Synthesis, molecular docking study and biological evaluation of new pyrrole scaffolds as potential antitubercular agents for dual targeting of enoyl ACP reductase and dihydrofolate reductase.

In this study, new series of N'-(2-(substitutedphenoxy)acetyl)-4-(1H-pyrrol-1-yl)benzohydrazides (3a-j) 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-(2-(substitutedphenoxy)acetyl)benzohydrazides (5a-j) were synthesized, characterized and assessed as inhibitors of enoyl ACP reductase and DHFR. Most of the compounds exhibited dual inhibition against the enzymes enoyl ACP reductase and DHFR. Several synthesized substances also demonstrated significant antibacterial and antitubercular properties. A molecular docking analysis was conducted in order to determine the potential mechanism of action of the synthesized compounds. The results indicated that there were binding interactions seen with the active sites of dihydrofolate reductase and enoyl ACP reductase. Additionally, important structural details were identified that play a critical role in sustaining the dual inhibitory activity. These findings were useful for the development of future dual inhibitors. Therefore, this study provided strong evidence that several synthesized molecules could exert their antitubercular properties at the cellular level through multi-target inhibition. By shedding light on the mechanisms through which these compounds exert their inhibitory effects, this research opens up promising avenues for the future development of dual inhibitors with enhanced antibacterial and antitubercular properties. The study's findings underscore the importance of multi-target approaches in drug design, providing a strong foundation for the design and optimization of novel compounds that can effectively target bacterial infections at the cellular level.

Clinical characteristics and surgical outcomes of transcutaneous versus transconjunctival excision of Wolfring gland ductal cysts.

PURPOSE: To analyze the clinicopathological characteristics and surgical outcomes of patients with Wolfring gland ductal cysts (WGDCs). METHODS: A retrospective, consecutive, interventional comparative case series was performed over a period of 7 years. Data on demographic and clinical characteristics, pathological findings and outcomes of surgically excised cysts were collected. A comparison between the transconjunctival and transcutaneous approaches was also assessed. RESULTS: Forty-eight patients (48 eyelids) were included in the final analysis. The most common presenting symptom was painless eyelid swelling (81.3%). The median symptom duration was 11.5 months (IQR, 18.25). The upper eyelid was involved in 31 (64.6%) patients, 29/31 of whom had cysts in a medial or centromedial location. Forty-five (93.8%) cysts were bluish gray and transilluminable with clear contents on lid eversion and a median largest dimension of 22 mm (IQR, 8). A transverse conjunctival fibrotic band was observed along the proximal tarsal border in the cyst area in all patients. Signs of chronic trachoma were noted in 38 (79.2%) patients. Preoperative significant ptosis was present in 28/31 (90.3%) of the upper eyelid cysts. Thirty cysts (62.5%) were excised through the skin, and 18 cysts (37.5%) were excised transconjunctivally. Intraoperative cyst rupture, the need for conjunctival grafting and postoperative residual upper lid ptosis were significantly greater in the transconjunctival group (p = 0.009, p < 0.001, and p = 0.016, respectively). CONCLUSION: The present study highlights the clinicopathological characteristics of a relatively large series of surgically excised WGDCs. Transcutaneous excision of WGDCs has proven to be an effective treatment with fewer adverse sequelae than the transconjunctival approach.

Characterization of Plant-Derived Natural Inhibitors of Dipeptidyl Peptidase-4 as Potential Antidiabetic Agents: A Computational Study.

