Prevalence and risk factors associated with multidrug-resistant bacteria in COVID-19 patients.

Bacterial coinfection among patients with confirmed coronavirus disease 2019 (COVID-19) is a critical medical concern that increases the disease severity and mortality rate. The current study is aimed at evaluating the effects of bacterial coinfections among COVID-19 patients, especially in relation to degree of severity and mortality. A retrospective study was conducted for patients with positive COVID-19 test, admitted to a regional COVID-19 hospital in Jeddah, Saudi Arabia, between May and August 2020. A specimen (e.g., blood, urine, or sputum) was collected from patients with confirmed COVID-19, and was cultured to determine bacterial coinfection caused by multidrug resistant (MDR) bacteria. COVID-19 patients were categorized into 2 groups based on the result of bacterial coinfection culture, as COVID-19 patients with coinfection and COVID-19 patients without coinfection. Independent sample t test or Mann-Whitney U test was used to compare age and hospitalization period between these groups. In addition, binominal logistic regression was applied to identify risk factors associated with mortality and bacterial coinfection. The study included 342 patients with laboratory confirmed COVID-19. Eighty (23.3%) patients were diagnosed with bacterial coinfection, while the remaining 262 (76.6%) patients did not test positive for bacterial coinfection. Length of hospital stay was prolonged among COVID-19 patients diagnosed with bacterial coinfection (16.01 ±â€…11.36 days) when compared with patients without bacterial coinfection (6.5 ±â€…6.12 days). Likewise, the mortality rate was significantly higher among COVID-19 patients with bacterial coinfection (90%) compared to those without bacterial coinfection (49.2%). Gram-negative bacteria were predominant compared to gram-positive, as Klebsiella pneumoniae (35 [43.8%]) and Acinetobacter baumanni (32 [40%]). On the other hand, Staphylococcus aureus (4 [5%]), Enterococcus faecalis (1 [1.3%]), and Enterococcus faecium (1 [1.3%]) were identified as gram-positive bacterial species from recruited patients. The findings of the current study showed that prolong hospitalization is the main risk factor associated with bacterial coinfection and death. Thus, health care providers should minimize hospitalization as well as following a continuous monitoring for bacterial coinfection among COVID-19 patients, to control the spread of infection and reducing the severity and mortality rate among COVID-19 patients.

GC-MS screening of the phytochemical composition of Ziziphus honey: ADME properties and in vitro/in silico study of its antimicrobial activity.

A revival interest has been given to natural products as sources of phytocompounds to be used as alternative treatment against infectious diseases. In this context, we aimed to investigate the antimicrobial potential of Ziziphus honey (ZH) against twelve clinical bacterial strains and several yeasts and molds using in vitro and computational approaches. The well-diffusion assay revealed that ZH was able to induce growth inhibition of most Gram-positive and Gram-negative bacteria. The high mean growth inhibition zone (mGIZ) was recorded in E. coli (Clinical strain, 217), S. aureus followed by E. coli ATCC 10536 (mGIZ values: 41.00 ± 1 mm, 40.67 ± 0.57 mm, and 34.67 ± 0.57 mm, respectively). The minimal bactericidal concentrations (MBCs) and minimal fungicidal concentration values (MFCs) from approximately 266.33 mg/mL to over 532.65 mg/mL. Molecular docking results revealed that the identified compounds maltose, 2-furoic acid, isopropyl ester, 2,4-imidazolidinedione, 5-(2-methylpropyl)-(S)- and 3,4,5-trihydroxytoluene, S-Methyl-L-Cysteine, 2-Furancarboxylic acid, L-Valine-N-ethoxycarbonyl, Hexanoic acid, 3,5,5-trimethyl-, Methyl-beta-D-thiogalactoside, gamma-Sitosterol, d-Mannose, 4-O-Methylmannose, 2,4-Imidazolidinedione, 5-(2-methylpropyl)- (S) were found to have good affinity for targeted receptor, respectively. Through a 100-ns dynamic simulation research, binding interactions and stability between promising phytochemicals and the active residues of the studied enzymes were confirmed. The ADMET profiling of all identified compounds revealed that most of them could be qualified as biologically active with good absorption and permeation. Overall, the results highlighted the efficiency of ZH against the tested clinical pathogenic strains. The antimicrobial potential and the potency displayed by the identified compounds could imply their further pharmacological applications.Communicated by Ramaswamy H. Sarma.

Antimicrobial, Anticancer, and Antioxidant Activities of Maize and Clover Pollen Grains Extracts: A Comparative Study with Phytochemical Characterizations.

