Dysregulated Apoptosis and Autophagy in Childhood Epilepsy: Correlation to Clinical and Pharmacological Patterns.

OBJECTIVES: We aimed to assess the serum levels of caspase-3 as a marker of apoptosis and microtubule-associated protein 1A/1B-light chain 3 (MAP1-LC3) as an autophagy marker in epileptic children with various clinical and pharmacological types. METHODS: This case-control study was carried out on 90 participants (50 pediatric patients with epilepsy and 40 healthy matched children), the patients were categorized into three groups: Group (A): 25 pharmacosensitive epilepsy, Group (B): 25 pharmacoresistant epilepsy, and Group (C): 40 (age, sex, and body mass index) matched healthy children selected as controls. Serum caspase-3 and MAP1-LC3 were measured in all study groups, using commercially available ELISA kits. RESULTS: Serum caspase-3 was significantly higher among epileptic children, especially in the pharmacoresistant group, cases managed with multiple antiepileptic drugs, and cases with abnormal EEG findings. Conversely, circulating MAP1-LC3 levels showed a significant reduction in epilepsy cases, particularly in pharmacoresistant cases, in cases treated with multiple antiepileptic drugs, and in cases with abnormal EEG data. A significant negative correlation between serum caspase-3 and MAP1-LC3 was found among epileptic children (r = -0.369, p = 0.0083). Serum caspase-3 was a more valid biomarker in helping diagnose childhood epilepsy, while serum MAP1-LC3 was more valid in predicting pharmacoresistant type. CONCLUSION: The study reveals that serum caspase-3 levels were significantly elevated, particularly in pharmacoresistant cases and those managed with multiple drugs. Conversely, MAP1-LC3 levels were significantly reduced in epilepsy cases, suggesting potential involvement of altered apoptosis and autophagy in childhood epilepsy.

Validity of Serum Zinc/Copper Ratio as a Potential Novel Biomarker in Childhood Epilepsy.

BACKGROUND: Alterations in zinc and copper homeostasis may contribute to seizure susceptibility, development, termination, and response to antiepileptic medications. The current study examined the profile of zinc, copper, and their ratio in childhood epilepsy and its pharmacological variants (pharmacoresistant and pharmacoresponsive). METHODS: The study included 100 epileptic children (50 pharmacoresistant and 50 pharmacoresponsive) and 50 healthy, age- and gender-matched controls. History, clinical examination, and assays of serum zinc and copper were performed. Zinc/copper ratio was calculated. RESULTS: Serum zinc and the zinc/copper ratio were significantly lower in epileptic children than in controls (p < 0.001). Significantly lower zinc and zinc/copper ratio and higher copper levels were found in children treated with levetiracetam/sodium valproate/oxcarbazepine than those treated with levetiracetam alone or combined with sodium valproate (p < 0.05 for all). Epileptic children, particularly pharmacoresistant, exhibited significant negative correlations between the serum levels of zinc and copper (r = -0.279, p = 0.005, and r = -0.363 and p = 0.010, respectively). At cutoff value of zinc/copper ratio < 1.118 in diagnosing children with epilepsy, it gives a sensitivity of 64% and a specificity of 85% with the AUC = 0.8092. At cutoff value of zinc/copper ratio ≤ 0.7826 in distinguishing pharmacoresistant epilepsy, it produced 52% sensitivity, 64% specificity with AUC = 0.576 Conclusions: Low zinc and high copper levels were associated with childhood epilepsy especially those with pharmacoresistant type and treated with Oxcarbazepine. Zinc/copper ratio might be a potential biomarker in diagnosing childhood epilepsy and to some extent in predicting pharmacoresistant type.

Profile of plasma free amino acids, carnitine and acylcarnitines, and JAK2v617f mutation as potential metabolic markers in children with type 1 diabetic nephropathy.

Fifty diabetic nephropathy (DN) children with type 1 diabetes mellitus (T1DM) and 50 healthy matched controls were included. Chromatographic assays of 14 amino acids, free carnitine and 27 carnitine esters using high-performance liquid chromatography/electrospray ionization-mass spectroscopy, and genetic testing for JAK2v617f mutation using real-time PCR were performed. Patients had significantly lower levels of tyrosine, branched-chain amino acids (BCAAs), and BCAA/AAA (aromatic chain amino acids) ratios, glycine, arginine, ornithine, free carnitine and some carnitine esters (C5, 6, 12 and 16) and higher phenylalanine, phenylalanine/tyrosine ratio and C18 compared with the controls and in the macro-albuminuria vs. the microalbuminuria group (p < 0.05 for all) except for free carnitine. Plasma carnitine was negatively correlated with eGFR (r = -0.488, p = 0.000). There were significant positive correlations between tyrosine with UACR ratio (r = 0.296, p = 0.037). The plasma BCAA/AAA ratio showed significant negative correlations with UACR (r = -0.484, p = 0.000). There was a significantly higher frequency of the JAK2V617F gene mutation in diabetic nephropathy patients compared with the control group and in macro-albuminuria than the microalbuminuria group (p = 0.000) for both. When monitoring children with T1DM, plasma free amino acids and acylcarnitine profiles should be considered, especially if they have tested positive for JAK2V617F for the early diagnosis of DN.

