ARID5B rs10821936 and rs10994982 gene polymorphisms and acute lymphoblastic leukemia: relation to disease susceptibility and outcome.

ARID5B rs10821936 and rs10994982 single nucleotide polymorphism (SNP) have been associated with the risk of acute lymphoblastic leukemia (ALL) in different ethnic populations. We investigated the association between the ARID5B rs10821936 C > T, rs10994982 A > G, and susceptibility to ALL in a cohort of Egyptian individuals and investigated their role in relation to disease outcome. Real-time PCR typing was done for ARID5B rs10821936 and rs10994982 SNPs for 128 pediatric ALL (pALL), 45 adult ALL (aALL), and 436 healthy controls. Significant risk associations were found between the C allele (p < 0.001, OR = 2.02), CC genotype (p < 0.001, OR = 2.72), CT genotype (p = 0.011, OR = 1.45) of ARID5B rs10821936 and pediatric ALL especially T-ALL and adult ALL (p < 0.05). The CA haplotype (C allele of rs10821936 + A allele of rs10994982) was associated with the risk of ALL either pediatric ALL or adult ALL (p < 0.001). In the studied Egyptian population, it can be concluded that the C allele, CC, and CT genotypes of ARID5B rs10821936 and the CA haplotype may be a susceptibility risk factor for pediatric and adult ALL. However, the SNPs of ARID5B rs10821936 and rs10994982 were not found to be strongly associated with ALL outcomes.

Apparent diffusion coefficient value of hepatic fibrosis and inflammation in children with chronic hepatitis.

PURPOSE: This study was done to prospectively evaluate the usefulness of apparent diffusion coefficient (ADC) in the diagnosis and grading of hepatic fibrosis and inflammation in children with chronic hepatitis. MATERIALS AND METHODS: Institutional Review Board approval was obtained. This prospective study was carried out on 50 children with chronic hepatitis (mean age 8.3 ± 3.2 years; 33 boys and 17 girls) and 20 age- and sex-matched healthy control children. The children underwent diffusion-weighted magnetic resonance imaging of the liver. The ADC value of the liver was calculated. The hepatic fibrosis stages (F1-F6) and necroinflammatory activity grades (A1-A4) were calculated. The ADC values of different stages of hepatic fibrosis and grades of necroinflammatory activity were calculated. RESULTS: The mean ADC value of the liver parenchyma was 1.53 ± 0.17 × 10(-3) mm(2)/s in children with chronic hepatitis and 1.74 ± 0.16 × 10(-3) mm(2)/s in controls. The ADC value was significantly lower in children with hepatic fibrosis compared to controls (p = 0.001). There was a significant difference (p = 0.001) in ADC between mild (F1-F3) and advanced (F4-F6) stages of fibrosis. There was a significant difference (p = 0.004) in ADC between mild (A1-A2) and advanced (A3-A4) grades of necroinflammation. The cut-off ADC values used to differentiate mild from advanced fibrosis and necroinflammation were 1.62 and 1.64 mm(2)/s with an area under the curve of 0.898 and 0.807, respectively. The ADC value negatively correlated with stages of hepatic fibrosis (r = -0.799, p = 0.001) and necroinflammatory activity grade (r = -0.468, p = 0.001). CONCLUSIONS: We conclude that ADC value is an effective noninvasive parameter for the diagnosis and grading of hepatic fibrosis and inflammation in children with chronic hepatitis.

Tranexamic acid loaded in a physically crosslinked trilaminate dressing for local hemorrhage control: Preparation, characterization, and in-vivo assessment using two different animal models.

This work aimed at formulating a trilaminate dressing loaded with tranexamic acid. It consisted of a layer of 3 % sodium hyaluronate to initiate hemostasis. It was followed by a mixed porous layer of 5 % polyvinyl alcohol and 2 % kappa-carrageenan. This layer acted as a drug reservoir that controlled its release. The third layer was 5 % ethyl cellulose backing layer for unidirectional release of tranexamic acid towards the wound. The 3 layers were physically crosslinked by hydrogen bonding as confirmed by Infrared spectroscopy. Swelling and release studies were performed, and results proposed that increasing number of layers decreased swelling properties and sustained release of tranexamic acid for 8 h. In vitro blood coagulation study was performed using human blood and showed that the dressing significantly decreased coagulation time by 70.5 % compared to the negative control. In vivo hemostatic activity was evaluated using tail amputation model in Wistar rats. Statistical analysis showed the dressing could stop bleeding in a punctured artery of the rat tail faster than the negative control by 59 %. Cranial bone defect model in New Zealand rabbits was performed to check for bone hemostasis and showed significant decrease in the hemostatic time by 80 % compared to the control.

Effect of different timings of umbilical cord clamping on the level of CD34+ cells in full-term neonates.