The failure to treat infectious diseases due to the continual emergence of drug-resistant microbes poses a huge and serious challenge for human health globally. Currently, the discovery and development of natural therapeutic compounds are attracting considerable attention from researchers worldwide. In this project, two types of pollen grains (maize and clover) were evaluated for potential antimicrobial activities. Extracts of both pollen grains were purified using HPLC, which has been shown to have numerous phenolic and flavonoid compounds. Pyro catechol and methyl gallate were detected in high concentrations (1145.56 and 1056.57 µg/mL, respectively) in the maize extract, while caffeic acid, quercetin, and kaempferol (464.73, 393.05, and 390.93 µg/mL, respectively) were among the compounds observed at high concentrations in the clover pollen grains extract. Staphylococcus aureus, Escherichia coli, Salmonella typhi, and Candida albicans were more sensitive to the clover pollen grains extract with inhibition zones of 22 ± 0.2, 18 ± 0.1, 29 ± 0.3, and 42 ± 0.4 mm compared to the size of the inhibitory zones caused by the maize pollen grains extract (19 ± 0.3, 15 ± 0.4, 27 ± 0.1, and 22 ± 0.4 mm, respectively). Moreover, lower MIC values for the clover pollen grains extract were recorded against C. albicans (1.97 ± 0.04 µg/mL), S. aureus (62.5 ± 1.00 µg/mL), and E. coli (62.5 ± 0.07 µg/mL) than the MICs caused by the maize pollen grains extract. The use of a transmission electron microscope revealed that the E. coli that had been treated with the clover pollen grains extract showed changes in its cell walls compared to that treated with the maize pollen grains extract. The clover pollen grains extract exhibited a stronger antioxidant potential, with an IC50 value of 22.18 µg/mL, compared to an IC50 value of 54.85 µg/mL for the maize pollen grains extract, via a DPPH scavenging assay. Regarding anticancer activity, the maize pollen grains extract was revealed to be more effective in terms of inhibiting the human colon cancer cell line HCT-116, with an IC50 value of 67.02 ± 1.37 µg/mL, compared with the observed toxicity caused by the clover extract, with an IC50 value of 75.03 ± 1.02 µg/mL. Overall, the clover pollen grains extract demonstrated potent antibacterial and antioxidant activities, but not anticancer activity, when compared to the maize grains extract. Thus, the current findings related to both types of pollen grains (clover and maize) highlight their potential therapeutic applications for the treatment of certain infectious diseases and malignancies.

Prevalence and risk factors associated with drug resistant bacteria in neonatal and pediatric intensive care units: A retrospective study in Saudi Arabia.

Successful empirical antibiotic therapy for infected patients with multi drug resistant bacteria (MDR) can be challenging task in various healthcare settings, including neonatal and pediatric intensive care units (NICU and PICU, respectively), unless an up-to-date comprehensive local antibiogram data is available. Thus, this project aimed to investigate the prevalence of MDR among PICU and NICU patients as well as the identification of risk factors associated with recovered MDR bacteria. This was a retrospective study of PICU and NICU patients admitted with bacterial infection of MDR organisms between October 2020 and May 2021. Frequency distribution, Chi-square test were applied to verify the significance differences among subgroups and to identify risk factor associated with each group. About 36.4% of recruited patients were neonates, while the remaining percentage (63.6%) were pediatric. The most predominant site of infection among these patients were revealed as urinary tract (35%), followed by bloodstream (20.0%), wound/skin (12.9%) and respiratory system (11.4%). Methicillin-resistant Staphylococcus aureus (MRSA) was identified as the most common microbe across these sites of infections (30.7%), followed by Escherichia coli (25.0%), Klebsiella pneumoniae (22.9%) and Serratia (10.0%). High mortality rate was significantly associated with patients who were on mechanical ventilators (28.9%, OR 5.5; 95% CI), followed by patients had invasive operation (27.5%, OR, 8.04; 95% CI) and those who required a total parental nutrition (TPN) since almost one-half of these cases have (46.2%) died. In addition, mortality rate was relatively higher among patients infected with species of Serratia (28.6%) and Enterobacter (20.0%). These data highlighted that MRSA was the main MDR bacteria isolated from PICU and NICU followed by gram-negative bacteria, which were associated with high mortality rate. Therefore, infection control measures and continuous monitoring of emerging MDR bacteria should be applied to limit the bacterial infections in NICU and PICU patients.

Knowledge, attitude, and practice of the Saudi population toward COVID-19 vaccination: A cross-sectional study.

Coronavirus Disease 2019 (COVID-19) vaccination is the most effective protective measure to control the spread of infections and provide protection against hospitalization and mortality during the pandemic. There was a necessity to measure public knowledge and acceptance for COVID-19 vaccines in different countries. Thus, the current study is aimed at evaluating the knowledge, attitude, and practice of the population in all regions of Saudi towards COVID-19 vaccination. This was a cross-sectional, online self-reported survey of Saudi residents that was conducted between March 2021 and April 2021. To be eligible for the study, participants had to be above 18 years old. All participants were adult, Arabic speakers and residents of Saudi Arabia. In total, 1658 adults participated in this study and showed high knowledge (81.8%), attitude (71.2%), and practice (59.3%). The level of knowledge, attitude, and practice differed based on different demographic characteristics. Regression analysis showed that having a low income, low education level, and middle-aged status, living in a village, and being married were associated with lower scores in knowledge, attitude, or practice. Targeted education and campaigns should be provided for these populations to increase their knowledge, attitude, and practice towards COVID-19 vaccination.

