (n=51 (40%)). The perceived HRQoL estimated by the mean (±SD) visual analogue scale (VAS) score among injured workers was 61.6±17.9. Multivariate linear regression showed an association between poor VAS score and amputations, mobility limitation, self-care problems, pain/discomfort and anxiety/depression. Conclusions Some people with occupational injuries experience significant problems such as pain/discomfort, functional limitations and anxiety/depression, long after the injury. Improvement in pain management strategies and physical and psychological rehabilitation may improve their health-related quality of life.