Despite the fact that delayed cord clamping (DCC) is recommended by many international organizations, early cord clamping is still widely practiced worldwide. The overarching goal of the DCC practice is to maximize neonatal benefits as achieving higher hemoglobin levels and decreasing the incidence of anemia as well as avoiding the adverse consequences. The current study was conducted to identify the effect of of DCC on the number of CD34+ stem cells in cord blood of full term neonates after two different timings (30 and 60 s after birth). One hundred and three full-term (FT) newborn babies (gestational age 37-40 weeks) delivered by elective cesarean section were randomly assigned into 2 groups: Group 1: babies were subjected to DCC 30 s after birth (50 newborns). Group 2: babies were subjected to DCC 60 s after birth (53 newborns). Neonates in group 2 had significantly higher levels of hemoglobin, hematocrit, total nucleated cells and CD34+ cells compared to those in group 1. The practice of DCC 60 s after birth achieved better CD34+ stem cells transfer in FT neonates than clamping the cord after 30 s.

Flexible Intramedullary Nail Versus Submuscular Locked Plate with the Cluster Technique in Pediatric Femoral Shaft Fractures Fixation.

Purpose of the Study: The aim of this study is the comparison between the flexible intramedullary nail and submuscular Locked Plate with the cluster technique in fixation of pediatric femoral shaft fractures at the age group between 6 and 12 years old with simple diaphyseal closed or Gustilo open grade I fractures. Methods: Fifty children aged 6-12 years with femoral fractures were enrolled in this study. The children were randomly assigned equally to the two groups for fractures fixation. The follow-up period was 1 year. A comparison of various parameters and outcomes between both groups was documented. Results: No significant differences were detected between both groups regarding the age, gender, affected side, mechanisms of fracture, or fracture classifications. The operative time and radiation time were longer in the plating group, while the amount of blood loss was lesser in the nail group. The patients treated with plating had better results concerning knee range of motion, weight-bearing, malalignment, and length discrepancy, with fewer complications and better functional outcomes. Conclusion: The result of the present study supports the use of submuscular locked plate with cluster technique in the treatment of studied fractures over flexible IMN.

A Novel Cost-Effective Simulation Model for Continuous Curvilinear Capsulorhexis.

Introduction: We describe and validate a low-cost simulation model for practicing anterior lens capsule continuous curvilinear capsulorhexis (CCC). Methods: A simulation model for CCC was developed from widely available low-cost materials. Ophthalmologists attending the annual scientific meeting of the Research Institute of Ophthalmology, Giza, Egypt, were asked to perform a five CCC model task and then anonymously answer a questionnaire that assessed the realism and training utility of the model using a five-point Likert scale (1 = unacceptable, 2 = poor, 3 = acceptable, 4 = favorable and 5 = excellent). Results: Twenty-seven ophthalmologists completed the task and the anonymous questionnaire. Overall, participants felt that the model simulated CCC step in cataract surgery well (mean: 3.5) and was comparable to other kinds of CCC simulation models (mean: 3.3). The model scored highly for its overall educational value (mean: 4.00) and for enlarging a small CCC (mean:3.7), while the feasibility of this model in practicing the management of a runaway leading edge of CCC scored 2.9. Conclusion: This model may provide an alternative method for training for CCC and other anterior lens capsule-related maneuvers. This option may be particularly helpful for residency training programs with limited access to virtual reality simulators or commercially available synthetic eye models.

Effect of the COVID-19 Pandemic on the Rate of Interventional Pain Management Therapies. Could the Application of Personal Protective Equipment Help?

BACKGROUND: Chronic pain symptoms are distressing conditions that necessitate regular visits to  pain therapists and may require interventions, however, the COVID-19 pandemic has caused patients and their therapists to limit both visits and interventions with the transition to telehealth, with little or no preparation or training. This has resulted in the extensive use of over-the counter analgesia and corticosteroids. OBJECTIVES: Our study aimed to evaluate the effect of the COVID-19 pandemic on the rates of counseling and interventional pain management therapies (IPMT), and determine the effects of implementing an infection control program (ICP) and mandating personal protective equipment (PPE) on these rates. STUDY DESIGN: Prospective multicenter survey, based on an online self-assessed questionnaire. SETTING: Departments of Anesthesia, Pain, Intensive Care Unit, Physical Medicine, Rheumatology, and  Rehabilitation at Egyptian University hospitals. METHODS: A self-assessed questionnaire was uploaded on Google forms and links were sent to enrolled therapists with an identification number to allow self-administration and privacy. Feedback was analyzed by 2 authors who were blinded to the identity of the responders. RESULTS: A total of 57.9% of responders increased their patients' contact by phone and video conference. Within 1-4 months after the outbreak began, 59% stopped in-person contact and 38.2% stopped their IPM practice. Prescriptions of analgesics and oral steroids increased by about 50%. The majority of responders complained of a shortage of ventilation appliances in their workplaces. About 50% of them always use ICP, 85% use surgical masks, 61% use gloves, and 45% wear gowns when meeting with patients. After the application of PPE, 45.5% of responders increased their consultation rate and 40% increased their rate of IPMT. LIMITATIONS: This study is limited to being a national study, and so lacked comparative data. CONCLUSION: The COVID-19 outbreak seriously affected the rates of in-person consultations and IPMT for patients with chronic pain and increased the rates of consumption of analgesia and oral steroids. Most responders reported a shortage of PPE especially ventilation appliances in workplaces. A high percentage of responders lack interest in ICP and PPE, despite the positive effects of its application on consultation and IPMT rates.

