Circulating ceramide levels and ratios in Emirati youth under 18 years: associations with cardiometabolic risk factors.

BACKGROUND: Circulating ceramide (Cer) drives various pathological processes associated with cardiovascular diseases, liver illness, and diabetes mellitus. Although recognized as predictors of cardiometabolic diseases (CMD) in research and clinical settings, their potential for predicting CMD risk in individuals under 18 remains unexplored. OBJECTIVES: This study was designed to utilize Liquid Chromatography-Mass Spectrometry (LC-MS/MS) methodology to determine the biological reference ranges for Cer in plasma samples of Emirati children and develop a risk assessment score (CERT-1) based on Cer concentrations. METHODS: Using LC-MS/MS, we developed a method to measure five Cer species in plasma samples of 582 Emirati participants aged 5-17. We used the circulating concentrations of these Cer to determine their reference intervals in this population. We employed traditional statistical analyses to develop a risk score (CERT-1) and assess the association between Cer levels and conventional biomarkers of CMD. RESULTS: We validated a high-throughput methodology using LC-MS/MS to quantify five Cer species in human plasma. Reference values for this population (n = 582) were quantified: CerC16:0 (0.12-0.29 µmol/L), CerC18:0 (0.019-0.067 µmol/L), CerC22:0 (0.102-0.525 µmol/L), CerC24:0 (0.65-1.54 µmol/L) and CerC24:1 (0.212-0.945 µmol/L). We devised a risk assessment score (CERT-1) based on plasma Cer content in the study participants, showing that 72.5% have low to moderate risk and 9.3% are at a higher risk of developing CMD. Our analyses also revealed a significant correlation (P < 0.05) between this score and the conventional risk factors linked to CMD, indicating its potential clinical implication. CONCLUSION: This study presents a clinical-scaled LC-MS/MS methodology for assessing clinically relevant Cer, setting reference ranges, and developing a risk score (CERT-1) for young Emirati individuals. Our findings can enhance primary risk prediction and inform the management and follow-up of CMD from an early age.

Epigenetics of conotruncal congenital heart disease: Protocol for a systematic review and meta-analysis.

BACKGROUND: Conotruncal congenital heart defects (CTD) are a subset of congenital heart diseases (CHD) that involve structural anomalies of the right, left, or both cardiac outflow tracts. CHD is caused by multifactorial inheritance and changes in the genes or chromosomes. Recently, CHD was found to be due to epigenetic alterations, which are a combination of genetic and other environmental factors. Epigenetics is the study of how a gene's function changes as a result of environmental and behavioral influences. These causative factors can indirectly cause CHD by altering the DNA through epigenetic modifications. This is a protocol for a systematic review and meta-analysis that aims to explore whether the strength of association between various epigenetic changes and CTD types varies by race. Furthermore, to determine and compare the changes in gene expression of each mutation. METHODS: Our protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. A comprehensive pre-search has been developed in PubMed and PubMed's Medical Subject Headings (MeSH). The final search will be performed in June 2023 in PubMed, Embase, Scopus, Web of Science, Cochrane Library, CIANHL, and PsycInfo, without restrictions on publication years. The Covidence systematic review software will be used for blinded screening and selection. Conflicts will be resolved by a third, independent reviewer. The risk of bias in selected studies will be assessed using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The data to be extracted will cover basic information on the included studies, study sample size, number of patients with various types of epigenetic changes, number of patients with various CTD types, measures of association and their 95% confidence interval between each epigenetic change and each CTD. The protocol has been registered with the International Prospero Register of Systematic Review (PROSPERO) [CRD42023377597]. DISCUSSION: To the best of our knowledge, this protocol outlines the first systematic review and meta-analysis of the epigenetics of CTD. There is a growing body of evidence on epigenetics and its indirect involvement in disease by altering the DNA through epigenetic modifications in the genes associated with the causative factors for CHD. We will conduct a comprehensive and systematic search for literature in the above-mentioned seven core biomedical databases. It is very important to identify population-specific risk factors for CHD, which will have significant creative, custom-made, and effective prevention programs for the future generation.

Distribution and Association of Cardiometabolic Risk Factors Among Youth From Al Ain City, United Arab Emirates.

