Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19.

BACKGROUND: Given the sparse data on vitamin D status in pediatric COVID-19, we investigated whether vitamin D deficiency could be a risk factor for susceptibility to COVID-19 in Egyptian children and adolescents. We also investigated whether vitamin D receptor (VDR) FokI polymorphism could be a genetic marker for COVID-19 susceptibility. METHODS: One hundred and eighty patients diagnosed to have COVID-19 and 200 matched control children and adolescents were recruited. Patients were laboratory confirmed as SARS-CoV-2 positive by real-time RT-PCR. All participants were genotyped for VDR Fok1 polymorphism by RT-PCR. Vitamin D status was defined as sufficient for serum 25(OH) D at least 30 ng/mL, insufficient at 21-29 ng/mL, deficient at <20 ng/mL. RESULTS: Ninety-four patients (52%) had low vitamin D levels with 74 (41%) being deficient and 20 (11%) had vitamin D insufficiency. Vitamin D deficiency was associated with 2.6-fold increased risk for COVID-19 (OR = 2.6; [95% CI 1.96-4.9]; P = 0.002. The FokI FF genotype was significantly more represented in patients compared to control group (OR = 4.05; [95% CI: 1.95-8.55]; P < 0.001). CONCLUSIONS: Vitamin D deficiency and VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. IMPACT: Vitamin D deficiency could be a modifiable risk factor for COVID-19 in children and adolescents because of its immune-modulatory action. To our knowledge, ours is the first such study to investigate the VDR Fok I polymorphism in Caucasian children and adolescents with COVID-19. Vitamin D deficiency and the VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. Clinical trials should be urgently conducted to test for causality and to evaluate the efficacy of vitamin D supplementation for prophylaxis and treatment of COVID-19 taking into account the VDR polymorphisms.

Optimization of electrochemical activation of persulfate by BDD electrodes for rapid removal of sulfamethazine.

Boron-doped diamond electrodes have been employed for the removal of sulfamethazine (SMZ) from water by electrochemical activation of persulfate (EO/BDD-PS). A set of experiments with a central composite design (CCD) was conducted to optimize the operating parameters such as persulfate dose, solution pH, and current density by response surface methodology (RSM). The experimental results indicated a rapid degradation of SMZ even at high initial concentrations. For instance, complete degradation of 50 mg L-1 of SMZ was attained after 15 min at the optimum operating conditions (persulfate loading = 0.40 g L-1, pH = 4, and current density = 21 mA cm-2). The oxidation mechanism of EO/BDD-PS process was studied based on the reactive oxidant species (ROS) revealing that both (OH) and contributed to the degradation of SMZ in the EO/BDD-PS system. Furthermore, the oxidation pathway has been proposed by the suspect screening and tandem mass spectrometry analysis. The performance of EO/BDD-PS showed faster SMZ degradation than electro-Fenton and anodic oxidation processes using the same BDD electrochemical reactor under the same conditions. Furthermore, we provided a cost estimation study revealing that a full-scale application of the EO/BDD-PS system for the treatment of similar contaminated water costs about $2.23 m-3.

Cytokine profile in Egyptian children and adolescents with COVID-19 pneumonia: A multicenter study.

BACKGROUND: To date, the cytokine profile in children and adolescent with novel coronavirus disease 2019 (COVID-19) has not been reported. OBJECTIVES: We investigated serum levels of a panel of key cytokines in children and adolescent with COVID-19 pneumonia with a primary focus on "cytokine storm" cytokines such as interleukin (IL)-1ß, IL-6, IL-17, IL-2, IL-4, IL-10, interferon (IFN-γ), tumor necrosis factor (TNF)-α, and two chemokines interferon-inducible protein-10 (IP-10) and IL-8. We also studied whether these cytokines could be potential markers for illness severity in COVID-19 pneumonia. METHODS: Ninety-two symptomatic patients aged less than 18 years with confirmed COVID-19 pneumonia and 100 well-matched healthy controls were included in this multi-center study. For all patients, the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory fluid specimens was detected by real-time reverse-transcriptase polymerase chain reaction. We measured serum concentrations of studied cytokines by using flow cytometry. RESULTS: Patients with COVID-19 had significantly higher median IL-1ß, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 serum levels than did control children (all p < 0.01). Patients with severe COVID-19 pneumonia had significantly higher median IL-1ß, IL-6, and IP-10 serum levels as compared with those with moderate COVID-19 pneumonia; all p < 0.01. ROC analysis revealed that three of the studied markers (IL-6, IL-1ß, and IP-10) could predict severe COVID-19 pneumonia cases with the largest AUC for IL-6 of 0.893 (95% confidence interval: 0.84-0.98; p < 0.01). CONCLUSION: Our study shows that pediatric patients with COVID-19 pneumonia have markedly elevated serum IL-1ß, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 levels at the initial phase of the illness indicating a cytokine storm following SARS-CoV-2 infection. Moreover, serum IL-6, IL-1ß, and IP-10 concentrations were independent predictors for severe COVID-19 pneumonia.

