β-Thalassemia: Genotypes and Phenotypes

β-Thalassemias are extremely heterogeneous at the molecular level. More than 200 disease-causing mutations have been identified. The majority of mutations are single nucleotide substitutions. Rarely, β-thalassemia results from gross gene deletion. The degree of globin chain imbalance is determined by the nature of the mutation of the β-gene. β0 refers to the complete absence of production of β-globin on the affected allele. β+ refers to alleles with some residual production of β-globin (around 10%). In β++, the reduction in β-globin production is very mild. The broad spectrum of β-thalassemia alleles can produce a wide spectrum of different β-thalassemia phenotypes. In this chapter, we review the molecular basis of the marked heterogeneity of the thalassemia syndromes or in other words the genotype-phenotype relationship in β-thalassemia

Assessment of livin expression in childhood B-lineage acute lymphoblastic leukemia patients

Background: When it comes to childhood acute lymphoblastic leukemia (ALL) patients, Livin is related with good prognostic characteristics.Objective: The aim of the work was to assess livin expression in childhood B-lineage acute lymphoblastic leukemia to determine its significance.Patients and Methods: From September 2018 and September 2019, at Zagazig University Hospitals Clinical Pathology and Pediatric departments, our case control trial was conducted on 50 subjects, patients’ group (25 cases of newly diagnosed ALL) and control group (25 healthy children). Assessment of livin expression was done using real time polymerase chain reaction (PCR).Results: There was statistically significant difference between the age of livin positive and livin negative cases (the mean age of livin positive cases was 6.2±3 years while the mean age of livin negative cases was 12.3±1.4 years). Mean livin expression level was significantly higher in age group < 10 than in age group group ≥ 10 years (294.53± 154.03 in age group <10 years versus 31 ±12.37 in age group ≥ 10). In livin negative group there were 3 patients with leucocytic count> 50.000/mm3 at diagnosis while 5 patients with leucocytic count ≤ 50.000/mm3 or more at diagnosis compared to 14 and 3 patients among livin positive group respectively (p=0.025). Regarding age, sex, WBCs, and risk stratification, there were statistically significant differences between the livin negative and positive groups.Conclusion: It could be concluded that livin was associated with favorable prognostic factors among ALL patients: (age<10 years, female patients, WBCs <50,000/mm3)

Frequency of neurological manifestations in β-thalassaemic patients in Zagazig University Hospitals

Background: Beta thalassemia syndrome is a hereditary disorder characterized by reduced or absent synthesis of thebeta chains of hemoglobin that disturbs the normal shape of red blood cells. Chronic hypoxia of the nerves resulting from severe anemia may contribute to the pathogenesis of the peripheral neuropathy in patients with β-thalassemia. The aim of this study was to find out the frequency of neurological manifestations in β- thalassemia patients and to determine the contributing factors that lead to these manifestations.Patients and Methods: This study was prospective cross sectional study conducted during the period from June 2019 to December 2020. This study was carried out on 120 thalassemia patients (67 males and 53 females), with ages ranged from 11 to 22 years old with a mean age of 16.45+3.31 years.Results: About 31.7% of the studied cases had neurological manifestations. Tingling and numbness were the main neurological symptoms among cases (24.1% and 23.3% respectively) followed by headache (21.7%), joint and muscle pain (20.8%) and tremors in hands (3.3%). Hypotonia was found in 25 cases (20.8%). Grade 4 muscle power was reported in 13 cases (10.8%) and normal (grade 5) muscle power was reported in 107 cases (89.1%). Deep tendon reflexes were normal in (89.2%) cases, while (10.8%) cases had brisk deep tendon reflexes.Conclusion: Frequency of neurological manifestations in beta thalassemia patients was 31.7%. About 26.3% of them had abnormal nerve conduction study (NCS). Age >16 years old, short stature, prolonged duration of the disease, transfusion frequency >10 times/year, delayed puberty and jaundice were risk factors for neurological manifestations in our studied cases

Reduction of Hepato-Metabolic Changes in Rat Model of Metabolic Syndrome by Metformin and Atorvastatin Combination: submitted: Apr 18, 2018 Accepted: Jun 29, 2018 Published online: Aug 30, 2018

