Surgical Site Bacterial Infection in a General Hospital, Al-Jouf Region, Saudi Arabia: A Retrospective Study.

Background Surgical site infection (SSI) is a major healthcare problem with a great impact on patient morbidity, mortality, and healthcare cost all over the world. It accounts for 20% of healthcare-associated infections (HAIs), with higher frequency in low- and middle-income countries where it affects about 30% of the patients undergoing surgery. Aim The current study aims to assess the prevalence of SSI in a general hospital in Sakaka, Al-Jouf region, Saudi Arabia. The types of bacteria causing SSI were also determined. Subjects and methods A retrospective cross-sectional study was done by reviewing the hospital records of patients who got SSI during the period between 2020 and 2022. Data collection was done during 2022 and 2023 after taking ethical approval and permission from the hospital management. Results The number of patients who underwent surgical procedures during 2020, 2021, and 2022 were 689, 867, and 1119, respectively. Most of the cases were cholecystectomy and appendectomy. The cases that developed surgical site infection after cholecystectomy and/or appendectomy during 2021 and 2022 were 15.45% and 9.29% cases, respectively, and they were mainly associated with appendectomy. A culture and sensitivity test revealed methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella pneumonia. Nearly all patients have received ciprofloxacin for seven days and improved with treatment. Conclusion The number of cases that developed SSI has decreased gradually due to the application of infection control measures and strict follow-up.

Influence of IL-6 rs1800795 and IL-8 rs2227306 polymorphisms on COVID-19 outcome.

INTRODUCTION: Severe coronavirus disease 2019 (COVID-19) is mainly precipitated by an uncontrolled inflammatory response and cytokine storm. Pro-inflammatory cytokines such as IL-6 and IL-8 levels were markedly increased in complicated cases. Genetic polymorphisms may have a role in this dysregulated expression during SARS-CoV-2 infection. Our aim was to assess the influence of IL-6 and IL-8 single nucleotide polymorphisms (SNPs) on COVID-19 outcomes. METHODOLOGY: 240 subjects were involved in the study; 80 cases with severe COVID-19, 80 cases with mild COVID-19, and 80 healthy subjects. IL-6rs1800795(G/C) and IL-8 rs2227306(C/T) genotyping was performed using real-time polymerase chain reaction (PCR). RESULTS: Ages ranged between 20-67 years in all groups. There was a statistically significant association between the male gender and severe COVID-19. A significantly higher expression of IL-6rs1800795GG and IL-8rs2227306CC genotypes was observed among patients with severe COVID-19 than other groups. At the allele level, IL-6rs1800795G and IL-8rs2227306C alleles were more frequent among patients with severe COVID-19 when compared with other groups. Haplotypes' frequency clarified that the coexistence of IL-6 rs1800795G and IL-8rs2227306C alleles in the same person increased the risk of severe COVID-19 outcomes. Carriers of IL-6rs1800795C and IL-8 rs2227306T alleles are at lower risk of developing severe COVID-19. Multivariate logistic regression analysis showed that old age, male gender, IL-6 rs1800795CG+GG, and IL-8 rs2227306CT+CC genotypes could be independent risk factors for severe COVID-19 outcomes. CONCLUSIONS: IL-6 rs1800795G and IL-8 rs2227306C alleles are significantly associated with severe COVID-19 outcomes, especially if they coexist. They may be used as prognostic markers for COVID-19.

Relevance of HLA-DP/DQ and INF-λ4 Polymorphisms to COVID-19 Outcomes.

Background: Single nucleotide polymorphisms provide information on individuals' potential reactions to environmental factors, infections, diseases, as well as various therapies. A study on SNPs that influence SARS-CoV-2 susceptibility and severity may provide a predictive tool for COVID-19 outcomes and improve the customized coronavirus treatment. Aim: To evaluate the role of human leukocyte antigens DP/DQ and IFNλ4 polymorphisms on COVID-19 outcomes among Egyptian patients. Participants and Methods: The study involved 80 patients with severe COVID-19, 80 patients with mild COVID-19, and 80 non-infected healthy volunteers. Genotyping and allelic discrimination of HLA-DPrs3077 (G/A), HLA-DQrs7453920 (A/G), and IFNλ4 rs73555604 (C/T) SNPs were performed using real-time PCR. Results: Ages were 47.9 ± 8, 44.1 ± 12.1, and 45.8 ± 10 years in severe, mild and non-infected persons. There was a statistically significant association between severe COVID-19 and male gender (p = 0.002). A statistically significant increase in the frequency of HLA-DPrs3077G, HLA-DQrs7453920A, and IFNλ4rs73555604C alleles among severe COVID-19 patients when compared with other groups (p < 0.001). Coexistence of these alleles in the same individual increases the susceptibility to severe COVID-19 by many folds (p < 0.001). Univariate and multivariate logistic regression analysis for the studied parameters showed that old age, male gender, non-vaccination, HLA-DQ rs7453920AG+AA, HLA-DPrs3077GA+GG, and IFNλ4rs73555604CT+CC genotypes are independent risk factors for severe COVID-19 among Egyptian patients. Conclusion: HLA-DQ rs7453920A, HLA-DPrs3077G, and IFNλ4rs73555604C alleles could be used as markers of COVID-19 severity.

