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Abnormal transcriptomic profiles of coagulation genes have been linked to coagulopathies in patients with coronavirus disease 2019 (COVID-19). The objective of the present study was to explore the frequency of genotypes and potential association of polymorphisms in genes encoding coagulation factors with the disease severity in COVID-19 patients. The patients were clinically categorized into four groups of COVID-19 disease severity (asymptomatic, mild, moderate, and severe). Three variants of genes, involving the coagulation genes rs3136516 (F2 gene), rs6042 (F7 gene), and rs6123 (PROS1 gene), were studied. Polymorphisms were genotyped by Sanger DNA sequencing. Most of the subjects had moderate COVID-19 infection (n = 53, 62.4%), followed by mild (n = 16, 18.8%), and severe infections (n = 15, 17.6%). The frequency of the rs3136516 AG genotype was considerably higher in non-ICU patients compared to ICU patients (51.3% vs 34.1%, OR 3.167, 95% CI 1.094-9.170, P = .031). Furthermore, the dominant genetic model (AA + AG vs GG) was significantly associated with a decreased probability of admission to the ICU in COVID-19 patients (OR 0.340, 95% CI 0.127 - 0.905, and P = .028). No other variants of the coagulation genes studied were found to be associated with the severity of COVID-19 disease, admission to the ICU, and mortality (P > .05). The rs3136516 AG genotype could predispose COVID-19 patients to increased disease severity and therefore admission to the ICU, while the dominant genetic model (AA + AG vs GG) of rs3136516 exerts a protective role.

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) is a major public health problem that is globally associated with disease outbreaks and high mortality rates. As the world seeks solutions to such pathogens, global and regional surveillance is required. The aim of the present study was to examine the antimicrobial susceptibility pattern and clonal relatedness of Klebsiella pneumoniae isolates collected for a period of three years through pulse field gel electrophoresis (PFGE). Isolate IDs, antimicrobial assays, ESBL-production, and minimum inhibitory concentrations (MICs) were examined with the Vitek 2 Compact Automated System. IDs were confirmed by 16S rRNA gene sequencing, with the resulting sequences being deposited in NCBI databases. DNA was extracted and resistance genes were detected by PCR amplification with appropriate primers. Isolates were extensive (31%) and multidrug-resistant (65%). Pulsotype clusters grouped the isolates into 22 band profiles that showed no specific pattern with phenotypes. Of the isolates, 98% were ESBL-KP, 69% were carbapenem-resistant Enterobacteriaceae (CRE) strains, and 72.5% comprised the carriage of two MBLs (SIM and IMP). Integrons (ISAba1, ISAba2, and IS18) were detected in 69% of the MDR-KP. Additionally, OXA-23 was detected in 67% of the isolates. This study therefore demonstrates clonal diversity among clinical K. pneumoniae, confirming that this bacterium has access to an enormous pool of genes that confer high resistance-developing potential.

Neonatal sepsis is a great challenge for clinicians and infection control practitioners, especially in facilities with limited resources. Carbapenem-resistant Klebsiella pneumoniae (CRKP) is rapidly increasing and carriages a major threat to neonates. We aimed to examine phenotypes causing neonatal late onset sepsis (NLOS) in comparison with neonatal early onset sepsis (NEOS) with further investigations of genotypes, and genetic relatedness of CRKP in neonatal late-onset sepsis. Our study included 88 neonates diagnosed with sepsis: 58 with (NLOS) and 30 with (NEOS) from November 2015 to April 2016, at neonatal intensive care unit (NICU) of Cairo University Hospital. K. pneumoniae was the most common encountered pathogen in the NLOS group (37.9%) with a mean sepsis score of 6.39 when compared to the NEOS group (p < 0.05). In Klebsiella group, C-reactive protein and interleukin-6 levels were significantly high (p ˂ 0.001) and 56.5% of the isolates were meropenem resistant. The most prevalent carbapenemase gene was OXA-48 which was identified in 14/23 (60.8%) followed by NDM-1 which was identified in 12/23 (52.2%) as detected by multiplex PCR. Coexistence of both carbapenemases was found in 52.2% (12/23). The blaKPC, blaIMP, and blaVIM genes were not harbored in the isolates. By investigating the genetic relatedness of CRKP by pulsed-field gel electrophoresis, 23 isolates of K. pneumoniae revealed various pulsed-field gel electrophoresis (PFGE) patterns, demonstrating that the isolates were non-clonal. Awareness of the existing phenotypes and genotypes is important for proper treatment and infection control practices.