Diabetes, characterized by elevated blood sugar levels, poses significant health and economic risks, correlating with complications like cardiovascular disease, kidney failure, and blindness. Dipeptidyl peptidase-4 (DPP-4), also referred to as T-cell activation antigen CD26 (EC 3.4.14.5.), plays a crucial role in glucose metabolism and immune function. Inhibiting DPP-4 was anticipated as a potential new therapy for diabetes. Therefore, identification of plant-based natural inhibitors of DPP-4 would help in eradicating diabetes worldwide. Here, for the identification of the potential natural inhibitors of DPP-4, we developed a phytochemicals library consisting of over 6000 phytochemicals detected in 81 medicinal plants that exhibited anti-diabetic potency. The library has been docked against the target proteins, where isorhamnetin, Benzyl 5-Amino-5-deoxy-2,3-O-isopropyl-alpha-D-mannofuranoside (DTXSID90724586), and 5-Oxo-7-[4-(trifluoromethyl) phenyl]-4H,6H,7H-[1,2]thiazolo[4,5-b]pyridine 3-carboxylic acid (CHEMBL3446108) showed binding affinities of -8.5, -8.3, and -8.3 kcal/mol, respectively. These compounds exhibiting strong interactions with DPP-4 active sites (Glu205, Glu206, Tyr547, Trp629, Ser630, Tyr662, His740) were identified. ADME/T and bioactivity predictions affirmed their pharmacological safety. Density functional theory calculations assessed stability and reactivity, while molecular dynamics simulations demonstrated persistent stability. Analyzing parameters like RMSD, RG, RMSF, SASA, H-bonds, MM-PBSA, and FEL confirmed stable protein-ligand compound formation. Principal component analysis provided structural variation insights. Our findings suggest that those compounds might be possible candidates for developing novel inhibitors targeting DPP-4 for treating diabetes.

Comparative phenotypic and genotypic analysis of community-acquired and hospital-acquired intra-abdominal infections among liver transplanted patients.

AIM: During liver transplantation, both hospital-acquired (HA) and community-acquired (CA) intra-abdominal infections (IAIs) are involved causing life-threatening diseases. Therefore, comparative studies of aerobic and facultative anaerobic HA-IAIs and CA-IAIs after liver transplantation surgery are necessary. METHODS AND RESULTS: The species of detected isolates (310) from intra-abdominal fluid were identified and classified into hospital-acquired intra-abdominal infections (HA-IAIs) and community-acquired intra-abdominal infections (CA-IAIs). Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii were the most commonly detected species. The resistant phenotypes were commonly detected among the HA-IAIs; however, the virulent phenotypes were the predominant strains of CA-IAIs. Regrettably, the resistance profiles were shocking, indicating the inefficacy of monotherapy in treating these isolates. Therefore, we confirmed the use of empirical combination therapies of amikacin and meropenem for treating all IAIs (FICI ≤ 0.5). Unfortunately, the high diversity and low clonality of all identified HA and CA-IAIs were announced with D-value in the range of 0.992-1. CONCLUSION: This diversity proves that there are infinite numbers of infection sources inside and outside healthcare centers.

Metagenomic analysis of the ocular toxoplasmosis in children uveitis from Fayoum governorate, Egypt.

Granulomatous anterior uveitis with single or numerous gelatinous nodules was found in children living in rural Egypt. All ocular diseases were originally thought to be water-born and related to digenic flukes. The current study sought to learn more about the causes of anterior granulomatous uveitis in Egyptian youngsters who used to swim in rural water canals. 50 children with eye lesions that had not responded to medical treatment were recruited. Four samples were surgically extracted and examined using real-time PCR, transmission electron microscopy (TEM), and shotgun metagenomic sequencing (SMS). Toxoplasma gondii was detected free within the syncytium's distal section, while the proximal part exhibited active synthesis of a presumably extra-polymeric material, possibly released by the microbial population. Toxoplasma gondii was found in 30 samples. Serologically, distinct anti-Toxoplasma antibodies were not found in 91.6% of patients. SMS showed that the T. gondii ME 49 strain had the greatest percentage (29-25%) in all samples within an Acinetobacter-containing microbial community. These findings suggested that these bacteria entered the body via the exterior route rather than the circulatory route. The lack of genetic evidence for subsequent parasite stages invalidates the prior findings about the assumed trematode stage.

Prevalence of Positive Rapid Antigen Detection Test for Group A Streptococcus Among Patients With Respiratory Symptoms in Eastern Province, Kingdom of Saudi Arabia.