Impact of ACE and Endoplasmic Reticulum Aminopeptidases Polymorphisms on COVID-19 Outcome.

Background: COVID-19 outcomes display multiple unexpected varieties, ranging from unnoticed symptomless infection to death, without any previous alarm or known aggravating factors. Aim: To appraise the impact of ACErs4291(A/T) and ERAP1rs26618(T/C) human polymorphisms on the outcome of COVID-19. Subjects and methods: In total, 240 individuals were enrolled in the study (80 with severe manifestations, 80 with mild manifestations, and 80 healthy persons). ACErs4291(A/T) and ERAP1rs26618(T/C) genotyping was performed using RT-PCR. Results: The frequency of the ACErs4291AA genotype was higher among the severe COVID-19 group than others (p < 0.001). The ERAP1rs26618TT genotype frequency was higher among the severe COVID-19 group in comparison with the mild group (p < 0.001) and non-infected controls (p = 0.0006). The frequency of the ACErs4291A allele was higher among severe COVID-19 than mild and non-infected groups (64.4% vs. 37.5%, and 34.4%, respectively), and the ERAP1rs26618T allele was also higher in the severe group (67.5% vs. 39.4%, and 49.4%). There was a statistically significant association between severe COVID-19 and ACErs4291A or ERAP1rs26618T alleles. The coexistence of ACErs4291A and ERAP1rs26618T alleles in the same individual increase the severity of the COVID-19 risk by seven times [OR (95%CI) (LL−UL) = 7.058 (3.752−13.277), p < 0.001). A logistic regression analysis revealed that age, male gender, non-vaccination, ACErs4291A, and ERAP1rs26618T alleles are independent risk factors for severe COVID-19. Conclusions: Persons carrying ACErs4291A and/or ERAP1rs26618T alleles are at higher risk of developing severe COVID-19.

Genetic polymorphisms of Endoplasmic reticulum amino peptidase 1 (ERAP1) and Interferon lambda 4 (IFN-λ4) in Egyptian patients with type 1 diabetes mellitus.

Different genetic and environmental factors are implicated in type I diabetes (T1DM) pathogenesis. About 50% of the genetic susceptibility for T1DM is related to human leukocyte antigen (HLA) genes. Other non-HLA genes have variable roles in the destruction of pancreatic ß cells. A highly variable gene called endoplasmic reticulum associated with antigen processing gene 1(ERAP1) shares in activating autoreactive CD8+ T lymphocytes, peptide trimming, and subsequent pancreatic ß cells destruction. Local production of inflammatory cytokines within the cells of islets of Langerhans is linked to T1DM progression. Different viral and autoimmune disorders have been linked to genetic variations in type III interferon (IFNλs). This study aimed to determine genetic polymorphisms of interferon lambda 4 (IFNλ4rs 73555604) and endoplasmic reticulum aminopeptidases 1 (ERAP1 rs26618) in Egyptian patients with T1DM. The study recruited 120 patients with T1DM from Kafrelsheikh University Hospital and 100 normal controls who were age and sex matched with the patients' group. Single-nucleotide polymorphism (SNP) genotyping of ERAP1(rs26618) and IFN-λ-4(rs73555604) was performed using real-time polymerase chain reaction. Patients with CC genotype were less likely to develop T1DM than those with TC and TT genotypes for both genes. In addition, T allele frequency in comparison to C allele frequency was significantly increased in T1DM patients when compared to control group (p < 0.001). There were positive correlations between studied SNPs for both genes, fasting and postprandial blood glucose levels which suggest the association of these genes with T1DM occurrence. We concluded that the studied SNPs of ERAP1gene (rs26618) and IFNλ-4 gene(rs73555604) may be associated with T1DM development. In addition, T alleles for both genes could be considered risk alleles while C alleles would be regarded as a protective allele. Patients with TC and TT genotypes would be at a higher risk for T1DM than those carrying CC genotype.