Cadmium telluride quantum dots (CdTe-QDs) are acquiring great interest in terms of their applications in biomedical sciences. Despite earlier sporadic studies on possible oncogenic roles and anticancer properties of CdTe-QDs, there is limited information regarding the oncogenic potential of CdTe-QDs in cancer progression. Here, we investigated the oncogenic effects of CdTe-QDs on the gene expression profiles of Chang cancer cells. Chang cancer cells were treated with 2 different doses of CdTe-QDs (10 and 25 μg/ml) at different time intervals (6, 12, and 24 h). Functional annotations helped identify the gene expression profile in terms of its biological process, canonical pathways, and gene interaction networks activated. It was found that the gene expression profiles varied in a time and dose-dependent manner. Validation of transcriptional changes of several genes through quantitative PCR showed that several genes upregulated by CdTe-QD exposure were somewhat linked with oncogenesis. CdTe-QD-triggered functional pathways that appear to associate with gene expression, cell proliferation, migration, adhesion, cell-cycle progression, signal transduction, and metabolism. Overall, CdTe-QD exposure led to changes in the gene expression profiles of the Chang cancer cells, highlighting that this nanoparticle can further drive oncogenesis and cancer progression, a finding that indicates the merit of immediate in vivo investigation.

Interleukin-37 (IL-37) has recently been recognized as a strong anti-inflammatory cytokine having anti-tumor activity against hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected patients. HCC is a typical inflammation-related cancer, and genetic variations within the IL-37 gene may be associated with the risk of HBV infection. Identification of the allelic patterns that genetically have a high disease risk is essential for the development of preventive diagnostics for HBV-mediated liver disease pathogenesis. In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within the IL-37 gene and disease sequelae associated with HBV infection. We genotyped ten IL-37 SNPs in 1274 patients infected with HBV and 599 healthy controls from a Saudi Arabian population. Among the selected SNPs, two SNPs (rs2723175 and rs2708973) were strongly associated with HBV infection, and six SNPs (rs2723176, rs2723175, rs2723186, rs364030, rs28947200, rs4392270) were associated with HBV clearance, comparing healthy controls and HBV infected-patients respectively. A suggestive association of rs4849133 was identified with active HBV surface antigen (HBsAg) carrier and HBV-related liver disease progression. In conclusion, our findings suggest that variations at the IL-37 gene may be useful as genetic predictive risk factors for HBV infection and HBV-mediated liver disease progression in the Saudi Arabian population.

Background: Shigella flexneri is a major cause of shigellosis in developing regions and is known to cause outbreaks in institutional settings. Transmission occurs via the fecal–oral route. It invades intestinal epithelial cells, causing diarrhea, systemic symptoms, and complications such as hemolytic uremic syndrome. This study aimed to characterize the clinical presentation, administered treatment, infection outcomes, and infection control measures during a local S. flexneri outbreak at a rehabilitation center. Methods: This case series at King Saud University Medical City (Oct–Dec 2024) investigated S. flexneri infections from a rehabilitation center. Stool and blood samples were cultured and analyzed using microbiological methods. Molecular studies were used to verify the genetic linkage between the isolates and to study their virulence genes. Results: Four cases of S. flexneri were included, involving patients with various comorbidities, residing in a rehabilitation center, and presenting with symptoms like fever and diarrhea. Laboratory investigations revealed leukocytosis, electrolyte imbalances, and elevated inflammatory markers. Imaging studies showed findings consistent with colitis in two cases. Patients were managed with IV fluids and targeted antibiotics, leading to symptom resolution. Molecular studies confirmed the genetic relatedness between the S. flexneri isolates, with virulence genes indicating cellular invasion and inflammation as primary drivers of disease severity. Outbreak management comprised contact isolation, environmental disinfection, and education. Conclusions: S. flexneri outbreaks in long-term care facilities pose challenges among bedbound patients. Diapers may facilitate transmission, and infections may cause severe complications. Robust infection control, identifying outbreak sources, and strengthening prevention strategies are essential to protect vulnerable populations.

Introduction: Serratia marcescens is a significant hospital-acquired pathogen, and many outbreaks of S. marcescens infection have been reported in neonates. We report a sudden breakout of S. marcescens harboring the blaIMP-4 and blaVIM-2 metallo-β-lactamase (MBL) genes that occurred from March to August 2015 in the neonatal intensive care unit of Cairo University Hospital, Cairo, Egypt. Methods: During the study period, 40 nonduplicate clinical isolates of S. marcescens were collected from blood culture samples. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to identify each isolate. Then, minimum inhibitory concentrations of different antibiotics were assessed by the Vitek 2 compact system. Screening of the MBL genes blaIMP, blaVIM, blaSIM-1, blaSPM-1, and blaGIM-1 as well as the carbapenemase genes KPC, NDM, OXA-48, SME-1, and SME-2 were evaluated. Pulsed field gel electrophoresis was preformed to detect the genetic relationship of the isolates. Results: Analysis showed that 37.5% of the S. marcescens clinical isolates were resistant to meropenem (minimum inhibitory concentrations ≥ 2 µg/mL), and blaIMP-4 and blaVIM-2 were the most prevalent MBL genes (42.5% and 37.5%, respectively). None of the other investigated genes were observed. Pulsed field gel electrophoresis typing revealed two discrete clones; 33/40 (82.5%) were pulsotype A and 7/40 (17.5%) were pulsotype B. Conclusion: Here, we report for the first time the detection of MBL-producing S. marcescens isolates, particularly IMP-4 and VIM-2 recovered from inpatients with bacteremias from the intensive care unit at Cairo University Hospital.