Evaluation of right and left ventricular function using speckle-tracking echocardiography in thalassemic patients.

Background: Beta-thalassemia major is the most common chronic hemolytic anemia among children and adolescents across the world. Several studies have demonstrated that thalassemic patients who have preserved left ventricle systolic function could still have subtle systolic dysfunction. Among patients with beta-thalassemia, early detection of transfusion-induced myocardial iron loading and its intervention with aggressive chelation therapy may delay or reverse heart failure. Two-dimensional speckle-tracking echocardiography (2D-STE) is a novel tool that may detect early myocardial dysfunction in these patients. Objective: The aim of this study was to investigate whether longitudinal strain based on speckle tracking can detect subtle right or left ventricular dysfunction. Patients and Methods: Fifty thalassemic patients with preserved left ventricular ejection fraction (>55%), mean age of 14.75 ± 4.73 years, and thirty age-matched healthy control subjects have been included in the study. Conventional echo Doppler, tissue Doppler echocardiography, and 2D-STE were performed in all patients and control subjects. Results: The right ventricular and left ventricular longitudinal strains were significantly lower in patients than in controls (21.67 ± 5.59 vs. 25.32 ± 2.29, P = 0.001 for right ventricular and 21.29 ± 3.49 vs. 24.90 ± 0.97, P = 0.001 for left ventricular). Conclusions: The 2D-STE can detect early ventricular (left and right) systolic dysfunction in thalassemic patients in the presence of normal systolic function by conventional methods. It may be suggested that the assessment of global longitudinal strain (GLS) can be used as a useful and less expensive tool for screening myocardial iron overload, especially in countries with a limited magnetic resonance imaging (MRI) availability for logistic and economic reasons. Hence, we can refer positive cases with GLS to a higher center to do MRI and start intensive iron chelation treatment.

Association of Plasminogen Activator Inhibitor 1 (PAI-1) 4G/5G Polymorphism and Susceptibility to SLE in Egyptian Children and Adolescents: A Multicenter Study.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is a key molecule residing at the nexus between thrombosis and inflammatory processes. Recently, PAI-1 and its gene expression have emerged as a potential candidate for autoimmune disorders such as SLE. OBJECTIVE: To investigate whether the PAI-1 4G/5G polymorphism at position -675 could be a genetic marker for susceptibility to childhood-onset SLE and development of lupus nephritis among Egyptian children and adolescents. METHODS: Three hundred fifty patients diagnosed with childhood-onset SLE and 350 well-matched healthy controls were included in this multi-center study. All subjects were genotyped for the PAI-1 promoter 4G/5G polymorphism at position -675 using PCR- restriction fragment length polymorphism (RFLP). Serum PAI-1 levels were measured by ELISA. RESULTS: The PAI-1 (- 675) 4G/4G genotype was more represented in c-SLE patients, as compared to the control group (38% vs 23%; OR =2.7; [95% CI: 1.47-2.9]; P < 0.001). Patients carrying the PAI-1 4G/4G genotype or 4G allele were more likely to develop lupus nephritis (OR: 3.38; [95% CI: 1.9-5.9]; P <0.001, for the 4G/4G genotype and OR: 2.6; [95% CI: 1.85-3.67]; for the 4G allele; P < 0.01). The PAI-1 4G/4G genotype was associated with higher PAI-1 serum concentrations (mean; 86.6±22.7 ng/mL) as compared to those with a 4G/5G genotype (mean; 48.3±16.5 ng/mL) and the lowest for the 5G/5G genotype (mean; 34.7±11.4 ng/mL); P = 0.004. CONCLUSION: The PAI-1 4G/5G polymorphism may confer susceptibility to childhood-onset SLE and development of lupus nephritis among Egyptian children and adolescents. Moreover, the PAI-1 4G/4G genotype and 4G allele were associated with higher PAI-1 serum levels and higher disease activity scores.

Association of interleukin-17A gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multi-centre study.