Role of HLA-DPrs3077 and HLA-DQrs3920 Polymorphisms as Risk Factors for Type 1 Diabetes Mellitus.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic disease caused by the destruction of insulin-producing pancreatic ß-cells. During disease progression, inflammatory insulitis increases the presentation of islet antigens on human leukocyte antigen (HLA) molecules to T lymphocytes. This complex system plays a pivotal role in cellular immunity. Thus, genetic variability in HLA can affect the susceptibility to and clinical outcomes of DM. AIM: This case-control study aimed to assess the role of HLA-DP-rs3077 (A/G) and HLA-DQrs3920 (A/G) polymorphism in T1DM. SUBJECTS AND METHODS: This study enrolled 400 individuals: 200 patients with T1DM and 200 ageand sex-matched healthy controls. Hemoglobin A1C and random, fasting, and postprandial blood sugar levels were determined for all subjects. Genotypic and allelic distributions of HLA-DPrs3077 (A/G) and HLA-DQrs3920 (A/G) SNPs were determined using real-time polymerase chain reaction (PCR). RESULTS: Frequency of the HLA-DPrs3077A allele was high among the diabetic group (91.3%); however, the difference was non-significant [OR (95% C.I) = 1.422(0.89-2.252), P=0.098]. The frequency of the HLA-DQrs3920 GG genotype was higher in control than the diabetic group (52.5% vs.12%), whereas that of the AA genotype was higher in the person with diabetes than in the control group (34% vs.4%). Individuals carrying the HLA-DQrs3920A allele were 4.5 times more likely to have T1DM than those carrying the G allele [OR (95% C.I) = 4.510 (3.338- 6.094), P<0.001*]. The presence of HLA-DPrs3077A and HLA-DQ rs3920A in the same person increases T1DM risk by 3.6 times that of G allele [OR (95%C.I) = 3.608(2.173-5.991), P<0.001*]. CONCLUSION: HLA-DPrs3077 and HLA-DQrs3920 SNPs have a role in T1DM as the coexistence of HLA-DPrs3077A and HLA-DQrs3920A alleles increases the risk.

Pregnancy-associated asymptomatic bacteriuria and antibiotic resistance in the Maternity and Children's Hospital, Arar, Saudi Arabia.

INTRODUCTION: The Ministry of Health in Saudi Arabia provides comprehensive antenatal care for all pregnant women with all required investigations. However, it does not include urine culture for diagnosis of asymptomatic bacteriuria (ASB). This is the first study to evaluate the prevalence of ASB among pregnant females, identify the causative organisms and determine their antibiotic susceptibility patterns in the Maternity and Children's Hospital, Arar, Saudi Arabia. METHODOLOGY: This cross-sectional study included 400 pregnant women attending an antenatal clinic. Two midstream urine samples were aseptically collected and screened using standard microbiological techniques including microscopic examination, dipstick testing, and urine culture. In order to interpret the urine culture results, ≥ 105 CFUs/mL was considered significant bacteriuria. Identification of the isolates and their antibiotic sensitivity testing was performed using the Vitek 2 system (BioMérieux, Marcy l'Etoile, France) with the available test kits. RESULTS: The prevalence of ASB was 8.25% (35/400). Significant positive correlations (p ˂ 0.05) were detected between positive urine culture results and random blood sugar, leucocytes, nitrites, pus cells, urine red blood cells, epithelial cells, and mucus. Escherichia coli was the most common causative organism (45.7%), followed by Staphylococcus aureus (22.9%). Klebsiella pneumoniae represented 11.4% of the isolates. Most of the isolated Gram-positive organisms were sensitive to many of the tested antibiotics; most of the detected Gram-negative isolates were resistant. CONCLUSIONS: ASB caused by antibiotic resistant organisms is alarming. Screening for ASB during pregnancy using urine culture and sensitivity testing is of vital importance to improve the maternal and neonatal outcome.

The Pre-Vaccination Donated Blood Is Free from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) but Is Rich with Anti-SARS-CoV-2 Antibodies: A Cross-Section Saudi Study.