AIM: The purpose of this study was to examine the distribution of cardiometabolic risk factors (CMRF) among UAE University students. METHODS: The present study employed a cross-sectional design to investigate the characteristics of a sample of young individuals aged 17-26 years. The participants were exclusively drawn from the student population of UAE University. Anthropometric measurements, including weight, height, blood pressure, and random blood collection, were conducted. The statistical methods employed for comparison included the Chi-square test, Fisher's exact test, and either the two-sample t-test or the Wilcoxon rank sum test. Logistic models, both adjusted and unadjusted, were utilized to evaluate the correlation between excessive body weight and various cardiovascular and metabolic risk factors (CMRFs). All P-values were calculated using a two-sided test, and a significance level of P < 0.05 was used to determine statistical significance. The statistical computing and graphics software R (version 4.2.2) was utilized to perform all data analyses. RESULTS: Among the 269 individuals who took part in the study, a significant proportion of 55% (n=148) were identified as males. Additionally, 36% (n=97) of the participants reported having a family history of hypertension. It is worth noting that the total sample consisted of younger individuals, with a mean age of 19 years (standard deviation ±1.8). There was a significant association between overweight/obesity and male gender (p=0.003), as well as having a family history of heart attack (p=0.038), high lipid profile, and high-sensitivity C-reactive protein (hs-CRP). There was no observed correlation between a family history of hypertension and HbA1C levels in individuals with a non-normal weight. substantially elevated cardiometabolic risk variables, including systolic blood pressure (SBP) equal to or greater than 130 mmHg, diastolic blood pressure (DBP) equal to or greater than 80 mmHg, triglyceride (TG) levels equal to or greater than 150 mg/dL, high-density lipoprotein cholesterol (HDL-C) levels equal to or less than 35 mg/dL, apolipoprotein B (Apo B) levels equal to or greater than 1.3 g/L, and high-sensitivity C-reactive protein (hs-CRP) levels equal to or more than 1 mg/L, were observed to be substantially more prevalent in individuals with excess body weight compared to those with normal weight. Furthermore, the likelihood of having low HDL levels is observed to increase by 14% (Adjusted Odds Ratio = 1.14, 95% Confidence Interval [1.07 to 1.23]) among students who have extra body weight, while accounting for age and gender as controlling factors. CONCLUSIONS: Excess body weight, already in youth, was associated with increased CMRF, particularly high SBP and TG plus low HDL-C.

Cross-Sectional Association Between Body Fat Composition and Biomarkers of Inflammation and Endothelial Dysfunction in Children with Overweight/Obesity.

Background: Childhood obesity is most prevalent nutritional disorder worldwide. Studies on clinical correlations between body fat (BF) composition, lipid profile, inflammatory biomarkers, and endothelial dysfunction (ED) parameters in children from United Arab Emirates (UAE) are limited. Therefore, we aimed to study obesity pattern in children and determine clinical correlations with biomarkers. Methods: Children (6-13 years) from different schools were divided into obese, overweight, and normal groups based upon Centers for Disease Control and Prevention weight-for-age centiles study (n=166). Anthropometric, BF composition, lipid profile, inflammatory, and ED biomarkers were determined and analyzed using SPSS software. Results: The mean age and weight ± SD of participants were 10.6 ± 2.6 years and 48.2 ± 19.5 kg with 65% as overweight or obese. In normal, overweight, and obese group male were 40 (70.2%), 35 (67.3%), and 40 (70.2%) and female were 17 (29.8%), 17 (32.7%) and 17 (29.8%). There was significant difference in age (p<0.01), height (p< 0.01), weight (p< 0.01) among groups. Obesity markers (MCP-1, leptin, adiponectin) showed positive correlation with age, height, weight, WC, BF%, body fat mass (BFM), body muscle mass (BMM). A significant correlation (all p<0.01) of BMM with SBP (r=0.412), DBP (r=0.255), MCP-1 (r=0.558), adiponectin (r=0.635), hs-CRP (r=0.263), IL-6 (r=0.348), TNF-alpha (r=0.370), ICAM-1 (r=0.237), and VCAM-1 (r=0.343). The inflammatory markers (ICAM-1, VCAM-1) showed significant correlations with age, height, weight, WC, BF%, BFM, BMM. Leptin significantly (all p<0.01) correlated with age (r=0.470), height (r=0.423), weight (r=0.677), WC (r=0.606), BF (r=0.700), BFM (r=0.752), and BMM (r=0.524) and negatively correlated with TBW (r=-0.701). Adiponectin also showed a significant (all p<0.01) positive correlation with age, height, weight, WC, BF, BFM, and BMM. Conclusion: A strong association between BF composition, lipid profile, and inflammatory and ED biomarkers was observed in the study. Thus, immediate measures should be implemented to reduce risk of obesity and associated diseases.

Combined Treatment with KV Channel Inhibitor 4-Aminopyridine and either γ-Cystathionine Lyase Inhibitor ß-Cyanoalanine or Epinephrine Restores Blood Pressure, and Improves Survival in the Wistar Rat Model of Anaphylactic Shock.

