How does a Saccharomyces cerevisiae extract influence the components of isolated rotavirus particles from stool samples collected in a clinical setting from children?

Human Rotavirus (HRV) is the causative pathogen of severe acute enteric infections that cause mortality among children worldwide. This study focuses on developing a new and effective treatment for rotavirus infection using an extract from Saccharomyces cerevisiae, aiming to make this treatment easily accessible to everyone. 15 antigens and 26 antibodies were detected in serum and stool using ELISA. The titers of HRVq1, HRVq2, HRVC1, and HRVC2 on Vero cells were determined to be 1.2x106, 3.0x106, 4.2x106, and 7.5x105 (Plaque forming unit, PFU/ml) four days after infection, respectively. The HRVq1 isolate induced cytopathic effects, i.e., forming multinucleated, rounded, enlarged, and expanding gigantic cells. RT-PCR identified this isolate, and the accession number 2691714 was assigned to GeneBank. The molecular docking analysis revealed that nonstructural proteins (NSPs) NSP1, NSP2, NSP3, NSP4, NSP5, and NSP6 exhibited significant binding with RNA. NSP2 demonstrated the highest binding affinity and the lowest binding energy (-8.9 kcal/mol). This affinity was maintained via hydrophobic interactions and hydrogen bonds spanning in length from 1.12 Å to 3.11 Å. The ADMET and bioactivity predictions indicated that the yeast extract possessed ideal solubility, was nontoxic, and did not cause cancer. The inhibitory constant values predicted for the S. cerevisiae extract in the presence of HRV vital proteins varied from 5.32 to 7.45 mM, indicating its potential as a viable drug candidate. Saccharomyces cerevisiae extract could be utilized as a dietary supplement to combat HRV as an alternative dietary supplement.

Outcome of Cyclophosphamide Treatment Following Hematopoietic Stem Cell Transplantation in a Thalassemia Patient: A Case Study.

Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for ß-thalassemia major in children. However, it often induces graft-versus-host-disease (GVHD), which is associated with complications. In the present study, we used cyclophosphamide (Cy) to treat a thalassemia patient post-HSCT to reduce the adverse effects of GVHD. We monitored the numbers and phenotype of granulocytes. In this case study, an 11-year-old female patient, diagnosed with ß-thalassemia major (Pesaro class II), was treated with Cy before and after HSCT with mobilized CD34+ cells. Both the relative and absolute granulocyte counts, as well as CD33+CD11b+ cell counts, increased significantly after HSCT until day 56. However, they suddenly began to decrease after day 56, accompanied by severe diarrhea, skin rash, and a decrease in bilirubin levels compared to day -12. Furthermore, compared to day -12, IL-22 levels increased until day 56, and then decreased, while IDO levels continued to rise after day 56. Our data suggest the potential use of IL-22 and IDO as biomarkers for GVHD assessment. It also indicates that Cy promotes HSCT reconstitution by increasing CD33+CD11b+ cells, which may play a crucial role in reducing GVHD risks. However, further studies are needed to elucidate the mechanism behind GVHD recurrence.

Beta Thalassemia Carrier Rate: Problem Burden among High School Children.

Background & Aim of the Work: ß-Thalassemia (ßT) is highly prevalent in some countries like Egypt. Accurate data about actual disease prevalence and heavily prevalent geographic locations are essential to help in early detection and in setting up effective preventive programs. We aim for screening ßT carriers among Egyptian high school students in the Delta region. SUBJECTS AND METHODS: A cross-sectional multicenter study was carried out on 4320 randomly selected students from four governorates of the Nile Delta region, Egypt. All patients were to be tested for their complete blood count. Those with microcytic hypochromic anemia not caused by iron deficiency were tested for ßT carrier status using high-performance liquid chromatography. RESULTS: The total prevalence of ßT carrier rate was 6.13%. The highest prevalence was detected in Al-Sharkia Governorate, reaching 7.89%, followed by 6.90% in Al-Gharbia Governorate. Al- Dakahilia and Al-Menoufia showed lower rates of 4.86% and 3.73%, respectively. CONCLUSION: Despite the premarital national screening program for ßT in Egypt, the carrier rate is still high. More effort should be done into the proper implementation of national prevention programs.