(1) Backgrounds and Objectives: Since its discovery, information about the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has spread rapidly. However, many issues remain unresolved. Coronaviruses are primarily transmitted through respiratory secretions. The possibility of transmission via donated blood transfusion deserves studying. This is the first study in Saudi Arabia to look at pre-vaccination donated blood anti-SARS-CoV-2 antibody content as a marker for virus transmission via viral RNA positive blood and/or the potential therapeutic value of convalescent plasma. (2) Methods: A total of 300 blood samples were sequentially collected from unvaccinated donors who donated blood to the blood bank of Prince Mutaib Bin Abdulaziz Hospital in Sakaka, Al-Jouf, Saudi Arabia. Specific ELISA was used to detect anti-SARS-CoV-2 IgG and IgM antibodies. SARS-CoV-2 was detected using specific real-time reverse-transcription PCR (rRT-PCR). (3) Results: The prevalence of anti-SARS-CoV-2 IgG was low (9%), whereas the prevalence of anti-SARS-CoV-2 IgM was high (65%). Relevant demographics, anthropometrics, and lifestyle factors revealed significant associations (p < 0.05) between IgM-positivity only vs. age (age group 21−30 years), postgraduate education, no history of international travel, IgG-negativity, and absence of experience with COVID-19-like symptoms. Furthermore, there are significant associations (p < 0.05) between IgG-positivity only vs. age (age group 21−30 years), postgraduate education, and being a non-healthcare worker. All donors in the anti-SARS-CoV-2 IgG-positive group (n = 27) had previously experienced symptoms similar to COVID-19 (p < 0.001) and most of them (n = 24) showed anti-SARS-CoV-2 IgM-positive test (p = 0.006). However, all the samples tested negative for SARS-CoV-2 RNA using rRT-PCR. (4) Conclusion: Our findings add to the growing body of evidence that donated blood is safe, with the added benefit of convalescent plasma rich in potentially neutralizing IgG and IgM against SARS-CoV-2.

Bacterial Ghosts of Pseudomonas aeruginosa as a Promising Candidate Vaccine and Its Application in Diabetic Rats.

Infections with Pseudomonas aeruginosa (PA) pose a major clinical threat worldwide especially to immunocompromised patients. As a novel vaccine network for many kinds of bacteria, bacterial ghosts (BGs) have recently been introduced. In the present research, using Sponge-Like Reduced Protocol, P. aeruginosa ghosts (PAGs) were prepared to maintain surface antigens and immunogenicity. This is the first study, to our knowledge, on the production of chemically induced well-structured bacterial ghosts for PA using concentrations of different chemicals. The research was carried out using diabetic rats who were orally immunized at two-week intervals with three doses of PAGs. Rats were subsequently challenged either by the oral route or by the model of ulcer infection with PA. In challenged rats, in addition to other immunological parameters, organ bioburden and wound healing were determined, respectively. Examination of the scanning and transmission electron microscope (EM) proved that PAGs with a proper three-dimensional structure were obtained. In contrast to control groups, oral PAGs promoted the generation of agglutinating antibodies, the development of IFN-γ, and the increase in phagocytic activity in vaccinated groups. Antibodies of the elicited PAGs were reactive to PA proteins and lipopolysaccharides. The defense against the PA challenge was observed in PAGs-immunized diabetic rats. The resulting PAGs in orally vaccinated diabetic rats were able to evoke unique humoral and cell-mediated immune responses and to defend them from the threat of skin wound infection. These results have positive implications for future studies on the PA vaccine.

Association of human leukocyte antigen DQ-rs3920AG genotype with Helicobacter pylori recurrence in Kafrelsheikh, Egypt.

