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Advances in aging studies brought about by heterochronic parabiosis suggest that agingmight be a reversable process that is affected by changes in the systemic milieu of organs andcells. Given the broadness of such a systemic approach, research to date has mainly questioned theinvolvement of “shared organs” versus “circulating factors”. However, in the absence of a clearunderstanding of the chronological development of aging and a unified platform to evaluate thesuccesses claimed by specific rejuvenation methods, current literature on this topic remains scattered.Herein, aging is assessed from an engineering standpoint to isolate possible aging potentiators via ajuxtaposition between biological and mechanical systems. Such a simplification provides a generalframework for future research in the field and examines the involvement of various factors in aging.Based on this simplified overview, the kidney as a filtration organ is clearly implicated, for the firsttime, with the aging phenomenon, necessitating a re-evaluation of current rejuvenation studies tountangle the extent of its involvement and its possible role as a potentiator in aging. Based on thesefindings, the review concludes with potential translatable and long-term therapeutics for aging whileoffering a critical view of rejuvenation methods proposed to date.

Aims: To conduct a systematic review and meta-analysis of retinopathy prevalence in patients with type 1 diabetes (T1D) in 22 Arab countries. Methods: We systematically searched 4 different literature databases (PubMed, Science Direct, Web of Science and Embase), from the date of inception until December 2017, to collect all the information about patients with T1D who developed retinopathy complications; for statistical analysis, we used MetaXL to evaluate the pooled prevalence estimate and the subgroup prevalence estimates employing double arcsine transformation and inverse variance heterogeneity models. Results: Our search strategy returned 475 studies, of which 39 met our inclusion criteria; of those, 16 were eligible for meta-analysis that were captured only in 15 Arab countries, through 45 years (1969–2014). The number of retinopathy patients was 396 out of 1,931 patients with T1D. The prevalence of retinopathy was 19% (95% CI 10–28%). Substantial heterogeneity was observed (Q 240.78, p < 0.0001, I2 93.77%, 95% CI 91.35–95.52%); however, no single study considerably affected the overall pooled prevalence estimate. Conclusion: Almost one fifth of T1D patients in 15 Arab countries have diabetic retinopathy, therefore it is important to improve the care of patients with T1D and in Arab countries to avoid the development of such a devastating complication.

Introduction Previous reports have found that polymorphisms in the close homologue of L1 (CHL1) gene located on chromosome 3p26 are associated with schizophrenia among different ethnic populations. The aim of this study was to examine the associations of single nucleotides polymorphisms (SNPs) of the CHL1 gene locus, including rs2055314 (C/T), rs2272522 (C/T) and rs331894 (A/G), with schizophrenia in the Qatari population. Methods An association case control study was carried out on 86 Qatari schizophrenic patients from the Psychiatry Hospital, Hammed Medical Corporation, Qatar and 88 Qatari unrelated, healthy, control subjects. Schizophrenia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM-IV) criteria for schizophrenia by two independent psychiatrists. Genotyping of the SNPs rs2055314 (C/T), rs2272522 (C/T) and rs331894 (A/G) was conducted using the 5′ nuclease assay with the TaqMan MGB probe and an ABI 7500. Results Individuals with the rs2272522 TT genotype had approximately 4.2 times greater risk of schizophrenia compared to individuals with the CC genotype (OR = 4.21; 95% CI: 1.12–15.53; P = 0.047). In addition, individuals carrying a T allele of the rs2272522 SNP had a significantly increased risk of schizophrenia (1.78 times) among the population (P = 0.028). SNPs rs2055314 and rs331894 had no significant association with schizophrenia. Pairwise linkage disequilibrium (LD) between the three polymorphisms was modest in the schizophrenic group. Discussion The rs2272522 polymorphism was found to exhibit a highly significant association with schizophrenia in the Qatari population. This finding supports the hypothesis that cell adhesion molecules may be involved in the etiology of this disease among Qatari patients.