Altered microRNA expression profile is linked to T-cell exhaustion-related pathways in pediatric patients with acute lymphoblastic leukemia.

BACKGROUND: Although the phenotype and functions of exhausted T cells in several cancers have been identified, the involved molecular mechanisms remain to be further elucidated. In this regard, we have recently reported that the immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), share common dysregulated miRNAs that target specific immunosuppressive pathways in patients with in acute lymphoblastic leukemia (ALL). AIM: In this study, we aimed to further explore whether similar dysregulation in miRNA expression is linked to T cell exhaustion and dysfunctionality in B cell ALL patients. METHODS: Peripheral blood samples from pediatric patients with ALL were recruited before and after induction chemotherapy as well as from healthy donors. Affymetrix microarray platform was used for miRNA profiling, and qRT-PCR was used to validate the expression of certain miRNAs that are related to T cell exhaustion. Bioinformatics analysis was performed to explore whether the dysregulated miRNAs were linked to T-cell exhaustion related pathways. RESULTS: A total of 516 miRNAs were dysregulated in ALL patients as compared to the healthy donor. Furthermore, among the total analyzed miRNAs, 10 were found to be linked to the key genes implicated in three exhaustion-related pathways; TGF-ß, FOXO, and MAPK, as revealed by miR-pathway analysis. Moreover, qRT-PCR analysis showed similar expression pattern to those obtained by microarray analysis. CONCLUSION: Our pilot study suggests the implication of certain miRNAs in T cell exhaustion pathways via targeting the specific key genes in those pathways.

Randomized Clinical and Biochemical Study Comparing the Effect of L-arginine and Sildenafil in Beta Thalassemia Major Children With High Tricuspid Regurgitant Jet Velocity.

BACKGROUND: Pulmonary hypertension (PHT) is common in ß-thalassemia patients due to hemolysis, iron overload and diminished nitric oxide (NO) levels. Biochemical markers can help to understand the pathophysiology and to introduce new therapies for this condition. AIM: This study aimed to evaluate the effectiveness of L-arginine and sildenafil in thalassemia children with PHT at both clinical and biochemical levels. METHODS AND RESULTS: In a randomized controlled study, 60 ß-thalassemia major children with PHT were divided into 3 equal groups; Control group (Conventional thalassemia and PHT management), L-arginine group (Conventional + Oral L-arginine 0.1 mg.kg-1 daily), and sildenafil group (Conventional + Oral sildenafil 0.25 mg.kg-1 two times a day) for 60 days. Tricuspid Regurgitant Jet Velocity (TRJV) with Doppler echocardiography along with serum levels of NO, asymmetric dimethylarginine (ADMA), interleukin 1-beta (IL-1ß), E-selectin, and visfatin were followed-up at baseline, 30, and 60 days after treatment. Both drugs reduced the TRJV significantly. NO was significantly higher in both L-arginine and sildenafil groups after 60 days compared to baseline, while visfatin levels were lower. Only L-arginine reduced ADMA levels compared to baseline, while sildenafil did not. E-selectin and IL-1ß levels did not change remarkably by both drugs. NO and TRJV showed significant negative correlations in both treatment groups. CONCLUSION: L-arginine and sildenafil could clinically ameliorate chronic PHT whereas, L-arginine showed superiority to sildenafil on some biochemical markers.

The Value of SIRT1/FOXO1 Signaling Pathway in Early Detection of Cardiovascular Risk in Children with ß-Thalassemia Major.