AIMS: The aim was to evaluate the role of HLA-DP/DQ single-nucleotide polymorphisms (SNPs) in Helicobacter pylori infection in Kafrelsheikh governorate, Egypt. METHODS AND RESULTS: The study enrolled 120 persons; 48 naïve H. pylori-infected patients, 42 relapsers and 30 H. pylori-free controls. Gastroscopy, H. pylori stool antigen, anti-CagA and anti-VacA antibodies were determined. Genotyping of HLA-DPA1rs3077 (A/G) SNP and HLA-DQ-rs3920(A/G) SNP was done using real-time PCR. The antibody profile against H. pylori showed that 85.7% of patients with recurrent infection have IgG against CagA (p = 0.001*). There was a significant association between the occurrence of H. pylori infection and both HLA-DPA1rs3077AA and HLA-DQ-rs3920AG genotypes. Concerning H. pylori relapse, the HLA-DQ-rs3920AG genotype was detected in 78.6% of patients with recurrent infection (p = 0.002*). Patients carrying this genotype tend to be relapsers 9.8 times more than patients carrying other genotypes. CONCLUSIONS: HLA-DPA1rs3077AA and/or HLA-DQ-rs3920AG genotypes could be risk factors for the occurrence of H. pylori infection. HLA-DQ-rs3920AG genotype is markedly linked to recurrent H. pylori infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Host factors as HLA gene polymorphism could be a predisposing factor for susceptibility, recurrence or chronicity of H. pylori and should be studied in different ethnic groups.

Activity of Ozonated Water in Sterilising and Disinfecting Dental Unit Water Pipelines System: A Comparative Study.

PURPOSE: A number of disinfectants and sanitisers are used in dentistry, and there are numerous commercial solutions available. Nonetheless, because each cleaning solution has its own set of indications and limits, there is no one-size-fits-all approach for processing all types of dental equipment. Functional water, such as electrolysed hypochlorite microbubbled water, efficiently eliminates and sterilises biofilms. The objective of the study was to evaluate whether ozonated water could be used to sterilise and disinfect dental-unit water pipelines (DUWP) that had been contaminated with micro-organisms, including Gram-positive and Gram-negative bacilli and cocci. MATERIALS AND METHODS: Three different groups were formed: group A - ozonated water (Cantoosh); group B - 1% povidine iodine; and group C: conventional distilled water. Group A was the test group, group B the control group, and group C was the positive control group. The water sterilising system was replaced with the appropriate sterilising agent as per the allocated group classification, with 2 min of purging, so that the complete DUWP was filled with the water sterilising system. Samples were collected and analysed, along with a 2-min purge after 24 h, 7 days and 21 days, at the 3 outlet (OL) points: the 3-way syringe at the dental tray(OL1), the cup filler (OL2), and the 3-way syringe of the assistant zone (OL3). Repeated measures ANOVA was used to test for statistical significance between colony-forming units of control and experimental groups (p < 0.05). RESULTS: The cup filler yielded higher counts than did the 3-way syringe at the dental tray (OL1) (6.40 and 8.05 on the log scale, respectively). A statistically significant difference in the CFUs was also observed between samples taken after 24 h vs 21 days between groups A, B and C. CONCLUSION: The findings showed that exposing DUWP tube systems to ozonated water for an extended length of time drastically lowered the number of microorganisms adhering to their surfaces.

Relevance of Interleukins 6 and 8 Single Nucleotide Polymorphisms in Prostate Cancer: A Multicenter Study.

The diverse roles of cytokines as IL-6 and IL-8 have been studied in terms of their SNPs in many diseases but their role in prostate cancer (PCa) is still uncertain. Aim. To determine the relevance of IL-6 rs1800795 SNP and/or IL-8 rs2227306 SNP with prostate cancer's risk. Subjects and Methods. 40 PCa patients, 40 benign prostate hyperplasia (BPH) patients, and 40-age-matched-control group were enrolled in the study. Genotyping of IL-6 rs1800795 (G/C) SNP and IL-8 rs2227306 (C/T) SNP was determined using real-time PCR. Results. High frequency of IL-6 rs1800795GG and IL-8 rs2227306CC genotypes was noticed among PCa patients with associated OR 10.091 and 8.143, respectively. Comparisons based on allele frequencies revealed that IL-6G and IL-8C alleles are more frequent among PCa patients than other groups. Presence of IL-6 rs1800795G and IL-8 rs2227306C alleles in the same patient increase PCa risk by 16.7 times. Statistical correlations between PSA ratio and both of IL-6 and IL-8 SNP did not show any significant relation among PCa patients. Conclusion. IL-6 rs1800795G and IL-8 rs2227306C alleles could be considered risk factors for PCa development, particularly if presented together. However, no relation was found between both cytokines SNP and severity of prostate cancer.

The Weight of HLA-DPA1 rs3077 Single Nucleotide Polymorphism in Prostate Cancer, a Multicenter Study.