The role of complement in neurodevelopmental impairment following neonatal hypoxic-ischemic encephalopathy.

Evidence has accumulated implicating complement activation in the pathogenesis of acute post-hypoxic-ischemic cerebral injury in infants who develop hypoxic-ischemic encephalopathy (HIE). However, the relationship between complement activation and subsequent neurological impairment is not known. We tested the hypothesis that in human neonates, post-hypoxic-ischemic complement activation within the central nervous system is positively associated with the acquisition of subsequent neurodevelopmental abnormalities. This prospective study included 18 full-term infants diagnosed with HIE following resuscitation at birth and seven control infants. Cerebrospinal fluid (CSF) samples were obtained from all infants in the first 24 hours of life as part of routine investigations to exclude sepsis and meningitis. Concentrations of terminal complement complexes (TCC), complement component 9 (C9), and albumin were quantified by enzyme-linked immunosorbent assay in all CSF samples. Neurological examination and Denver Developmental Screening Test II were performed at 6 and 12 months of life. Of the 18 HIE subjects, nine died, six survived with significant neurological impairment, and three had normal neurological outcomes. In the CSF of the 15 HIE infants who died or survived with abnormal outcomes, the mean concentration of TCC was increased compared with controls (p = 0.026) and the mean C9 concentration appeared to be decreased but the difference was not statistically significant (p = 0.056). Similar to the TCC concentration, the concentration of albumin in the CSF was significantly increased in infants with abnormal outcomes (p = 0.005). This study indicates that complement activation following resuscitation at birth, as manifested by increased TCC in the CNS, is positively correlated with the combination of the development of subsequent neurological sequelae and death. Further study incorporating larger sample sizes will be required to confirm this association. This step is essential before clinical trials of complement inhibitors can be justified in human neonates who suffer birth asphyxia.

IL-1beta, IL-6 and TNF-alpha and outcomes of neonatal hypoxic ischemic encephalopathy.

The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates is not fully defined. We hypothesize that interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) correlate with the severity of brain injury and can predict neurological deficits in infants who suffered from hypoxic ischemic encephalopathy (HIE). A prospective study was conducted on 24 term infants diagnosed with HIE and 13 controls. HIE was clinically classified into mild, moderate and severe according to Sarnat and Sarnat grading. Blood and CSF samples were obtained from all infants in the first 24h of life as part of routine investigations for suspected meningitis and/or sepsis. Neurological examination and Denver Developmental Screening Test II (DDST II) were performed at 6 and 12 months of life. IL-1beta, IL-6 and TNF-alpha were all significantly increased in HIE infants when compared to control. IL-1beta in the CSF correlated with the severity of HIE (r=0.61, P=0.001) more than IL-6 (r=0.45, P=0.004) or TNF-alpha (r=0.47, P=0.003). IL-1beta exhibited the highest CSF/serum ratio among the three studied cytokines suggesting its local release in the brain after the initial hypoxic injury. Abnormal neurological findings and/or abnormal DDST II at 6 and 12 months were best predicted by IL-1beta in the CSF (sensitivity=88% and specificity=80%). This study confirms the role of IL-1beta in the ongoing neuronal injury that occurs in the latent phase following the original HIE insult.

Excitatory amino acids and magnesium sulfate in neonatal asphyxia.

