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.

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.

Prognostic role of immunohistochemical PTEN (phosphatase and tensin homolog) expression and PTEN (rs701848) genotypes among Egyptian patients with different stages of colorectal cancer.

Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second major cause of cancer-related death. Thus, we attempted to ascertain the relationship between the genotype and allele frequencies of phosphatase and tensin homolog (PTEN) and immunohistochemical PTEN expression with clinicopathological characteristics in patients with CRC. 150 individuals were allocated into two groups for this cross-sectional randomized case-control study: Group I consisted of 100 patients with histopathologically proven CRC of various stages. Group II: Fifty healthy volunteers. Genetic analysis of PTEN (rs701848 T / C) single nucleotide polymorphism (SNP) was performed using TaqManTM assays and real-time PCR, while PTEN expressions were assessed using immunohistochemical staining. PTN SNP genotypes and alleles did not significantly differ between CRC patients and controls. PTEN expression was lost in 28% of CRC patients, while all healthy controls exhibited PTEN expression. Negative PTEN expression was present in 16 (80%) of stage IV CRC cases, 9 (23.7%) of stage III cases, 3 (37.5%) of stage II cases, and none of stage I cases. It was shown that PTEN expression was weakly positive, moderately positive, and strongly positive in 15, 10, and 9 (respectively) cases of CRC stage I. However, the expression was only weekly positive in 4 (20%) of the patients in stage IV. In the stage IV group, neither moderately nor strongly positive PTEN expressions were found. So, Among Egyptians, the emergence or course of colorectal cancer is unrelated to the PTEN gene mutation. However, the formation and progression of CRC may be influenced by weak or lost PTEN expression.

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.

Social Media Effect on Personal Self-Esteem Among the Population in Saudi Arabia.

Background Self-esteem is a self-valuation; it is how people perceive their own worth and how valuable they believe they are to others. In this study, our primary objective was to explore the association between social media use and self-esteem among individuals who actively engage with social media platforms in Saudi Arabia. Method This study involved individuals aged 15 and above who are active social media users residing in Saudi Arabia. The data were collected through an anonymous online cross-sectional survey. Participants were recruited using snowball and convenience sampling method. A questionnaire was administered through Google Forms to collect data from participants. The questionnaire was structured into three sections, which included gathering social and demographic information, assessing personal usage patterns, and evaluating individual self-esteem levels using an Arabic valid version of the Rosenberg Self-Esteem Scale.  Results The survey included a total of 2,551 participants. Among them, 51.3% (n = 1,309) were female, 29% (n = 741) fell within the 21-25 age group, 95.7% (n = 2,441) were of Saudi nationality, and 51.6% (n = 1,316) were single. The social media platform most frequently used by participants was TikTok 98.5% (n = 2,512), followed by Facebook 95.7% (n = 2,441), Telegram 89.8% (n = 2,291), YouTube 72.2% (n = 1,942), WhatsApp 66.0% (n = 1,683), and finally, Snapchat 30.7% (n = 1,769). In total, 14.3% (n= 366) have low self-esteem, participants scored around 16.10 ± 1.80, ranging from 5 to 25. The following variables were significantly associated with self-esteem: female sex (83.88% vs 87.52%, X2 = 6.87, p = 0.009), nationality (X2 = 13.507, p < 0.001), marital status (X2 = 12.313, p = 0.006), region (X2 = 18.36, p = 0.001), using Tik Tok (X2 = 4.11, p = 0.043), the frequency of posting comments (X2 = 12.01, p = 0.017), comparing oneself to others (X2 = 27.94, p < 0.001), using social media because of weak personal communication (X2 = 6.56, p = 0.010), using social media to follow news (X2 = 6.89, p = 0.009), and the perceived effect of social media (X2 = 16.28, p < 0.001). Conclusions Our findings revealed that a minority of participants exhibited low self-esteem, and individuals from the Northern region were more likely to report such issues. Sociodemographic factors, including gender, nationality, and marital status, demonstrated associations with self-esteem. Additionally, the frequency of comments, TikTok usage, and peer comparison significantly influenced self-esteem levels.