Abdullah M. Al-Rubaish

Lack of MERS Coronavirus Neutralizing Antibodies in Humans, Eastern Province, Saudi Arabia

We used a lentiviral vector bearing the viral spike protein to detect neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) in persons from the Eastern Province of Saudi Arabia. None of the 268 samples tested displayed neutralizing activity, which suggests that MERS-CoV infections in humans are infrequent in this province.

Medical students’ perception of professionalism: A qualitative study from Saudi Arabia

Background: Professionalism has emerged as a core competency for the medical professionals globally. However, few studies have been reported from the Gulf region to assess the situation and take steps to promote professionalism. Aim: To elicit the views of final year medical students, interns, and residents to explore what professionalism meant to them, what problems they encountered, and what can be done to promote professionalism. Method: We adopted qualitative approach including 10 focus group discussions. The proceedings were tape-recorded, transcribed, and analyzed independently by two researchers. Results: The respondents admitted that that they were deficient in the acquisition of professional values. According to them, professionalism was not taught or assessed. They followed “hidden curriculum”. They considered very few teachers as positive role models. The deficiencies could be attributed to negative role modeling by the faculty or deficiencies in the curriculum such as lack of rich clinical experiences, limited interaction with health team, and absence of feedback besides organizational issues. Conclusion: The students’ views should be tallied with other sources of evidences. Nevertheless, they have policy implications on faculty recruitment, development, curriculum reform, and an organizational culture that supports professionalism.

BCL11A enhancer haplotypes and fetal hemoglobin in sickle cell anemia

BACKGROUND Fetal hemoglobin (HbF) levels in sickle cell anemia patients vary. We genotyped polymorphisms in the erythroid-specific enhancer of BCL11A to see if they might account for the very high HbF associated with the Arab-Indian (AI) haplotype and Benin haplotype of sickle cell anemia. METHODS AND RESULTS Six BCL112A enhancer SNPs and their haplotypes were studied in Saudi Arabs from the Eastern Province and Indian patients with AI haplotype (HbF ~20%), African Americans (HbF ~7%), and Saudi Arabs from the Southwestern Province (HbF ~12%). Four SNPs (rs1427407, rs6706648, rs6738440, and rs7606173) and their haplotypes were consistently associated with HbF levels. The distributions of haplotypes differ in the 3 cohorts but not their genetic effects: the haplotype TCAG was associated with the lowest HbF level and the haplotype GTAC was associated with the highest HbF level and differences in HbF levels between carriers of these haplotypes in all cohorts were approximately 6%. CONCLUSIONS Common HbF BCL11A enhancer haplotypes in patients with African origin and AI sickle cell anemia have similar effects on HbF but they do not explain their differences in HbF.

Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies

BackgroundIn addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation.MethodsWe describe here the design and implementation of a customized genome-wide genotyping array, the ‘TxArray’, comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios.ResultsWe show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms.ConclusionsWe have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies.

Academic job satisfaction questionnaire: Construction and validation in Saudi Arabia

Background: Colleges and universities are becoming increasingly accountable for teaching outcomes in order to meet rigorous accreditation standards. Job satisfaction (JS) seems more difficult to measure in the academic field in view of the complexity of roles, duties and responsibilities. Objectives: To compile and determine the psychometric properties of a proposed Academic Job Satisfaction Questionnaire (AJSQ) suitable for university faculty, and amenable to future upgrading. Materials and Methods: A 46-item five-option Likert-type draft questionnaire on JS was distributed for anonymous self-reporting by all the academic staff of five colleges in University of Dammam (n=340). The outcome measures were (1) factor analysis of the questionnaire items, (2) intra-factor α-Coefficient of Internal Consistency Reliability, (3) inter-factor correlations, (4) comparison of psychometric properties in separately analyzed main faculty subgroups. Results: The response rate was 72.9 percent. Factor analysis extracted eight factors which conjointly explained 60.3 percent of the variance in JS. These factors, in descending order of eigenvalue, were labeled “Authority”, “Supervision”, “Policies and Facilities”, “My Work Itself”, “Interpersonal Relationships”, “Commitment”, “Salary” and “Workload”. Cronbachs-α ranged from 0.90 in Supervision to 0.63 in Salary and Workload. All inter-factor correlations were positive and significant, ranging from 0.65 to 0.23. The psychometric properties of the instrument in separately analyzed subgroups divided by sex, nationality, college and clinical duties produced fairly comparable findings. Conclusion: The AJSQ demonstrated good overall psychometric properties in terms of construct validity and internal consistency reliability in both the overall sample and its separately analyzed subgroups. Recommendation: To replicate these findings in larger multicenter samples of academic staff.