Metabolic Analysis of Methylenetetrahydrofolate Reductase Single Nucleotide Polymorphisms (MTHFR 677C

Neural tube defects (NTDs) are among the most prevalent and debilitating birth defects with their causes are still unknown, despite mounting evidence that genetic and/or environmental factors may play a role. We aimed to analyze two single nucleotide polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene, serum folate and vitamin B12 status among a cohort of Egyptian children with NTDs and their mothers. A case-control study has been conducted on 50 Egyptian children with various types of NTDs and their mothers. They were comparable with 50 unrelated healthy, age and sex matched children and their mothers (50) selected as controls. Pediatric and neurosurgical assessments were performed to the included cases. Serum folate and vitamin B12 were measured using ELISA kits. MTHFR 677C

Validity of B-Type Natriuretic Peptide, Growth Differentiation Factor 15, and High-Sensitivity Troponin I Levels in Ischemic Heart Failure.

BACKGROUND: Heart failure (HF) is a major medical, and epidemiological problems with ischemic heart disease (IHD) is the most common cause of HF. We aimed to assess the plasma B-type natriuretic peptide (BNP) levels, serum growth differentiation factor 15 (GDF15), and high-sensitivity troponin I (hsTnI) in HF patients with and without IHD. METHODS: The study included 120 HF patients, categorized into 51 patients with IHD and 69 patients without apparent IHD. Clinical and echocardiographic assessments of the included patients were performed. ELISA assays of plasma BNP and serum GDF15 were done, while serum hsTnI was measured using chemiluminescent immunoassay. RESULTS: There were significantly higher median values of serum levels for GDF15 (pg/mL) and hsTnI (pg/mL) among IHD group (1,630.5 and 141.8, respectively) compared to non-IHD group (895 and 14.3, respectively, p ˂ 0.05 for both), with non-significant differences regarding to the BNP plasma levels (p ˃ 0.05). In the IHD group, significant positive correlations were observed between GDF15 with both BNP (r = 0.655, p = < 0.001) and hsTnI (r = 0.496, p = < 0.001). Serum GDF15 at a cutoff of ≤ 717 pg/mL has the highest specificity [85.51% vs. 50.72% for BNP (at cutoff > 264 pg/mL) and 59.42% for hsTnI]. Additionally, hsTnI at a cutoff of > 45.2 pg/mL has the highest sensitivity (70.59% vs. 68.63% for BNP and 33.33% for GDF15) in discriminating heart failure with IHD from heart failure without IHD. CONCLUSIONS: A multimarker approach, particularly GDF15 and hsTnI, is helpful in identifying HF patients with underlying IHD, thus enabling their proper management.

Vitamin D Receptor Gene Polymorphisms and Risk of Knee Osteoarthritis: Possible Correlations with TNF-α, Macrophage Migration Inhibitory Factor, and 25-Hydroxycholecalciferol Status.

Osteoarthritis (OA) etiology and pathogenesis not yet fully understood. We studied the role of vitamin D receptor single-nucleotide polymorphisms (VDR-SNPs), vitamin D3, serum and synovial macrophage migration inhibitory factor (MIF), and tumor necrosis factor-α (TNF-α) in the development and progression of knee OA (KOA). This study included 205 Egyptian subjects (105 patients with KOA and 100 unrelated, healthy matched subjects selected as controls). The patient group was divided into three groups according to KOA severity (mild, moderate, and severe), with 35 patients in each group. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for the ApaI and TaqI SNPs. Vitamin D, serum and synovial TNF-α, and MIF assays were performed using ELISA kits. There were significantly lower serum levels of 25-hydroxycholecalciferol with significant increasing TNF-α and MIF levels in relation to disease severity among the cases (all: p˂0.05).Wild homozygous and heterozygous mutant genotypes (GG+GT) and G allele of ApaI demonstrated risk for KOA development, with odds ratio OR = 6.313 (95% confidence interval (CI) 2.074-19.210) and OR = 1.532 (95%CI 1.013-2.317), respectively. Homozygous mutant CC genotype and C allele of TaqI could be considered a risk factor associated with KOA development, with OR = 2.667 (95%CI 1.270-5.601) and OR = 0.737 (95%CI 0.496-1.095), respectively. VDR-SNPs, vitamin D3, TNF-α, and MIF could play an essential role in the pathogenesis and progression of KOA with mechanistic associations.