Antibiofilm, Antimicrobial, Anti-Quorum Sensing, and Antioxidant Activities of Saudi Sidr Honey: In Vitro and Molecular Docking Studies.

Sidr honey is a valuable source of bioactive compounds with promising biological properties. In the present study, antimicrobial, antioxidant, and anti-quorum sensing properties of Saudi Sidr honey were assessed, along with phytochemical analysis, via gas chromatography-mass spectrometry (GC-MS). In silico study was also carried out to study the drug-likeness properties of the identified compounds and to study their affinity with known target proteins assessed using molecular docking approach. The results showed that Saudi Sidr honey exhibited promising antibacterial activity, with MIC values ranging from 50 to 400 mg/mL and MBC values from 50 to >450 mg/mL. Interestingly, the Saudi Sidr honey was active against Candida auris and Candida neoformans, with an MIC value of about 500 mg/mL. Moreover, the Sidr honey showed important antioxidant activities (ABTS assay: IC50 5.41 ± 0.045 mg/mL; DPPH assay: IC50 7.70 ± 0.065 mg/mL) and ß-carotene bleaching test results (IC50 ≥ 20 mg/mL). In addition, the Saudi Sidr honey was able to inhibit biofilm formation on glass slides at 1/2 MIC by 77.11% for Bacillus subtilis, 70.88% for Staphylococcus aureus, 61.79% for Escherichia coli, and 56.64% for Pseudomonas aeruginosa. Similarly, violacein production by Chromobacterium violaceum was reduced by about 56.63%, while the production of pyocyanin by P. aeruginosa was decreased to 46.27% at a low concentration of Saudi Sidr honey. ADMET properties showed that five identified compounds, namely, 1-cyclohexylimidazolidin-2-one, 3-Butyl-3-methylcyclohexanone, 4-butyl-3-methoxy-2-cyclo penten-1-one, 2,2,3,3-Tetramethyl cyclopropane carboxylic acid, and 3,5-dihydroxy-2-(3-methylbut-2-en-1-yl showed promising drug-likeness properties. The compound 3,5-dihydroxy-2-(3-methylbut-2-en-1-yl exhibited the highest binding energy against antimicrobial and antioxidant target proteins (1JIJ, 2VAM, 6B8A, 6F86, 2CDU, and 1OG5). Overall, the obtained results highlighted the promising potential of Saudi Sidr honey as a rich source of bioactive compounds that can be used as food preservatives and antimicrobial, antioxidant, and anti-quorum sensing molecules.

Comparison of Hematological Parameters Between Survivors and Non-Survivors COVID-19 Patients in Saudi Arabia.

Objective: Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a communicable disease transmitted through the respiratory route and bodily contact. The severity of infection and mortality rate of COVID-19 cases was significantly high in the initial stages of the pandemic. This study aims to investigate the hematological profile of COVID-19 survivors and non-survivors. Methods: This is a single-center retrospective study. A total of 108 hospitalized patients with laboratory-confirmed COVID-19 at East Jeddah Hospital between April and August 2020 were categorized into two groups based on outcome as survivors (n = 54) and non-survivors (n = 54). Hematological parameters and clinical profiles were analyzed and compared between the two groups. Results: The mean age and standard deviation of the survived (30-71 years) and non-survived (33-83) groups was 53 ± 10.8 and 57.9 ± 12.2 years, respectively, with no statistically significant difference in age between groups (p = 0.0513). Non-survivors had a significantly longer median length of stay in the intensive care unit (ICU) (7 days, IQR: 4.24 to 12) compared to survivors COVID-19 patients (5 days, IQR: 0 to 11.75) (p = 0.0151). For the survivors group, the participant's age positively correlated with the length of hospital stay (r(52) = 0.21, p = 0.0005) and ICU length of stay r(52) = 0.18, p = 0.001). The median red blood cells (RBC) counts were significantly higher in the survived group (4.56x109/L, IQR: 4.02 to 5.11) in comparison with the non-survived (4.23x109/L, IQR: 3.75 to 4.23) group (p = 0.0011). All COVID-19 patients exhibited lymphocytopenia and a significant negative correlation was observed between the lymphocyte values and length of hospital stay among the survived group (p < 0.001) as well as length of ICU stay among the survived group (p < 0.0480). Disease-related mortality was significantly associated with reduced white blood cells (WBCs) (8.5×109/L, IQR: 6.1 to 11.7) and reduced basophils (0.09%, IQR: 0.02 to 0.19). Additionally, statistically significant differences were found between the survived and non-survived groups with respect to prothrombin time (PT) (12.5 sec. vs 14 sec., p < 0.0001) and partial thromboplastin time (PTT) (31.8 sec. vs 40 sec., p = 0.0008). Conclusion: Hematological parameters can serve as valuable indicators to identify patients with severe COVID-19 and expected poor-prognosis/outcomes upon hospital admission. Cell counts of lymphocytes, WBCs, basophils and parameters such as PT and PTT can serve as clinical indicators to assess disease severity and predict progression to critical illness.

