Influences of Different Torques on the Size of the Microgap and Bacterial Leakage in Different Implant Systems: An In-vitro Study.

PURPOSE: To evaluate the adherence of three types of bacteria [Staphylococcus (S) aureus, Escherichia (E) coli, Pseudomonas (Ps) aeruginosa] and the size of the microgap of three different implant systems (JD, ORA, and Ankylos) under four different screw torque values. MATERIALS AND METHODS: Ten samples for each tested implant system were used under different torques to determine the width of the gaps. The abutments were connected to the fixtures using a universal digital wrench. A torque value of 10 N/cm was applied for all samples. After the assessment of the microgap, the fixture was repositioned into the Bench Vice, and the torque was increased to 20, 30, and, finally, 40 N/cm. The microgap assessment was done using a Scanning Electron Microscope. Before the torque increased to 40, eleven samples for each tested implant system were used under 30 N/cm torque to determine the leakage in the tested implants for S. aureus, E. coli, and Ps. aeruginosa. Data were analyzed with multiple one-way ANOVA, Post Hoc, and chi-square tests. RESULTS: The Ankylos system showed the widest gap under all torques (p < 0.005), whereas the JD system demonstrated the lowest (p < 0.005). Regarding the bacteria leakage, JD showed the highest adherence to the bacteria, and the adherence was mainly to the Ps. Aeruginosa, while the Ankylos system showed the lowest (p < 0.005). CONCLUSION: Within limits, the higher torque provides a higher fit to the IAI, offering more stability. Ankylos implant showed the widest gap, while JD showed the narrowest. Regarding the bacteria leakage, JD showed the highest adherence to Ps. Aeruginosa, while the ORA system showed the highest adherence to E. coli.

The Proinflammatory Role of ANGPTL8 R59W Variant in Modulating Inflammation through NF-κB Signaling Pathway under TNFα Stimulation.

BACKGROUND: Angiopoietin-like protein 8 (ANGPTL8) is known to regulate lipid metabolism and inflammation. It interacts with ANGPTL3 and ANGPTL4 to regulate lipoprotein lipase (LPL) activity and with IKK to modulate NF-κB activity. Further, a single nucleotide polymorphism (SNP) leading to the ANGPTL8 R59W variant associates with reduced low-density lipoprotein/high-density lipoprotein (LDL/HDL) and increased fasting blood glucose (FBG) in Hispanic and Arab individuals, respectively. In this study, we investigate the impact of the R59W variant on the inflammatory activity of ANGPTL8. METHODS: The ANGPTL8 R59W variant was genotyped in a discovery cohort of 867 Arab individuals from Kuwait. Plasma levels of ANGPTL8 and inflammatory markers were measured and tested for associations with the genotype; the associations were tested for replication in an independent cohort of 278 Arab individuals. Impact of the ANGPTL8 R59W variant on NF-κB activity was examined using approaches including overexpression, luciferase assay, and structural modeling of binding dynamics. RESULTS: The ANGPTL8 R59W variant was associated with increased circulatory levels of tumor necrosis factor alpha (TNFα) and interleukin 7 (IL7). Our in vitro studies using HepG2 cells revealed an increased phosphorylation of key inflammatory proteins of the NF-κB pathway in individuals with the R59W variant as compared to those with the wild type, and TNFα stimulation further elevated it. This finding was substantiated by increased luciferase activity of NF-κB p65 with the R59W variant. Modeled structural and binding variation due to R59W change in ANGPTL8 agreed with the observed increase in NF-κB activity. CONCLUSION: ANGPTL8 R59W is associated with increased circulatory TNFα, IL7, and NF-κB p65 activity. Weak transient binding of the ANGPTL8 R59W variant explains its regulatory role on the NF-κB pathway and inflammation.

Targeted Metabolomics Analysis of Individuals Carrying the ANGPTL8 R59W Variant.