Clinico-Radiological Correlation in 26 Egyptian Children with Glutaric Acidemia Type 1.

BACKGROUND: Glutaric acidemia type 1 (GA1) is an inherited neurometabolic disease with significant morbidity. However, neuro-radiological correlation is not completely understood. OBJECTIVE: The study aimed to characterize the neuroimaging findings and their association with neurological phenotype in GA1 children. METHODS: Twenty-six Egyptian children (median age = 12 months) diagnosed with GA1 underwent clinical evaluation and brain magnetic resonance imaging (MRI). We objectively assessed the severity of neurological phenotype at the time of MRI using movement disorder (MD) and morbidity scores. Evaluation of brain MRI abnormalities followed a systematic and region-specific scoring approach. Brain MRI findings and scores were correlated with MD and morbidity scores, disease onset, and presence of seizures. RESULTS: Fifteen (57.7%) cases had insidious onset, eight (30.8%) manifested acute onset, whereas three (11.5%) were asymptomatic. Ten (38.5%) cases had seizures, five of which had no acute encephalopathic crisis. Putamen and caudate abnormalities (found in all acute onset, 93.3 and 73.3% of insidious onset, and one of three asymptomatic cases) were significantly related to MD (p = 0.007 and 0.013) and morbidity (p = 0.005 and 0.003) scores. Globus pallidus abnormalities (50% of acute onset, 46.7% of insidious onset, and one of three of asymptomatic cases) were significantly associated with morbidity score (p = 0.023). Other MRI brain abnormalities as well as gray and white matter score showed no significant association with neurological phenotype. Younger age at onset, acute onset, and seizures were significantly associated with worse neurological manifestations. CONCLUSION: Patients with GA1 manifest characteristic and region-specific brain MRI abnormalities, but only striatal affection appears to correlate with neurological phenotype.

25-Hydroxy cholecalciferol, anti-Müllerian hormone, and thyroid profiles among infertile men.

BACKGROUND AND AIM: We examined the relationship among vit.D3, AMH, FT3, FT4, and TSH, in addition to the serum levels of reproductive hormones (FSH, LH, prolactin, and free testosterone), in oligoasthenoteratozoospermia and azoospermia patients in a cohort of infertile men from Egypt to establish a clinical marker/cause-effect relationship. METHODS: This cross-sectional cohort study was carried out on 301 men (105 males with oligoasthenoteratozoospermia and 96 males with azoospermia), in addition to 100 controls. Measurements of serum vit.D3, AMH, FT3, FT4, and TSH levels, in addition to reproductive hormone assays, were performed on all included subjects, using ELISA kits. RESULTS: Overall, results showed significantly lower serum levels of vit.D3 in infertile men than in the controls, with a greater decrease observed in men with azoospermia than in oligoasthenoteratozoospermia patients, (p < .05 for all). Significantly higher serum TSH and FSH levels and significantly lower serum free testosterone levels were observed in males with azoospermia than in males with oligoasthenoteratozoospermia and the controls (p < .05 for both). There were no significant differences between the studied groups in terms of AMH, FT3 or FT4 levels. LH levels were negatively correlated with TSH levels and positively correlated with AMH levels among men with oligoasthenoteratozoospermia, while among men with azoospermia, LH levels were positively correlated with vit.D3 levels (p < .05 for all). CONCLUSION: Decreased Vit.D3 could play a role in male infertility, in addition to abnormal thyroid function, which needs further investigation.

