Prediction of Putative Epitope Peptides against BaeR Associated with TCS Adaptation in Acinetobacter baumannii Using an In Silico Approach.

Background and Objectives: The BaeR protein is involved in the adaptation system of A. baumannii and is associated with virulence factors responsible for systemic infections in hospitalized patients. This study was conducted to characterize putative epitope peptides for the design of vaccines against BaeR protein, using an immune-informatic approach. Materials and Methods: FASTA sequences of BaeR from five different strains of A. baumannii were retrieved from the UNIPROT database and evaluated for their antigenicity, allergenicity and vaccine properties using BepiPred, Vaxijen, AlgPred, AntigenPro and SolPro. Their physio-chemical properties were assessed using the Expasy Protparam server. Immuno-dominant B-cell and T-cell epitope peptides were predicted using the IEDB database and MHC cluster server with a final assessment of their interactions with TLR-2. Results: A final selection of two peptide sequences (36aa and 22aa) was made from the 38 antigenic peptides. E1 was considered a soluble, non-allergenic antigen, and possessed negative GRAVY values, substantiating the hydrophilic nature of the proteins. Further analysis on the T-cell epitopes, class I immunogenicity and HLA allele frequencies yielded T-cell immuno-dominant peptides. The protein-peptide interactions of the TLR-2 receptor showed good similarity scores in terms of the high number of hydrogen bonds compared to other protein-peptide interactions. Conclusions: The two epitopes predicted from BaeR in the present investigation are promising vaccine candidates for targeting the TCS of A. baumannii in systemic and nosocomial infections. This study also demonstrates an alternative strategy to tackling and mitigating MDR strains of A. baumannii and provides a useful reference for the design and construction of novel vaccine candidates against this bacteria.

Synchronised Video-assisted Clinical Skill Lab Sessions (SVCSLSs). Can SVCSLSs fill some gaps in virtual medical education? A mixed-method study.

Despite the recent advancement of virtual education during the last pandemic, mastering clinical competencies remains challenging. The current study endorsed Synchronised Video-assisted Clinical Skill lab Sessions (SVCSLS) as a novel instructional design aiming to improve medical students' clinical competencies during virtual learning. The current study is a mixed-method study that was carried out among 210 medical students at a medical college in Saudi Arabia. It was revealed that students viewed SVCSLSs as an effective and safe tool during times of crisis. Students' performance did not show significant variations in all program phases compared with face-to-face learning. SVCSLSs has many advantages, including enjoyment, continuous access to learning material, Self-Directed Learning, fostering recall and memorisation, and enhancing higher cognitive skills. Students suggested that the sessions' content be updated, that workplace-related videos be added, and that constructive feedback is provided. Students recommended updating the contents of the sessions, enriching them with workplace-based videos, and providing constructive feedback. Though SVCSLSs have been proven to be an effective tool, we recommend using them during a crisis rather than replacing the face-to-face mode of learning in normal circumstances.

Serum beta-2 microglobulin as a predictor of nephritis, disease activity, and damage score in systemic lupus erythematosus: a cross-sectional study.

A strong correlation between lupus nephritis (LN), disease activity, and serum beta 2-microglobulin (b2MG) was observed. The current study examines the correlation between serum b2MG and renal involvement, damage score, and disease activity in systemic lupus erythematosus (SLE) patients. One hundred SLE patients from Ain Shams University Hospital were enrolled and categorized into two groups. Group I had 40 patients with negative b2MG, while Group II had 60 patients with positive b2MG levels. Medical history, clinical examination, and assessing disease activity based on SLE disease activity index (SLEDAI-2 K), and damage score were recorded for all patients. Laboratory examinations, such as serum b2MG, complete blood count, blood urea nitrogen (BUN), serum creatinine, glomerular filtration rate (GFR), urine analysis, 24 h urinary protein excretion, Antinuclear antibodies (ANA), anti-dsDNA antibody, and serum complement (C3, C4). BUN, 24 h urinary protein, serum creatinine, active urinary sediment, SLEDAI score, and damage score were all elevated in group II compared to group I (p < 0.001). There is a positive correlation between serum b2MG and 24 h urinary protein, BUN, serum creatinine, disease activity, and damage score (p < 0.001), while it was negatively correlated with GFR, C3, and C4 (p < 0.001). Serum b2MG has proven to be a predictor of LN in SLE patients (Sensitivity 92.45%, Specificity 74.47%), also being a predictor of the activity of the disease as well as damage index (Sensitivity 96.67%, Specificity 85%) (Sensitivity 92.45%, Specificity 74.47%), respectively. Serum b2MG level can be used as a valuable predictor for LN, clinical disease activity, and damage score.

Can Complete Blood Count Picture Tell Us More About the Activity of Rheumatological Diseases?