ANGPTL8 is recognized as a regulator of lipid metabolism through its role in inhibiting lipoprotein lipase activity. ANGPTL8 gene variants, particularly rs2278426 leading to the R59W variant in the protein, have been associated with lipid traits in various ethnicities. We aimed to use metabolomics to understand the impact of the ANGPTL8 R59W variant on metabolites in humans. We used the Biocrates-p400 kit to quantify 408 plasma metabolites in 60 adult male Arab individuals from Kuwait and identify differences in metabolite levels between individuals carrying reference genotypes and those with carrier genotypes at ANGPTL8 rs2278426. Individuals with carrier genotypes (CT+TT) compared to those carrying the reference genotype (CC) showed statistically significant differences in the following metabolites: acylcarnitine (perturbs metabolic pathways), phosphatidylcholine (supports liver function and cholesterol levels), cholesteryl ester (brings chronic inflammatory response to lipoprotein depositions in arteries), α-aminoadipic acid (modulates glucose homeostasis), histamine (regulates glucose/lipid metabolism), sarcosine (links amino acid and lipid metabolism), diacylglycerol 42:1 (regulates homeostasis of cellular lipid stores), and lysophosphatidylcholine (regulates oxidative stress and inflammatory response). Functional aspects attributed to these metabolites indicate that the ANGPTL8 R59W variant influences the concentrations of lipid- and inflammation-related metabolites. This observation further highlights the role of ANGPTL8 in lipid metabolism.

Changes in serum hypoxia-inducible factor-1α and erythropoietin in allergic rhinitis patients: Correlation with the Th inflammatory profile and disease comorbidities.

OBJECTIVES: The balance between proinflammatory IFN-γ Th1 vs. the anti-inflammatory allergy-mediating IL-4-heralded Th2 reactions is pivotal in IgE-mediated allergic rhinitis (AR). Hypoxia-Inducible Factor (HIF)-1α is inducible by hypoxia and various cytokines. HIF-1α activates different anti-pathogen and allergic immune cells. This cross-sectional study assessed the changes in serum HIF-1α and its dependent erythropoietin (EPO) levels among hospital-characterized AR patients. Type of the immune reaction, Th1 vs. Th2, was stratified based on the calculated IL-4/IFN-γ direct ratio, after being measured using specific ELISA assays. METHODS: 147 AR patients (83 males/64 females), and age-, BMI-, and gender-matched 24 healthy controls (13 males/11 females) were sequentially enrolled at ENT Unit, Prince Muteb General Hospital, Sakaka, Saudi Arabia. Measurement of serum parameters was carried out using specific ELISA assays. RESULTS: Contrary to the majority of previous publications, all controls and the majority of patients (n = 137/147) exhibited naive Th0 immune response. IFN-γ and HIF-1α levels were greater in controls than in patients (168.9 ± 173.9 vs 108 ± 94.5 pg/mL; p<.012) and controls had a lower IL-4/IFN-ratio (2.439 ± 0.897 vs 3.33 ± 1.19; p<.001) than patients. The HIF-1α results disagree with earlier studies. Due to the wide inter-individual variations, serum IL-4 and EPO levels in controls were non-significantly higher than patients. Lower IL-4 levels (267.3 ± 79.95 vs 353.4 ± 320.6 pg/mL; p < .01) and the ratio (2.814 ± 1.335 vs 3.431 ± 1.137; p < .05) were associated with obstructive sleep apnea. Lower ratio was also associated with inferior turbinate hypertrophy (3.051 ± 1.026 vs 3.787 ± 1.310; p < .001). EPO and IL-4 levels were lower in patients with deviated nasal septum (66.69 ± 26.81 vs 84.24 ± 61.5 pg/mL; p < .021; and 299.5 ± 137.3 vs 391.1 ± 52.780 pg/mL; p < .001, respectively). Significant correlations were found between the recorded levels and AR comorbidities. CONCLUSION: These results confirmed a pathogenic implication for HIF-1α and IFN-γ in AR that warranted future bigger and longitudinal studies.

Anti­inflammatory effect of metformin against an experimental model of LPS­induced cytokine storm.