Background: Atherosclerosis represents one of the major causes of morbidity in children with ß-thalassemia major (ß-TM). Aim: This study was designed to investigate SIRT1-FOXO1 signaling in ß-TM children and their role in early detection of premature atherosclerosis. Methods: We equally subdivided 100 Egyptian children aged 6−14 years with ß-TM according to carotid intima media thickness (CIMT) into 50 with CIMT < 0.5 mm and 50 with CIMT ≥ 0.5 mm, and 50 healthy children of matched age were included. They were subjected to evaluation of SIRT1, heat shock protein 72 (HSP72), and hepcidin levels via ELISA and forkhead box protein 1 (FOXO1) mRNA expression using real-time PCR in PBMCs; meanwhile, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase activities were evaluated spectrophotometrically. Results: Our results show significantly high values for CIMT, ß-stiffness, atherogenic index of plasma (AIP), MDA, HSP72 and FOXO1, ferritin with significantly low hepcidin, SOD, catalase, and SIRT1 in ß-TM as compared to controls with a more significant difference in ß-TM with CIMT ≥ 0.5 mm than those with CIMT < 0.5 mm. A significant positive correlation between CIMT and MDA, HSP72, and FOXO1 gene expression was found, while a significant negative correlation with hepcidin, SOD, catalase, and SIRT1 was found. FOXO1 gene expression and HSP72 levels were the strongest independent determinants of CIMT. Conclusion: In ß-TM, FOXO1 signaling is activated with low levels of SIRT1, and this is attributed to accelerated atherosclerosis in ß-TM, which would be crucial in prediction of atherosclerosis.

Al-hijamah (the triple S treatment of prophetic medicine) significantly increases CD4/CD8 ratio in thalassemic patients via increasing TAC/MDA ratio: a clinical trial.

Beta thalassemia is associated with decreased immunity possibly due to iron overload. Al-hijamah (Hijamah) is wet cupping therapy (WCT) of prophetic medicine. Prophet Muhammad Peace be upon him said: "The best among your treatments is Al-hijamah". Al-hijamah is a promising excretory treatment to clear blood of causative pathological substances. Al-hijamah is a three-step technique (skin suction, scarification and suction) i.e. triple S technique). Recently, we introduced Al-hijamah as a novel iron excretion therapy (through pressure-dependent filtration then excretion via the skin dermal capillaries) that significantly decreased serum iron overload and related oxidative stress using a physiological excretory mechanism (Taibah mechanism). Iron overload was reported to impair both humoral immunity and cell mediated immunity in patients with beta thalassemia. In this study, twenty patients having ß-thalassemia major (maintained on iron chelation therapy) underwent a single session of Al-hijamah (30-60 minutes) using 4-5 sucking cups only. Another age and sex-matched control group of thalassemic patients received iron chelation therapy only. Al-hijamah enhanced the immunity of thalassemic patients in the form of increased CD4+ T cell count, from 124.10±36.98 to 326.20±57.94 cells/mm3, and an increased CD8+ T cell count from 100.30±36.98 to 272.40±46.37 cells/mm3. CD4/CD8 ratio significantly increased from 1.29 to 1.7 (P<0.001). There was a significant increase of ten times (P<0.001) in serum TAC/MDA ratio (reflects increased antioxidant capacity vs decreased oxidative load and stress) induced by Al-hijamah. After Al-hijamah, both CD4+ and CD8+ T cell counts significantly increased and positively correlated with TAC/MDA ratio (r = 0.246) and (r = 0.190), respectively. Moreover, CD4/CD8 ratio positively correlated with TAC/MDA after Al-hijamah (r = 0.285). In conclusion, Al-hijamah significantly increased CD4/CD8 ratio in thalassemic patients via increasing TAC/MDA ratio. Our study strongly recommends medical practice of Al-hijamah in hospitals for its immune potentiating effects in agreement with the evidence-based Taibah mechanism. Al-hijamah should be generalized for treating other immune-deficiency conditions. Al-hijamah-induced bloody excretion is so minimal and never aggravates the anaemic status.

