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) ß-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. © 2016 Wiley Periodicals, Inc.

Gender Differences in Prevalence of Sleepy Driving Among Young Drivers in Saudi Arabia.

Introduction: Sleepy driving is associated with Motor Vehicles Accidents (MVAs). In Saudi Arabia, previous studies have addressed this association among men only. Therefore, the aim of this study was to compare the prevalence of sleepy driving and associated factors between genders. Methods: In a cross-sectional study design, we offered a self-administered online questionnaire to 3272 participants from different regions of Saudi Arabia. The questionnaire included 46 questions covering sociodemographics, driving habits, sleeping habits, Epworth Sleepiness Scale, and Berlin questionnaire to assess the risk of sleep apnea. Univariable and multivariable logistic regression analyses were used to determine the significant factors associated with self-reported sleepy driving, defined as operating a motor vehicle while feeling sleepy in the preceding six months. Results: Of the 3272 invitees, 2958 (90%) completed the questionnaire, of which 1414 (48%) were women. The prevalence of sleepy driving in the preceding six months was 42% (men: 50% and women 32%, p<0.001). Specifically, participants reported the following: 12% had had to stop their vehicle due to sleepiness (men: 16.2% and women 7%, p<0.001), 12.4% reported near-miss accidents (men: 16.2% and women: 8.2%, p<0.001) and 4.2% reported an accident due to sleepiness (men: 4.3% and women: 4%, p=0.645). In multivariable analysis, being male, younger age, use of any type of medications, shift working, working more than 12 hours per day, driving duration of 3-5 hours per day, driving experience of more than 2 years, excessive daytime sleepiness and risk of having obstructive sleep apnea were all associated with increased likelihood of falling asleep while driving in the preceding 6 months. Conclusion: Sleepy driving and MVA are prevalent in both gender but was higher in men. Future public health initiatives should particularly focus on men, since men reported a greater likelihood of both sleep-related MVA and "near miss" events.

Association Between FeNO, Total Blood IgE, Peripheral Blood Eosinophil and Inflammatory Cytokines in Partly Controlled Asthma.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a convenient to use biomarker of airway inflammation. However, the mutual relationship between FeNO, peripheral blood eosinophil, total immunoglobulin E (IgE) and inflammatory cytokines showed some controversy. OBJECTIVE: This study was carried out to determine the accuracy of peripheral blood eosinophil and total IgE to detect eosinophilic airway inflammation as determined by two FeNO cutoff points. The correlation between FeNO, peripheral blood eosinophil, total IgE and certain inflammatory cytokines was also examined. METHODS: Seventy-six patients with partly controlled asthma performed the following tests on the same day: FeNO, pulmonary function tests (PFTs), peripheral blood eosinophils, total IgE, and inflammatory cytokine assay. The correlation between these markers was investigated and the diagnostic accuracy of peripheral blood eosinophils and total IgE to identify eosinophilic asthma phenotype was calculated using receiver operating characteristics area under the curve (ROC AUC). RESULTS: FeNO was positively correlated with percentage of blood eosinophils (r=0.276, p=0.017) and total blood IgE (r=0.3647; p=0.0013). No relationship between FeNO and serum inflammatory cytokines was detected. AUC of blood eosinophils and total IgE were 57% and 64% at FeNO ≥25 ppb and were 67% and 64% at FeNO >50, respectively. The higher predictive ability was detected at FeNO >50 ppb where the best cutoff point for blood eosinophil % was ≥4.0% (sensitivity 66.7%, specificity 60.0%) and the best cutoff point for total IgE was ≥350 (sensitivity 66.7%, specificity 63.6%). CONCLUSION: In patients with partly controlled asthma, peripheral blood eosinophil and total IgE showed equal useful accuracy in predicting eosinophilic airways. However, higher predictive values were reported at FeNO level >50 ppb. FeNO was positively correlated with peripheral blood eosinophil, total IgE but not with any of the studied cytokines.

