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.

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.

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.

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.

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.

National growth charts for United Arab Emirates children with Down syndrome from birth to 15 years of age.

BACKGROUND: Specific centile growth charts for children with Down syndrome (DS) have been produced in many countries and are known to differ from those of normal children. Since growth assessment depends on the growth pattern characteristic for these conditions, disorder-specific charts are desirable for various ethnic groups. AIMS: To provide cross-sectional weight, height, and head circumference (HC) references for healthy United Arab Emirates (UAE) children with DS. METHODS: A retrospective and cross-sectional growth study of Emirati children with DS, aged 0 to 18 years old, was conducted. Height, weight, and HC were measured in each child. Cole's LMS statistical method was applied to estimate age-specific percentiles, and measurements were compared to UAE reference values for normal children. RESULTS: Incidence of DS in the UAE population is 1 in 374 live births (267 in 10 000 live births). We analyzed 1263 growth examinations of 182 children with DS born between 1994 and 2012. The male-to-female ratio was 1.6:1. Height, weight, and HC centile charts were constructed for ages 0 to 13 years. The prevalence of overweight and obesity in DS children aged 10 to 13 years of age was 32% and 19%, respectively. The DS children were significantly shorter and heavier than normal children in the UAE. CONCLUSIONS: Weight, height, and HC growth charts were created for children with DS. These can be used as a reference standard for the UAE children with DS. Overweight and obesity are quite common in DS children ≥ 10 years of age, as DS children tend to be shorter and heavier than non-DS children.

Inhibition of murine cardiomyocyte respiration by amine local anesthetics.

The hydrophobic amino acyl amide-linked local anesthetics (e.g., lidocaine and bupivacaine) impose potent cardiac toxicity and direct mitochondrial dysfunction. To investigate these adverse events, an in vitro system was employed to measure their effects on O2 consumption (cellular respiration) by murine myocardium. Specimens were collected from the ventricular myocardium and immediately immersed in ice-cold Krebs-Henseleit buffer saturated with 95 % O2:5 % CO2. O2 concentration was determined as a function of time from the phosphorescence decay rates of Pd(II)-meso-tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin. Myocardial O2 consumption was linear with time (zero-order kinetics); its rate (k, in µM O2 min(-1)), thus, was the negative of the slope of [O2] vs. time. Cyanide inhibited O2 consumption, confirming the oxidation occurred in the respiratory chain. Lidocaine and bupivacaine produced immediate and sustained inhibition of cellular respiration at plasma concentrations of the drugs (low micromolar range). Bupivacaine was twice as potent as lidocaine. The inhibition was dose-dependent, saturating at concentrations ≥30 µM. At saturating doses, lidocaine produced ~20 % inhibition and bupivacaine ~40 % inhibition. Cellular ATP was also decreased in the presence of 30 µM lidocaine or bupivacaine. The studied amines inhibited myocardial cellular respiration. This effect is consistent with their known adverse events on mitochondrial function. The described approach allows accurate assessments and comparisons of the toxic effects of local anesthetics on heart tissue bioenergetics.

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.

Biocompatibility of calcined mesoporous silica particles with ventricular myocyte structure and function.

In vivo and in vitro systems were employed to investigate the biocompatibility of two forms of calcined mesoporous silica microparticles, MCM41-cal and SBA15-cal, with ventricular myocytes. These particles have potential clinical use in delivering bioactive compounds to the heart. Ventricular myocytes were isolated from 6 to 8 week male Wistar rats. The distribution of the particles in ventricular myocytes was investigated by transmission electron microscopy and scanning electron microscopy. The distribution of particles was also examined in cardiac muscle 10 min after intravenous injection of 2.0 mg/mL MCM41-cal. Myocyte shortening and the Ca(2+) transient were determined following exposure to 200 µg/mL MCM41-cal or SBA15-cal for 10 min. Within 10 min of incubation at 25 °C, both MCM41-cal and SBA15-cal were found attached to the plasma membrane, and some particles were observed inside ventricular myocytes. MCM41-cal was more abundant inside the myocytes than SBA15-cal. The particles had a notable affinity to mitochondrial membranes, where they eventually settled. Within 10 min of intravenous injection (2.0 mg/mL), MCM41-cal traversed the perivascular space, and some particles entered ventricular myocytes and localized around the mitochondrial membranes. The amplitude of shortening was slightly reduced in myocytes superperfused with MCM41-cal or SBA15-cal. The amplitude of the Ca(2+) transient was significantly reduced in myocytes superperfused with MCM41-cal but was only slightly reduced with SBA15-cal. Overall, the results show reasonable bioavailability and biocompatibility of MCM41-cal and SBA15-cal with ventricular myocytes.

Early changes in myocardial repolarization and coronary perfusion after cardiopulmonary bypass surgery for ASD repair in children.