Trichrome-positive intrahepatic cytoplasmic globules are potential histopathological clue for COVID-19-induced hepatitis: a case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mainly affects respiratory system. Later, liver affection has also been reported in the form of marked elevated liver enzymes. However, the association of coronavirus disease-19 (COVID-19) and autoimmune diseases is not clear. CASE PRESENTATION: A female patient with a known history of autoimmune hemolytic anemia (AIHH) for which she was treated with prednisolone was admitted for uncontrolled anemia followed by fever and elevated liver enzymes. All the laboratory and radiological investigations were not typical for COVID-19 or any other etiology. Liver biopsy revealed numerous pale eosinophilic trichrome-positive intracytoplasmic globules. The pathology raised the suspicion for SARS-CoV-2-associated hepatitis, which was confirmed by a positive IgG titer. The patient showed a dramatic improvement on the maintenance dose of prednisolone. CONCLUSIONS: AIHA patients co-infected with SARS-CoV-2 may be at risk of uncontrolled disease and should continue their treatment regimen. Histopathology has a role in the diagnosis of liver affection due to SARS-CoV-2 infection.

Prevalence of iron deficiency anemia and beta thalassemia carriers among relatives of beta thalassemia patients in Nile Delta region, Egypt: a multicenter study.

BACKGROUND: Screening of ß thalassemia among close relatives is more feasible in highly prevalent countries with limited resources. The purpose of this study is to determine the prevalence of ß thalassemia carriers and iron deficiency anemia among relatives of ß thalassemia patients in Mid Delta, Egypt. METHODS: This is a cross-sectional multi-center study conducted on 2118 relatives of patients with ß thalassemia from different Egyptian governorates in the Mid Delta region. They were subjected to history taking with precise determination of geographic location, general examination, and the following investigations: complete blood counts, serum ferritin for those who showed microcytic hypochromic anemia, and high-performance liquid chromatography for those who were not diagnosed as iron deficiency anemia. RESULTS: The total prevalence of iron deficiency anemia among close relatives of confirmed ß thalassemia patients in the Nile Delta region was 17.19%. The highest prevalence of iron deficiency anemia (45.05%) was reported in Al-Gharbia Governorate, followed by Al-Menoufia Governorate (21.67%), and the lowest prevalence was that of Al-Sharkia Governorate (4.91%). The differences were highly statistically significant (p < 0.001). ß thalassemia carrier prevalence rate in the studied relatives was 35.84%, with the highest prevalence detected in Al-Sharkia Governorate (51.32%), followed by Kafr-Alsheikh and Al-Dakahilia Governorates (41.78%, 37.13%) respectively, while Al-Menoufia Governorate had the lowest prevalence rate (25.00%). These differences were also highly statistically significant (p < 0.001). CONCLUSION: More than one-third of relatives of patients with ß thalassemia are carriers of the disease, while 17.19% suffer from iron deficiency anemia. This study demonstrates the importance of tracing the high number of beta thalassemia carriers among relatives of patients with ß thalassemia in Egypt.

Evaluation of MicroRNA92, MicroRNA638 in Acute Lymphoblastic Leukemia of Egyptian Children.

OBJECTIVE: miRNA considers a small non-coding RNA molecule that has tumor suppressor or oncogenic functions and regulates gene expression. miRNA may be involved in the pathogenesis of acute lymphoblastic leukemia (ALL).  miRNA was evaluated in patients with ALL to correlate their importance in the clinical prediction and the response to chemotherapy. SUBJECT AND METHODS: The study population included 30 healthy control and 71 children with ALL is divided into 4 groups: healthy, newly diagnosed, remitted, and relapsed groups. We quantify miRNA 92a, miRNA 638 expression using real-time PCR in childhood ALL. RESULTS: plasma miRNA 92a and miRNA 638 expressions were elevated in ALL cases at the time of diagnosis (2.51 and 2.19 folds), and relapsed (2.1 and 1.61 folds) than that of patients with remitted ALL. There was a positive correlation between miRNA 92a and miRNA 638 patients with ALL. Also, total leukocyte and blast correlated with miRNA 92a and miRNA 638 unlike hemoglobin, and platelets didn't correlate with miRNA 92a and miRNA 638. The sensitivity of miRNA 92a and miRNA 638 were 41.5% and 54.7% respectively while the specificity was 100 % of miRNA 92a and miRNA 638. CONCLUSION: miRNA 92a and miRNA 638 are recommended to be used as potential predictive and follow-up markers in children with ALL remitted and relapsed cases.