Effect of Acid Suppression on Peripheral T-Lymphocyte Subsets and Immunohistochemical Esophageal Mucosal Changes in Patients With Gastroesophageal Reflux Disease.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a common prevalent disease. We aimed to assess the dynamic changes in the peripheral T lymphocytes and lymphocytes infiltrating the esophageal mucosa after treatment with proton-pump inhibitor (PPI) in patients with GERD. PATIENTS AND METHODS: A total of 200 patients who presented with upper GIT symptoms were included in this prospective study. All patients were subjected to full history taking, clinical examination, and complete blood count. Upper endoscopy was performed to detect the grade of GERD, followed by 4 quadrant biopsies before and 1 month after acid suppressive drug therapy. Histopathologic and immunohistochemical examination were carried out for all biopsies. Flow cytometry analysis for the peripheral T lymphocytes and cytokine profile assay before therapy and after therapy were also carried out. RESULTS: In total, 200 patients comprising 132 male individuals (66%) and 68 female individuals (34%) with a mean age of 47.9±18.3 were included. The risk factors for development of GERD were smoking in 87 (43.5%), spicy food intake in 26 (13%), analgesics in 46 (23%), excessive tea and coffee in 35 (17.5%), and nondetected risk factors in 6 (3%). Endoscopic examination using Los Angeles grading system revealed that 102 patients (51%) were grade A, 57 patients (28.5%) were grade B, 38 patients (19%) were grade C, and 3 patients (1.5%) were grade D. No statistically significant differences could be detected in HGB levels and WBC, PLT, monocyte, granulocyte, and eosinophil counts before and after treatment with PPI. Histopathologic examination of esophageal biopsies showed significant posttreatment improvement in 132 cases (66%); however, 66 cases (33%) including the 2 cases (1%) of Barrett's esophagus showed nonsignificant pathologic improvement compared with the pretreatment picture. Immunohistochemical staining of esophageal biopsies with CD3 (T-cell marker) and CD20 (B-cell marker), before and 1 month after treatment, showed the presence of a very large number of infiltrating B cells in the esophageal mucosa (700±30/10 HPF) with large aggregations; in contrast, T-cell infiltration appeared less marked (570±23/10 HPF), and they formed smaller aggregates than those of B cells in pretreated patients, with P<0.01. However, 1 month after treatment with PPI, esophageal biopsies revealed a marked decrease in the number of both B (10±2/10 HPF) and T (290±12/HPF) cells in 66% of patients, with a P<0.01 in comparison with the pretherapy pattern. However, the remaining 33% of patients still showed a significantly high number of T cells (490±28/HPF), with a P <0.05 in comparison with the responder group that formed small aggregates with larger cell sizes, indicating their activation. Cytokine profiles before and after treatment revealed significant posttreatment reduction in their levels in the 132 cases with improvement in their clinical manifestations, and endoscopic and histopathologic findings, but there is no obvious change in the measured cytokine levels in 66 patients who simultaneously had no improvement in their endoscopic, histopathologic findings and mild improvement in their clinical manifestations. Moreover, significant posttreatment reduction of IL-8 and IL-1ß in the 98 (49%) patients with Los Angeles grading B, C, and D was observed. With regard to serum levels of IL-10 and IL-4, there were no statistically significant differences before and after treatment with PPI. Peripheral blood immunologic parameters revealed a statistically significant reduction of the total CD3 absolute count, T-helper lymphocyte (CD4/CD3) percentage, T-helper lymphocyte absolute count, and the percentage and absolute cytotoxic T-lymphocyte count (CD8/CD3) after treatment with PPI. Moreover, the same significant difference of peripheral blood lymphocytes was detected after exclusion of patients with Los Angeles grade A, which may be considered normal. CONCLUSIONS: Acid-induced T-cell-related cytokine production plays an important role in inflammation occurring in patients with GERD. Mucosal and peripheral inflammation reduces with PPI use.

Metabolic profile of oxidative stress and trace elements in febrile seizures among children.

Febrile seizures (FS) are frequent convulsive disorders, occurring in infants and young children. The present study aims to assess and compare the serum levels of oxidative stress markers and some essential trace minerals in FS with normal or abnormal EEG and evaluate the effect of antioxidant therapy on the clinical outcome. This study has been carried out on 80 children with FS (40 with simple FS and 40 with complex FS) and 40 febrile children without seizures. Clinical and EEG findings were recorded for the included patients. Biochemical assays of serum nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), copper (Cu), zinc (Zn) and selenium (Se), using colorimetric methods, were measured in the studied groups. The overall results showed an increased values of NO, MDA and Cu with decreased values of SOD, Zn and Se in patients with FS (simple and complex) in comparison with febrile children without seizures (p < 0.05 for all). Additionally, NO and MDA was increased in complex FS patients with EEG abnormalities in comparison with complex FS with normal EEG findings (p < 0.05); NO and MDA were also significantly decreased after valproate therapy in complex FS patients (p < 0.05 for all). In conclusions, oxidative stress, decreased Zn and Se with increased Cu may play a role in FS. Valproate improves the oxidative stress status in complex FS.