Cytokine storm is one of the leading causes of death in patients with COVID-19. Metformin has been shown to inhibit the action of a wide range of proinflammatory cytokines such as IL-6, and TNF-α which may ultimately affect cytokine storm due to Covid-19. The present study analyzed the anti-inflammatory effect of oral and intraperitoneal (IP) metformin administration routes in a mouse model of lipopolysaccharide (LPS)-induced cytokine storm. A total of 60 female BALB/c mice were randomly assigned to one of six groups: i) Control; ii) LPS model; iii) oral saline + LPS; iv) oral metformin + LPS; v) IP saline + LPS; and vi) IP metformin + LPS. Metformin or saline were administered to the mice for 30 days, after which an IP injection of 0.5 mg/kg LPS induced a cytokine storm in the five treatment groups. Mice were sacrificed and serum cytokine levels were measured. Pretreatment of mice with either oral or IP metformin significantly reduced the increase in IL-1, IL-6 and TNF-α following LPS injection. Both metformin administration routes significantly reduced IL-1 and TNF-α levels, although IP metformin appeared to be significantly more effective at reducing IL-6 levels compared with oral metformin. Neither the oral or IP route of administration of metformin demonstrated a significant effect on IL-17 levels. Based on its ability to suppress the proinflammatory LPS-induced cytokine storm, metformin may have future potential benefits in ameliorating human diseases caused by elevated cytokine levels.

Prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae among clinical isolates in Turaif general hospital, northern borders- Saudi Arabia.

INTRODUCTION: Enterobacteriaceae that produce extended-spectrum beta-lactamase (ESBL) are quickly spreading, posing a threat to world healthcare. METHODOLOGY: 138 gram-negative bacteria were collected from different samples (stool, urine, wound, blood, tracheal aspirate, catheter tip, vaginal swab, sputum, and tracheal aspirate) from hospitalized patients. Samples were subcultured and identified in accordance with their biochemical reactions and culture characteristics. Against all the isolated Enterobacteriaceae, an antimicrobial susceptibility test was performed. VITEK®2 system, phenotypic confirmation, and Double-Disk Synergy Test (DDST) had been utilized to identify the ESBLs. RESULTS: Of the 138 samples studied, the prevalence of ESBL-producing infections among the clinical samples of the present study was 26.8 % (n = 37). E. coli was the commonest ESΒL producer at 51.4% (n = 19) followed by K. pneumoniae at 27% (n = 10). The potential risk factors for the ESBL development that produces bacteria were as follows, patients with the presence of indwelling devices, previous history of hospital admission, and usage of antibiotics. ESBL is statistically (p ≤ 0.05) higher among the patients with indwelling devices, ICU admission, who had a previous hospital admission in the last 6 months as well as who was given antibiotics (quinolones and/or cephalosporins) in the last 6 months. One hundred thirty-two (95.7%) of ESBL isolates were resistant to amoxicillin, while the lowest resistance was for fosfomycin (15.2%). CONCLUSIONS: ESBL-producing Enterobacteriaceae are highly prevalent in Turaif General Hospital setting with some potential risk factors. A strict policy to be made available on the usage of antimicrobials in hospitals and clinics should be established.

Detection and Quantification of Some Ethanol-Producing Bacterial Strains in the Gut of Mouse Model of Non-Alcoholic Fatty Liver Disease: Role of Metformin.

Ethanol-producing dysbiotic gut microbiota could accelerate the progress of non-alcoholic fatty liver disease (NAFLD). Metformin demonstrated some benefits in NAFLD. In the present study, we tested the ability of metformin to modify ethanol-producing gut bacterial strains and, consequently, retard the progress of NAFLD. This 12-week study included forty mice divided into four groups (n = 10); normal diet, Western diet, Western diet with intraperitoneal metformin, and Western diet with oral metformin. Oral metformin has a slight advantage over intraperitoneal metformin in ameliorating the Western diet-induced changes in liver function tests and serum levels of different cytokines (IL-1ß, IL-6, IL-17, and TNF-α). Changes in liver histology, fibrosis, lipid content, Ki67, and TNF-α were all corrected as well. Faecal ethanol contents were increased by the Western diet but did not improve after treatment with metformin although the numbers of ethanol-producing Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) were decreased by oral metformin. Metformin did not affect bacterial ethanol production. It does not seem that modification of ethanol-producing K. pneumoniae and E. coli bacterial strains by metformin could have a significant impact on the therapeutic potentials of metformin in this experimental model of NAFLD.