Background. Several polymorphisms of a locus on chromosome 1p13.3 have a significant effect on low-density lipoprotein cholesterol (LDL-C), atherosclerosis, and acute coronary syndrome (ACS).Methods. We aimed to investigate the association between rs599839, rs646776, and rs4970834 of locus 1p13.3 and serum LDL-C and severity of coronary artery stenosis in ACS patients. Genotyping of the rs599839, rs646776, and rs4970834 polymorphisms was performed on Arab patients undergoing coronary angiography for ACS. Patients were divided into group A (ACS with insignificant stenosis (Results. Patients carrying the minor G allele in rs599839 had significantly lower mean of LDL-C (2.58 versus 3.44 mM,P=0.026) than homozygous A allele carriers (GG versus AA). Carriers of minor C allele in rs64776 had significantly higher mean of HDL-C (2.16 versus 1.36 mM,P=0.004) than carriers of the T alleles (AA versus GG). The odd ratio and 95% confidence interval for dominant model for G allele carriers of rs599839 were 0.51 (0.30–0.92),P=0.038, among patients with significant stenosis.Conclusions. Polymorphisms rs646776 and rs599839 of locus 1p13.3 were significantly associated with LDL-C and other lipid parameters. In addition, the G-allele carriers of variant rs599839 had a significant protective effect against the atherosclerosis.

AIM: To investigate the association between interleukin-28B (IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus (HCV) genotype 4. METHODS: Two hundred and one HCV-genotype 4 patients were included. All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk. End of treatment response (ETR) was defined as loss of detectable serum HCV RNA at the end of treatment. Sustained viral response (SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up. Genotyping of IL28B rs12979860 was performed using the TaqMan assay. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95%CI. RESULTS: The study included 201 HCV-genotype 4 patients. The majority of patients were men (89.6%), with a median age of 47 years, inter-quartile range (40-51). Approximately 62.5% of patients had ETR, and 49.6% had SVR. Individuals who achieved SVR were more likely to be younger (χ2 = 4.91, P = 0.027), and less likely to have fibrosis (χ2 = 15.54, P < 0.0001), or inflammation (χ2 = 7.58, P = 0.006). The genotype distribution of rs12979860 was 36.2%, 49.0% and 14.8% for genotypes CC, CT, and TT, respectively. In these participants, rs12979860 genotype distribution did not differ by gender (P = 0.466), pretreatment viral load (P = 0.600), inflammation (P = 0.435), or fibrosis (P = 0.291). The frequencies of IL28B rs12979860 genotypes were TT (14.8%), CT (49.0%), and CC (36.2%). Compared to rs12979860 genotype TT, aORs (95%CI) for ETR and SVR were: CC genotype, [17.55 (5.34-57.69) and 5.92 (2.09-16.76), respectively]; CT genotype, [5.15 (1.80-14.78) and 2.48 (0.94-6.52), respectively]. In the current study, the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC (17.4% and 23.3%, respectively) than individuals who had ETR or SVR (47.9% and 47.2%, respectively). Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype (aOR = 5.92; 95%CI: 2.09-16.76). Similarly, patients with CT genotype had SVR more often than patients with TT genotype (aOR = 2.48; 95%CI: 0.94-6.52). Carrying at least one copy of the C allele (genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT (aOR = 7.87; 95%CI: 2.84-21.82), and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT (aOR = 3.46; 95%CI: 1.37-8.74). In addition, data were consistent with a significant gene-dose relationship (aOR = 4.05/allele; 95%CI: 2.27-7.22). The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR. CONCLUSION: In HCV-genotype 4 patients, rs12979860 is a sensitive predictor of viral clearance, independent of viral load, age, gender or fibrosis, with no similar relation to severity of fibrosis.