The mechanism of anaphylactic shock (AS) remains incompletely understood. The potassium channel blocker 4-aminopyridine (4-AP), the inhibitors of cystathionine γ-lyase (ICSE), dl-propargylglycine (DPG) or ß-cyanoalanine (BCA), and the nitric oxide (NO) synthase produce vasoconstriction and could be an alternative for the treatment of AS. The aim of this study was to demonstrate the ability of L-NAME, ICSE alone or in combination with 4-AP to restore blood pressure (BP) and improve survival in ovalbumin (OVA) rats AS. Experimental groups included non-sensitized Wistar rats (n = 6); AS (n = 6); AS (n = 10 per group) treated i.v. with 4-AP (AS+4-AP), epinephrine (AS+EPI), AS+DPG, AS+BCA, or with L-NAME (AS+L-NAME); or AS treated with drug combinations 4-AP+DPG, 4-AP+BCA, 4-AP+L-NAME, or 4-AP+EPI. AS was induced by i.v. OVA (1 mg). Treatments were administered i.v. one minute after AS induction. Mean arterial BP (MAP), heart rate (HR), and survival were monitored for 60 min. Plasma levels of histamine, prostaglandin E2 (PGE2) and F2 (PGF2α), leukotriene B4 and C4, angiotensin II, vasopressin, oxidative stress markers, pH, HCO3, PaO2, PaCO2, and K+ were measured. OVA induced severe hypotension and all AS rats died. Moreover, 4-AP, 4-AP+EPI, or 4-AP+BCA normalized both MAP and HR and increased survival. All sensitized rats treated with 4-AP alone or with 4-AP+BCA survived. The time-integrated MAP "area under the curve" was significantly higher after combined 4-AP treatment with ICSE. Metabolic acidosis was not rescued and NO, ICSE, and Kv inhibitors differentially alter oxidative stress and plasma levels of anaphylactic mediators. The AS-induced reduction of serum angiotensin II levels was prevented by 4-AP treatment alone or in combination with other drugs. Further, 4-AP treatment combined with EPI or with BCA also increased serum PGF2α, whereas only the 4-AP+EPI combination increased serum LTB4. Serum vasopressin and angiotensin II levels were increased by 4-AP treatment alone or in combination with other drugs. Moreover, 4-AP alone and in combination with inhibition of cystathionine γ-lyase or EPI normalizes BP, increases serum vasoconstrictor levels, and improves survival in the Wistar rat model of AS. These findings suggest possible investigative treatment pathways for research into epinephrine-refractory anaphylactic shock in patients.

Continuous subcutaneous insulin infusion is associated with a better glycemic control than multiple daily insulin injections without difference in diabetic ketoacidosis and hypoglycemia admissions among Emiratis with Type 1 diabetes.

AIMS: To characterizes Emiratis patients with Type 1 diabetes (T1D) and compares outcomes between continuous subcutaneous insulin infusion (CSII) versus multiple daily insulin injections (MDI) users. The WHO-Five Well-Being Index (WHO-5) score was used to screen for depression. METHODS: In this cross-sectional study; sociodemographic, clinical characteristics and insulin replacement regimens were collected on patients with T1D between 2015-2018. RESULTS: 134 patients with mean age of 20.9±7.5 years were included. Females constitute 56.7% and 50.7% had diabetes duration of >10 years. Diabetic ketoacidosis (DKA) at presentation was reported in 46.3%. Average glycemic control over preceding 12months was satisfactory (less than 7.5%), suboptimal (7.5-9%), and poor (more than 9%) in 26.6%, 42.7% & 30.6% of the patients, respectively. Higher proportion of patients using CSII achieved satisfactory or suboptimal glycemic control compared to patients with MDI (P = 0.003). The latest median /IQR HbA1c was significantly lower (P = 0.041) in patients using CSII (8.2 /1.93%) compared to MDI (8.5/2.45%). There was no significant difference between two groups in DKA, severe hypoglycemia or total WHO-5 score. CONCLUSIONS: CSII usage was associated with better glycemic control than MDI, although no difference in DKA and severe hypoglycemia. The overall glycemic control among Emiratis subjects with T1D is unsatisfactory and needs more rigorous patient counseling and education.

Relationship between lipid profile, inflammatory and endothelial dysfunction biomarkers, and type 1 diabetes mellitus: a case-control study.