Histopathology of Corneal Lenticules Obtained from Small Incision Lenticule Extraction (SMILE) versus Microkeratome Excision.

Purpose: To study the alterations on the lenticules extracted after femtosecond (Femto) small incision lenticule extraction (SMILE) versus the corneal free cap removed using a microkeratome. Methods: The visuMax (500 kHz; laser energy: 180 nJ) was used for small-incision lenticule extraction. Free caps from human cadaveric corneas were excised by microkeratome. The collected lenticules were examined with the light and transmission electron microscope (TEM) for histological analysis, DNA fragmentation was assessed by agarose gel electrophoresis, DNA damage was evaluated using comet assay, and corneal proteins secondary structure was assessed by Fourier transform infrared spectroscopy (FTIR). Results: Light microscopic examination showed the presence of more edematous stroma under Femto SMILE than under free cap with a percentage change of 101.6%. In the Femto SMILE group, TEM examination showed pyknotic keratocytes, disruption, and cavitation of the collagen arrays stromal area under Femto SMILE. The DNA fragmentation for the Femto SMILE group revealed one undefined band with a size of 1.1 Kbp. The comet assay analysis indicated the presence of 3% and 8.0% tailed cells for the free cap and Femto SMILE groups, respectively. The tail lengths were 1.33 ± 0.16 and 1.67 ± 0.13 µm (P < 0.01), the percentage of tail DNA was 1.41 ± 0.18% (P < 0.01) and 1.72 ± 0.15%, and the tail moments were 1.88 ± 0.12 AU and 2.87 ± 0.14 AU (P < 0.001) for the free cap and Femto SMILE groups, respectively. FTIR spectroscopy of the Femto smile group revealed disorders in the secondary and tertiary structure of the proteins. Conclusion: Femto SMILE technique induced more structural changes, DNA fragmentation, DNA damage, and corneal proteins secondary structure alteration than those induced by a microkeratome cutting. These changes may be attributed to the deep penetration of high energy levels to the corneal layer. These findings may highlight the potential impact of the Femto SMILE on the cornea and the necessity for managing the laser parameters used.

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.

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.

MRSA as an indicator of infection control measures in Turaif General Hospital, Northern Area-Saudi Arabia.

INTRODUCTION: Saudi Arabia can be considered a hot spot for Methicillin-resistant Staphylococcus aureus (MRSA) infections with significant regional variations. As far as we know, this is the first study to evaluate the prevalence of MRSA in clinical samples obtained from Turaif general hospital (TGH), Northern Area-Saudi Arabia, and screening the resistance profile to the most regularly used antimicrobials as an indicator for evaluation of the implemented infection control measures. METHODOLOGY: Totally, 410 Samples were collected from patients in TGH with clinically suspected nosocomial infections. MRSA isolates were identified by the classical bacteriological, biochemical, and cefoxitin-based methods as recommended by the Clinical Laboratory Standard Institute. Confirmation of isolates and testing of their antimicrobial susceptibilities were performed by the automated Vitek 2 compact system. RESULTS: Totally, 130 nosocomial isolates were detected. Staphylococcus aureus (29.23%) was the most frequently isolated Gram-positive pathogen. MRSA represented 39.47% of Staphylococcus aureus and 11.54% of all isolates. MRSA-causing surgical site infections were the most predominant type of MRSA nosocomial infections representing (25.00%). Recent antibiotic therapy, prolonged hospital stays, and indwelling devices were significant risk factors for the development of MRSA infections. Although all MRSA isolates were sensitive to vancomycin, teicoplanin, linezolid, Fosfomycin, and tigecycline, many isolates were resistant to other tested antimicrobials. CONCLUSIONS: Hospital administrators should strengthen the ideal use of antibiotics according to the local hospital policy to control the selective drug pressure on Staphylococcus aureus strains with minimizing exposure to the risk factors by implementing the proper infection control policies.

Dimethoate residues in Pakistan and mitigation strategies through microbial degradation: a review.

