Search

Cytochrome P450 (CYP450) is a group of enzymes that play an essential role in Phase I metabolism, with 57 functional genes classified into 18 families in the human genome, of which the CYP1, CYP2, and CYP3 families are prominent. Beyond drug metabolism, CYP enzymes metabolize endogenous compounds such as lipids, proteins, and hormones to maintain physiological homeostasis. Thus, dysregulation of CYP450 enzymes can lead to different endocrine disorders. Moreover, CYP450 enzymes significantly contribute to fatty acid metabolism, cholesterol synthesis, and bile acid biosynthesis, impacting cellular physiology and disease pathogenesis. Their diverse functions emphasize their therapeutic potential in managing hypercholesterolemia and neurodegenerative diseases. Additionally, CYP450 enzymes are implicated in the onset and development of illnesses such as cancer, influencing chemotherapy outcomes. Assessment of CYP450 enzyme expression and activity aids in evaluating liver health state and differentiating between liver diseases, guiding therapeutic decisions, and optimizing drug efficacy. Understanding the roles of CYP450 enzymes and the clinical effect of their genetic polymorphisms is crucial for developing personalized therapeutic strategies and enhancing drug responses in diverse patient populations.

Septic shock is a major public health concern. However, the clinical and laboratory criteria for sepsis overlap with those for hemophagocytic lymphohistiocytosis (HLH), and their differentiation can be challenging. The aim of this study was to compare HLH criteria among patients diagnosed with neonatal sepsis and childhood sepsis and to study the outcomes in patients fulfilling the diagnostic criteria for HLH. A cross-sectional study included 50 neonates and children with severe sepsis and/or septic shock. Clinical and laboratory data and HLH diagnostic criteria were studied in relation to patients outcome. Of all patients, 18% fulfilled three of the eight HLH diagnostic criteria, 2% fulfilled four criteria, and 4% fulfilled five criteria. All patients who fulfilled three or more of the criteria died. Mortality was higher in the presence of more positive HLH criteria and in pediatric age groups. However, the distributions of the HLH criteria were comparable for pediatric and neonatal patients with severe sepsis/septic shock, and their mortality rates were not significantly different when based on the criteria.

Translators face some problems when they translate swear words and taboo expressions, as they belong to different cultures and they have different impacts on the audience. Although some studies examined the problems faced in translating swear words and how to deal with them, little is known about studies that examined the strategies employed in translating such words and expressions from English into Arabic. Therefore, this study examines the strategies employed in translating such words and expressions from English into Arabic in the " Training Day " movie; and to assess the quality of subtitling these expressions. Samples from the movie were selected and analyzed. The results of the study showed that the subtitler used different strategies to subtitle swear and taboo words and expressions. Two of the most common strategies were found to be translating the swear and taboo words euphemistically, and by omission. As regards, the quality of the subtitles, they were found to be of good quality. This study concludes by proposing a model for subtitling swear words and Taboo expressions., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier Ltd.)

Background: Neonatal septicemia is a critical medical situation; current conventional laboratory methods still have many limitations and diagnostic obstacles. For this purpose, last decades have witnessed a challenge between the battery of sepsis biomarkers including many leukocyte surface antigens, not only for early diagnostic purposes but also for better follow-up and good management of sepsis patients., Aim: To evaluate the diagnostic, prognostic, and monitoring performance of both neutrophil CD64 (nCD64) and presepsin as sepsis biomarkers compared to each other and to the conventional laboratory sepsis parameters aiming to decide which is the best fitting for routine daily use in neonatal intensive care units (NICUs)., Methods: 235 neonates were enrolled from three Egyptian neonatal ICUs, during the period from November 2015 till March 2018; they were classified into two main groups: the control group ( n  = 102) and the sepsis group ( n  = 133). Laboratory sepsis evaluation included highly sensitive CRP (hs-CRP), CBC, in addition to nCD64 (flow cytometry technique), and presepsin measurement (CLEIA technique combined with Magtration® technology); the diagnosis was confirmed thereafter by positive blood culture results (BacT/Alert system). Sixty-two of the enrolled sepsis neonates were subjected to follow-up assessment; they were reclassified according to their clinical improvement at the second time assessment into (group 1: sepsis group without improvement) ( n  = 20) and (group 2: improved sepsis group) ( n  = 42)., Results: Significant increase in nCD64 and presepsin values was found in sepsis groups compared to the controls. At cutoff 41.6%, nCD64% could discriminate the presence of septicemia with sensitivity 94.7%, specificity 93.6 %, and AUC 0.925, while presepsin at cutoff 686 pg/ml achieves sensitivity 82.7%, specificity 95.5%, and AUC 0.887, respectively. Significant increase in nCD64 ( P < 0.001) and hs-CRP ( P =0.018) values was observed in severe sepsis/septic shock patients compared to nonsevere sepsis patients. Delta change percentage (dC%) between initial and follow-up evaluations for both improved and nonimproved sepsis patients was dC Z value -5.904 for nCD64% followed by dC Z value -4.494 for presepsin., Conclusion: nCD64 and presepsin are valuable early diagnostic and monitoring sepsis biomarkers; the highest sensitivity could be achieved by a univariant sepsis marker in this study was recorded by the nCD64% biomarker, while the highest specificity was documented by presepsin. Combined measurement of both achieves the highest diagnostic performance in sepsis neonates. Either of CD64 or presepsin combined with hs-CRP associated with better performance than any of them alone. nCD64 carries an additional promising role in reflecting sepsis prognosis., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Heba E. Hashem et al.)