In Vitro Antiproliferative Apoptosis Induction and Cell Cycle Arrest Potential of Saudi Sidr Honey against Colorectal Cancer.

A range of natural products have been extensively studied for their chemopreventive potential for cancer, including those that inhibit growth and induce apoptosis. Sidr honey derived from the Ziziphus or Lote tree (Ziziphus spina-christi, Ziziphus lotus, or Ziziphus jujuba) is used in a wide range of traditional medicine practices. In the current study, the Saudi Sidr honey was analyzed by means of a GC-MS chromatogram and investigated for its antiproliferative effects on colorectal cancer cells (HCT-116), breast cancer cells (MCF-7), and lung cancer cells (A-549), as well as its apoptosis induction and cell cycle arrest potentials against human colorectal cancer cells (HCT-116). The effects of Saudi Sidr honey on cells were determined using the MTT assay and the clonogenic assay. The induction of apoptosis was studied using Annexin V-FITC flow cytometry analysis. The propidium iodide staining method was used to detect cell cycle arrest via flow cytometry. By means of performing GS-MS and HR-LCMS analysis, 23 different chemical components were identified from Saudi Sidr honey. A dose-response analysis showed that Saudi Sidr honey was more effective against HCT-116 (IC50 = 61.89 ± 1.89 µg/mL) than against MCF-7 (IC50 = 78.79 ± 1.37 µg/mL) and A-549 (IC50 = 94.99 ± 1.44 µg/mL). The antiproliferation activity of Saudi Sidr honey has been found to be linked to the aggregation of cells during the G1 phase, an increase in early and late apoptosis, and necrotic cell death in HCT-116 cells. Considering these promising findings that highlight the potential use of Saudi Sidr honey as an antitumor agent, further research should be carried out with the aim of isolating, characterizing, and evaluating the bioactive compounds involved in Sidr honey's antiproliferative activity to better understand the mechanism of their action.

Revisiting the Green Synthesis of Nanoparticles: Uncovering Influences of Plant Extracts as Reducing Agents for Enhanced Synthesis Efficiency and Its Biomedical Applications.

Background: Conventional nanoparticle synthesis methods involve harsh conditions, high costs, and environmental pollution. In this context, researchers are actively searching for sustainable, eco-friendly alternatives to conventional chemical synthesis methods. This has led to the development of green synthesis procedures among which the exploration of the plant-mediated synthesis of nanoparticles experienced a great development. Especially, because plant extracts can work as reducing and stabilizing agents. This opens up new possibilities for cost-effective, environmentally-friendly nanoparticle synthesis with enhanced size uniformity and stability. Moreover, bio-inspired nanoparticles derived from plants exhibit intriguing pharmacological properties, making them highly promising for use in medical applications due to their biocompatibility and nano-dimension. Objective: This study investigates the role of specific phytochemicals, such as phenolic compounds, terpenoids, and proteins, in plant-mediated nanoparticle synthesis together with their influence on particle size, stability, and properties. Additionally, we highlight the potential applications of these bio-derived nanoparticles, particularly with regard to drug delivery, disease management, agriculture, bioremediation, and application in other industries. Methodology: Extensive research on scientific databases identified green synthesis methods, specifically plant-mediated synthesis, with a focus on understanding the contributions of phytochemicals like phenolic compounds, terpenoids, and proteins. The database search covered the field's development over the past 15 years. Results: Insights gained from this exploration highlight plant-mediated green synthesis for cost-effective nanoparticle production with significant pharmacological properties. Utilizing renewable biological resources and controlling nanoparticle characteristics through biomolecule interactions offer promising avenues for future research and applications. Conclusion: This review delves into the scientific intricacies of plant-mediated synthesis of nanoparticles, highlighting the advantages of this approach over the traditional chemical synthesis methods. The study showcases the immense potential of green synthesis for medical and other applications, aiming to inspire further research in this exciting area and promote a more sustainable future.

Effects of Repeated in-vitro Exposure to Saudi Honey on Bacterial Resistance to Antibiotics and Biofilm Formation.