Organophosphate pesticides (OPs) are used extensively for crop protection worldwide due to their high water solubility and relatively low persistence in the environment compared to other pesticides, such as organochlorines. Dimethoate is a broad-spectrum insecticide that belongs to the thio-organophosphate group of OPs. It is applied to cash crops, animal farms, and houses. It has been used in Pakistan since the 1960s, either alone or in a mixture with other OPs or pyrethroids. However, the uncontrolled use of this pesticide has resulted in residual accumulation in water, soil, and tissues of plants via the food chain, causing toxic effects. This review article has compiled and analyzed data reported in the literature between 1998 and 2021 regarding dimethoate residues and their microbial bioremediation. Different microorganisms such as bacteria, fungi, and algae have shown potential for bioremediation. However, an extensive role of bacteria has been observed compared to other microorganisms. Twenty bacterial, three fungal, and one algal genus with potential for the remediation of dimethoate have been assessed. Active bacterial biodegraders belong to four classes (i) alpha-proteobacteria, (ii) gamma-proteobacteria, (iii) beta-proteobacteria, and (iv) actinobacteria and flavobacteria. Microorganisms, especially bacterial species, are a sustainable technology for dimethoate bioremediation from environmental samples. Yet, new microbial species or consortia should be explored.

Pulmonary tuberculosis susceptibility and association with Toll-Like receptor 2 Arg753Gln polymorphism.

INTRODUCTION: Tuberculosis has been a concern of healthcare professionals due to the serious threats it poses on public health safety. However, regardless all the efforts, no appropriate goals for immunological diagnosis or tuberculosis treatment were established. Toll-like receptor 2 is one of the toll-like receptors, which plays a fundamental role in recognizing and hosting defense against Mycobacterium tuberculosis infection. Toll-like receptor 2's genetic polymorphism (arginine-to-glutamine substitution at residue 753 (Arg753Gln)) was linked to negative effects on the function of Toll-like receptor 2 which, in turn, impacts the body's resistance or susceptibility to tuberculosis. The current study aimed at investigating the single Arg753Gln nucleotide polymorphism of the Toll-like receptor 2 gene in patients with tuberculosis infection versus a sample of healthy subjects as controls. METHODOLOGY: A comparative study was conducted to investigate Toll-like receptor 2 polymorphism of the single nucleotide gene Arg753Gln in 30 patients with pulmonary tuberculosis and compare their results with other 20 healthy controls matched by age and sex. RESULTS: TLR-2-Arg polymorphism allele A occurred in 36.7% of the patient group. Homozygous carriers of allele A/A polymorphism occurred in 13.4% compared to 5% among controls, while GA genotype was found in 23.3% among the study group and 10% among controls. The association between GA genotype and pulmonary tuberculosis was found statistically significant (p = 0.002) than other genotypes. Allele frequency for both G and A were (p =0.002) in patient groups and (p =0.000) among the control group. CONCLUSIONS: TLR-2 Arg753Gln polymorphisms may have a crucial role in pulmonary tuberculosis susceptibility among Egyptian patients.

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.

Electron microscopic comparison of the donor cut edges using femtosecond laser-assisted keratoplasty versus conventional keratoplasty.

PURPOSE: To describe and compare the histological changes in the cut edges of the remaining donor corneal rim using femtosecond laser-assisted keratoplasty (FAK) versus conventional penetrating keratoplasty (PK) via light and transmission electron microscopic examination. METHODS: This was a prospective observational study of 10 eyes; 5 FAK (top-hat technique) and 5 conventional PK. Main outcomes were histological findings at the cut edge of the donor corneal rim (at 3, 6, 9, and 12 o'clock). RESULTS: Cellular and ultra-cellular changes in the form of stromal edema, disorganized collagen fibers, and nuclear changes were more prominent in the FAK eyes as compared to the conventional PK ones. CONCLUSION: FAK induces more collateral damage in the cut edge of corneal donor graft at cellular and ultra-cellular levels, compared to conventional trephination. Further studies are required to investigate the clinical ramifications of this observation.

Relevance between COVID-19 and host genetics of immune response.