Background To assess the relationship between serial serum leptin levels in patients with acute myocardial infarction (AMI) who received thrombolysis and the degree of coronary atherosclerosis, coronary reperfusion, echocardiographic findings, and clinical outcome. 51 consecutive patients presenting with AMI were studied. Clinical characteristics including age, sex, body mass index (BMI) and cardiovascular risk factors were recorded. Serial serum leptin levels at the time of admission and subsequently at 0, 6, 12, 24, 36, 60 hours afterwards were obtained. Coronary angiography was performed in 34 patients; the relation between serum leptin levels and evidence of coronary reperfusion as well as the extent of coronary atherosclerosis according to the coronary artery surgery study classification (CASS) were evaluated. Echocardiographic evaluation was performed in all patients. 36 matched patients were enrolled as control group who had serum leptin level 9.4 ± 6.5 ng/ml. Results The patients mean age was 50.5 ± 10.6 years. There were 47 males and 3 females. 37.1% were diabetics, 23.5% were hypertensive, 21.6% were dyslipidemic and 22.7% were obese (BMI ≥ 30). Leptin concentrations (ng/ml) increased and peaked at the 4th sample (36 hrs) after admission (mean ± SD) sample (1) =9.55 ± 7.4, sample (2) =12.9 ± 8.4, sample (3) =13.8 ± 10.4, sample (4) =18.9 ± 18.1, sample (5) =11.4 ± 6.5, sample (6) =10.8 ± 8.9 ng/ml. There was a significant correlation between serum leptin and BMI (r = 0.342; p = 0.03). Leptin levels correlated significantly to creatine kinase level on the second day (r = 0.43, p ≤ 0.01). Significant correlation of mean serum leptin with the ejection fraction (P p = 0.8). There was a trend for an increase in the mean serum leptin levels with increasing number of diseased vessels. There was no correlation between serum leptin levels and outcome neither during the hospitalization nor at 9 months follow up. Conclusion Serum leptin levels increase after myocardial infarction. Serum leptin level may be a predictor of the left ventricular ejection fraction and the degree of atherosclerosis but not of coronary reperfusion.

Nasser Rizk, Mona Amin, Mervat YousefHealth Sciences Department, University of Qatar, Doha, QatarAim: This pilot study aimed to evaluate the individual features of the metabolic syndrome (MeS) and its frequency in Qatari schoolchildren aged 6–12 years.Background: MeS has a strong future risk for development of diabetes and cardiovascular diseases. Childhood obesity is increasing the likelihood of MeS in children.Methods: The associated features of MeS were assessed in 67 children. They were recruited from the outpatient pediatric clinic at Hamad Medical Corporation, Qatar. Height, weight, and waist circumference were measured and body mass index was calculated for each child. Fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol and triglycerides (TG) were measured. MeS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-III) which was modified by Cook with adjustment for fasting glucose to ≥5.6 mM according to recommendations from the American Diabetes Association.Results: The overall prevalence of MeS according to NCEP-III criteria was 3.0% in children aged 6–12 years. Overweight and obesity was 31.3% in children aged 6–12 years, according to the International Obesity Task Force criteria. The prevalence of MeS was 9.5% in overweight and obese subjects. Increased TG levels represented the most frequent abnormality (28.4%) in metabolic syndrome features in all subjects, followed by HDL-C (19.4%) in all subjects.Conclusion: Increased TG levels and low HDL-C were the most frequent components of this syndrome. This study showed a significant prevalence of MeS and associated features among overweight and obese children. The overall prevalence of MeS in Qatari children is in accordance with data from several other countries.Keywords: metabolic syndrome, National Cholesterol Education Program Adult Treatment Panel III, schoolchildren, Qatar