Introduction: Although Sumra and Sidr Saudi honey is widely used in traditional medicine due to its potent activity, it is unknown whether its prolonged usage has impact upon bacterial virulence or leading to reduced antibiotic sensitivity. Thus, the study aims to investigate the effect of prolonged (repeated) in-vitro exposure to Saudi honey on the antibiotic susceptibility profiles and biofilm formation of pathogenic bacteria. Methods: Several bacteria, including Staphylococcus aureus, Escherichia coli, and Acinetobacter baumannii, were in-vitro exposed ten times [passaged (P10)]to Sumra and Sider honey individually to introduce adapted bacteria (P10). Antibiotic susceptibility profiles of untreated (P0) and adapted (P10) bacteria were assessed using disc diffusion and microdilution assays. The tendency regarding biofilm formation following in-vitro exposure to honey (P10) was assessed using the Crystal violet staining method. Results: Adapted (P10) bacteria to both Sumra and Sidr honey showed an increased sensitivity to gentamicin, ceftazidime, ampicillin, amoxycillin/clavulanic acid, and ceftriaxone, when compared with the parent strains (P0). In addition, A. baumannii (P10) that was adapted to Sidr honey displayed a 4-fold increase in the minimal inhibitory concentration of the same honey following in-vitro exposure. 3-fold reduction in the tendency toward biofilm formation was observed for the Sumra-adapted (P10) methicillin resistant S. aureus strain, although there was a lower rate of reduction (1.5-fold) in biofilm formation by both the Sumra- and Sidr-adapted A. baumannii (P10) strains. Conclusion: The data highlight the positive impact of prolonged in-vitro exposure to Saudi honey (Sumra and Sider) for wound-associated bacteria since they displayed a significant increase in their sensitivity profiles to the tested antibiotic and a reduction in their ability to form biofilm. The increased bacterial sensitivity to antibiotics and a limited tendency toward biofilm formation would suggest the great potential therapeutic use of this Saudi honey (Sumra and Sidr) to treat wound infections.

Phytochemical Characterization of Saudi Mint and Its Mediating Effect on the Production of Silver Nanoparticles and Its Antimicrobial and Antioxidant Activities.

The green synthesis of nanoparticles (NPs) is attracting enormous attention as a new area of study that encompasses the development and discovery of new agents for their utilization in different fields, such as pharmaceuticals and food. Nowadays, the use of plants, particularly medicinal plants, for the creation of NPs has emerged as a safe, ecofriendly, rapid, and simple approach. Therefore, the present study aimed to use the Saudi mint plant as a medicinal plant for the synthesis of silver nanoparticles (AgNPs) and to evaluate the antimicrobial and antioxidant activities of AgNPs compared to mint extract (ME). A phenolic and flavonoid analysis that was conducted by using HPLC indicated the presence of numerous compounds in the ME. Through an HPLC analysis, chlorogenic acid at a concentration of 7144.66 µg/mL was the main detected component in the ME, while catechin, gallic acid, naringenin, ellagic acid, rutin, daidzein, cinnamic acid, and hesperetin were identified in varying concentrations. AgNPs were synthesized by using ME and were confirmed via UV-visible spectroscopy at 412 nm of the maximum absorption. The mean diameter of the synthesized AgNPs was measured by TEM to be 17.77 nm. Spectra obtained by using energy-dispersive X-ray spectroscopy indicated that silver was the main element formation in the created AgNPs. The presence of various functional groups, analyzed by using Fourier transform infrared spectroscopy (FTIR), indicated that the mint extract was responsible for reducing Ag+ to Ag0. The spherical structure of the synthesized AgNPs was confirmed by X-ray diffraction (XRD). Furthermore, the ME showed reduced antimicrobial activity (a zone of inhibition of 30, 24, 27, 29, and 22 mm) compared with the synthesized AgNPs (a zone of inhibition of 33, 25, 30, 32, 32, and 27 mm) against B. subtilis, E. faecalis, E. coli, P. vulgaris, and C. albicans, respectively. The minimum inhibitory concentration of the AgNPs was lower than that of the ME for all of the tested micro-organisms, except for P. vulgaris. The MBC/MIC index suggested that the AgNPs revealed a higher bactericidal effect compared to the ME. The synthesized AgNPs exhibited antioxidant activity with a reduced IC50 (IC50 of 8.73 µg/mL) compared to that of the ME (IC50 of 13.42 µg/mL). These findings demonstrate that ME could be applied as a mediator for AgNPs synthesis and natural antimicrobial and antioxidant agents.

Antibiotic Susceptibility Profiling of Human Pathogenic Staphylococcus aureus Strains Using Whole Genome Sequencing and Genome-Scale Annotation Approaches.

Staphylococcus species are major pathogens with increasing importance due to the rise in antibiotic resistance. Whole genome sequencing and genome-scale annotation are promising approaches to study the pathogenicity and dissemination of virulence factors in nosocomial methicillin-resistant and multidrug-resistant bacteria in intensive care units. Draft genome sequences of eight clinical S. aureus strains were assembled and annotated for the prediction of antimicrobial resistance genes, virulence factors, and phylogenetic analysis. Most of the studied S. aureus strains displayed multi-resistance toward the tested drugs, reaching more than seven drugs up to 12 in isolate S22. The mecA gene was detected in three isolates (S14, S21, and S23), mecC was identified in S8 and S9, and blaZ was commonly identified in all isolates except strain S23. Additionally, two complete mobile genomic islands coding for methicillin resistance SCCmec Iva (2B) were identified in strains S21 and S23. Numerous antimicrobial resistance genes (norA, norC, MgrA, tet(45), APH(3')-IIIa, and AAC(6')-APH(2″)) were identified in chromosomes of different strains. Plasmid analysis revealed the presence of blaZ, tetK, and ermC in different plasmid types, located in gene cassettes containing plasmid replicons (rep) and insertion sequences (IS). Additionally, the aminoglycoside-resistant determinants were identified in S1 (APH(3')-IIIa), while AAC(6)-APH(2″) was detected in strains S8 and S14. The trimethoprim (dfrC) resistance gene was detected in S. aureus S21, and the fosfomycin (fosB) resistance gene was detected only in S. aureus S14. We also noted that S. aureus S1 belongs to ST1-t127, which has been reported as one of the most frequent human pathogen types. Additionally, we noted the presence of rare plasmid-mediated mecC-MRSA in some of our isolates.