Viral mutations acquired during the course of chronic hepatitis B virus (HBV) infection are known to be associated with the progression and severity of HBV-related liver disease. This study of HBV-infected Saudi Arabian patients aimed to identify amino acid substitutions within the precore/core (preC/C) region of HBV, and investigate their impact on disease progression toward hepatocellular carcinoma (HCC). Patients were categorized according to the severity of their disease, and were divided into the following groups: inactive HBV carriers, active HBV carriers, liver cirrhosis patients, and HCC patients. Two precore mutations, W28 and G29D, and six core mutations, F24Y, E64D, E77Q, A80I/T/V, L116I, and E180A were significantly associated with the development of cirrhosis and HCC. Six of the seven significant core mutations that were identified in this study were located within immuno-active epitopes; E77Q, A80I/T/V, and L116I were located within B-cell epitopes, and F24Y, E64D, and V91S/T were located within T-cell epitopes. Multivariate risk analysis confirmed that the core mutations A80V and L116I were both independent predictors of HBV-associated liver disease progression. In conclusion, our data show that mutations within the preC/C region, particularly within the immuno-active epitopes, may contribute to the severity of liver disease in patients with chronic hepatitis. Furthermore, we have identified several distinct preC/C mutations within the study population that affect the clinical manifestation and progression of HBV-related disease. The specific identity of HBV mutations that are associated with severe disease varies between different ethnic populations, and so the specific preC/C mutations identified here will be useful for predicting clinical outcomes and identifying the HBV-infected patients within the Saudi population that are at high risk of developing HCC.

The thrombospondin related anonymous protein (TRAP) is considered one of the most important pre-erythrocytic vaccine targets. Earlier population genetic studies revealed the TRAP gene to be under strong balancing natural selection. This study is the first attempt to analyze genetic diversity, natural selection, phylogeography and population structure in 199 clinical samples from Saudi Arabia using the full-length PfTRAP gene. We found the rate of nonsynonymous substitutions to be significantly higher than that of synonymous substitutions in the clinical samples, indicating a strong positive or diversifying selection for the full-length gene and the Von Willebrand factor (VWF). The nucleotide diversity was found to be π~0.00789 for the full-length gene; however, higher nucleotide diversity was observed for the VWF compared to the thrombospondin repeat region (TSP). Deduction of the amino acid sequence alignment of the PNP repeat region in the Saudi samples revealed six genotypes characterized by tripeptide repeat motifs (PNP, ANP, ENP and SNP). Haplotype network, population structure and population differentiation analyses indicated four distinct sub-populations in spite of the low geographical distance between the sampling sites. Our results suggest the likeliness of independent parasite evolution, creating opportunities for further adaptation, including host transition, and making malaria control even more challenging.

Introduction: In early 2009, a novel influenza A (H1N1) virus appeared in Mexico and rapidly disseminated worldwide. Little is known about the phylogeny and evolutionary dynamics of the H1N1 strain found in Saudi Arabia. Methodology: Nucleotide sequencing and bioinformatics analyses were used to study molecular variation between the virus isolates. Results: In this report, 72 hemagglutinin (HA) and 45 neuraminidase (NA) H1N1 virus gene sequences, isolated in 2009 from various regions of Saudi Arabia, were analyzed. Genetic characterization indicated that viruses from two different clades, 6 and 7, were circulating in the region, with clade 7, the most widely circulating H1N1 clade globally in 2009, being predominant. Sequence analysis of the HA and NA genes revealed a high degree of sequence identity with the corresponding genes from viruses circulating in the South East Asia region and with the A/California/7/2009 strain. New mutations in the HA gene of pandemic H1N1 (pH1N1) viruses, that could alter viral fitness, were identified. Relaxed-clock and Bayesian Skyline Plot analyses, based on the isolates used in this study and closely related globally representative strains, indicated marginally higher substitution rates than the type strain (5.14×10-3 and 4.18×10-3 substitutions/nucleotide/year in the HA and NA genes, respectively). Conclusions: The Saudi isolates were antigenically homogeneous and closely related to the prototype vaccine strain A/California/7/2009. The antigenic site of the HA gene had acquired novel mutations in some isolates, making continued monitoring of these viruses vital for the identification of potentially highly virulent and drug resistant variants.