OBJECTIVE: Inflammation is a major factor in endothelial dysfunction (ED) which is the earliest predictor of cardiovascular disease and premature mortality in type 1 diabetes mellitus (T1DM) patients. This study aimed to describe the possible relationship between plasma lipids and inflammatory and ED biomarkers in young Emirati patients with and without T1DM. METHODS: This case-control study included 158 patients with T1DM and 157 healthy controls from the local population of the United Arab Emirates (UAE). Anthropometric data, clinical variables, lipid profiles, liver enzymes, HbA1c, inflammatory, and ED biomarkers were measured for all participants using sophisticated techniques and assays. RESULTS: The mean ages ± SD of patients with T1DM and healthy controls was 19.3 ± 6.4 years (59.5% females) and 9.2 ± 6.8 years (61.5% females), respectively. The mean duration of T1DM was 9.3 ± 5.7 years, with HbA1c of 8.9 ± 2.1%. BMI, WC, SBP, and DBP significantly differed between the two groups. The mean lipid profiles (HDL, TG, TC, ApoA, and ApoB), liver enzymes (GGT, ALT), inflammatory (IL-6, adiponectin, TNF-α, hs-CRP), and ED biomarker levels (ICAM-1, VCAM-1, selectin, and ET-1) were also significantly different between patients and controls. Based on Spearman's rank and logistic regression analysis, there was a significant association between elevated lipid profile, liver enzymes, inflammatory markers, and ED markers in T1DM patients compared to controls. Among the biomarkers studied, ApoA, ApoB, and TC were significantly increased in T1DM patients compared to controls. CONCLUSION: This study revealed a strong association between an elevated lipid profile and inflammatory and ED markers with T1DM, which could lead to cardiovascular events in the UAE population.

Effect of Nitric Oxide Pathway Inhibition on the Evolution of Anaphylactic Shock in Animal Models: A Systematic Review.

Nitric oxide (NO) induces vasodilation in various types of shock. The effect of pharmacological modulation of the NO pathway in anaphylactic shock (AS) remains poorly understood. Our objective was to assess, through a systematic review, whether inhibition of NO pathways (INOP) was beneficial for the prevention and/or treatment of AS. A predesigned protocol for this systematic review was published in PROSPERO (CRD42019132273). A systematic literature search was conducted till March 2022 in the electronic databases PubMed, EMBASE, Scopus, Cochrane and Web of Science. Heterogeneity of the studies did not allow meta-analysis. Nine hundred ninety unique studies were identified. Of 135 studies screened in full text, 17 were included in the review. Among six inhibitors of NO pathways identified, four blocked NO synthase activity and two blocked guanylate cyclase downstream activity. Pre-treatment was used in nine studies and post-treatment in three studies. Five studies included both pre-treatment and post-treatment models. Overall, seven pre-treatment studies from fourteen showed improvement of survival and/or arterial blood pressure. Four post-treatment studies from eight showed positive outcomes. Overall, there was no strong evidence to conclude that isolated blockade of the NO/cGMP pathway is sufficient to prevent or restore anaphylactic hypotension. Further studies are needed to analyze the effect of drug combinations in the treatment of AS.

Length-of-Stay in the Emergency Department and In-Hospital Mortality: A Systematic Review and Meta-Analysis.

The effect of emergency department (ED) length of stay (EDLOS) on in-hospital mortality (IHM) remains unclear. The aim of this systematic review and meta-analysis was to determine the association between EDLOS and IHM. We searched the PubMed, Medline, Embase, Web of Science, Cochrane Controlled Register of Trials, CINAHL, PsycInfo, and Scopus databases from their inception until 14−15 January 2022. We included studies reporting the association between EDLOS and IHM. A total of 11,337 references were identified, and 52 studies (total of 1,718,518 ED patients) were included in the systematic review and 33 in the meta-analysis. A statistically significant association between EDLOS and IHM was observed for EDLOS over 24 h in patients admitted to an intensive care unit (ICU) (OR = 1.396, 95% confidence interval [CI]: 1.147 to 1.701; p < 0.001, I2 = 0%) and for low EDLOS in non-ICU-admitted patients (OR = 0.583, 95% CI: 0.453 to 0.745; p < 0.001, I2 = 0%). No associations were detected for the other cut-offs. Our findings suggest that there is an association between IHM low EDLOS and EDLOS exceeding 24 h and IHM. Long stays in the ED should not be allowed and special attention should be given to patients admitted after a short stay in the ED.

Distribution of Cardiometabolic Risk Factors in School-Aged Children with Excess Body Weight in the Al Ain City, United Arab Emirates: A Cross-Sectional Study.