IκΒα inhibits apoptosis at the outer mitochondrial membrane independently of NF‐κB retention

IκBα resides in the cytosol where it retains the inducible transcription factor NF‐κB. We show that IκBα also localises to the outer mitochondrial membrane (OMM) to inhibit apoptosis. This effect is especially pronounced in tumour cells with constitutively active NF‐κB that accumulate high amounts of mitochondrial IκBα as a NF‐κB target gene. 3T3 IκBα−/− cells also become protected from apoptosis when IκBα is specifically reconstituted at the OMM. Using various IκBα mutants, we demonstrate that apoptosis inhibition and NF‐κB inhibition can be functionally and structurally separated. At mitochondria, IκBα stabilises the complex of VDAC1 and hexokinase II (HKII), thereby preventing Bax recruitment to VDAC1 and the release of cytochrome c for apoptosis induction. When IκBα is reduced in tumour cells with constitutively active NF‐κB, they show an enhanced response to anticancer treatment in an in vivo xenograft tumour model. Our results reveal the unexpected activity of IκBα in guarding the integrity of the OMM against apoptosis induction and open possibilities for more specific interference in tumours with deregulated NF‐κB.

Association of beta 2 -adrenergic receptor gene polymorphisms and nocturnal asthma in Saudi patients

BACKGROUND AND OBJECTIVES: Two polymorphisms of beta2-adrenergic receptor (β2-AR) gene, namely the substitution from arginine (Arg) to glycine (Gly) at codon 16 and from glutamine (Gln) to glutamic (Glu) at codon 27, are linked with functional changes in the β2-AR in the respiratory system even though they are not deemed to be susceptibility genes for asthma per se. The objective of this study was to investigate this association in a subset of asthmatic patients, namely those with nocturnal asthma. METHODS: The β2-AR gene polymorphisms at codon 16 and 27 were assessed in 40 patients clinically diagnosed with nocturnal asthma and 96 normal controls. Genomic DNA was obtained from whole blood and genotyping was carried out by a PCR based restriction fragment length polymorphism technique. RESULTS: There was a statistically significant difference in genotype frequencies at codon 16 (Arg/Gly) between nocturnal asthmatic patients and normal control subjects (P < 0.05). However, there was no statistically significant difference in allele frequencies between the two groups. In addition, there was a significant association between Arg16-Gly genotype with nocturnal asthma compared to homozygous Gly16 (codominant model P = 0.0033, OR = 3.69: 95% CI: 1.49-9.12). However, there were no statistically significant differences in genotype and allele frequencies at codon 27 (Gln/Glu) between the normal control and nocturnal asthmatic groups (χ2 = 1.81, P = 0.41). The results also indicate that linkage disequilibrium existed between the β2-AR codon 16 and β2-AR codon 27 polymorphism (|D´| = 0.577). The data for all haplotypes did not show a statistically significant association. CONCLUSION: We present the genotype and allele frequencies of β2-AR gene polymorphisms in normal Saudi subjects and nocturnal asthmatic patients. There was a significant difference in genotype frequencies at codon 16 (Arg/Gly). However, our study indicates a poor association of individual single nuceotide polymorphisms with nocturnal asthma.