BACKGROUND: Recently, the interleukin-17A (IL-17A) gene has emerged as a potential candidate gene for autoimmune disorders, including systemic lupus erythematosus (SLE). OBJECTIVES: This study aimed to investigate whether IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T could be susceptibility markers for juvenile-onset SLE (JSLE) and lupus nephritis (LN) in Egyptian children and adolescents. METHODS: In this multi-centre study, we genotyped 320 patients diagnosed with JSLE and 320 matched control children for three IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T using TaqMan probe-based real-time polymerase chain reaction. Meanwhile, IL-17A serum levels were assessed using ELISA. RESULTS: The IL-17 rs2275913 A/A genotype and A allele were more represented in JSLE patients compared to the control group (21% vs. 7%, odds ratio (OR) = 3.8, 95% confidence interval (CI) 1.78-5.5, p = 0.001, pBonf = 0.003 for the A/A genotype; 37% vs. 29%, OR = 1.4, 95% CI 1.11-1.8, p = 0.003, pBonf = 0.009 for the A allele. No significant difference was found for IL-17 rs8193036 and rs3748067 single nucleotide polymorphisms (SNPs) in genotype distribution or allele frequencies (p>0.05). Patients carrying the IL-17 rs2275913 A/A genotype and A allele were more likely to develop LN (OR = 5.64, 95% CI 2.39-13.77, pBonf = 0.001 for the A/A genotype; OR = 2.73, 95% CI 1.84-4.07, pBonf = 0.02 for the A allele). CONCLUSION: The IL-17 rs2275913 A allele and A/A genotype were associated with high IL-17 serum levels and may contribute to susceptibility to JSLE and the development of LN in Egyptian children and adolescents. However, no significant association was evident between the studied IL-17A SNPs and other clinical phenotypes, disease activity scores or laboratory profile of JSLE.

Cardiac injury after convulsive status epilepticus in children.

OBJECTIVE: Convulsive status epilepticus (CSE) is a medical emergency with high mortality that usually occurs within 30 days following the seizure activity. One of the potential mechanisms contributing to mortality in this period following CSE is cardiac injury. The aim of the present study was to evaluate cardiac injury after CSE in children. PATIENTS AND METHODS: Sixty children presented with CSE were enrolled in this study. Thirty healthy children with matched age and sex were taken as a control. Electrocardiogram (ECG), echocardiographic examinations, plasma concentration of cardiac troponin I (cTnI) and brain-type natriuretic peptide (BNP) were done 6 h after control of seizure for patients and control groups. RESULTS: Thirty three patients were presented with CSE for the first time. ECG changes were present in 55% of patients with CSE in the form of conduction abnormalities, ischemic changes, and arrhythmias. Echocardiographic examinations revealed a significant increase in left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic dimension (LVESD) in patients with CSE than control group. Moreover, a significant decrease in LV systolic function and RV diastolic function were detected by tissue Doppler. The mean plasma concentrations of BNP and cTnI were significantly higher in patients with CSE than the control group (p value < 0.001). The overall mortality in our study was 8.3% (5/60); four of them had ECG changes. There was significant increase in duration of CSE, length of intensive care and hospital admission in CSE patients with ECG changes than those without ECG changes with p values 0.001, 0.031 and <0.001 respectively. CONCLUSION: Cardiac injury in convulsive SE is common and may be under recognized. So, cardiac assessment should be a routine step in CSE patients' management.

Spectrophotometric and atomic absorption determination of ramipril, enalapril maleate and fosinopril through ternary complex formation with molybdenum (V)-thiocyanate (Mo(V)-SCN).

Three different sensitive and accurate spectroscopic procedures were developed for the determination of three angiotensin-converting enzyme inhibitors, namely, ramipril, enalapril maleate and fosinopril. The first two spectrophotometric (extractive and non-extractive) procedures were based on ternary complex formation with molybdenum(V) thiocyanate. The formed complex can be determined by extraction with chloroform measured at lambdamax 517 nm Beer's law was obeyed in the concentration range from (10--90 microg ml(-1)) for ramipril and fosinopril and (4--36 microg ml(-1)) for enalapril maleate with molar absorptivity 1.2x10(4), 2x10(4) and 3.4x10(4) l mol(-1) cm(-1), respectively, or by direct measurement after addition of benzalkonium chloride as surfactant and measuring the formed ternary complex at lambdamax 545 nm with a linear relationship in the concentration range from (8-7-2 microg ml(-1)), (3--27 microg ml(-1)) and (8--72 microg ml(-1)) for ramipril, enalapril maleate and fosinopril with molar absorptivity 1.5x10(4), 5x10(4) and 2.1x10(4) l mol(-1) cm(-1), respectively. The third procedure is atomic absorption measurement through the quantitative determination of molybdenum content of the complex. These methods hold their accuracy and precision well when applied to the determination of ramipril, enalapril maleate and fosinopril in their dosage forms.