Background During the COVID-19 pandemic, there was a dramatic upsurge in the prevalence of respiratory symptoms, which may have altered the usual pattern of bacterial infections and relevant decision-making. Objectives This study aimed to investigate the prevalence of rapid antigen detection test (RADT) positivity for group A Streptococcus (GAS) in patients with respiratory symptoms and signs during the COVID-19 pandemic. In addition, we evaluated the association between a positive test and the modified Centor criteria in a population of children and adults with upper respiratory tract infections (URTIs). Methods A prospective study was conducted in primary health care centres (PHCCs) and the paediatric emergency department (ED) of the Maternity and Children Hospital in Dammam City, Kingdom of Saudi Arabia (KSA). Trained physicians collected data from patients aged three years and older or their guardian(s) regarding URTI symptoms. The modified Centor score was calculated, and RADT was performed for all patients. Results Data were collected from 469 patients. The prevalence of positive RADT was 19 (4.1%), and the setting was associated with RADT positivity, as 14% of ED visitors tested positive compared with 0.6% of PHCC visitors. The RADT results had an area under the curve of 0.856 (95% confidence interval (CI)=0.774-0.939), with Centor scores of 2 and 3 having a sensitivity of 89.5%/78.9% and specificity of 70.6%/80.8%, respectively. Individuals with a score of 5 had the highest rate of positive RADT (33.3%, P<0.001); a score less than 0 excluded the possibility of GAS infection. Conclusion The Centor score can improve effective antibiotic prescribing; however, Centor scores ≥2 should be supplemented with an additional confirmatory test. The high specificity of RADT makes it a useful tool in preventing the prescription of unneeded antibiotics.

Partnering essential oils with antibiotics: proven therapies against bovine Staphylococcus aureus mastitis.

Introduction: There is an urgent need to develop therapeutic options for biofilm-producing Staphylococcus aureus (S. aureus). Therefore, the renewed interest in essential oils (EOs), especially carvacrol, linalool and eugenol, has attracted the attention of our research group. Methods: Multidrug resistance and multivirulence profiles in addition to biofilm production of S. aureus strains isolated from cows with mastitis were evaluated using both phenotypic and genotypic methods. The antimicrobial and antibiofilm activities of EOs were tested using both in vitro and molecular docking studies. Moreover, the interactions between commonly used antibiotics and the tested EOs were detected using the checkerboard method. Results: We found that all our isolates (n= 37) were biofilm methicillin resistant S. aureus (MRSA) producers and 40.5% were vancomycin resistant S. aureus (VRSA). Unfortunately, 73 and 43.2% of the recovered MRSA isolates showed multidrug resistant (MDR) and multivirulence patterns, respectively. The antimicrobial activities of the tested EOs matched with the phenotypic evaluation of the antibiofilm activities and molecular docking studies. Linalool showed the highest antimicrobial and antibiofilm activities, followed by carvacrol and eugenol EOs. Fortunately, synergistic interactions between the investigated EOs and methicillin or vancomycin were detected with fractional inhibitory concentration index (FICI) values ≤ 0.5. Moreover, the antimicrobial resistance patterns of 13 isolates changed to sensitive phenotypes after treatment with any of the investigated EOs. Treatment failure of bovine mastitis with resistant S. aureus can be avoided by combining the investigated EOs with available antimicrobial drugs. Conclusion: We hope that our findings can be translated into a formulation of new pharmaceutical dosage forms against biofilm-producing S. aureus pathogens.

Application of CRISPR-Cas System to Mitigate Superbug Infections.

Multidrug resistance in bacterial strains known as superbugs is estimated to cause fatal infections worldwide. Migration and urbanization have resulted in overcrowding and inadequate sanitation, contributing to a high risk of superbug infections within and between different communities. The CRISPR-Cas system, mainly type II, has been projected as a robust tool to precisely edit drug-resistant bacterial genomes to combat antibiotic-resistant bacterial strains effectively. To entirely opt for its potential, advanced development in the CRISPR-Cas system is needed to reduce toxicity and promote efficacy in gene-editing applications. This might involve base-editing techniques used to produce point mutations. These methods employ designed Cas9 variations, such as the adenine base editor (ABE) and the cytidine base editor (CBE), to directly edit single base pairs without causing DSBs. The CBE and ABE could change a target base pair into a different one (for example, G-C to A-T or C-G to A-T). In this review, we addressed the limitations of the CRISPR/Cas system and explored strategies for circumventing these limitations by applying diverse base-editing techniques. Furthermore, we also discussed recent research showcasing the ability of base editors to eliminate drug-resistant microbes.

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New Serratia marcescens JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of Serratia Species for Biological Applications.