Antibiotics Resistance and Adhesive Properties of Clinical Staphylococcus aureus Isolated from Wound Infections.

Staphylococcus aureus (S. aureus) is a ubiquitous pathogen responsible for several severe infections. This study aimed to investigate the adhesive properties and antibiotic resistance among clinical S. aureus isolated from Hail Hospital Province, Kingdom of Saudi Arabia (KSA), using molecular approaches. This study was conducted according to the ethical committee at Hail's guidelines on twenty-four S. aureus isolates. A polymerase chain reaction (PCR) was performed to identify genes encoding the ß-lactamase resistance (blaZ), methicillin resistance (mecA), fluoroquinolone resistance (norA), nitric oxide reductase (norB), fibronectin (fnbA and fnbB), clumping factor (clfA) and intracellular adhesion factors (icaA and icaD). This qualitative study tested adhesion based on exopolysaccharide production on Congo red agar (CRA) medium and biofilm formation on polystyrene by S. aureus strains. Among 24 isolates, the cna and blaz were the most prevalent (70.8%), followed by norB (54.1%), clfA (50.0%), norA (41.6%), mecA and fnbB (37.5%) and fnbA (33.3%). The presence of icaA/icaD genes was demonstrated in almost all tested strains in comparison to the reference strain, S. aureus ATCC 43300. The phenotypic study of adhesion showed that all tested strains had moderate biofilm-forming capacity on polystyrene and represented different morphotypes on a CRA medium. Five strains among the twenty-four harbored the four genes of resistance to antibiotics (mecA, norA, norB and blaz). Considering the genes of adhesion (cna, clfA, fnbA and fnbB), these genes were present in 25% of the tested isolates. Regarding the adhesive properties, the clinical isolates of S. aureus formed biofilm on polystyrene, and only one strain (S17) produced exopolysaccharides on Congo red agar. All these results contribute to an understanding that the pathogenesis of clinical S. aureus isolates is due to their antibiotic resistance and adhesion to medical material.

Increased inflammatory cytokines and oxidative stress enhanced antibody production in breast and prostate cancer patients with COVID-19 related depression.

Cancer management is highly dependent on the immune status of the patient. During the COVID-19 pandemic, a large number of people suffered from anxiety and depression, especially cancer patients. The effect of depression on breast cancer (BC) and prostate cancer (PC) patients, during the pandemic has been analyzed in this study. Levels of proinflammatory cytokines (IFN-γ, TNF-α, and IL-6) and oxidative stress markers malondialdehyde (MDA) and carbonyl content (CC) were estimated in patients' serum samples. Serum antibodies against in vitro hydroxyl radical (•OH) modified pDNA (•OH-pDNA-Abs) were estimated using direct binding and inhibition ELISA. Cancer patients showed increased levels of proinflammatory cytokines (IFN-γ, TNF-α, and IL-6) and oxidative stress markers (MDA and CC levels), which were further significantly enhanced in cancer patients with depression compared to normal healthy (NH) individuals. Increased levels of •OH-pDNA-Abs were detected in breast cancer (0.506 ± 0.063) and prostate cancer (0.441 ± 0.066) patients compared to NH subjects. Serum antibodies were found to be significantly elevated in BC patients with depression (BCD) (0.698 ± 0.078) and prostate cancer patients with depression (PCD) (0.636 ± 0.058). Inhibition ELISA also exhibited significantly high percent inhibition in BCD (68.8% ± 7.8%) and PCD (62.9% ± 8.3%) subjects compared to BC (48.9% ± 8.1%), and PC (43.4% ± 7.5%) subjects. Cancer is characterized by enhanced oxidative stress and increased inflammation, which may be exaggerated with COVID-19 related depression. High oxidative stress and compromised antioxidant homeostasis exerts alterations in DNA, leading to formation of neo-antigens, subsequently leading to the generation of antibodies. COVID-19 pandemic related depression needs to be addressed globally for improved cancer patient care and cancer disease management.

Dihydropyrimidone Derivatives as Thymidine Phosphorylase Inhibitors: Inhibition Kinetics, Cytotoxicity, and Molecular Docking.

