Soha R. Dargham

Estimating Seroprevalence of Herpes Simplex Virus Type 1 among Different Middle East and North African Male Populations Residing in Qatar

HSV‐1 epidemiology in the Middle East and North Africa (MENA) remains poorly understood. Our study aimed to measure HSV‐1 antibody prevalence (seroprevalence) and its age‐distribution among select MENA populations residing in Qatar. Sera were collected from male blood donors attending Hamad Medical Corporation 2013‐2015. A total of 2,077 sera were tested for anti‐HSV‐1 antibodies using HerpeSelect® 1 ELISA IgG kits (Focus Diagnostics, Cypress, CA). Robust Poisson regression was conducted to estimate adjusted infection prevalence ratios. Country‐specific HSV‐1 seroprevalence was estimated for 10 national populations: 97.5% among Egyptians, 92.6% among Yemenis, 90.7% among Sudanese, 88.5% among Syrians, 86.5% among Jordanians, 82.3% among Qataris, 81.4% among Iranians, 81.4% among Lebanese, 80.5% among Palestinians, and 77.0% among Pakistanis. Age‐specific HSV‐1 seroprevalence was estimated for Egypt, the Fertile Crescent (Iraq, Jordan, Lebanon, Palestine, and Syria), and Qatar. Seroprevalence increased with age among Fertile Crescent and Qatari nationals. Seroprevalence increased from 70.0% among those aged ≤ 24 years up to 98.0% among those aged ≥55 years among Fertile Crescent nationals. Seroprevalence was consistently above 90% for all ages among Egyptians. HSV‐1 seroprevalence is high in MENA, though with some variation across countries. The seroprevalence appears to have declined among current young age cohorts compared to its levels a few decades ago.

A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis.

Genetic factors underlying susceptibility to rheumatoid arthritis (RA) in Arab populations are largely unknown. This genome‐wide association study (GWAS) was undertaken to explore the generalizability of previously reported RA loci to Arab subjects and to discover new Arab‐specific genetic loci.

Single-Nucleotide Variations of the Human Nuclear Hormone Receptor Genes in 60,000 Individuals

Nuclear hormone receptors (NRs) mediate biologic actions of lipophilic molecules to gene transcription and are phylogenetically and functionally categorized into seven subfamilies and three groups, respectively. Single-nucleotide variations (SNVs) or polymorphisms are genetic changes influencing individual response to environmental factors and susceptibility to various disorders, and are part of the genetic diversification and basis for evolution. We sorted out SNVs of the human NR genes from 60,706 individuals, calculated three parameters (percentage of all variants, percentage of loss-of-function variants, and ratio of nonsynonymous/synonymous variants in their full protein-coding or major domain–coding sequences), and compared them with several valuables. Comparison of these parameters between NRs and control groups identified that NRs form a highly conserved gene family. The three parameters for the full coding sequence are positively correlated with each other, whereas four NR genes are distinct from the others with much higher tolerance to protein sequence-changing variants. DNA-binding domain and N-terminal domain are respectively those bearing the least and the most variation. NR subfamilies based on their phylogenetic proximity or functionality as well as diversity of tissue distribution and numbers of partner molecules are all not correlated with the variation parameters, whereas their gene age demonstrates an association. Our results suggest that the natural selection driving the NR family evolution still operates in humans. Gene age and probably the potential to adapt to various new ligands, but not current functional diversity, are major determinants for SNVs of the human NR genes.

Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted With Acute Ischemic Stroke

Background and Purpose— Corneal confocal microscopy can identify corneal nerve damage in patients with peripheral and central neurodegeneration. However, the use of corneal confocal microscopy in patients presenting with acute ischemic stroke is unknown. Methods— One hundred thirty patients (57 without diabetes mellitus [normal glucose tolerance], 32 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus) admitted with acute ischemic stroke, and 28 age-matched healthy control participants underwent corneal confocal microscopy to quantify corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length. Results— There was a significant reduction in corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length in stroke patients with normal glucose tolerance (P<0.001, P<0.001, P<0.001), impaired glucose tolerance (P=0.004, P<0.001, P=0.002), and type 2 diabetes mellitus (P<0.001, P<0.001, P<0.001) compared with controls. HbA1c and triglycerides correlated with corneal nerve fiber density (r=−0.187, P=0.03; r=−0.229 P=0.01), corneal nerve fiber length (r=−0.228, P=0.009; r=−0.285; P=0.001), and corneal nerve branch density (r=−0.187, P=0.033; r=−0.229, P=0.01). Multiple linear regression showed no independent associations between corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length and relevant risk factors for stroke. Conclusions— Corneal confocal microscopy is a rapid noninvasive ophthalmic imaging technique that identifies corneal nerve fiber loss in patients with acute ischemic stroke.

Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction

Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.

Salivary testosterone measurement in women with and without polycystic ovary syndrome

Clinical and/or biochemical hyperandrogenism is one of the diagnostic criteria for PCOS. An evaluation of the role of salivary testosterone (salT) and androstenedione (salA) for the diagnosis of PCOS was undertaken in a cross sectional study involving 65 women without PCOS and 110 women with PCOS fulfilling all 3 diagnostic Rotterdam criteria. Serum and salivary androgen measurements were determined by LC-MS/MS. salT and salA were significantly elevated in PCOS compared to controls (P < 001). No androgen marker was more predictive than another using ROC curves, but multiple logistic regression suggested salT was more predictive than free androgen index (FAI) (p < 0.01). The combination of salT or FAI identified 100% of PCOS women. PCOS women with both biochemical and clinical hyperandrogenism as opposed to clinical hyperandrogenism alone showed a metabolic phenotype (p < 0.05) and insulin resistance (p < 0.001). PCOS patients with an isolated elevated FAI showed increased insulin resistance compared to those with an isolated salT (P < 0.05). salT appeared to be at least as predictive as FAI for the diagnosis of the classical PCOS phenotype, and the combination of salT or FAI identified 100% of PCOS patients. This suggests that salT measurement by LC-MS/MS holds the promise of complementing existing laboratory tests as a means of assessing hyperandrogenemia.

The prevalence and metabolic characteristics of polycystic ovary syndrome in the Qatari population

Objective The prevalence of polycystic ovary syndrome (PCOS) in the Qatari population is unknown and hence the estimated impact on the local population cannot be determined. The purpose of this study was to estimate the prevalence and metabolic features of PCOS among Qatari women. Design Cross sectional analysis. Patients 3,017 Qatari subjects volunteered to be phenotyped and genotyped for the Qatar Biobank from which all women between the ages of 18–40 years were identified (750). Measurements 720 women had testosterone and sex hormone binding globulin (SHBG) measurements. PCOS was diagnosed according the National Institute of Health (NIH) Guidelines of a raised androgen level (free androgen index >4.5 or a raised total testosterone) and menstrual irregularity after the exclusion of other conditions. Results All results are reported as mean value of PCOS versus control. 87 of 720 women fulfilled the NIH guidelines (12.1%) for PCOS specifically using a free androgen index greater than 4.5 or a total testosterone greater than 2.7nmol/l and menstrual irregularity. Subjects were heavier with a more metabolic profile of a greater systolic and diastolic blood pressure, higher levels of C reactive protein, insulin (p<0.01) and HbA1c (P<0.02), and decreased HDL levels (p<0.01). Pulse wave velocity as a marker of arterial stiffness was also increased (p<0.05) Conclusions By NIH guidelines the prevalence of PCOS in this Qatari cohort was 12.1% that would likely reflect 20% by Rotterdam criteria, with a markedly more metabolic phenotype than Qatari controls.