Diagnostic validity of flow cytometry vs manual counting of polymorphonuclear leukocytes in spontaneous bacterial peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is frequently occurring infection among patients with liver cirrhosis, defined by polymorphonuclear (PMN) leukocytic count ≥250 cell/mm3 with or without a positive ascitic fluid (AF) bacterial culture. So, this study aimed to investigate the diagnostic value of flow cytometry versus manual counting of ascitic fluid PMNL in cirrhotic patients, with clinical suspicion of SBP. METHODS: A hospital-based cross-sectional study was carried out on 320 cirrhotic patients with clinical suspicion of SBP. Abdominal paracentesis was performed in all cases for microscopic manual and flow cytometry counting of PMNL. Anti-HLA-DR, anti-CD15, anti-CD16, and anti-CD45 monoclonal antibodies were used for flow cytometry method. RESULTS: Flow cytometric PMNL count had 100% sensitivity and specificity, while manual PMNL count had a sensitivity of 65.52% and specificity of 90% with significant difference (P value < .05). CONCLUSION: Flow cytometry is more reliable rapid method for PMNL counting, than the manual method that is less accurate and time-consuming in diagnosing clinically suspected SBP.

Pharmacogenetic study of phosphatase and tensin homolog polymorphism (rs701848) in childhood epilepsy: relation to circulating Wnt signaling.

OBJECTIVE: The present study aimed at evaluating the potential contribution of Phosphatase and Tensin Homolog (PTEN) and its gene polymorphism (PTEN rs701848 T/C) in relation to Wingless/integrase-1 (Wnt) signaling in childhood epilepsy and the impact of antiepileptic medications on their serum levels. METHODS: This study included 100 children with epilepsy (50 pharmacoresistant and 50 pharmacoresponsive) and 50 matched controls. All subjects had their genotypes for the PTEN rs701848T/C polymorphism assessed using TaqManTM assays and real-time PCR. By using the sandwich ELISA technique, the blood concentrations of PTEN and Wnt3a were measured. RESULTS: Serum Wnt3a levels in epileptic patients were significantly higher than in the control group, p < 0.001. Children with epilepsy who received oxcarbazepine had considerably lower serum Wnt3a levels than those who didn't, p < 0.001.With an AUC of 0.71, the cutoff value for diagnosing epilepsy as serum Wnt3a > 6.2 ng/mL has a sensitivity of 55% and a specificity of 80%. When compared to controls, epileptic children had considerably more (TT) genotype and less (TC and CC) genotypes, p < 0.05 for all. Epileptic children had significantly higher (T) allele frequency than controls, p = 0.006 with OR (95%CI) = 1.962(1.206-3.192). Pharmacoresistant epileptic children had significantly higher (TT) genotype compared to pharmacoresponsive type (p = 0.020). CONCLUSION: We originally found a strong association between PTEN rs701848 T/C and childhood epilepsy, in particular pharmacoresistant type. Serum Wnt3a levels increased in epilepsy, but were not significantly different between different alleles of PTEN. In pharmaco-responsive children Wnt3a levels differed significantly between the different PTEN genotypes. Antiepileptics may affect Wnt3a levels.

Plexin B2 tissue expression and related gene polymorphisms in psoriasis and their relation to NB-UVB and Acitretin therapy.

Psoriasis is a chronic, immune-mediated, hyperproliferative skin disease. Etiopathogenesis of psoriasis is not well understood. Plexin B2 was found to have effects on CD100-mediated T-cell morphology and expressed in the immune system. It may play a role in the pathogenesis of psoriasis. To assess the tissue level of plexin-B2 and plexin B2 related gene polymorphism which is signal regulatory protein gamma (SIRPγ-rs71212732) in psoriatic patients before and after NB-UVB, acitretin therapy alone or in combination and to detect correlation between level of tissue plexin B2 and disease severity and improvement. This single blinded randomized controlled trial was carried on 50 psoriatic patients and 50 healthy controls. Psoriasis Area and Severity Index score (PASI) was used to evaluate the disease severity. Tissue plexin-b2 level was measured using ELISA and SIRPγ-rs71212732 (T\C) was assessed using TaqMan™ assays and real-time PCR. A significant lower tissue plexin-B2 level was observed in control group (2.9 ± 0.6 pg/g) than cases (25.8 ± 2.8, pg/g) (p < 0.001). Also, a significantly higher tissue plexin-B2 level was observed in sever psoriasis (32.7 ± 3.8 pg/ml) in than moderate psoriasis (13.6 ± 2.1 pg/ml, p = 0.001). Tissue plexin B2 was positively correlated with diseases severity. Significantly higher (TC& TT) genotypes and mutant (C) allele among patients compared to the controls, p < 0.001 for all. Tissue plexin-b2 level was high in psoriasis vulgaris with positive correlation with disease severity and decreased after treatment. This may indicate a role of plexin-b2 in psoriasis vulgaris pathogenesis.