Myeloid-derived suppressor cells and regulatory T cells share common immunoregulatory pathways-related microRNAs that are dysregulated by acute lymphoblastic leukemia and chemotherapy.

BACKGROUND: Relapse remains a critical challenge in children with acute lymphoblastic leukemia (ALL). The emergence of immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs), and T regulatory (Treg) cells, has been considered one potential mechanism of relapse in children with ALL. AIM: This study aimed to address the microRNAs (miRNAs) related to MDSCs and Treg cells and to explore their targeted immunoregulatory pathways. METHODS: Affymetrix microarray was used for global miRNA profiling in B-ALL pediatric patients before, during, and after induction of chemotherapy. Bioinformatics analysis was performed on MDSCs and Treg cells-related dysregulated miRNAs, and miR-Pathway analysis was performed to explore their targeted immunoregulatory pathways. RESULTS: 516 miRNAs were dysregulated in ALL patients as compared to the healthy donor. Among them, 13 miRNAs and 8 miRNAs related to MDSCs and Treg cells, respectively, were common in all patients. Besides, 12 miRNAs were shared between MDSCs and Treg cells; 4 of them were common in all patients. Four immune-related pathways; TNF, TGF-ß, FoxO, and Hippo were found implicated. CONCLUSION: Our pilot study concluded certain miRNAs related to MDSCs and Treg cells, these miRNAs were linked to immunoregulatory pathways. Our results open avenues for testing those miRNA as molecular biomarkers for the immunosuppressive tumor microenvironment.

Impact of maternal and neonatal factors on umbilical cord CD34+ cells.

BACKGROUND: The achievement of optimal number of CD34+ umbilical cord stem cells is essential for successful umbilical cord stem cell transplantation. So the aim of this study was to assess the potential effect of both maternal and neonatal factors on the umbilical cord blood CD34+ cell count. METHODS: The study was done on umbilical cord blood samples obtained from 20 mothers during labor. Their ages ranged from 22 to 34 years and were subjected to history taking, physical examination of the baby and assessment of the CD34+ cells count in umbilical cord blood. RESULTS: Number of previous live births and weight of the baby had a significant effect on CD34+ cells count while the sex of the baby, delivery route, maternal age and gestation period had no significant effect on CD34+ cells count. CONCLUSIONS: Umbilical cord blood-derived CD34+ cell count is better with good weight and first babies and decreased with subsequent babies.

Al-hijamah (the triple S treatment of prophetic medicine) exerts cardioprotective, tissue-protective and immune potentiating effects in thalassemic children: a pilot clinical trial.

Thalassemia is a major health problem in affected children due to iron overload, increased oxidative stress, atherogenic lipid profile and tissue-damage. This study aims at investigating the cardioprotective and tissue-protective benefits of Al-hijamah and their impact on cell-mediated immunity for treating thalassemic children. This study aimed also at investigating the tissue-clearance principle of Taibah mechanism: whenever pathological substances are to be cleared from the human body, Al-hijamah is indicated. Al-hijamah was done to thalassemic children (15 males and 5 females having a mean age of 9.07 ± 4.26 years) using sterile disposable sets in a complete aseptic hospital environment. Prior ethical committee agreement (in addition to written patient's consents) was obtained from Tanta Faculty of Medicine, Egypt. Twenty thalassemic children received iron chelation therapy plus Al-hijamah for one session (30-60 minutes) versus an age and sex-matched thalassemic control group treated with iron chelation therapy only. Al-hijamah is a quite safe outpatient hematological procedure that significantly decreased serum cholesterol (from 129.75 ± 3.67 to 103.5 ± 4.18 mg/dl) and decreased serum triglycerides (from 109.25 ± 8.96 to 91.95 ± 7.22 mg/dl). Interestingly, Al-hijamah exerted significant tissue-protective effects (it decreased serum GPT from 98.65 ± 12.27 to 71.65 ± 32.78 U/L and serum GOT from 96.35 ± 14.33 to 69.35 ± 34.37 U/L). Al-hijamah-induced ferritin excretion caused decreased serum ferritin (high serum ferritin negatively correlated with cell mediated immunity). Al-hijamah exerted cardioprotective and tissue-protective and hypolipidemic effects. Al-hijamah decreased serum cholesterol and is cardioprotective for thalassemic patients as it protects against atherogenesis and atherosclerosis. Medical practice of Al-hijamah is strongly recommended in hospitals. Al-hijamah cleared blood significantly from causative pathological substances e.g. serum ferritin resulting in enhanced cell-mediated immunity (in agreement with the evidence-based Taibah mechanism).