Prostate cancer (PCa) has almost the highest genetic transmission that mimics an autosomal dominance hereditary pattern of cancers in some families. Its incidence in Arab countries was reported to be steadily increasing. Aim. To determine the relevance of HLA-DPA1 rs3077 (A/G) SNP with prostate cancer's risk and/or severity. Subjects and Methods. Forty PCa patients and forty age matched patients with benign prostatic hyperplasia (BPH), as a control group, were enrolled in the study. Serum levels of urea, creatinine, total prostate-specific antigen (PSA), and free PSA were measured. PSA ratio was determined as well. Genotyping of HLA-DPA1 rs3077 (A/G) SNP was done using real-time PCR. Results. The measured lab parameters, except free PSA, were significantly higher among PCa patients in comparison to controls (P < 0.001 ∗ ). Moreover, PSA ratio was significantly high among PCa patients (P < 0.001 ∗ ). HLA-DPA1 rs3077 GG genotype was more frequent in PCa patients and the associated OR was 2.546 (P=0.059), while AA genotype was more frequent in the control group and the associated OR was 0.145 (P=0.081). Frequency of G allele was higher among PCa patients than the control group while A allele frequency was significantly decreased (P=0.034 ∗ ) (protective allele). On multivariate analysis, there is no significant correlation found between HLA-DPA1 rs3077 SNP and PSA ratio (OR = 4.5, 95% CI = 1.2-17.4, P=0.856). Conclusion. HLA-DPA1 rs3077 G allele could be a risk factor for prostate cancer. However, HLA-DPA1 rs3077 SNP has no relation to PCa severity.

Otitis media with effusion is not a sterile inflammatory process: scanning electron microscope evidence.

PURPOSE: We aimed to demonstrate whether chronic otitis media with effusion (OME) is a sterile condition or biofilms-related disease through direct visualization of middle ear mucosa by Scanning electron microscopy (SEM) and culture of the effusion. METHODS: This case-control study included 60 children in two groups; the case group included 50 patients undergoing ventilation tube insertion (VTI) for Chronic OME (COME), and the control group included ten patients undergoing cochlear implantation (CI) surgery presenting normal middle ear mucosa. Biopsies from both groups' middle ear mucosa were evaluated for biofilm formation using scanning electron microscopy (SEM). Middle ear effusion (MEE) samples from COME patients were cultured on blood agar to detect and identify any bacterial growth. The adenoid size was evaluated and correlated to the biofilm formation in COME patients. RESULTS: There was a significant difference between case and control groups regarding biofilm formation (p-value < 0.001*). Biofilm was evident in 84% of the COME patients (cases group) and absent in the control group. Only 12 COME patients (24%) had positive MEE culture, however, 76.2% of patients with biofilm had a negative culture. Streptococcus pneumonia was the most common otopathogen found either alone or combined with other otopathogens. There was a significant negative correlation between adenoid size and biofilm grade among the studied patients. CONCLUSION: The visual identification of middle ear biofilms indicated their role in chronic OME. Middle ear biofilms need to be expected in children with OME, especially those who do not need adenoid surgery.

Relation between HLA-DP/DQ Polymorphisms, Serum IP-10 and Response to Direct Acting Antiviral Therapy among HCV Infected Patients.

HCV infection represents a worldwide health problem with many attempts to control. This study aimed to assess the relation between HLA-DQ-rs3920 SNP, HLA-DP-rs3077 SNP, serum IP-10 levels and response to direct acting antiviral (DAA) drugs among HCV infected Egyptian patients. The study included 100 HCV infected patients (received sofosbuvir, Daclatsvir and Ribavirin) and 50 apparently healthy volunteers as controls. Serological, hematological and viral investigations were done to all participants. Whole DNA was extracted, HLA-DQ-rs3920 SNP and HLA-DP-rs3077 SNP were evaluated using RT-PCR and serum IP-10 levels were determined. Higher frequencies of HLA-DQ rs3920 AG and HLA-DP rs3077 AA variants was observed among HCV infected patients (P<0.001* and P=0.029*, respectively). There was a statistically significant association between both genotypes and response to DAA. However, HLA-DQ rs3920 A allele was markedly expressed among non-responders group and could be correlated with resistance to DAA therapy. IP-10 levels were significantly decreased among the non-responder group with 95% sensitivity and 15% specificity. We concluded that HLA-DP-rs3077 and/or HLA-DQ-rs3920 SNP may represent independent predictors for susceptibility to infection and response to direct antiviral drugs among HCV infected Egyptian patients. Serum IP-10 could be a predictive marker for disease progression and response to DAA.