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound's structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 µg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets.

Health Coaching for Weight Loss Among Overweight and Obese Individuals in Saudi Arabia: A Retrospective Analysis.

Background Health coaching is an increasingly used strategy to help in adopting lifestyle changes for weight loss. While Saudi Arabia has one of the highest obesity prevalences worldwide, research on lifestyle interventions for weight loss is limited. Aim We aimed to investigate the effectiveness of health coaching for weight loss among the Saudi population in real-world primary healthcare settings. Methods This is a retrospective observational study. Secondary data from the health coach national program in the Eastern Health Cluster were retrieved. Obese and overweight individuals aged 15 years or older with weight-related goals who completed at least 12 weeks of coaching were included in the analysis. The primary outcomes are weight change (kg) and weight change percent (%) of the initial weight. We further compared the weight change% between different follow-up methods (i.e., physical, virtual, and hybrid) and studied the factors associated with -5% weight loss. Results In total, 465 participants were included in the analysis, with a female predominance (66.2%) and a median initial weight of 90 kg (interquartile range (IQR): 77, 101). The median follow-up duration was 127 days (IQR: 101, 157), and the median total number of coaching sessions was three (IQR: 2, 5). The mean weight change was -2.68 kg (95% confidence interval (CI): -3.12, -2.24), p<0.001. Comparing each follow-up group, no statistically significant difference was found when controlling for number of visits (p=0.059). The adjusted means for weight change% were -3.77%, -2.59%, and -2.54% for hybrid, physical, and virtual visits, respectively. Factors that were associated with achieving at least -5% weight loss were male sex (adjusted odds ratio (aOR)=1.87, 95% CI: 1.16, 3.02), five or more total coaching visits (aOR=5.23, 95% CI: 2.88, 9.50), longer follow-up duration (aOR=1.09, 95% CI: 1.03, 1.15), and having a weight management goal (aOR=4.5, 95% CI: 1.63, 12.45) as the reason for initial coaching visit. Conclusion We found statistically significant weight change among clients who completed 12 weeks of coaching in primary care settings. The findings in this paper contribute to the importance of lifestyle interventions for weight loss among the Saudi population. However, stronger controlled studies are needed to confirm this finding.

The antioxidant activity, preliminary phytochemical screening of Zingiber zerumbet and antimicrobial efficacy against selective endodontic bacteria.

Antibiotic resistance is rising across the world. For a very long time, bitter ginger (Zingiber zerumbet) has been used as one of the most popular herbal remedies to treat a wide range of common diseases. Ginger has been shown to have antioxidant and antibacterial activity. It has various bioactive chemicals that might be utilized as an alternative treatment option for many infectious diseases. The present study aimed to examine the biochemical profile of ginger, antioxidant, and antibacterial activity against selective endodontic microbes. Antioxidant was measured using DPPH and antibacterial activity was performed using disk diffusion tests. Streptococcus mutants, Enterococcus faecalis, Staphylococcus spp., and Lactobacillus spp. were tested for antibacterial activity. Before evaluating the dried extracts, all solvents were eliminated using rotary evaporation. The obtained IC50 value revealed that ethanol extract had the greatest antioxidant activity. Concerning each bacterium, the plant extracts demonstrated considerable antibacterial activity (p = .001). Ethanol extracts showed the strongest antibacterial activity against the studied microorganisms. This study highlights that the Zingiber zerumbet (Z. zerumbet) is a strong antibacterial herb against multidrug-resistant (MDR) gram-positive bacteria. It may also be employed as a possible natural antioxidant source.

In Silico Analysis Reveals High Levels of Genetic Diversity of Plasmodium knowlesi Cell Traversal Protein for Ookinetes and Sporozoites (PkCelTOS) in Clinical Samples.