The deleterious effects of sofosbuvir and ribavirin (antiviral drugs against hepatitis C virus) on different body systems in male albino rats regarding reproductive, hematological, biochemical, hepatic, and renal profiles and histopathological changes.

Sofosbuvir is one of the crucial drugs used in the treatment of chronic hepatitis C virus (HCV) in adults and children with compensated liver disease, including cirrhosis. It may be used alone or with other drugs. Ribavirin is an antiviral medication used to treat HCV infection. It is not effective when used alone and must be used in combination with other medications, such as sofosbuvir. This study pertains to a comprehensive assessment of the deleterious effects of sofosbuvir (an antiviral drug against chronic HCV) or sofosbuvir combined with ribavirin (an antiviral drug against RNA and DNA viruses) on several biological activities of the body, including hematological, hormonal, biochemical, histological, and immunohistochemical examinations during a long-standing period on male healthy rats. In addition, fertility assessments were performed, including sperm collections and semen parameter investigations. This study was conducted on 21 male rats divided into three equal groups. Group I (control group) received distilled water; group II (sofosbuvir group) received sofosbuvir (4 mg/kg); and group III (sofosbuvir + ribavirin) received sofosbuvir (4 mg/kg) plus ribavirin (30 ml/kg). All groups received the specific drug for six months. Blood and tissue samples were collected for hematological, hormonal, biochemical, histological, and immunohistochemical examinations. In addition, sperm collection and assessments of semen parameters were performed. Results revealed that sofosbuvir causes a highly significant decrease in the mean of most hematological, immunological, hormonal, and biochemical parameters, except for a few numbers of parameters such as neutrophils, monocytes, basophils, cortisol, GOT, and lipase, which exhibit a significant increase. The same occurred in the sofosbuvir + ribavirin group, but at much higher levels, as most hematological, immunological, hormonal, and biochemical parameters exhibit a highly significant decrease except for monocytes, triglyceride, and lipase, which exhibit a significant increase. When compared to the sofosbuvir group alone, the sofosbuvir + ribavirin group demonstrated a highly significant decline in the mean of most hematological, immunological, hormonal, and biochemical parameters except lymphocytes and triglycerides, which exhibit a substantial increase. For the reproductive parameters, both groups exhibit a significant decrease in the total sperm motility percentage. Finally, it can be concluded that sofosbuvir causes acute pancreatitis and combined immunodeficiency. Ribavirin is associated with hormonal deficiency, which indicates the occurrence of hypopituitarism. Moreover, sofosbuvir and ribavirin synergistically affect myelosuppression and cause iron-deficiency anemia. However, sofosbuvir, or its combination with ribavirin, is associated with a reduced risk of hepatocellular carcinoma. Besides, adding ribavirin to be combined with sofosbuvir improved the immunodeficiency caused by sofosbuvir; this confirms that using ribavirin with sofosbuvir reduces the side effects of both alone.

Clinical reappraisal of the composite international diagnostic interview version 3.3 in Qatar's National Mental Health Study.

OBJECTIVES: Lifetime DSM-5 diagnoses generated by the lay-administered Composite International Diagnostic Interview for DSM-5 (CIDI) in the World Mental Health Qatar (WMHQ) study were compared to diagnoses based on blinded clinician-administered reappraisal interviews. METHODS: Telephone follow-up interviews used the non-patient edition of the Structured Clinician Interview for DSM-5 (SCID) oversampling respondents who screened positive for five diagnoses in the CIDI: major depressive episode, mania/hypomania, panic disorder, generalized anxiety disorder, and obsessive-compulsive disorder. Concordance was also examined for a diagnoses of post-traumatic stress disorder based on a short-form versus full version of the PTSD Checklist for DSM-5 (PCL-5). RESULTS: Initial CIDI prevalence estimates differed significantly from the SCID for most diagnoses ( χ 1 2 ${\chi }_{1}^{2}$  = 6.6-31.4, p = 0.010 < 0.001), but recalibration reduced most of these differences and led to consistent increases in individual-level concordance (AU-ROC) from 0.53-0.76 to 0.67-0.81. Recalibration of the short-form PCL-5 removed an initially significant difference in PTSD prevalence with the full PCL-5 (from χ 1 2 ${\chi }_{1}^{2}$  = 610.5, p < 0.001 to χ 1 2 ${\chi }_{1}^{2}$  = 2.5, p = 0.110) while also increasing AU-ROC from 0.76 to 0.81. CONCLUSIONS: Recalibration resulted in valid diagnoses of common mental disorders in the Qatar National Mental Health Survey, but with inflated prevalence estimates for some disorders that need to be considered when interpreting results.