BACKGROUND: Serum adiponectin inversely correlates with the extent of coronary artery disease (CAD). OBJECTIVES: To investigate the clinical significance of measuring high molecular weight (HMW) adiponectin in addition to total adiponectin from different samples (peripheral veins and ostia of coronary arteries) in patients with CAD. METHODS: We studied 134 patients; 57 with acute coronary syndrome (ACS), 44 with stable angina and 33 healthy patients. Total and HMW adiponectin were measured in the coronary ostia and peripheral veins simultaneously. Venous levels of lipid profile, C-reactive protein, tumour necrosis factor-alpha, interleukin-6 and insulin were measured. RESULTS: Mean levels of HMW adiponectin in the coronary ostia were significantly correlated with the venous levels of total (r = 0.33, P = 0.002) and HMW (r = 0.37, P = 0.002) adiponectin. Mean levels of total and HMW adiponectin were lower in CAD patients versus controls (6.9 +/- 0.5 versus 7.9 +/- 0.7 microg/ml, P = 0.3 and 1.9 +/- 0.2 versus 3.1 +/- 0.3 microg/ml, P = 0.003). In the coronary ostia, levels of HMW adiponectin were higher in ACS than those with stable angina (1.1 +/- 0.1 versus 0.8 +/- 0.1 microg/ml, P = 0.2). In patients with CAD, levels of ostial adiponectin (total and HMW) were significantly lower in diabetic than non-diabetic patients (6.5 +/- 0.8 versus 9.4 +/- 1.1 microg/ml, P = 0.04 and 0.8 +/- 0.12 versus 1.2 +/- 0.1 microg/ml, P = 0.03). Mean levels of venous adiponectin (total and HMW) were non-significantly lower in diabetic patients (5.9 +/- 0.7 versus 7.7 +/- 0.7, P = 0.12 and 1.8 +/- 0.4 versus 1.9 +/- 0.1, P = 0.8). CONCLUSION: Measurement of HMW adiponectin and its ratio to total adiponectin may be a better marker for CAD than total adiponectin levels. Ostial levels of adiponectin in ACS may indicate re-distribution of adiponectin molecules towards the acute lesions. The low HMW adiponectin levels in diabetes mellitus may in part explain the worse outcome of CAD in diabetics.

Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) production from adipose tissue is elevated in obese animal models and in obese humans. It plays an important role in the induction of insulin resistance in experimental animals. In this study, we examined hypothalamic tissue expression of TNF-alpha and its receptors and TNF-alpha expression of adipose tissue in lean C57BLKSJ+/+ and obese polygenic New Zealand obese (NZO) mice. Obese animals exhibited hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and hypercholesterinemia. Using RT-PCR, we observed increased expression (2.4-fold) of TNF receptor 2 (p75) in the hypothalamus of obese mice. TNF-alpha expression in adipose tissue of obese mice was eight times higher than in controls. TNF-alpha and TNF receptor 1 (p55) expression in hypothalamic tissue was similar in obese and lean animals. These results suggest that the hypothalamic TNF receptor 2 (p75) might play a role in obesity by modulating the actions of TNF-alpha in conditions of leptin resistance.

Background: Adiponectin is a fat derived hormone, known to decrease in type-2 diabetes (DM) and coronary artery disease (CAD). Moreover, our previous study showed that total adiponectin and its HMW isoform decreased in acute coronary syndrome (ACS) patients compared to healthy controls. The adiponectin gene ADIPOQ is located on chromosome 3q27. Two single nucleotide polymorphisms (SNPs) (rs1501299 and rs2241766) in ADIPOQ gene and their possible associations with ACS were investigated among Arab patients resident in Qatar. Methods: A case-control association study was performed on 142 (ACS) Arab patients and 115 Arab healthy controls from Qatar. Genotypes were determined using TaqMan real time PCR assay. Serum adiponectin level was determined using ELISA. Results: The GG, GT and TT genotype frequencies of the rs2241766 [+45 T/G] variant showed significant difference between the control and (ACS) cases (45.2%, 40.0%, 14.8% vs. 46.2%, 25.0%, and 28.8%, p=0.0001), respectively. In contrast, there wa...