Significance of Intracellular Adhesion Molecule-1 Polymorphism and IP-10 among Breast Cancer Patients.

Breast cancer (BC) is the second leading cause of women's death worldwide. Intercellular adhesion molecule-1 (ICAM-1) is involved in cell-cell interaction, migration and recruitment of immune cells. Polymorphisms in ICAM-1 gene may be involved in BC progression. IFN-gamma inducible protein-10 (IP-10) has the ability to recruit T-cells to induce cellular immunity and may have protective effect against BC development. The current study aimed to shed light on the role of of ICAM-1 SNP and/or serum levels of IP10 in BC in Egyptian female patients and detect possible correlation between these two factors and pathological prognostic markers. 40 breast cancer patients and 40 healthy females were enrolled in the study. Genotyping of ICAM-1 rs281437 SNP was done using real time PCR and serum levels of IP-10 were measured using ELISA. Allelic distribution demonstrated high frequency of ICAM-1 rs281437 CC genotype among BC patients (60%) compared to CT and TT alleles (30% and 10%, respectively). ICAM-1 rs281437 CC genotype showed 9.8 folds more risk to develop BC than other genotypes (95% CI=5.8-21.8, P<0.05). Relation between the studied alleles and hormonal receptors (ER, PR) showed that both ICAM-1 rs281437 CC and CT genotype have 5 folds more to be ER+, PR+ BC compared to TT allele (95% CI=0.21-117.8 and 0.15-125.4, respectively). Serum IP-10 levels were markedly decreased among breast cancer patients when compared with healthy controls (P = 0.001). In conclusion, ICAM-1 rs281437 CC genotype is significantly associated with breast cancer; females carrying CC allele may be at higher risk to develop BC than those carrying CT or TT genotypes. On the other hand, IP-10 may have a protective effect against breast cancer.

Impact of Interleukin 28B and ICAM-1 Genetic Polymorphisms on Response to Direct Antiviral Treatment Among HCV Infected Patients.

BACKGROUND: Single nucleotide polymorphisms (SNPs) of IL-28B and/or ICAM-1 could have a role in expecting a response from HCV infected patients to direct antiviral agents (DAAs). OBJECTIVE: The aim of the current study was to investigate the impact of IL-28B rs12979860 and rs8099917, and, ICAM-1 rs281437 SNPs on response to treatment with sofosbuvir + Daclatsvir ± Ribavirin, among HCV-infected Egyptian patients. METHODS: Whole blood genomic DNA was extracted from 120 participants (80 HCV-infected patients and 40 healthy volunteers). HCV-infected patients were subdivided into responders and nonresponders to DAAs. Liver function testing, anti-HCV antibodies, HCV-RNA viral load and HCV genotyping were performed. IL-28B and ICAM-1 SNPs were evaluated by real-time PCR. RESULTS: ALT and AST levels were significantly higher among non-responder HCV infected patients (P = 0.001*). 90% of the patients had HCV genotype 4a and the remaining 10% had 4l genotype. Allelic discrimination revealed that IL-28B rs12979860 T, IL-28B rs809917 T and ICAM-1 rs281437 C alleles were more frequent among HCV-infected patients (responders or non-responders) than controls. However, IL-28B rs8099917 G allele was more frequent among healthy controls. Regarding the response to DAAs treatment, HCV-infected patients with IL-28B rs8099917 GG genotype showed a significantly earlier viral response compared to those carrying TT alleles. ICAM-1 rs281437 CT alleles were non significantly more frequent among responders. However, IL-28B rs12979860 alleles did not show any difference. CONCLUSION: Genotyping of IL-28B rs8099917 is a useful independent tool for expecting a response of Egyptian HCV-infected patients to DAAs.

Concanavalin-A as a Model for Induction of Murine Autoimmune Hepatitis: Role of TNF-α and NF-κß During The Acute Phase.