Overexpression of the thymidine phosphorylase (TP) enzyme induces angiogenesis, which eventually leads to metastasis and tumor growth. The crucial role of TP in cancer development makes it an important target for anticancer drug discovery. Currently, there is only one US-FDA-approved drug, i.e., Lonsurf, a combination of trifluridine and tipiracil, for the treatment of metastatic colorectal cancer. Unfortunately, numerous adverse effects are associated with its use, such as myelosuppression, anemia, and neutropenia. Since the last few decades, the discovery of new, safe, and effective TP inhibitory agents has been rigorously pursued. In the present study, we evaluated a series of previously synthesized dihydropyrimidone derivatives 1-40 for their TP inhibitory potential. Compounds 1, 12, and 33 showed a good activity with IC50 = 314.0 ± 0.90, 303.5 ± 0.40, and 322.6 ± 1.60 µM, respectively. The results of mechanistic studies revealed that compounds 1, 12, and 33 were the non-competitive inhibitors. These compounds were also evaluated for cytotoxicity against 3T3 (mouse fibroblast) cells and were found to be non-cytotoxic. Finally, the molecular docking suggested the plausible mechanism of non-competitive inhibition of TP. The current study thus identifies some dihydropyrimidone derivatives as potential inhibitors of TP, which can be further optimized as leads for cancer treatment.

Pharmacological Evaluation of Acacia nilotica Flower Extract against Helicobacter pylori and Human Hepatocellular Carcinoma In Vitro and In Silico.

The resistance of cancer and Helicobacter pylori to several drugs reflects a worldwide problem, and it has been the intention of numerous researchers to overcome this problem. Thus, in this study, Acacia nilotica fruits were subjected to HPLC analysis to detect their phenolic compounds and flavonoids. Moreover, A. nilotica's anti-H. pylori activity and its inhibitory activity against human hepatocellular carcinoma (HepG-2 cells) were reported. Various compounds with different concentrations, such as ferulic acid (5451.04 µg/mL), chlorogenic acid (4572.26 µg/mL), quercetin (3733.37 µg/mL), rutin (2393.13 µg/mL), gallic acid (2116.77 µg/mL), cinnamic acid (69.72 µg/mL), hesperetin (121.39 µg/mL) and methyl gallate (140.45 µg/mL), were detected. Strong anti-H. pylori activity at 31 mm was reported, compared to the positive control of the 21.67 mm inhibition zone. Moreover, the MIC and MBC were 7.8 µg/mL and 15.62 µg/mL, respectively, while the MIC and MBC of the positive control were 31.25 µg/mL. The concentration of MBC at 25%, 50% and 75% reflected H. pylori's anti-biofilm activity of 70.38%, 82.29% and 94.22%, respectively. Good antioxidant properties of the A. nilotica flower extract were documented at 15.63, 62.50, 250 and 1000 µg/mL, causing the DPPH scavenging percentages of 42.3%, 52.6%, 65.5% and 80.6%, respectively, with a IC50 of 36.74 µg/mL. HepG-2 cell proliferation was inhibited (91.26%) using 500 µg/mL of flower extract with an IC50 of 176.15 µg/mL, compared to an IC50 of 395.30 µg/mL used against human normal melanocytes. Molecular docking was applied to investigate ferulic acid with the H. pylori (4HI0) crystal structure to determine the best binding mode that interacted most energetically with the binding sites. Molecular docking indicated that ferulic acid was a proper inhibitor for the 4HI0 protein enzyme of H. pylori. A low energy score (-5.58 Kcal/mol) was recorded as a result of the interaction of ferulic acid with the residue's SER 139 active site caused by the O 29 atom, which was important for its antibacterial activity.

Antimicrobial Potential of Pithecellobium dulce Seed Extract against Pathogenic Bacteria: In Silico and In Vitro Evaluation.

Clinical multi-drug-resistant bacteria continue to be a serious health problem. Plant-derived molecules are an important source of bioactive compounds to counteract these pathogenic bacteria. In this paper, we studied the chemical composition of the methanol (80%) extract from Pithecellobium dulce seed (Hail, Saudi Arabia) and its ability to inhibit the growth of clinically relevant multi-drug-resistant bacteria. Molecular docking analysis was performed to predict the best compounds with low binding energy and high affinity to interact with two Staphylococcus aureus receptors. Data showed that P. dulce extract is a rich source of D-turanose (55.82%), hexadecanoic acid (11.56%), indole-1-acetic acid (11.42%), inositol (5.78%), and octadecanoic acid (4.36%). The obtained extract showed antibacterial activity towards tested clinical bacterial strains with MIC values ranging from 233 mg/mL for Acinetobacter baumannii to 300 mg/mL for S. aureus and Escherichia coli. Turanose interaction has resulted in -7.4 and -6.6 kcal/mol for 1JIJ and 2XCT macromolecules, while inositol showed energy values (-7.2 and -5.4 kcal/mol) for the same receptors. Multiple identified compounds showed desirable bioavailability properties indicating its great potential therapeutic use in human. Overall, current investigation highlights the possible use of P. dulce extract as a valuable source for drug development against pathogenic drug-resistant bacteria.