Background: Genetic and environmental factors are highly related with gestational diabetes mellitus (GDM) and type 2 diabetes (T2D). Our objective was to explore whether some genetic variants such as rs12255372, rs7903146 of TCF7L2 gene are significantly associated with the risk of gestational diabetes mellitus among Arabian population. Methods: A case control study was designed for such genetic association study. A total of 159 unrelated pregnant women (114 Arab; 40 gestational diabetes mellitus cases and 74 controls and 45 non-Arab; 11 gestational diabetes mellitus and 34 controls) were recruited from antenatal care unit of HMC. Blood sample were drawn for DNA extraction, then genotyped for TCF7L2 gene variants (rs12255372, and rs7903146) using TaqMan real time PCR assay. Plasma was used for biochemical analysis including glucose, insulin and adiponectin. Results: The CC, CT and TT genotype frequencies of the TCF7L2 rs7903146 variants was not significantly different between the control and gestational diabetes mellitus cases (39.4%, 50,0%, 10.6% vs. 40.6%, 43.8%, and 15.6%, p=0.444) among Arab populations, respectively. Only, the T allele of rs12255372 variant was significantly associated with risk of gestational diabetes mellitus with odds ratio of 2.370, (95% of CI 1.010–5.563) with the p value of 0.047 among Arab subjects using the genetic dominant model after adjustment of BMI and age. The other polymorphism rs7903146 was not significantly associated with GDM among Arab and non-Arab subjects. No significant difference was observed for glucose, insulin and adiponectin hormone after 50g glucose load by genotyping of both variants. Conclusion: The TCF7L2 rs12255372 variant is associated with an increased risk of gestational diabetes mellitus in Arab women. Further studies are needed with larger sample sizes.

The prevalence of insulin resistance and diabetes has shown a dramatic worldwide increase. In Qatar, the prevalence of diabetes is twice that of the United States today, possibly due to lifestyle and dietary changes. Diabetes has an enormously adverse impact on the afflicted population leading to patient mortality, morbidity and staggering health care costs to the nation. Untreated or inadequately treated diabetes results in serious health complications including eye, heart, kidney and nerve damage. Mass spectrometry based molecular profiling is a powerful tool for interrogation of the underlying molecular alterations which define the etiology and patho-physiology of a complex disease such as diabetes. As a part of the QNRF funded study, we have used ultra performance liquid chromatography (UPLC) in conjunction with high resolution quadrupole time of flight mass spectrometry (Q-TOFMS) for proteomic and metabolomic profiling of bio-fluids derived from diabetic and healthy individuals recruited at ...

Background: Previous studies demonstrated polymorphisms of adiponectin receptor type1 (AdipoR1) as a strong determinant of coronary artery diseases (CAD) susceptibility in type 2 diabetes. The aim of the study is to investigate the associations of the genetic marker (SNP) no of AdipoR1 locus; rs10920531 with CAD in patients with and without type 2 diabetes in the population of Qatar. Methods: Blood was drawn from a total of 189 subjects. For the detection of the SNP (rs10920531, and rs7539542), extracted DNA was carried out by the 5′ nuclease assay using TaqMan MGB probe by means of an ABI 7900 [Applied Biosystems]. Results: Both groups of CAD, with and without diabetes mellitus (DM) had insignificant difference within the following parameters; age, BMI, glucose, lipid profile, cardiac enzyme markers, insulin and adiponectin. Females were 8.4% of all studied patients. The odds ratio and the frequency distribution of the genotype (rs1092531, A>C) revealed that (35.1%), [35.8%], had AA and (41.5%), [41.1%] had AC, and (23.4.0%), [23.1%] had CC among in control and cardiac patients with and without DM, respectively with P value=0.94. The odds ratio was 1.02 and 95% CI was (0.85-1.43). The frequency distribution of the genotype (rs7539542, C>G) revealed that (34.0%), [41.1%], had CC and (47.9%), [34.7%] had CG, and (18.1.0%), [24.2%] had GG among control and cardiac patients with and without DM, respectively with P value=0.37. The odds ratio was 0.98 and 95% CI was (0.65-1.47). The odds ratio was 0.77 for rs1092531, A>C and 0.92 for rs7539542, C>G among cardiac patients with and without diabetes. Using logistic regression analysis, LDL-C was significantly associated with both rs1092531, A>C and rs7539542, C>G in CAD patients. Hypertension was significantly associated with rs7539542. Conclusion: No significant association was found between AdipoR1 locus; (rs1092531, A>C and rs7539542, C>G) and the cardiovascular disease (CVD) risks. Of all CVD risks, Only LDL-C correlated significantly with (rs1092531, A>C and rs7539542, C>G). Hypertension was significantly associated with s7539542. Further studies are needed among the Qatari population to screen polymorphisms of the entire diponectin gene and its receptors.