Serum Levels of Growth-Associated Protein-43 and Neurotrophin-3 in Childhood Epilepsy and Their Relation to Zinc Levels.

BACKGROUND: Epilepsy is one of the most common neurological disorders, and it places a significant economic strain on the healthcare system around the world. Although the exact mechanism of epilepsy has yet to be illustrated, various pathogenic cascades involving neurotransmitters and trace elements have been reported. We aimed to investigate the serum levels of growth-associated protein-43 (GAP-43) and neurotrophin-3 (NT-3) among cohort of Egyptian children with epilepsy and correlate these biomarkers with their zinc levels. METHODS: This case-control study included 50 pediatric patients with epilepsy who were comparable with 50 controls. Neurological assessment and electroencephalogram (EEG) were done to all included children. Biochemical measurements of serum GAP-43 and NT-3 using enzyme linked immunosorbent assays (ELISA), and total antioxidant capacity (TAC) and zinc using colorimetric assays, were performed to all participants. RESULTS: There was significantly frequent positive parental consanguinity among cases with significantly frequent generalized onset seizures (94%) than simple partial seizure (6%). There were significantly lower serum GAP-43 and zinc levels with significantly higher TAC among cases vs. the controls, p˂0.05 for all. There was no significant difference in the serum levels of NT-3 among epileptic children vs. the controls, p = 0.269. Serum Zn was positively correlated with GAP-43 level among epileptic children (r = 0.381, p = 0.006). Serum GAP-43 in diagnosing childhood epilepsy at cut-off point ≤ 0.6 ng/mL showed 78% sensitivity, 62% specificity, positive predictive value (PPV) = 50.6%, negative predictive value (NPP) = 84.9% with AUC = 0.574. CONCLUSION: GAP-43 can be considered a sensitive good negative biomarker in childhood epilepsy which correlated positively with the zinc status.

Impact of Myocardial Ischemia and Revascularization by Percutaneous Coronary Intervention on Circulating Level of Soluble ST2.

Background: The prognostic role of the soluble circulating suppression of tumorigenicity 2 marker (sST2) in different cardiovascular diseases (CVD) is still under investigation. This research aimed to assess the serum levels of sST2 in the blood of individuals with ischemic heart disease and its relation to disease severity, also to examine any changes in sST2 levels following a successful percutaneous coronary intervention (PCI) in those patients. Methods: A total of 33 ischemic patients and 30 non-ischemic controls were included. The plasma level of sST2 was measured using commercially available ELISA assay kit, at baseline and 24-48 h after the intervention in the ischemic group. Results: On admission, there was a significant difference between the group of acute/chronic coronary syndrome cases and controls regarding the sST2 plasma level (p < 0.001). There was an insignificant difference between the three ischemic subgroups at the baseline sST2 level (p = 0.38). The plasma sST2 level decreased significantly after PCI (from 20.70 ± 1.71 to 16.51 ± 2.43, p = 0.006). There was a modestly just significant positive correlation between the acute change in post-PCI sST2 level and the severity of ischemia as measured by the Modified Gensini Score (MGS) (r = 0.45, p = 0.05). In spite of the highly significant improvement in the coronary TIMI flow of ischemic group after PCI, there was insignificant negative correlation between the post- PCI delta change in the sST2 level and the post-PCI TIMI coronary flow grade. Conclusion: A significantly high plasma level of sST2 in patients with myocardial ischemia and controlled cardiovascular risk factors showed an immediate reduction after successful revascularization. The high baseline level of the sST2 marker and the acute post-PCI reduction was mainly related to the severity of ischemia rather than left ventricular function.

Genetic profile of MIF single nucleotide polymorphism (rs755622 G>C) in hepatocellular carcinoma among Egyptian patients.