(1) Background: This study aimed to examine the distribution of cardiometabolic risk factors (CMRF) in school-aged children with excess body weight (overweight and obese) in Al Ain City, United Arab Emirates and identify the factors associated with increased cardiovascular risk factors between boys and girls. (2) Methods: A cross-sectional survey of children aged 6-17 years was conducted in Al Ain from 1 August 2019 to 31 December 2020. Binary logistic regression analysis was performed to investigate the relationship between excess body weight and CMRF between the groups and reported odds ratios (OR) with 95% confidence intervals (CI). (3) Results: A total of 966 school-aged children (490 boys and 476 girls) participated in the study, and the mean age of the children was 11.8 ± 2.9 years. The proportions of overweight and obesity were 13.5% and 10.2% in boys and 11.1% and 10.3% in girls. Higher glucose of ≥100 mg/dL (26.4%), triglycerides of ≥150 mg/dL and low-density lipoprotein cholesterol: ≥130 mg/dL (23.2%) were more prevalent in children with excess body weight. These children were at least two times more likely to have higher triglycerides levels, high total cholesterol (≥200 mg/dL) in girls (OR:2.06, 95% CI: 1.01-4.21) and low high-density lipoprotein (<35 mg/dL) in boys (OR: 2.20; 95% CI: 1.12-4.31). (4) Conclusions: Excess body weight in school-aged children was associated with increased CMRF, particularly triglycerides.

Association of variants in PTPN22, CTLA-4, IL2-RA, and INS genes with type 1 diabetes in Emiratis.

Type 1 diabetes (T1D) is a chronic autoimmune disease with a complex interrelation of genetic and environmental factors. Genetic studies have reported HLA and non-HLA loci as significant contributors to T1D. However, the genetic basis of T1D among Emiratis is unexplored. This study aims to determine the contribution of four genes PTPN22, CTLA-4, IL2-RA, and INS to T1D risk among Emiratis. The association between variants in PTPN22 (rs2476601, rs1310182), CTLA-4 (rs11571316, rs231775, rs3087243, rs1427676, and rs231727), IL2-RA (rs7090530), and INS (rs7111341) with T1D was tested in 310 Emiratis (139 T1D patients and 171 controls). A significant association was found at rs1310182, and rs2476601 both in PTPN22, rs3087243, and rs231775 both in CTLA-4, and rs12251307 in IL2-RA. Moreover, a haplotype constituted from GG and AG genotypes at rs231727 and rs231775, respectively, in CTLA-4 was significantly associated with an increased T1D risk. The cumulative effects of risk alleles for all significantly associated SNPs showed 11.8 higher relative risk for T1D for those who carry 5-6 compared to 0-1 risk alleles. This study illustrated that PTPN22, CTLA-4, and IL2-RA gene variants could confer risk alleles for T1D among the Emirati population.

Life-threatening arrhythmias with autosomal recessive TECRL variants.

AIMS: Sudden death and aborted sudden death have been observed in patients with biallelic variants in TECRL. However, phenotypes have only begun to be described and no data are available on medical therapy after long-term follow-up. METHODS AND RESULTS: An international, multi-centre retrospective review was conducted. We report new cases associated with TECRL variants and long-term follow-up from previously published cases. We present 10 cases and 37 asymptomatic heterozygous carriers. Median age at onset of cardiac symptoms was 8 years (range 1-22 years) and cases were followed for an average of 10.3 years (standard deviation 8.3), right censored by death in three cases. All patients on metoprolol, bisoprolol, or atenolol were transitioned to nadolol or propranolol due to failure of therapy. Phenotypes typical of both long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT) were observed. We also observed divergent phenotypes in some cases despite identical homozygous variants. None of 37 heterozygous family members had a cardiac phenotype. CONCLUSION: Patients with biallelic pathogenic TECRL variants present with variable cardiac arrhythmia phenotypes, including those typical of long QT syndrome and CPVT. Nadolol and propranolol may be superior beta-blockers in this setting. No cardiac disease or sudden death was present in patients with a heterozygous genotype.

Cellular and Immunohistochemical Changes in Anaphylactic Shock Induced in the Ovalbumin-Sensitized Wistar Rat Model.