Asymmetric Dimethylarginine Levels and Its Correlation to Cerebral Blood Flow in Children with Sickle Cell Anemia.

Asymmetric dimethylarginine (ADMA) level may play a role in the pathogenesis of cerebrovascular stroke in Children with Sickle Cell Anemia (SCA). To assess the plasma level of ADMA in children with SCA and its correlation to cerebral blood flow. This is a cross sectional study was carried out on 30 children with homozygous SCA under follow up in the Out Patients Clinic, Pediatric Department at Tanta University Hospital and 30 healthy children as a control group. Both groups had undergone the following investigations: Complete blood count, lactate dehydrogenase enzyme, and plasma level of ADMA by a commercial ADMA ELISA Kit. Trans-cranial Doppler were done for both groups. ADMA plasma level was significantly higher in-patient group in comparison to the control group (p < 0.001), with a mean value 1.43 ± 0.20 µmol/l, 0.48 ± 0.16 µmol/l respectively. The time-averaged mean maximum velocities for middle cerebral artery, anterior cerebral artery, inferior cerebral artery and posterior cerebral artery were significantly different between patient and control group, p < 0.05. Trans-cranial Doppler data revealed that, 86.7% of patients have low velocity (< 70 cm/s) and 13.3% having very low velocity (< 10 cm/s) while control group have normal velocity. There was a significant negative correlation between ADMA plasma levels and cerebral blood flow. Elevated ADMA levels may have a role in the pathogenesis of the decreased cerebral blood flow in children with SCA.

Left Ventricular Regional Function in Children with Beta Thalassemia with No Cardiac Manifestations (Four-Dimensional Echocardiographic Study).

Early detection of myocardial dysfunction is essential for the management of patients with thalassemia. Four-dimensional echocardiography imaging technique may be useful for detecting subclinical cardiovascular disease. To evaluate the 4-dimensional echocardiographic strain in children with beta thalassemia major with no cardiac manifestation and correlate it with other echocardiographic parameters. This is a prospective cross-sectional cohort Study included 200 children, 1-18 years-old. They were divided into: One hundred children with p-Thalassemia major with no clinical cardiac manifestations and 100 healthy children as a control group. They were subjected to the following investigations: Complete blood count, serum ferritin and Four-dimensional echocardiographic strains (Longitudinal, Circumferential, Radial and Area strains). There was no significant difference between the two groups as regard mitral annulus systolic velocity (S wave), E/A ratio and iso-volumic acceleration, but there was a significant difference as regard to ejection fraction, left ventricle mass, sphericity index and myocardial performance index. The mean values of Left Ventricular Strains (Longitudinal, Circumferential, Radial and Area strains) were significantly lower in patients with thalassemia (- 14.86 ± 12.13, - 8.01 ± 3.829, 33.13 ± 10.61, - 19.45 ± 6.866) than controls (- 19.13 ± 1.502, - 16.32 ± 1.34, 37.28 ± 4.209, - 22.94 ± 3.06) than controls respectively with a positive correlation with 2-Dimensional strain. Strain parameters of the left ventricle obtained by four-dimensional.

Al-hijamah (wet cupping therapy of prophetic medicine) significantly and safely reduces iron overload and oxidative stress in thalassemic children: a novel pilot study.