Novel phytochemical inhibitors targeting monkeypox virus thymidine and serine/threonine kinase: integrating computational modeling and molecular dynamics simulation.

Due to the rapid spread of the monkeypox virus and rise in the number of cases, there is an urgent need for the development of effective drugs against the infection. Serine/threonine protein kinase (Ser/Thr kinase) and Thymidine Kinase (TK) plays an imperative role in the replication and virulence of monkeypox virus and thus is deliberated as an attractive target in anti-viral drug development. In the present study, the 3D structure of monkeypox virus Ser/Thr kinase and TK was generated via molecular modeling techniques and performed their thorough structural analysis. We have screened potent anti-viral phytochemicals from the literature to inhibit Ser/Thr kinase and TK. As part of the initial screening, the physicochemical properties of the compounds were examined. Following this, a structure-based molecular docking technique was used to select compounds based on their binding affinity towards Ser/Thr kinase and TK. In order to find more potent hits against Ser/Thr kinase and TK, further examinations of ADMET properties, PAINS patterns and blood-brain barrier permeability were conducted. As a result, thalimonine and galanthamine were identified from the screening process bearing appreciable binding affinity towards Ser/Thr kinase and TK respectively, which showed a worthy set of drug-like properties. In the end, molecular dynamics simulations were performed for 100 ns, which showed decent stability of both protein-ligand complex throughout the trajectory. Due to the possibility that both monkeypox virus target proteins may be inhibited by thalimonine and galanthamine, our study highlights the need to investigate in vivo effects of thalimonine and galanthamine.Communicated by Ramaswamy H. Sarma.

Development of national framework for health status and health system performance indicators in Saudi Arabia.

BACKGROUND: The global shift to value-based care has highlighted the necessity for performance measurement in healthcare. While the implementation may be incomplete, governments and providers have been moving towards value-based models of care delivery, funding and performance measurement. OBJECTIVES: The purpose of this report is to illustrate the steps taken in designing the framework in Kingdom of Saudi Arabia (KSA), using a 4-step approach: Key Input Analysis, Hierarchy Design, Indicator Analysis and Selection, and Indicator Profile Development. Furthermore, it presents a comprehensive view of the indicators collected to measure performance at the level of the Health System and Health Status in KSA and highlights main patient concerns, thus providing an overview of a new, unified national framework. METHODS: The methodology entailed examined the following components' remits and roles, reporting mechanisms and channels, and performance indicators across all pertinent National Health agencies (NHA), by conducting a SWOT analysis of each of the components across the ecosystem. Engagement with the Steering Committee members was achieved through research and interviews. RESULTS: A total of 109 indicators were identified, of which 51 were Health Status Indicator Profiles and 58 Health System Indicators. The indicator profiles were developed with consideration of the KSA context in terms of the healthcare ecosystem as it stands today. The findings of this report, alongside the best practices arising from the benchmarking, will be key inputs into the design of the National Framework. CONCLUSION: The regulatory entity has set out to establish a National Framework, which aims to unify performance measurement in KSA from both health system and public health perspectives across all sectors providing healthcare services, based on a list of prioritized KPIs and their complete profiles, outlining the formulae, key responsibilities, and reporting mechanisms pertaining to each one.

Current Insights into Diagnosis, Prevention Strategies, Treatment, Therapeutic Targets, and Challenges of Monkeypox (Mpox) Infections in Human Populations.

In the wake of the emergence and worldwide respread of a viral infection called Monkeypox (Mpox), there is a serious threat to the health and safety of the global population. This viral infection was endemic to the western and central parts of Africa, but has recently spread out of this endemic area to various countries, including the United Kingdom (UK), Portugal, Spain, the United States of America (USA), Canada, Sweden, Belgium, Italy, Australia, Germany, France, the Netherlands, Israel, and Mexico. This is a timely review focusing on recent findings and developments in the epidemiology, clinical features, therapeutic targets, diagnosis, prevention mechanisms, research challenges and possible treatment for Mpox. To date (29 November 2022), there have been around 81,225 reported cases of Mpox. In most cases, this illness is mild; however, there is a fatality rate ranging from 1 to 10%, which might be increased due to associated complications and/or secondary infections. There is a real challenge in the diagnosis of Mpox, since its symptoms are very similar to those of other infections, including smallpox and chickenpox. Generally, to prevent/limit the risk and transmission of Mpox, the detection and isolation of infected individuals, as well as hand hygiene and cleanliness, are essential and effective approaches to control/combat this viral infection. Nevertheless, updated information about Mpox from different angles is lacking. Thus, this review provides updated and comprehensive information about the Mpox illness, which should highlight the global burden, pathogenicity, symptoms, diagnosis, prevention measures and possible treatment of this emerging disease.