Background: Adipose tissue secretes several adipocytokines that may play an important role in development of insulin resistance during pregnancy. The aim of this study is to investigate the associations of these adipocytokines with anthropometric measurements of the newborns of pregnant women with abnormal 50g glucose tolerance test [GTT] results. Methods: The study subjects included all pregnant women (n=85) of matched age and BMI, that showed abnormal results to 50g [GTT]. During 100g [GTT], fasting blood samples were analyzed for glucose, lipid profile, IL-6, TNF-α, Hs-CRP, insulin, and total adiponectin. Results: 100g [GTT] showed that 60% were normal [C] and 40 % had impaired glucose tolerance [IGTT]. Of all biochemical measured, only glucose (fasting, 1h, 2h, and 3h) and insulin were significantly higher in [IGTT] group than [C] group. Mean values ±SD; Il-6 (2.56±1.16 vs. 2.49±1.63 pg/ml, p=0.80), TNF-α (3.86±2.52 vs. 5.16±3.45 pg/ml, p=0.07), Hs-CRP (48.59±17.03 vs. 50.18±18.19 ng/ml, p=0.69), and total adiponectin (15.97±8.09 vs. 14.65±7.15 μg/ml, p=0.31) among [C] and [IGTT], respectively. No significant differences were observed for anthropometric measurements studied such as birth weight (3209.66±463.57 vs. 3558.50±80.66 g, p=0.74), placenta weight [PW], ponderal index [PI] and birth weight/placental weight index [FPI] between [C] and [IGTT] groups, respectively. TNF-α was positively correlated significantly with Il-6 (r=0.29, P=0.012), PW (r=0.48, P=0.017) and negatively with FPI (r= -0.47, P=0.019), gestational age ”GA”(r=-0.41, P=-0.043) and total adiponectin (r=-0.28, P=0.016). Conclusion: Marked hyperglycemia and hyperinsulinemia were observed in IGTT. Of all adipokines measured, TNF-α had a significant relationship with PW, FPI, and GA.

Objectives: To investigate maternal and neonatal outcomes of pregnancies in women with different types of diabetes in Qatar. To identify factors such as age, family history of diabetes and obesity contributing to the increased risk of GD. Design: The design of this study is retrospective. Materials and Methods: il4 pregnant women with different types of diabetes including 143(28%) Impaired Glucose Tolerance Test (IGTT), 334(65%) Gestational Diabetes (GD), 26(5%) Insulin Dependent Diabetes Mellitus (IDDM) and 11(2%) Non Insulin Dependent Diabetes Mellitus (NIDDM) who delivered between Jan - June 2004formed the subject of this study.Data extracted from the files included maternal characteristics, fetal and maternal complications. Result: Eight women had abortions and two had stillbirths, leaving a final dataset comprising 504 women (141 IGTT, 332 GDM, 21 IDDM and 10 NIDDM). Two hundred and eighty three (56.2%) were Qatari.53 %(n = 267) aged >30 years, 57.5 %(n = 290) had family history of diabetes, only 16.1 %(n = 81) treated by insulin.Polyhydramnios was the most common antenatal complication occurred in 15 %(n = 76). No maternal mortality.The overall Cesarean section was 6.2 %(n = 31),.Preterm delivery 5.8 %(n = 29). Macrosomia appeared in 7.3 %(n = 37) infants and congenital malformations in 2 %(n = 10) infants. Conclusions: We observed that the risk factors for GDM found in other studies are generally valid for our population. Also we found that IDDM has a poorer outcome than NIDDM. However a future prospective study is need it to draw firm conclusions regarding the relative magnitudes of the adverse effects between the different diabetic groups