BACKGROUND: In adults, impaired myocardial repolarization and increased risk of arrhythmia are known consequences of open heart surgery. Little is known, however, about post-operative consequences of cardiopulmonary bypass surgery in children. The aim of this study was to assess ventricular repolarization and coronary perfusion after bypass surgery for atrial septal defect (ASD) repair in children. METHODS: Twelve patients with ASD were assessed one day before and 5-6 days after ASD repair. Myocardial repolarization (corrected QT interval, QTc, QT dispersion, QTd, and PQ interval) was determined on 12-lead electrocardiograms. Coronary flow in proximal left anterior descending artery (peak flow velocity in diastole, PFVd) was assessed by transthoracic Doppler echocardiography. RESULTS: Ten of the 12 (83%) children had normal myocardial repolarization before and after surgery. After surgery, QTc increased 1-9% in 5 (42%) patients, decreased 2-11% in 5 (42%) patients and did not change in 2 (16%) patients. Post-op QTc positively correlated with bypass time (R=0.686, p=0.014) and changes in PFVd (R=0.741, p=0.006). After surgery, QTd increased 33-67% in 4 (33%) patients, decreased 25-50% in 6 patients (50%) and did not change in 2 (16%) patients. After surgery, PQ interval increased 5-30% in 4 (33%) patients, decreased 4-29% in 6 (50%) patients and did not change in 1 (8%) patient. Post-op PQ positively correlated with bypass time (R=0.636, p=0.027). As previously reported, PFVd significantly increased after surgery (p<0.001). CONCLUSIONS: Changes in QTc, PQ and PFVd are common in young children undergoing surgery for ASD repair. Post-op QTc significantly correlates with bypass time, suggesting prolonged cardiopulmonary bypass may impair ventricular repolarization. Post-op QTc significantly correlates with PFVd changes, suggesting increased coronary flow may also impair ventricular repolarization. The clinical significance and reversibility of these alternations require further investigations.

Persistent wandering atrial pacemaker after epinephrine overdosing - a case report.

BACKGROUND: Long-term complications of sympathomimetic drug overdosing have not been adequately investigated in infants and young children. Despite reports discouraging their use in children, these formulations are frequently administered for "cold-like symptoms". Their frequent adverse events are different forms of arrhythmias, including multifocal atrial tachycardia. CASE PRESENTATION: A 3-year-old toddler developed multifocal atrial tachycardia following an iatrogenic overdose of epinephrine accidentally administered intravenously. His ECG showed wandering atrial pacemaker (p-waves with different origins and configurations) that persisted for at least one year. This event demonstrated the sensitivity of young children to the sympathomimetic drugs, especially overdosing. CONCLUSIONS: Health care providers and parents should be warned of toxicities associated with sympathomimetic drug overdosing. Future studies are needed to determine whether wandering atrial pacemaker is a potential long-term complication of high-dose sympathomimetics.

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.

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.

Lymphocyte respiration in children with Trisomy 21.

BACKGROUND: This study measured lymphocyte mitochondrial O(2) consumption (cellular respiration) in children with trisomy 21. METHODS: Peripheral blood mononuclear cells were isolated from whole blood of trisomy 21 and control children and these cells were immediately used to measure cellular respiration rate. [O(2)] was determined as a function of time from the phosphorescence decay rates (1/τ) of Pd (II)-meso-tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin. In sealed vials containing lymphocytes and glucose as a respiratory substrate, [O(2)] declined linearly with time, confirming the zero-order kinetics of O(2) conversion to H(2)O by cytochrome oxidase. The rate of respiration (k, in µM O(2) min(-1)), thus, was the negative of the slope of [O(2)] vs. time. Cyanide inhibited O(2) consumption, confirming that oxidation occurred in the mitochondrial respiratory chain. RESULTS: For control children (age = 8.8 ± 5.6 years, n = 26), the mean (± SD) value of kc (in µM O(2) per min per 10(7) cells) was 1.36 ± 0.79 (coefficient of variation, Cv = 58%; median = 1.17; range = 0.60 to 3.12; -2SD = 0.61). For children with trisomy 21 (age = 7.2 ± 4.6 years, n = 26), the values of k(c) were 0.82 ± 0.62 (Cv = 76%; median = 0.60; range = 0.20 to 2.80), p<0.001. Similar results (p<0.000) were obtained after excluding the five trisomy 21 children with elevated serum TSH (values >6.1 mU/L). Fourteen of 26 (54%) children with trisomy 21 had k(c) values of 0.20 to 0.60 (i.e., <-2SD). The values of kc positively correlated with body-mass index (BMI, R >0.302), serum creatinine (R >0.507), blood urea nitrogen (BUN, R >0.535) and albumin (R >0.446). CONCLUSIONS: Children with trisomy 21 in this study have reduced lymphocyte bioenergetics. The clinical importance of this finding requires further studies.

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.

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.

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.

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.