Background: In clinical practice, distinguishing disease activity in patients with rheumatological illnesses is challenging. Objectives: We aimed to investigate clinical associations of hemogram-derived indices, namely: red cell distribution width (RDW), mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) with disease activity in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS). Methods: In 250 patients with rheumatological disease and 100 healthy age-matched controls, we investigated disease activity scores and indicators and evaluated their association with hemogram-derived indices values. Results: Compared with the control group, RDW, MPV, and PLR significantly increased (P < .001) in the three studied disorders (RA, SLE, and AS), but LMR dramatically decreased. SII was considerably higher in RA and AS patients compared with controls but not in SLE patients. On the other hand, NLR rose dramatically in SLE patients compared with controls (P = .043), but did not change much in RA and AS patients (P > .05). RDW and MPV showed significant changes (P < .001) in the three studied diseases (RA, SLE, and AS) according to disease activity. They significantly increased across worsening activity scores. Only in the SLE group, PLR was significantly increased with disease activity (P < .001), while LMR showed a significant decrease (P = .016). Conclusions: Clinicians must pay close attention to complete blood count (CBC) analysis and its various derived ratios to better characterize the activity of rheumatological disorders and anticipate the disease course and prognosis.

Comparison of COVID-19 characteristics in Egyptian patients according to their Toll-Like Receptor-4 (Asp299Gly) polymorphism.

Background: Toll-like receptor (TLR)-4 plays a vital role in recognizing viral particles, activating the innate immune system, and producing pro-inflammatory cytokines. Objectives: This cross-sectional study aimed to compare COVID-19 severity, progression, and fate according to TLR-4 (Asp299Gly) polymorphism in Egyptian patients. Methods: A total of 145 COVID-19 patients were included in this study. TLR-4 (Asp299Gly) genotyping was done using the PCR restriction fragment length polymorphism (PCR-RFLP) approach. Results: The most commonly encountered TLR-4 genotype in relation to the amino acid at position 299 was the wild-type AA (73.1%); meanwhile, the homozygous mutant GG genotype (8.3%) was the least encountered. At hospital admission, 85.8% of the AA group had free (with no ground glass opacities) chest computed tomography (CT) examination, and 16.0% were asymptomatic. On the other hand, of the AG and GG groups, 81.5% and 83.3%, respectively showed bilateral ground-glass opacities in chest CT, as well as 25.9% and 75.0%, respectively were dyspneic. Values of the total leucocytic count, C-reactive protein (CRP), ferritin, and D dimer increased in the AAAG>GG sequence. ICU admission (83.3%) and in-hospital death (33.3%) rates were significantly higher in the GG group. Conclusions: In COVID-19 patients, the TLR-4 mutant G allele may be associated with a more aggressive disease course and in-hospital death. New therapeutic alternatives could be aimed at this area.

Toll-Like Receptor 4 Polymorphisms (896A/G and 1196C/T) as an Indicator of COVID-19 Severity in a Convenience Sample of Egyptian Patients.

BACKGROUND: The clinical spectrum of COVID-19 is extremely variable. Thus, it is likely that the heterogeneity in the genetic make-up of the host may contribute to disease severity. Toll-like receptor (TLR)-4 plays a vital role in the innate immune response to SARS-CoV-2 infection. The susceptibility of humans to severe COVID-19 concerning TLR-4 single nucleotide polymorphisms (SNPs) has not been well examined. OBJECTIVE: The goal of this research was to investigate the association between TLR-4 (Asp299Gly and Thr399Ile) SNPs and COVID-19 severity and progression as well as the cytokine storm in Egyptian patients. METHODS: We genotyped 300 adult COVID-19 Egyptian patients for TLR-4 (Asp299Gly and Thr399Ile) SNPs using PCR-restriction fragment length polymorphism (PCR-RFLP). We also measured interleukin (IL)-6 levels by enzyme-linked immunosorbent assay (ELISA) as an indicator of the cytokine storm. RESULTS: The minor 299Gly (G) and 399Ile (T) alleles were associated with a significant (P < 0.001) positive risk of severe COVID-19 (OR = 3.14; 95% CI = 2.02-4.88 and OR = 2.75; 95% CI = 1.66-4.57), their frequency in the severe group were 71.8% (84/150) and 70.7% (58/150), respectively. We detected significant differences between TLR-4 (Asp299Gly, Thr399Ile) genotypes with regard to serum levels of IL-6. Levels of IL-6 increased significantly with the presence of the mutant 299Gly (G) and 399Ile (T) alleles to reach the highest levels in the Gly299Gly (GG) and the Ile399Ile (TT) genotypes (170 pg/mL (145-208.25) and 112 pg/mL (24-284.75), respectively). CONCLUSION: The TLR-4 (Asp299Gly and Thr399Ile) minor alleles 299Gly (G) and 399Ile (T) are associated with COVID-19 severity, mortality, and the cytokine storm.