The outbreak of coronavirus disease 2019 (COVID-19) was caused by the newly emerged corona virus (2019-nCoV alias SARS-CoV-2) that resembles the severe acute respiratory syndrome virus (SARS-CoV). SARS-CoV-2, which was first identified in Wuhan (China) has spread globally, resulting in a high mortality worldwide reaching ~4 million deaths to date. As of first week of July 2021, ~181 million cases of COVID-19 have been reported. SARS-CoV-2 infection is mediated by the binding of virus spike protein to Angiotensin Converting Enzyme 2 (ACE2). ACE2 is expressed on many human tissues; however, the major entry point is probably pneumocytes, which are responsible for synthesis of alveolar surfactant in lungs. Viral infection of pneumocytes impairs immune responses and leads to, apart from severe hypoxia resulting from gas exchange, diseases with serious complications. During viral infection, gene products (e.g. ACE2) that mediate viral entry, antigen presentation, and cellular immunity are of crucial importance. Human leukocyte antigens (HLA) I and II present antigens to the CD8+ and CD4+ T lymphocytes, which are crucial for immune defence against pathogens including viruses. HLA gene variants affect the recognition and presentation of viral antigenic peptides to T-cells, and cytokine secretion. Additionally, endoplasmic reticulum aminopeptidases (ERAP) trim antigenic precursor peptides to fit into the binding groove of MHC class I molecules. Polymorphisms in ERAP genes leading to aberrations in ERAP's can alter antigen presentation by HLA class I molecules resulting in aberrant T-cell responses, which may affect susceptibility to infection and/or activation of immune response. Polymorphisms from these genes are associated, in global genetic association studies, with various phenotype traits/disorders many of which are related to the pathogenesis and progression of COVID-19; polymorphisms from various genes are annotated in genotype-tissue expression data as regulating the expression of ACE2, HLA's and ERAP's. We review such polymorphisms and illustrate variations in their allele frequencies in global populations. These reported findings highlight the roles of genetic modulators (e.g. genotype changes in ACE2, HLA's and ERAP's leading to aberrations in the expressed gene products or genotype changes at other genes regulating the expression levels of these genes) in the pathogenesis of viral infection.

Prognostic Genetic Markers for Thrombosis in COVID-19 Patients: A Focused Analysis on D-Dimer, Homocysteine and Thromboembolism.

COVID-19 is caused by Severe Acute Respiratory Syndrome Coronavirus-2, which has infected over thirty eight million individuals worldwide. Emerging evidence indicates that COVID-19 patients are at a high risk of developing coagulopathy and thrombosis, conditions that elevate levels of D-dimer. It is believed that homocysteine, an amino acid that plays a crucial role in coagulation, may also contribute to these conditions. At present, multiple genes are implicated in the development of these disorders. For example, single-nucleotide polymorphisms (SNPs) in FGG, FGA, and F5 mediate increases in D-dimer and SNPs in ABO, CBS, CPS1 and MTHFR mediate differences in homocysteine levels, and SNPs in TDAG8 associate with Heparin-induced Thrombocytopenia. In this study, we aimed to uncover the genetic basis of the above conditions by examining genome-wide associations and tissue-specific gene expression to build a molecular network. Based on gene ontology, we annotated various SNPs with five ancestral terms: pulmonary embolism, venous thromboembolism, vascular diseases, cerebrovascular disorders, and stroke. The gene-gene interaction network revealed three clusters that each contained hallmark genes for D-dimer/fibrinogen levels, homocysteine levels, and arterial/venous thromboembolism with F2 and F5 acting as connecting nodes. We propose that genotyping COVID-19 patients for SNPs examined in this study will help identify those at greatest risk of complications linked to thrombosis.

Prevalence, risk factors and impact of occult HCV infection on liver morbidity among haemodialysis patients: hospital-based cross-sectional study.