Background: Neonatal sepsis (NS) is a very critical medical situation associated with high morbidities and mortalities. There is an utmost need for a new tool helping in early diagnosis and proper management of sepsis neonates. Neutrophil CD64 (nCD64) shows a very promising value in this concerning issue., Aim: Evaluate the diagnostic, monitoring, and prognostic performances of nCD64 and highly sensitive CRP (hs-CRP) in NS as well as the possible best panel of biomarkers that can achieve the most desirable results., Methods: Patients were enrolled from three neonatal intensive care units (NICUs) ( n = 121 patients) and classified according to their initial sepsis evaluation into three groups: disease control group ( n = 30), proven sepsis group ( n = 17), and clinical sepsis group ( n = 74). Laboratory evaluation included hs-CRP, complete blood count (CBC), and blood culture in addition to nCD64 (done by flow cytometry technique). Besides the diagnostic evaluations, follow-up evaluations were done for 40 patients after five days from the first time; patients were reclassified according to their outcome into the improved sepsis neonates' group ( n = 26) and sepsis neonates without improvement ( n = 14)., Results: Significant increase in nCD64 and hs-CRP results were present in sepsis groups compared to the disease controls ( P < 0.001); nCD64 at 43% cutoff value could detect the presence of sepsis with 85.6% sensitivity and 93% specificity. Additionally, delta change percentage (dC%) between improved sepsis neonates and sepsis neonates without improvement showed a significant difference in the levels of both nCD64 ( P < 0.001) and hs-CRP ( P = 0.001)., Conclusion: Besides the promising diagnostic performance documented by nCD64 which is higher than the other laboratory sepsis biomarkers used routinely in NICUs, nCD64 has a valuable role in sepsis patients' monitoring and prognostic evaluation. hs-CRP was moderate in its diagnostic and monitoring results being less than that achieved by nCD64. Combined measurement of nCD64% and hs-CRP gives better diagnostic and monitoring performance than that achieved by any of them alone., Competing Interests: No conflict of interest was declared., (Copyright © 2020 Heba E. Hashem et al.)

Background: Pneumonia is the foremost cause of child death worldwide. M-ficolin is encoded by the FCN1 gene and represents a novel link between innate and adaptive immunity., Objectives: To investigate the FCN1 -144 C/A (rs10117466) polymorphism as a potential marker for pneumonia severity and adverse outcome namely complications or mortality in the under-five Egyptian children., Methods: This was a prospective multicenter study that included 620 children hospitalized with World Health Organization-defined severe pneumonia and 620 matched healthy control children. Polymorphism rs10117466 of the FCN1 gene promoter was analyzed by PCR-SSP, while serum M-ficolin levels were assessed by ELISA., Results: The FCN1 A/A genotype and A allele at the -144 position were more frequently observed in patients compared to the control children (43.4% vs 27.6%; odds ratio [OR]: 1.62; [95% confidence interval {CI}: 1.18-2.2]; for the A/A genotype) and (60.8% vs 52.5%; OR: 1.4; [95% CI: 1.19-1.65]; for the A allele); P < .01. The FCN1 -144 A/A homozygous patients had significantly higher serum M-ficolin concentrations (mean: 1844 ± 396 ng/mL) compared with those carrying the C/C or C/A genotype (mean: 857 ± 278 and 1073 ± 323 ng/mL, respectively; P = .002). FCN1 -144 A/A genotype was an independent risk factor for adverse outcomes in children with severe pneumonia (adjusted OR = 4.85, [95% CI: 2.96-10.25]; P = .01)., Conclusion: The FCN1 A/A genotype at the -144 position was associated with high M-ficolin serum levels and possibly contributes to enhanced inflammatory response resulting in the adverse outcome of pneumonia in the under-five Egyptian children., (© 2020 Wiley Periodicals, Inc.)