Autoimmune hepatitis (AIH) is a heterogeneous immune-mediated chronic liver disease affecting children and adults. It is important to rely on a specific animal model to study the hepatic changes and to evaluate the roles played by pro-inflammatory cytokines such as tumor necrosis factor alpha "TNF-α" and transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells "NF-κß" in the pathogenesis and outcome of the disease. This will help to identify specific targets for treatment of AIH. This study aimed at evaluating Concanavalin-A (Con A) as a model for induction of AIH and assessing splenocytes' TNF-α and hepatocytes' NF-κß levels at comparable durations after induction of hepatitis with Con A to evaluate the relationship between both factors. Materials and methods: A total of 130 outbreed CD1 mice were divided into group (1) which included 100 mice with induced AIH and group (2) included 30 normal mice as negative controls. Intra-peritoneal injection of Concanavalin-A was used to induce hepatitis. Hepatic injury was evaluated by the levels of liver enzymes, histopathological evidence for hepatic inflammatory infiltrate and/or apoptosis. Splenocytes and hepatocytes were cultured for assessment of TNF-α and NF-κß levels, respectively. Results: Con A injection caused a significant elevation in ALT and AST levels, portal inflammatory infiltrate, remarkable hepatocytes degeneration and marked increase of TNF-α levels, particularly within 24 hours, but all returned to normal within 1 week. Administration of another dose of Con A resulted in sharp significant elevation of liver enzymes, inflammatory infiltrate and hepatocyte apoptosis after 24 hours and sustained till the end of the study. There was a significant increase in NF-κß throughout most of the study duration following Con A injection as compared to that of normal mice. In conclusions, intra-peritoneal administration of Con A, particularly two doses, represents an efficient approach for induction of immune-mediated hepatitis. T-cells play a major role in AIH through release of TNF-α. Coincidently, hepatitis seems to be associated with elevation of NF-κß to protect hepatocytes. Thus TNF-α and NF-κß can represent targets for treatment of AIH either through inhibition or augmentation, respectively.

Role of Oxidative Stress in Prognosis of Ovarian Cancer.

Ovarian cancer is one of the most lethal gynecological malignancies. Mitochondria are the predominant source of reactive oxygen species (ROS) in the cell. Besides mitochondria nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) enzymes generate a significant amount of ROS in the cell. The present work establishes an interesting link between NOX4 enzyme (which is an important source of reactive oxygen species "ROS") and PHB1 (as a holdase type chaperone in mitochondrial stress). The current study was conducted on 60 patients with ovarian tumours (benign, borderline and malignant) and 20 healthy volunteers (as a control group). NOX4 expression was assessed by TaqMan® real time gene expression assay, while cellular expression of prohibitin was evaluated by immunohistochemistry. There was a significant increase in prohibitin expression from benign cystadenoma to malignant tumors. In addition, there was an increase in NOX4 expression. In conclusion, over-expression of PHB1 and NOX4 in malignant ovarian tissues suggest that PHB1 is associated with tumorigenesis via activation of NOX4 enzyme with subsequent release of ROS in the cells.

Relation between microRNA-21, transforming growth factor ß and response to treatment among chronic hepatitis C patients.

BACKGROUND: Persistence of hepatitis C virus (HCV) infection and response to antiviral therapy has been shown to be associated with inappropriate levels of cytokines and microRNAs (miRNAs). miRNA levels have been reported to fluctuate during treatment. Thus they could be useful predictors for responses to treatment among HCV infected patients, thereby reducing ineffective treatments. AIM: The current study aimed to investigate the relation between miRNA-21 expression profiles, transforming growth factor ß (TGF-ß) serum levels and response to treatment with the new direct antiviral drugs (sofosbuvir + daclatasvir ± ribavirin), among HCV infected Egyptian patients. SUBJECTS AND METHODS: This prospective study was conducted on 50 HCV infected patients (before and after treatment) and 20 healthy volunteers. miRNA expression profiles were determined by real-time polymerase chain reaction and TGF-ß1 serum levels were measured by using enzyme-linked immunosorbent assay. RESULTS: There was a significant increase in serum albumin, platelets count and a significant decrease in liver enzymes, serum bilirubin, and prothrombin time after treatment. Significant reduction of viral load among HCV patients after receiving the treatment was reported. Concomitantly, there was an increase in the relative quantity of miRNA-21 (P = .001*) and serum levels of TGF-ß1 ( P = .337) among HCV patients after receiving treatment. CONCLUSION: Nearly all responders to direct antiviral drugs showed increased levels of both miRNA-21 and TGF-ß1. This may indicate an interplay between TGF-ß1 and miRNA-21 during remission or progression of viral infection. Thus miRNA-21 could be used as promising serum biomarker, for assessment of antiviral treatment efficacy and improvement of fibrosis among chronically infected HCV patients.