Survey of Respiratory Care Professionals' Knowledge in Early Mobilization: A Pilot Study.

Early mobilization (EM) is practiced for intensive care unit (ICU) patients in many hospitals in the Eastern Province in Saudi Arabia. Respiratory care professionals' knowledge about using EM was, therefore, surveyed and investigated to improve and update its practice and ultimately to develop related regulations and policies. A survey including 156 respiratory care professionals was conducted using a validated questionnaire. The focus was on collecting information on participants' relevant backgrounds and on proper use of EM. Knowledge and proper use of EM were calculated in relation to participants' demographic and professional characteristics. The statistical analysis using analysis of variance and Student t-test showed that factors that affected knowledge of EM were the respiratory care professional's age, gender, nationality, and years of experience in intensive care medicine. How many patients these professionals treated using EM also significantly correlated with their knowledge of EM. The survey showed the extent of respiratory care professionals' knowledge about the proper use of EM. More importantly, the survey also identified important shortfalls in practice of some experienced medical practitioners.

Effect of Nigella sativa supplementation on lung function and inflammatory mediatorsin partly controlled asthma: a randomized controlled trial.

BACKGROUND: Nigella sativa and its derivatives have been reported to have anti-inflammatory and bronchodilator effects, but the effects have been evaluated in only a few clinical studies. OBJECTIVES: To determine the effect of N sativa supplementation on inflammation of the airways and limitation of airflow in partly controlled asthma patients. DESIGN: Single-blind, placebo-controlled, randomized study. SETTING: Asthma and allergy clinic of a university hospital in eastern Saudi Arabia. PATIENTS AND METHODS: Patients were divided into three groups. A control group (n=24) received the placebo, while NS-1 and NS-2 groups (n=26 each) received 1 and 2 g/day of N sativa, respectively, for 3 months along with maintenance inhaled therapy. MAIN OUTCOME MEASURE(S): Asthma control test (ACT) score, fractional exhaled nitric oxide (FeNO), peak expiratory flow (PEF) variability and other pulmonary function tests, IgE, serum cytokines, and frequency of exacerbations. RESULTS: FEF25-75% and FEV1 (% predicted) increased significantly (P < .05) at both 6 and 12 weeks in the NS-2 group. PEF variability significantly improved in both NS-1 and NS-2 groups at 6 and 12 weeks as compared with the controls (P < .05). FeNO and serum IgE decreased significantly after 12 weeks in both the NS-1 and NS-2 groups vs baseline (P < .05). Both doses of N sativa produced a significant increase in the serum IFN-gamma at 12 weeks vs baseline (P < .05) as well as a significant improvement in the ACT score at 6 and 12 weeks vs baseline (P < .001, < .01). Significantly fewer patients had exacerbations in the NS-1 group (P < .05). CONCLUSION: N sativa supplementation with inhaled maintenance therapy improves some measures of pulmonary function and inflammation in partly controlled asthma. LIMITATIONS: No bronchoalveolar lavage or sputum samples taken for measurement of asthma markers. ISRCTN registry: ISRCTN48853858 DOI 10.1186/ISRCTN48853858.

Metformin-related acidosis in a woman while performing Haj: a conservative approach.

Metformin is a first-line oral anti-hyperglycemic agent. It decreases insulin resistance, decreases hepatic glucose output and enhances peripheral glucose uptake. Metformin is used as a monotherapy in combination with other oral hypoglycemic agents. A major side-effect of metformin is lactic acidosis. The elimination of metformin is mainly through the kidneys, and raised plasma concentrations can cause lactic acidosis. Provided there is no overdose, metformin associated lactic acidosis rarely develops in patients without co-morbidities such as renal or hepatic insufficiency, acute infection or severe dehydration. Herein, we report a case of metformin-induced metabolic acidosis occurring in a woman who was severely dehydrated after performing Haj and treated conservatively.