Aim of the study: To evaluate the role of MIF gene polymorphism rs755622 G>C in occurrence and progression of hepatocellular carcinoma (HCC) among a cohort of Egyptian patients. Material and methods: This case-control study was conducted on 50 patients with HCC after chronic viral hepatitis and 50 healthy volunteers, recruited between July 2021 and January 2022. All patients with HCC were evaluated for severity of liver disease using a Child-Pugh score, and TNM and BCLC scoring systems. MIF 173 G>C (rs755622) single nucleotide polymorphism was performed for all participants by polymerase chain reaction using restriction fragment length polymorphism technique (RFLP-PCR). Results: Overall results showed significantly higher frequencies of GG (wild homozygous genotype) and mutant heterozygous genotype GC and G allele (OR = 6.303, 95% CI: 3.374-11.775) among patients with HCC compared to the control group (p = 0.001) for all. Also, significantly higher frequency of genotype GG was detected among patients with advanced Child scores (B and C) (p = 0.039) and TNM stages (III and IV) (p = 0.013). There was significantly higher frequency of the G allele among patients with multiple hepatic focal lesions compared to those with a single focal lesion (p = 0.01). Conclusions: An obvious role of MIF (rs755622) gene polymorphism could have an important role in susceptibility and progression of HCC among patients with chronic viral hepatitis induced liver cirrhosis.

Possible Role of Helicobacter pylori in Ear Nose and Throat Diseases.

Background: Helicobacter pylori is assumed to cause many gastric and extragastric diseases. We aimed to assess the possible association role of H. pylori in Otitis media with effusion (OME), nasal polyps and adenotonsillitis. Patients and Methods: A total of 186 patients with various ear, nose and throat diseases were included. The study comprised 78 children with chronic adenotonsillitis, 43 children with nasal polyps and 65 children with OME. OME patients were assigned to two subgroups: those who have and those who did not have adenoid hyperplasia. Among the patients with bilateral nasal polyps, 20 individuals had recurrent nasal polyps and 23 had de novo nasal polyps. Patients who have chronic adenotonsillitis were divided into three groups: those with chronic tonsillitis and those who underwent tonsillitis, those with chronic adenoiditis and adenoidectomy was performed, and those with chronic adenotonsillitis and underwent adenotonsillectomy. In addition to examination of H. pylori antigen in stool samples of all included patients, real-time polymerase chain reaction (RT-PCR) for detection of H. pylori in the effusion fluid was performed, additionally, Giemsa stain was used for detection of H. pylori organism within the tissue samples when available. Results: Frequency of H. pylori in effusion fluid was 28.6% in patients with OME and adenoid hyperplasia, while in those with OME it was only 17.4% with a p value of 0.2. Nasal polyp biopsies were positive in 13% patients of denovo, and 30% patients with recurrent nasal polyps, p=0.2. De novo nasal polyps were more prevalent in the positive stools than recurrent ones, p=0.7. All adenoid samples were negative for H. pylori, only two samples of tonsillar tissue (8.3%) were positive for H. pylori, and stool analysis was positive in 23 patients with chronic adenotonsillitis. Conclusion: Lack of association between Helicobacter pylori and occurrence of OME, nasal polyposis or recurrent adenotonsillitis.

Body Mass Index as a Major Prognostic Contributing Factor in COVID-19: A Multicentral Egyptian Study.

Background: Extreme body mass index (BMI) is an influential pathophysiological risk factor for serious illnesses following lower respiratory tract infection. The purpose of the current study was to examine how the BMI of Coronavirus disease-19 (COVID-19) patients affects their prognosis. Methods: Two hundred patients with COVID-19 admitted to Al-Azhar, Qena, Aswan, and Sohag University hospitals in Egypt were included and categorized into four groups according to their BMI. The diagnosis was made according to a real-time reverse transcription-polymerase chain reaction (rRT-PCR) positive result for the SARS-CoV-2 nucleic acid in swabs from upper respiratory tract. A detailed history, clinical examination, and outcomes (disease severity and complications, hospital stay, ICU admission, mortality) were recorded for all patients. SPSS version 24 software was used for data analysis. Results: Average age of participants (19-90 years old), 92 (46%) males and 108 females (54%). ICU admission was significantly higher among underweight patients (75%) and obese patients (78.6%). The majority of underweight (62.5%) and obese (57.1%) patients had critical disease. Invasive mechanical ventilation (MV) is frequently used in underweight (50%) and obese patients (42.9%) patients. Adult respiratory distress syndrome (ARDS), cardiac, neurological, and hematological complications, and incidence of myalgia and bed sores were most frequent among obese and overweight patients. Acute kidney injury was significantly higher among underweight patients (37.5%) and obese patients (28.6%) than among other classes (p=0.004). Frequency of endocrine complications was significantly higher in underweight patients than that in other classes (p=0.01). The majority of underweight (75%) and obese patients (50%) deteriorated and died, whereas the majority of normal-weight patients (90.3%) and overweight patients (75.8%) improved and were discharged (p< 0.001). Conclusion: Body mass index is a major contributing factor to the outcome of patients with COVID-19, and patients with extreme of body mass index were associated with the worst prognosis.