BACKGROUND: Thalassemia is a major health problem due to iron overload, iron deposition and oxidative stress-induced tissue damage. Here, we introduce Al-hijamah (a minor surgical excretory procedure) as a novel percutaneous iron excretion therapy. Al-hijamah is a wet cupping therapy of prophetic medicine, and prophet Muhammad, peace be upon him, strongly recommended Al-hijamah, saying: "The best of your treatment is Al-hijamah". AIM OF THE STUDY: Our study aimed at investigating the safety, iron chelation, pharmacological potentiation and oxidant clearance effects exerted by Al-hijamah to thalassemic children. PATIENTS AND METHODS: Ethical committee's approval and patients' written agreement consents were obtained. We treated 20 thalassemic children (15 males and five females aged 9.07±4.26 years) with iron chelation therapy (ICT) plus Al-hijamah (using sterile disposable sets and in a complete aseptic environment) vs a control group treated with ICT only. This clinical trial was registered in the ClinicalTrial.gov registry under the name "Study of the Therapeutic Benefits of Al-hijamah in Children with Beta Thalassemia Major" (identifier no NCT 02761395) on 30 January 2016. RESULTS: Al-hijamah was quite simple, safe, effective, tolerable (with no side effects) and time-saving procedure (30-60 minutes). A single session of Al-hijamah significantly reduced iron overload (P<0.001) in all thalassemic children. Al-hijamah significantly decreased serum ferritin by 25.22% (from 3,778.350±551.633 ng/mL to 2,825.300±558.94 ng/mL), significantly decreased oxidative stress by 68.69% (P<0.05; serum malondialdehyde dropped from 42.155±12.42 to 13.195±0.68 nmol/L), exerted pharmacological potentiation to ICT and significantly increased total antioxidant capacity (P<0.001) by 260.95% (from 13.195±0.68 nmol/L to 42.86±12.40 nmol/L through excreting reactive oxygen species). Moreover, therapeutic indices for evaluating Al-hijamah were promising. CONCLUSION: Al-hijamah is a novel, safe, effective percutaneous iron excretion therapy through percutaneous iron excretion with minimal blood loss in agreement with the evidence-based Taibah mechanism. Al-hijamah is an effective outpatient hematological procedure that is safer than many pediatric procedures such as catheterization, hemofiltration and dialysis. Increasing the number of cups during Al-hijamah session or the number of sessions reduces iron overload more strongly. Medical practice of Al-hijamah is strongly recommended in hospitals.

Chemotherapy alters the increased numbers of myeloid-derived suppressor and regulatory T cells in children with acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanism behind the relapse in this disease is not clearly known. One possible mechanism could be the accumulation of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) which we and others have reported to mediate suppression of anti-tumor immune responses. AIM: In this study, we aimed to analyze the numbers of these cells in a population of B-ALL pediatric patients. METHODS: Peripheral blood samples withdrawn from B-ALL pediatric patients (n = 45 before, during and after the induction phase of chemotherapy. Using multi parametric flow cytometric analysis. MDSCs were identified as Lin-HLA-DR-CD33+CD11b+; and Treg cells were defined as CD4+CD25+CD127-/low. RESULTS: Early diagnosed B-ALL patients showed significant increases in the numbers of MDSCs and Tregs as compared to healthy volunteers. During induction of chemotherapy, however, the patients showed higher and lower numbers of MDSCs and Treg cells, respectively as compared to early diagnosed patients (i.e., before chemotherapy). After induction of chemotherapy, the numbers of MDSCs and Treg cells showed higher increases and decreases, respectively as compared to the numbers in patients during chemotherapy. CONCLUSION: Our results indicate that B-ALL patients harbor high numbers of both MDSCs and Tregs cells. This pilot study opens a new avenue to investigate the mechanism mediating the emergence of these cells on larger number of B-ALL patients at different treatment stages.

Speckle tracking evaluation of right ventricular functions in children with sickle cell disease.