Developing questionnaires for students' evaluation of individual faculty's teaching skills: A Saudi Arabian pilot study

Background: The National Commission for Academic Accreditation and Assessment is responsible for the academic accreditation of universities in the Kingdom of Saudi Arabia (KSA). Requirements for this include evaluation of teaching effectiveness, evidence-based conclusions, and external benchmarks. Aims: To develop a questionnaire for students’ evaluation of the teaching skills of individual instructors and provide a tool for benchmarking. Setting: College of Nursing, University of Dammam [UoD], May-June 2009. Materials and Methods: The original questionnaire was “Monash Questionnaire Series on Teaching (MonQueST) - Clinical Nursing. The UoD modification retained four areas and seven responses, but reduced items from 26 to 20. Outcome measures were factor analysis and Cronbach’s alpha coefficient. Results: Seven Nursing courses were studied, viz.: Fundamentals, Medical, Surgical, Psychiatric and Mental Health, Obstetrics and Gynecology, Pediatrics, and Family and Community Health. Total number of students was 74; missing data ranged from 5 to 27%. The explained variance ranged from 66.9% to 78.7%. The observed Cornbach’s α coefficients ranged from 0.78 to 0.93, indicating an exceptionally high reliability. The students in the study were found to be fair and frank in their evaluation.

The anticancer gene ORCTL3 targets stearoyl-CoA desaturase-1 for tumour-specific apoptosis

ORCTL3 is a member of a group of genes, the so-called anticancer genes, that cause tumour-specific cell death. We show that this activity is triggered in isogenic renal cells upon their transformation independently of the cells’ proliferation status. For its cell death effect ORCTL3 targets the enzyme stearoyl-CoA desaturase-1 (SCD1) in fatty acid metabolism. This is caused by transmembrane domains 3 and 4, which are more efficacious in vitro than a low molecular weight drug against SCD1, and critically depend on their expression level. SCD1 is found upregulated upon renal cell transformation indicating that its activity, while not impacting proliferation, represents a critical bottleneck for tumourigenesis. An adenovirus expressing ORCTL3 leads to growth inhibition of renal tumours in vivo and to substantial destruction of patients’ kidney tumour cells ex vivo. Our results indicate fatty acid metabolism as a target for tumour-specific apoptosis in renal tumours and suggest ORCTL3 as a means to accomplish this.

A candidate transacting modulator of fetal hemoglobin gene expression in the Arab-Indian haplotype of sickle cell anemia.

Fetal hemoglobin (HbF) levels are higher in the Arab–Indian (AI) β‐globin gene haplotype of sickle cell anemia compared with African‐origin haplotypes. To study genetic elements that effect HbF expression in the AI haplotype we completed whole genome sequencing in 14 Saudi AI haplotype sickle hemoglobin homozygotes—seven selected for low HbF (8.2% ± 1.3%) and seven selected for high HbF (23.5% ± 2.6%). An intronic single nucleotide polymorphism (SNP) in ANTXR1, an anthrax toxin receptor (chromosome 2p13), was associated with HbF. These results were replicated in two independent Saudi AI haplotype cohorts of 120 and 139 patients, but not in 76 Saudi Benin haplotype, 894 African origin haplotype and 44 AI haplotype patients of Indian origin, suggesting that this association is effective only in the Saudi AI haplotype background. ANTXR1 variants explained 10% of the HbF variability compared with 8% for BCL11A. These two genes had independent, additive effects on HbF and together explained about 15% of HbF variability in Saudi AI sickle cell anemia patients. ANTXR1 was expressed at mRNA and protein levels in erythroid progenitors derived from induced pluripotent stem cells (iPSCs) and CD34+ cells. As CD34+ cells matured and their HbF decreased ANTXR1 expression increased; as iPSCs differentiated and their HbF increased, ANTXR1 expression decreased. Along with elements in cis to the HbF genes, ANTXR1 contributes to the variation in HbF in Saudi AI haplotype sickle cell anemia and is the first gene in trans to HBB that is associated with HbF only in carriers of the Saudi AI haplotype. Am. J. Hematol. 91:1118–1122, 2016.