Background: Pediatric-onset SLE (pSLE) is a multisystem autoimmune disease. Recently, the ficolin-2 (FCN2) gene has emerged as a potential candidate gene for susceptibility to SLE., Objectives: The objective of this study was to evaluate the association of the FCN2 gene polymorphisms at positions -986 (G/A), -602 (G/A), -4 (A/G) and SNP C/T (rs3124954) located in intron 1, with susceptibility to pSLE in Egyptian children and adolescents., Methods: This was a multicenter study of 280 patients diagnosed with pSLE, and 280 well-matched healthy controls. The FCN2 promoter polymorphisms at -986 G/A (rs3124952), -602 G/A (rs3124953), -4 A/G (rs17514136) and SNP C/T (rs3124954) located in intron 1 were genotyped by polymerase chain reaction, while serum ficolin-2 levels were assessed using enzyme-linked immunosorbent assay., Results: The frequencies of the FCN2 GG genotype and G allele at -986 and -602 positions were significantly more represented in patients with pSLE than in controls ( p  < 0.001). Conversely, the FCN2 AA genotype and A allele at position -4 were more common in patients than in controls ( p  < 0.001). Moreover, patients carrying the FCN2 GG genotype in -986 position were more likely to develop lupus nephritis (odds ratio: 2.6 (95% confidence interval: 1.4-4.78); p  = 0.006). The FCN2 AA genotype at position -4 was also identified as a possible risk factor for lupus nephritis (odds ratio: 3.12 (95% confidence interval: 1.25-7.84); p  = 0.024)., Conclusion: The FCN2 promoter polymorphisms may contribute to susceptibility to pSLE in Egyptian children and adolescents. Moreover, the FCN2 GG genotype at position -986 and AA genotype at position -4 were associated with low serum ficolin-2 levels and may constitute risk factors for lupus nephritis in pSLE.

Subtitling, one of the under-researched topics in translation studies, is a challenging task faced by many restrictions that compel subtitlers to use specific strategies to enhance the quality of the subtitles. In relation to this, this study aimed to identify the subtitling strategies adopted in subtitling the culture-bound terms in the American movie entitled 'The American Pie', and to assess the quality of the translation of these terms. For this purpose, the data was collected from the movie and qualitatively analyzed using Pedersen's (2005, 2011) typology and Pedersen's (2017) quality assessment model. The results of the study showed that most of the strategies proposed by Pedersen were used. It was also found that some other translation strategies were used in the subtitles. Two new subtitling strategies were identified by the author, viz., using euphemistic expressions and using formal language to render informal language. The quality assessment showed that most subtitles are of a good quality, as in few cases there were some serious errors or problems.

Background: Acute lower respiratory infection (ALRI) is the leading cause of child mortality, especially in the developing world. Polymorphisms in the interleukin 4 (IL-4) gene have been linked to a variety of human diseases., Objectives: To investigate whether the IL-4 -590C/T (rs2243250) polymorphism could be a genetic marker for susceptibility to ALRIs in young Egyptian children., Methods: This was a multicenter study conducted on 480 children diagnosed with pneumonia or bronchiolitis, and 480 well-matched healthy control children. Using PCR-RFLP analysis, we genotyped a -590C/T (rs2243250) single nucleotide polymorphism of the IL-4 gene promoter, meanwhile the serum IL-4concentration was measured by ELISA., Results: The frequency of the IL-4 -590 T/T genotype and T allele were overrepresented in patients with ALRIs in comparison to the control group (OR = 2.0; [95% confidence interval [CI]: 1.38-2.96]; for the T/T genotype) and (OR: 1.3; [95%CI: 1.07-1.56]; for the T allele; P < 0.01). The IL-4 -590 T/T genotype was associated with significantly higher mean serum IL-4 concentration (58.7 ± 13.4 pg/mL) compared to the C/T genotype (47.6 ± 11 pg/mL) and the C/C genotype (34.8 ± 9.6 pg/mL); P < 0.01., Conclusion: The IL-4 -590C/T (rs2243250) polymorphism may contribute to susceptibility to ALRIs in young Egyptian children., (© 2019 Wiley Periodicals, Inc.)

Background: Community-acquired pneumonia (CAP) is the leading cause of child deaths around the world. Recently, the vitamin D receptor (VDR) gene has emerged as a susceptibility gene for CAP., Objectives: To evaluate the association of the VDR gene Fok I polymorphism with susceptibility to CAP in Egyptian children., Methods: This was a multicenter case-control study of 300 patients diagnosed with CAP, and 300 well-matched healthy control children. The VDR Fok I (rs2228570) polymorphism was genotyped by PCR-restriction fragment length polymorphism (RFLP), meanwhile serum 25-hydroxy vitamin D (25D) level was assessed using ELISA method., Results: The frequencies of the VDR FF genotype and F allele were more common in patients with CAP than in our control group (OR = 3.6; (95% CI: 1.9-6.7) for the FF genotype; P = 0.001) and (OR: 1.8; (95% CI: 1.4-2.3) for the F allele; P = 0.01). Patients carrying the VDR FF genotype had lower serum (25D) level (mean; 14.8 ± 3.6 ng/ml) than Ff genotype (20.6 ± 4.5 ng/ml) and the ff genotype (24.5 ± 3.7 ng/ml); P < 0.01., Conclusion: The VDR gene Fok I (rs2228570) polymorphism confers susceptibility to CAP in Egyptian children.