Human Papillomavirus (HPV) Infection: Molecular Epidemiology, Genotyping, Seroprevalence and Associated Risk Factors among Arab Women in Qatar

Human Papillomavirus (HPV) infections are known to cause cervical cancer worldwide, however, limited information is currently available on prevalence, types distribution and risk factors for HPV infection in the Arab countries. We conducted a cross-sectional observational study exclusively of women of Arabic origin residing in Qatar (n = 406) who were selected from the Women’s Hospital at Hamad Medical Corporation (HMC) and Health Centers of the Primary Health Care Corporation in Doha, Qatar over the period March 2013 to August 2014. Socio-demographic, behavioral and clinical data were collected. Four hundred and six cervical smears and 292 blood samples were included in the study. HPV typing was done using HPV type-specific primers-based real-time PCR, and Sanger sequencing. HPV-IgG and IgM were quantified using ELISA assays. The prevalence of HPV infection amongst Qatari and non-Qatari Arab women were 9.8% and 6.1%, respectively and 7.6% and 16.7% in women with normal and abnormal cytology, respectively. HPV 81 was the most commonly found genotype in women with normal cytology (34.5%), whereas HPV 81, 16 and 59 in women with abnormal cytology (25.0% each). All the HPV DNA positive women were seronegative and HPV-IgG prevalence was higher in Qatari women than in non-Qatari Arab women. None of the studied factors had any significant association with HPV-DNA positivity or HPV-IgG seropositivity. The overall identified HPV DNA prevalence and HPV seroprevalence among Arab women in Qatar were on the low side compared to global levels.

Herpes Simplex Virus Type 2 Seroprevalence among Different National Populations of Middle East and North African Males.

Background There are limited data on herpes simplex virus type 2 (HSV-2) seroprevalence in the Middle East and North Africa (MENA). We examined country- and age-specific HSV-2 seroprevalence among select MENA populations residing in Qatar. Methods Sera were collected from male blood donors attending Hamad Medical Corporation between June 2013 and June 2016. Specimens were screened for anti-HSV-2 IgG antibodies following a 2-test algorithm: HerpeSelect 2 ELISA was used to identify HSV-2–positive specimens, and Euroline-WB was used to confirm positive and equivocal specimens for final HSV-2 status. Trends and associations with HSV-2 seropositivity were assessed. Results Of the 2077 tested sera, 61 were found and confirmed positive. The proportion of those confirmed positive increased steadily with HerpeSelect 2 ELISA index value, ranging from 16.3% for index values of 1.101 to 1.999 to 92.9% for index values of 4 or greater. Nationality-specific seroprevalence was 6.0% (95% confidence interval [CI], 4.1%–8.8%) in Qataris, 5.3% (95% CI, 2.5%–11.1%) in Iranians, 4.2% (95% CI, 1.8%–9.5%) in Lebanese, 3.1% (95% CI, 1.2%–7.7%) in Sudanese, 3.0% (95% CI, 1.4%–6.4%) in Palestinians, 2.2% (95% CI, 1.1%–4.3%) in Egyptians, 2.0% (95% CI, 1.0%–5.0%) in Syrians, 1.0% (95% CI, 0.3%–3.6%) in Jordanians, 0.7% (95% CI, 0.1%–3.7%) in Yemenis, and 0.5% (95% CI, 0.1%–2.8%) in Pakistanis. There was evidence for higher seroprevalence in older age groups. Conclusions The seroprevalence of HSV-2 was in the range of few percentage points. There were no major differences in seroprevalence by nationality. These findings add to our understanding of HSV-2 epidemiology in MENA and indicate unmet needs for sexual health and control of sexually transmitted infections.

Anti-Müllerian hormone measurement for the diagnosis of polycystic ovary syndrome

Anti‐Müllerian hormone (AMH) is derived from the small antral follicles, and an elevated level has been suggested to add value to the Rotterdam criteria for the diagnosis of PCOS in cases of diagnostic uncertainty. Therefore, the role of AMH in the classical phenotype of PCOS was defined within a Caucasian population.