OBJECTIVES: Haemodialysis (HD) patients are at risk for blood-borne infections as occult HCV infection, which justifies comprehensive studies. We aimed to determine the prevalence and risk factors of occult HCV infection (OCI) among HD patients. MATERIAL AND METHODS: One hundred eligible HD patients, with no evidence of overt HCV or HBV and HBV vaccinated were recruited, and tested for HCV, HBV markers and HCV RNA. Two HCV-positive patients were excluded and peripheral mononuclear cells of 98 patients were verified for viraemia. RESULTS: OCI was detected in eight (8.16%); with a median viral load of 7010copies/ml. Their mean age was 30.63 (±18.87 years) compared to others (41.73 ± 15.93) (p = .069). History of surgery, dental procedure, and blood transfusion was comparably high in both groups (p > .05). All OCI patients underwent dialysis twice weekly compared to 48.9% of non-OCI patients (p = .006). OCI patients had a significantly higher mean duration of dialysis (12.63 ± 6.74 years), and a significantly higher frequency (50%) of HCV Ab compared to 6.48 ± 4.76, and 10%, respectively, in non-OCI patients. None of OCI patients was reactive to HBcAb compared to 34 (37.8%) patients without (p = .048). Evidence of liver morbidity was detected in 5 (62.5%) OCI patients compared to 43 (47.7%) of non-OCI patients (p > .05). CONCLUSION: Among our HD patients, OCI is considered a comorbid finding associated with mild liver morbidity that warrants strict infection control and periodic testing for blood borne infections.

Oral Candidal carriage and associated risk indicators among adults in Sakaka, Saudi Arabia.

BACKGROUND: Candida is a ubiquitous organism in nature which inhabits the oral cavity as part of the normal microbial flora. The oral carriage of Candida is perpetuated by several predisposing factors. METHODS: This cross-sectional study was designed to investigate the carriage rate of Candida among 104 voluntary adults at the college of medicine - Jouf University. The concentrated oral rinse technique using Sabouraud Dextrose agar medium supplemented with 0.05% Chloramphenicol was used to isolate Candida. The relative factors affecting the colonization of Candida and the concentration of each type were also determined. RESULTS: Candida species were isolated from the oral cavity of 45 (43.4%) subjects. Of these 55.6% were identifies as C. albicans as determined by the Vitek 2 compact system. Other Candida species were represented by C. glabrata (11.1%), C. krusei (11.1%), C. dubliniensis (8.9%), C. parapsilosis (6.7%), C. tropicalis (4.4%), and C. famata (2.2%). Subjects with very poor plaque status, severe gingivitis and diabetes had significantly (P = 0.001) high concentration of Candida spp. CONCLUSION: Plague, severe gingivitis, and diabetes were found to be significantly associated with higher Candida colonization.

Surveillance of antibiotic resistance among uropathogens in Aljouf region northern Saudi Arabia.

BACKGROUND AND OBJECTIVES: Urinary tract infections are common health problem affecting millions worldwide. Antibiotic resistance among uropathogens (Ups) is prevalent in many countries. In the absence of any available data in the region, this hospital-based study investigated the pattern, frequency and susceptibility of Ups at Prince Mutaib Bin Abdulaziz Hospital, Aljouf Region, Saudi Arabia. MATERIALS AND METHODS: A retrospective assessment of UPs and their antibiotics susceptibility was conducted from January 2017 to December 2017 using the fully automated Vitek2 system (BioMérieux, France). RESULTS: Among the 415 uropathogens isolates, the most prevalent bacteria were Gram-negatives comprising 137 (51%) E. coli; 46 (17.2%) Klebsiella spp.; 30 (11.2%) Pseudomonas spp.; 25 (9.3%) Proteus spp.; 14 (5.2%) Acinetobacter baumanii and 16 (5.9%) others. On the other hand, Enterococcus spp. were predominant among Gram-positive isolates representing 54 (36.7%), 47 (32.0%) Staphylococcus spp., 22 (15.1%) Streptococcus spp., and 13 (8.8%) S. aureus, and 11 (7.5%) others. Gram-negative Ups showed multidrug resistance towards the majority of the tested antimicrobials (ampicillins, cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, aztreonam, and nitrofurantoin). While high resistance patterns by Gram-positives was also seen against cephalosporins, penicillins, amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, clindamycin, erythromycin and tetracycline. CONCLUSION: The observed widespread multidrug resistance clearly warrant implementing stricter control measures, local guidelines of antimicrobials usage, and continuous epidemiological surveys at hospitals and communities.