Anaphylactic shock (AS) is a life-threatening, multisystem disorder arising from sudden release of mast cell- and basophil-derived mediators into the circulation. In this study, we have used a Wistar rat model to investigate AS-associated histopathologic changes in various organs. Rats were sensitized with ovalbumin (1 mg s.c), and AS was induced by intravenous injection of ovalbumin (1 mg). Experimental groups included nonallergic rats (n = 6) and allergic rats (n = 6). Heart rate and blood pressure were monitored during one hour. Organs were harvested at the end of the experiment and prepared for histologic and immunohistochemical studies. Lung, small bowel mucosa and spleen were found to undergo heavy infiltration by mast cells and eosinophils, with less prominent mast cell infiltration of cardiac tissue. The mast cells in lung, small bowel and spleen exhibited increased expression of tryptase, c-kit and induced nitric oxide synthase (iNOS). Increased expression of endothelial nitric oxide synthase (eNOS) by vascular endothelial cells was noted principally in lung, heart and small bowel wall. The Wistar rat model of AS exhibited accumulation of mast cells and eosinophils in the lung, small bowel, and spleen to a greater extent than in the heart. We conclude that lung and gut are principal inflammatory targets in AS, and likely contribute to the severe hypotension of AS. Targeting nitric oxide (NO) production may help reduce AS mortality.

Dyslipidemia, subclinical inflammation, hepatic cholestasis and endothelial dysfunction in schoolchildren with excess fat: A study from the United Arab Emirates.

BACKGROUND: The impact of obesity on cardiovascular health of young children is still to be fully illustrated. This study measured biomarkers for glycemic control, lipid metabolism, systemic inflammation, endothelial dysfunction, and hepatic cholestasis in schoolchildren. Its main purpose was to determine whether metabolic derangements could be detected in young children with excess fat. METHOD: This cross-sectional study involved 967 children in the second, sixth, and tenth grades (median age, 7.3, 11.3, and 15.4 years, respectively). Using the International Obesity Task Force interpretation (IOTF) of body-mass-index (BMI), children were stratified as thin (<5th centiles), normal (5th to <85th centiles), overweight (85th to <95th centiles), obese (95th to <98th centiles), or extremely-obese (≥98th centiles). Waist circumference was also measured. Several metabolic determinations were then used as surrogate biomarkers for cardiovascular risks. RESULTS: Prevalence of BMI≥85th centile among the second graders was 13.1%, sixth graders 42.2%, and tenth graders 33.8%. BMI≥85th centile was associated with a tendency for higher hemoglobin A1c (p≥0.160) and higher blood glucose (p≥0.197). For the second graders, BMI≥85th centile was associated with higher high-sensitivity C-reactive protein (hs-CRP, p<0.001), higher tumor necrosis factor-α (TNF-alpha, p<0.001), higher interleukin-6 (IL-6, p<0.001), higher soluble intercellular cytoadhesive molecule-1 (sICAM-1), higher triglycerides (p≤0.024), and lower high-density lipoprotein (HDL, p<0.001). Additionally, for the sixth and tenth graders, BMI≥85th centile was associated with higher gamma-glutamyl transferase (GGT, p<0.001). In the sixth graders, BMI≥85th centile was insignificantly changed with sICAM-1 or the soluble vascular cytoadhesive molecule-1 (sVCAM-1). CONCLUSIONS: The studied children with excess fat had increased risks for developing systemic inflammation, dyslipidemia, endothelial dysfunction, cholestasis, and diabetes. These results suggest that metabolic biomarkers should be included in the routine assessment of children with an overweight problem.

Review findings included diminished coronary flow reserve after surgery in children with congenital heart disease and inflammation.

AIM: The aim of this review was to develop a deeper knowledge of the physiology of coronary blood flow and coronary flow reserve in young patients with congenital heart disease and inflammatory diseases. METHODS: We searched for papers published in English on coronary blood flow and coronary flow reserve using the PubMed and Google search databases. This identified 42 papers extending back to 1976 and a book from 2008 (Davis et al. Microcirculation. Boston, MA: Elsevier, 2008: 161-284). RESULTS: Our review showed that the implications of coronary blood flow and coronary flow reserve in paediatric patients with congenital heart disease and inflammatory diseases are still not fully understood. However, a key finding was that coronary flow reserve was diminished in patients with congenital heart disease and inflammation after surgery, with or without a cardiopulmonary bypass. Other findings discussed by this review relate to volume and pressure overload in acyanotic congenital heart disease, reduced myocardial perfusion and cyanotic congenital heart disease. CONCLUSION: We still have much to discover about paediatric patients with congenital heart disease and inflammatory diseases. Understanding the pathophysiology of coronary blood flow could help the postoperative treatment of such patients.

Occurrence of Hypothyroidism, Diabetes Mellitus, and Celiac Disease in Emirati Children with Down's Syndrome.