Metabolic syndrome (MetS) and the commonly associated nonalcoholic fatty liver disease (NAFLD) is an increasing health concern and hot topic in medical research. Together with lifestyle modification, metformin (MET) and statins are among drugs with potential therapeutic beneft. The aim of this study is to investigate the potential of synergistic combination of MET and atorvastatin (ATR) in rat model of MetS. Methods. Rats were fed on high-carbohydrate, highfat (HCHF) diet for 16 weeks and either of MET, ATR, or their combination were administered from the beginning of the 9th week to the end of the study. Body weight, insulin resistance, plasma lipids, serum transaminases, TNF-α, leptin and adiponectin as well as liver histopathology were assessed. Results. Both MET and ATR worked synergistically to reverse the biochemical and histological abnormalities of MetS and ameliorated steatohepatitis more than their individual effects. Conclusion. The present study clearly demonstrates a synergistic effect of MET an ATR combination to reverse hepato-metabolic abnormalities of MetS/NAFLD in rat model and calls for pursuing subsequent clinical studies to consolidate data at han

Target Therapy in Neuroblastoma

Neuroblastoma is an embryonal malignancy that originates in the sympathetic nervous system. It is the most common solid tumor in infants and the most frequent extracranial solid tumor in children. Neuroblastoma accounts for 10% of childhood malignancies with 75% occurring in children <4 years. Stage, age, clinical and tumor genomic features are the principal criteria for determining treatment policy. Treatment modalities traditionally employed in the management of neuroblastoma are surgery, chemotherapy, and radiotherapy. Intensive multimodal treatment in patients with neuroblastoma has resulted in improved survival rates. However, there is a considerable percentage of patients with refractory and relapsed disease. Targeted therapy for neuroblastoma involves treatment aimed at molecular targets that have a unique expression in this childhood cancer. A large number of molecular targets have been identified for the treatment of high-risk and relapsed neuroblastoma. Treatment in this way aims at providing a more selective way to treat the disease and decreasing toxicities associated with the conventional treatment regimen

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Atrial ejection force and brain natriuretic peptide as markers for mortality in sepsis

Background: In early stages of septic shock, impaired myocardial function plays an important prognostic role. AEF and Plasma BNP level may be a valuable prognostic factor for patients with sepsis. Objective: We aimed also to evaluate the value of atrial ejection force (AEF) B-type natriuretic peptide (BNP) in predicting the outcome of sepsis, severe sepsis and septic shock patients. Methods: 40 patients presenting with sepsis, severe sepsis or septic were included in the study. The patients had undergone transthoracic Echocardiographic examinations and BNP measurements on the 1st and 3rd day of admission. The patients were retrospectively divided into survivors and non survivors. Results: There was a significant statistical difference in BNP level (P = 0.0001) between the two groups. BNP showed a statistically significant rise in the non survival group from day 1 to day 3 (p = 0.002) and a statistically significant decrease from day 1 to day 3 in the survived group (p = 0.001). As regards the echo findings there was a statistically significant difference AEF 3rd day between survivors and non survivors (P = 0.0001). The ROC curve showed that BNP 1st day, 3rd day are good tests for prediction of mortality in patients with sepsis. Conclusion: Atrial ejection force on the first day of admission, unlike BNP level, might not be used as an independent predictor of mortality in patients with sepsis. BNP level correlates with the severity of sepsis. According to our study, AEF in the third day may be a good predictor for survival of patients presenting with sepsis

Adsorption behavior of some metal ions on nanoparticles used in pharmaceutical matrices: Application to laboratory made drug formulation

The adsorption behavior of some metal ions (Pb, Mn, Mg, Zn and Ca) was studied on silicon dioxide nanoparticles, SiO2 NP, alone and its mixture with microcrystalline cellulose, MCC, powder (1:1) as drug carriers in pharmaceutical preparations. The effect of different conditions as temperature and pH on adsorption was investigated. It was found that upon increasing the temperature, the ability of the adsorbent material increases. The pH of the metal solution has the same effect as temperature till pH 8. However, above pH 8 the adsorbent material began to lose its adsorption efficiency. Although, the use of SiO2 NP mixture with MCC powder can improve the excipient functionality, it is important to take into consideration their metal adsorption behavior. The study was applied on laboratory made drug formulation contains different drug carriers. The study points at the importance of adjusting the permissible level of metals in different active and inactive ingredients used in pharmaceutical preparations containing nanoparticles as drug carriers. The type of nanoparticles used and the pH of these preparations are important factors affecting the metal adsorption behavior. At the maximum temperature of adsorption, the calculated metal adsorption capacity of a mixture of MCC and SiO2 NP (1:1) compared to SiO2 NP alone was found to be 0.2043 and 0.1169 for Pb, 0.1948 and 0.1041 for Zn, 0.2114 and 0.1207 for Mg, 0.2220 and 0.1222 for Ca and 0.2068 and 0.1054 for Mn, respectively. Flame atomic spectrometry was used for determining metal remained concentration after adsorption