OBJECTIVE: The excitatory amino acids (EAA); glutamate and aspartate are released into the cerebrospinal fluids (CSF) of asphyxiated newborns. The objectives of this study were: (a) to examine the relation of the concentration of EAA in the CSF with the degree of brain injury, (b) To determine the time of the release of these EAA into the CSF, and (c) to detect the effect of magnesium sulfate (MgSO(4)) on their levels. DESIGNS AND METHODS. A randomized controlled trial was conducted on 47 full term asphyxiated newborns. Twenty three infants received an intravenous 10% solution of MgSO(4) at a dose of 250 mg/kg within the first 24h of life while the other 24 newborns received isotonic saline (0.9%) of an equal volume. Levels of glutamate and aspartate were measured before and 72 h after giving the trial solution. Results. In the study population (n=47) both glutamate and aspartate were significantly elevated in infants with higher grades of HIE compared to those with lower grades (P=0.013 and 0.031, respectively). Compared to baseline level, glutamate decreased significantly over time in placebo group (-8.28+/-14.26, P=0.025) and in MgSO(4) group (-14.39+/-18.72, P=0.005). Glutamate concentration did not differ between groups when measured at baseline (29.26+/-16.31 vs. 31.27+/-22.62, P=0.82) and at 72 h (19.28+/-15.63 vs. 19.6+/-16.54, P=0.87). The change in aspartate concentration over time was not significant in placebo group (-0.45+/-1.96, P=0.34) or in MgSO(4) group (-0.7+/-3.19, P=0.37). Aspartate did not differ between groups when measured at baseline (3.52+/-2.4 vs. 3.92+/-2.59, P=0.49) or at 72 h (2.79+/-1.24 vs. 3.05+/-2.48, P=0.92). Conclusions. The EAA; glutamate and aspartate are released in the CSF of asphyxiated newborns immediately after birth and declined by 72 h. Their initial concentrations correlated with the severity of HIE. Postnatal administration of MgSO(4) did not alter the levels of these 2 EAA.

Complement component 9 activation, consumption, and neuronal deposition in the post-hypoxic-ischemic central nervous system of human newborn infants.

The role of complement in neonatal hypoxic-ischemic brain injury is not known. Therefore, cerebral spinal fluid (CSF) and post-mortem cerebral tissue were analyzed to determine whether complement is activated and complement component 9 (C9) is deposited on neurons in the central nervous systems (CNS) of newborn infants who developed moderate to severe hypoxic-ischemic encephalopathy (HIE). Control CSF samples were obtained during routine evaluation for possible sepsis from infants who were not depressed at birth. In ELISA assays of CSF obtained from 16 infants with HIE, compared to CSF from 7 control infants, the mean concentration of terminal complement complexes was elevated and the mean C9 concentration was diminished. Immunofluorescence microscopy of post-mortem frozen brain tissue obtained from two infants who expired at 4-5 days of life after severe HIE revealed that activated C9 was deposited on cells in all lobes. Double label immunofluorescence microscopy demonstrated that nearly all of the C9-positive cells were neurons and essentially all of the neurons were C9-positive. Immunoperoxidase immunohistochemistry of formalin-fixed tissue also confirmed the presence of many C9-positive cells, particularly in the hippocampus. The C9-positive cells usually manifested morphology consistent with neurons, most of which contained fragmented nuclei. In summary, complement was activated in the CNS of newborn infants who developed moderate to severe HIE. C9 was deposited on neurons, including morphologically apoptotic neurons. Further investigations into a possible role of complement in the pathogenesis of neonatal hypoxic-ischemic cerebral injury are warranted.

Glucosidase acid beta gene mutations in Egyptian children with Gaucher disease and relation to disease phenotypes.

INTRODUCTION: More than 200 mutations have been found in patients with Gaucher disease (GD) and some mutations usually have a high frequency in certain populations. Genotype/phenotype correlation in patients with GD has not been established. This study was designed to determine underlying mutations in Egyptian children with GD and to assess their relation to disease phenotypes. METHODS: This study comprised 17 patients with GD and 10 healthy controls. Thirteen patients were type 1 GD, 2 type 2, and 2 type 3. DNA was extracted from peripheral blood leukocytes. Exons 9 and 10 were amplified by polymerase chain reaction, and deoxyribonucleic acid sequencing was done with an ABI 310 genetic analyzer. RESULTS: Wild type allele was detected in 95% (19/20) and a normal variant in 5% (1/20) of controls. L444P allele was encountered in 50% (13/26) of the alleles in type 1 patients, H451P in 7.7% (2/26) and recombinant alleles (RecNcil, RecNcil + M450L, RecFs, RecFs + M450L) in 34.6% (9/26). L444P and Rec alleles each occurred in 50% (2/4) of type 2 and 3 patients. A new mutation was seen in this study {g.7336A>C, (M450L)} and 2 mutant alleles were not determined. Type 1 GD patients had L444P/L444P genotype (23.1%) and Rec alleles/L444P (53.8%), while type 2 and 3 GD patients had Rec alleles/L444P genotypes (100%) with a poor phenotype/genotype correlation. CONCLUSIONS: L444P and Rec alleles are common in the studied patients. Novel mutations are continuously detected, adding to the expanding panel of GD mutations. No significant genotype-phenotype association was observed.