OBJECTIVES: Autoimmune diseases are known to occur in people with Down's syndrome (DS), especially celiac disease, type 1 diabetes mellitus (DM), and hypothyroidism. Since there are common genetic risk factors involved in the occurrence of these autoimmune disorders, the risks would differ in different populations. We sought to determine the prevalence of type 1 DM, celiac disease, and hypothyroidism in Emirati patients with DS in Abu Dhabi, UAE. METHODS: Ninety-two patients with DS were investigated for the presence of anti-thyroid antibodies, antithyroglobulin, and anti-thyroid peroxidase antibodies for hypothyroidism, anti-glutamic acid decarboxylase antibodies for type 1 DM, and anti-tissue transglutaminase immunoglobulin A antibodies for celiac disease. RESULTS: Karyotyping was performed on 89 patients. Eighty-seven had non-disjunction of chromosome 21 (97.8%), one was a mosaic, and one had translocation. Of the patients studied, 19.6% had hypothyroidism, 4.3% had type 1 DM, and 1.1% had celiac disease. Out of the 92 patients studied, 66 (71.7%) did not have any autoimmune disease, 25 (27.2%) had one autoimmune disease, and one (1.1%) had two autoimmune diseases. CONCLUSIONS: Celiac disease was the least prevalent autoimmune disease in patients with DS patients, while type 1 DM and hypothyroidism were both significantly associated with DS.

TECRL, a new life-threatening inherited arrhythmia gene associated with overlapping clinical features of both LQTS and CPVT.

Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole-exome sequencing (WES) was carried out on patients from three different families that presented with life-threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Arg196Gln), which encodes the trans-2,3-enoyl-CoA reductase-like protein. Both patients had cardiac arrest, stress-induced atrial and ventricular tachycardia, and QT prolongation on adrenergic stimulation. A third patient from a consanguineous Sudanese family diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT) had a homozygous splice site mutation (c.331+1G>A) in TECRL Analysis of intracellular calcium ([Ca2+]i) dynamics in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated from this individual (TECRLHom-hiPSCs), his heterozygous but clinically asymptomatic father (TECRLHet-hiPSCs), and a healthy individual (CTRL-hiPSCs) from the same Sudanese family, revealed smaller [Ca2+]i transient amplitudes as well as elevated diastolic [Ca2+]i in TECRLHom-hiPSC-CMs compared with CTRL-hiPSC-CMs. The [Ca2+]i transient also rose markedly slower and contained lower sarcoplasmic reticulum (SR) calcium stores, evidenced by the decreased magnitude of caffeine-induced [Ca2+]i transients. In addition, the decay phase of the [Ca2+]i transient was slower in TECRLHom-hiPSC-CMs due to decreased SERCA and NCX activities. Furthermore, TECRLHom-hiPSC-CMs showed prolonged action potentials (APs) compared with CTRL-hiPSC-CMs. TECRL knockdown in control human embryonic stem cell-derived CMs (hESC-CMs) also resulted in significantly longer APs. Moreover, stimulation by noradrenaline (NA) significantly increased the propensity for triggered activity based on delayed afterdepolarizations (DADs) in TECRLHom-hiPSC-CMs and treatment with flecainide, a class Ic antiarrhythmic drug, significantly reduced the triggered activity in these cells. In summary, we report that mutations in TECRL are associated with inherited arrhythmias characterized by clinical features of both LQTS and CPVT Patient-specific hiPSC-CMs recapitulated salient features of the clinical phenotype and provide a platform for drug screening evidenced by initial identification of flecainide as a potential therapeutic. These findings have implications for diagnosis and treatment of inherited cardiac arrhythmias.

Factors influencing medical students' self-assessment of examination performance accuracy: A United Arab Emirates study.

BACKGROUND: Assessment of one's academic capabilities is essential to being an effective, self-directed, life-long learner. The primary objective of this study was to analyze self-assessment accuracy of medical students attending the College of Medicine and Health Sciences, United Arab Emirates University, by examining their ability to assess their own performance on an MCQ examination. METHODS: 1 st and 2 nd year medical students (n = 235) self-assessed pre and post-examination performance were compared with objectively measured scores (actual examination performance). Associations between accuracy of score prediction (pre and post assessment), and students' gender, year of education, perceived preparation, confidence and anxiety were also determined. RESULTS: Expected mark correlated significantly with objectively assessed marks (r = 0.407; P < 0.01) but with low predictability (R 2 = 0.166). The average objectively determined mark was 69% and the average expected mark was equivalent to 83%; indicating that students significantly overestimate their examination performance. Self-assessed pre-examination score range was significantly different between males and females (P < 0.05) with females expecting higher marks. Preparation and confidence correlated significantly with actual examination score (P < 0.05; r = 0.459 and 0.569 respectively). DISCUSSION: Gender, self-reported preparation and confidence are associated with self-assessment accuracy. Findings reinforce existing evidence indicating that medical students are poor self-assessors. There are potentially multiple explanations for misjudgment of this multidimensional construct that require further investigation and change in learning cultures. The study offers clear targets for change aimed at optimizing self-assessment capabilities.