BACKGROUND: Cardiac dysfunction is a risk factor for death in patients with sickle cell disease (SCD). AIM OF THE WORK: Aim of the work is to evaluate the right ventricular systolic and diastolic functions by tissue Doppler and speckling tracking imaging in children with SCD. SUBJECTS AND METHODS: Thirty children with SCD and thirty controls were subjected to clinical, laboratory evaluations, and echocardiographic study using GE Vivid 7 (GE Medical System, Horten, Norway with a 3.5-MHz multifrequency transducer) including; Two-dimensional and tissue Doppler echocardiographic study (lateral tricuspid valve annulus peak E' velocity, lateral tricuspid valve annulus peak A' velocity, E'/A' ratio, isovolumetric relaxation time, lateral tricuspid valve annulus S' and septal S' waves and peak longitudinal systolic strain [PLSS] and time to PLSS) were done in six right ventricular segments. RESULTS: There was a significant decrease in right ventricular systolic and diastolic function in patients group when compared to controls. CONCLUSIONS: Children with SCD have impaired right ventricular systolic and diastolic functions when compared to healthy children with early evaluation of the systolic dysfunction by speckle tracking imaging technique.

Study of peripheral stem cells mobilization as a treatment line of pediatric dilated cardiomyopathy.

BACKGROUND: Mobilizing hematopoietic stem cells may be a promising intervention for the treatment of idiopathic dilated cardiomyopathy (IDCM) in infant and children. So the aim of the work is to evaluate the efficacy of granulocyte-colony stimulating factor (G-CSF) as a therapeutic modality in pediatric IDCM. METHODS: A randomized clinical trial was conducted on 40 pediatric patients with IDCM. They were subjected to history taking, clinical examination, serum lactate dehydrogenase (LDH), total creatinine phosphokinase (CPK), creatinine phosphokinase isoenzyme B (CK-MB) isoenzyme, and peripheral blood CD34(+) cell assessment before and at day 7 after subcutaneous G-CSF injection for 5 consecutive days. Echocardiography was done before and 1, 3 and 6 months after therapy. RESULTS: Clinical improvement in the form of regression of patients Modified Ross heart failure (MRHC) classification classes. Increased percentage of CD34(+) mobilized cells from the bone marrow, and significant increase in blood counts especially white blood cells 7 days after G-CSF injection. Significant improvement was found in echocardiographic data evaluating systolic function of the heart [Ejection fraction, Fractional shortening and systolic velocity at mitral annulus (Sm)]. CONCLUSIONS: Administration of G-CSF may be beneficial in improving systolic functions of the heart in pediatric IDCM and more studies with a large number of patients are needed.

Asymmetric dimethylarginine levels in children with sickle cell disease and its correlation to tricuspid regurgitant jet velocity.

BACKGROUND: Pulmonary hypertension (PH) is an increasingly recognized life-threatening complication in sickle cell disease (SCD), with associated high mortality in adults. The prevalence of PH in children with SCD is still unknown. The etiology and pathophysiologic mechanisms are still not well understood. AIM OF THE STUDY: To assess the plasma levels of asymmetric dimethylarginine (ADMA) in children with SCD and its correlation with elevated tricuspid regurgitant jet velocity and other hemolytic markers. SUBJECTS & METHODS: This study was carried out on a cohort of patients (30) with SCD and 30 healthy children as a control group. Certain investigations were carried out for all subjects: CBC, lactate dehydrogenase (LDH), ferritin, reticulocytic count, bilirubin, AST, ALT, and plasma levels of ADMA. Doppler echocardiography was carried out for all subjects. RESULTS: The prevalence of high tricuspid regurgitant velocity (TRV) was 30% in SCD patients. ADMA mean plasma level was significantly higher in patients than in controls (0.79 ± 0.15 µmol/L and 0.46 ± 0.11 µmol/L, respectively, P < 0.001). ADMA was significantly higher in patients with high TRV than those with normal TRV (1.10 ± 0.11 µmol/L, 0.80 ± 0.06 µmol/L, respectively, P < 0.001). There was a significant positive correlation between ADMA plasma levels and TRV ≥2.5 m/s (r = 0.475). CONCLUSION: High plasma ADMA levels may be implicated in the pathogenesis of increased tricuspid regurgitant jet velocity in children with SCD.