Subclinical Inflammation and Endothelial Dysfunction in Young Patients with Diabetes: A Study from United Arab Emirates.

BACKGROUND: The impact of obesity and dyslipidemia on cardiovascular health in adolescents and young adults with diabetes is incompletely understood. This study evaluated the effects of these co-morbidities on markers of inflammation and endothelial dysfunction in young patients with the disease. METHODS: The study investigated sets of inflammatory, endothelial, and adipocyte biomarkers in 79 patients with type 1 diabetes, 55 patients with type 2 diabetes, and 47 controls. RESULTS: Mean (±SD) age was 20±6 y (median = 17, range = 12-31). Patients with diabetes had higher levels of cytoadhesive molecules (sICAM-1 and sVCAM-1, p<0.001), adiponectin (p<0.001), and haptoglobin (p = 0.023). Their heart rate variability assessment revealed lower standard deviation of beat-to-beat intervals and lower total power (p≤0.019), reflecting autonomous nervous dysfunction. Hemoglobin A1c >8.0% (estimated average blood glucose >10 mmol/L) was associated with higher adiponectin (p<0.001) and obesity was associated with lower adiponectin (p<0.001); thus, obesity damped the effect of hyperglycemia on adiponectin. Obesity was associated with higher sICAM-1 (p≤0.015), tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP), p<0.001. Similarly, high-density lipoprotein (HDL) <1.02 mmol/L was associated with higher sICAM-1, TNFα, IL-6, and hsCRP (p≤0.009) and lower adiponectin (p<0.001). Adiponectin correlated negatively with the inflammatory biomarkers in patients with diabetes. CONCLUSION: Subclinical inflammation and endothelial dysfunction are common among young patients with diabetes. Poor diabetes control is associated with higher adiponectin. Obesity and dyslipidemia are associated with lower adiponectin and higher inflammatory and endothelial biomarkers. Intuitively, these predictors of cardiovascular disease are amenable to proper glycemic control, nutritional choices, and regular exercise.

4-Aminopyridine, A Blocker of Voltage-Dependent K+ Channels, Restores Blood Pressure and Improves Survival in the Wistar Rat Model of Anaphylactic Shock.

OBJECTIVES: Anaphylactic shock is associated with severe hypotension. Potassium channel blockers, such as 4-aminopyridine, induce vasoconstriction. The objective of this study was to test the ability of 4-aminopyridine to restore blood pressure and increase survival in anaphylactic shock. DESIGN: Experimental study. SETTING: Physiology laboratory. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Rats were sensitized with ovalbumin (1 mg SC), and anaphylactic shock was induced by IV injection of ovalbumin (1 mg). Experimental groups included non-allergic rats (NA) (n = 6); allergic rats (Controls) (n = 6); allergic rats treated with 4-aminopyridine (4-aminopyridine) (1 mg/kg) (n = 6); and allergic rats treated with epinephrine (EPI) (10 µg/kg) (n = 6). Treatments were administered 1 minute after induction of anaphylactic shock. MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure, heart rate, and survival were measured for 60 minutes. Plasma levels of histamine, leukotriene B4, prostaglandin E2, prostaglandin F2, pH, and HCO3 were measured. Mean arterial blood pressure was normal in the NA group; severe hypotension and high mortality were observed in controls; normalization of mean arterial blood pressure, heart rate, and increased survival were observed in 4-aminopyridine and EPI groups. All allergic 4-aminopyridine-treated rats survived after the induction of anaphylactic shock. Histamine level was higher in controls and the 4-aminopyridine group but reduced in the EPI group. Prostaglandin E2 increased in controls and EPI group and decreased in 4-aminopyridine group; prostaglandin F2 increased in controls but decreased in 4-aminopyridine and EPI groups. Leukotriene B4 decreased in 4-aminopyridine and EPI groups. Metabolic acidosis was prevented in the 4-aminopyridine group. CONCLUSIONS: Our data suggest that voltage-dependent K+ channel inhibition with 4-aminopyridine treatment restores blood pressure and increases survival in the Wistar rat model of anaphylactic shock. 4-aminopyridine or related voltage-dependent K channel blockers could be a useful additional therapeutic approach to treatment of refractory anaphylactic shock.