The cell-traversal protein for ookinetes and sporozoites (CelTOS), expressed on the surface of ookinetes and sporozoitesin Plasmodium species, is a promising malaria vaccine candidate. CelTOS is essential for parasite invasion into mosquito midgut and human hepatocytes, thereby contributing to malaria transmission and disease pathogenesis. This study explores the genetic diversity, polymorphisms, haplotypes, natural selection, phylogenetic analysis, and epitope prediction in the full-length Plasmodium knowlesi CelTOS gene in clinical samples from Sarawak, Malaysian Borneo, and long-term laboratory strains from Peninsular Malaysia and the Philippines. Our analysis revealed a high level of genetic variation in the PkCelTOS gene, with a nucleotide diversity of π ~ 0.021, which was skewed towards the 3' end of the gene. This level of diversity is double that observed in PfCelTOS and 20 times that observed in PvCelTOS from worldwide clinical samples. Tests of natural selection revealed evidence for positive selection within clinical samples. Phylogenetic analysis of the amino acid sequence of PkCelTOS revealed the presence of two distinct groups, although no geographical clustering was observed. Epitope prediction analysis identified two potential epitopes (96AQLKATA102 and 124TIKPPRIKED133) using the IEDB server and one epitope (125IKPPRIKED133) by Bcepred server on the C' terminal region of PkCelTOS protein. Both the servers predicted a common epitope region of nine amino acid length (IKPPRIKED) peptide, which can be studied in the future as a potential candidate for vaccine development. These findings shed light on the genetic diversity, polymorphism, haplotypes, and natural selection within PkCelTOS in clinical samples and provide insights about its future prospects as a potential candidate for P. knowlesi malaria vaccine development.

Antibiotic-Prescribing Patterns Among Patients With Respiratory Symptoms in the Eastern Province, Kingdom of Saudi Arabia.

Background Upper respiratory tract infections (URTIs) represent the most common diagnosis in ambulatory care settings. Some of these infections are properly treated with antibiotics, but evidence points to an inappropriate overuse of antibiotics in URTI management. This overuse is linked to antibiotic resistance, drug-related adverse effects, and increased costs. Objective This study evaluated the prevalence and predictors of antibiotic prescription for patients with URTI symptoms at the primary healthcare centers (PHCCs) and pediatric emergency department (ED) of the Maternity and Children Hospital (MCH) in Dammam, Saudi Arabia. Methods A prospective study was conducted in the PHCCs and pediatric ED of MCH. Trained physicians collected data on patients with URTI symptoms aged three years and older. Scores based on modified Centor criteria were calculated, and rapid antigen detection tests (RADTs) were conducted for all study participants. Results Out of 469 patients with a URTI, 141 (30.1%) received a prescription for an antibiotic, with a smaller proportion in the PHCCs (n=85; 24.4%) than in the pediatric ED (n=56; 46.3%). The main significant predictors of antibiotic prescription in terms of odds ratio (OR) and 95% confidence interval (95%CI) were a positive RADT result (OR=41.75, 95%CI=4.76-366.28), the presence of tonsillar exudate (OR=5.066, 95%CI=3.08-8.33), tender and/or swollen anterior cervical lymph nodes (OR=4.537, 95%CI=1.96-10.54), and fever (OR=3.519, 95%CI=2.33-5.31). A higher Centor score was also a predictor (2 to 5 vs. -1 to 1) (OR=2.72, 95%CI=1.8-4.12). The absence of a cough was not a significant predictor (OR=1.13, 95%CI=0.74-1.72). Conclusions Although a positive RADT increased the likelihood that a patient would be prescribed an antibiotic at the time of assessment, most antibiotic prescriptions were not justified. To control expenses, prevent adverse effects, and limit the spread of antibiotic resistance, efforts should be made to reduce unnecessarily high antibiotic usage.

Comparison of corneal measurements in normal and keratoconus eyes using Anterior Segment Optical Coherence Tomography (AS-OCT) and Pentacam HR topographer.

BACKGROUND: Keratoconus (KC) is easily recognized by its unique topographic pattern, but it can be difficult to distinguish subclinical form of the disease from the normal cornea. Optovue anterior segment optical coherence tomography (AS-OCT) helps diagnose KC. AIM OF THE WORK: To assess and the level of agreement of Keratometry-readings (K), Central Corneal Thickness (CCT) and Thinnest Corneal Thickness (TCT) measurements obtained by Optovue AS-OCT and Wavelight Oculyzer Pentacam HR in two groups: KC eyes and normal eyes. PATIENTS AND METHODS: This is a prospective clinical observational study. The study included 110 eyes divided into two groups. The study group included 62 eyes with topographic evidence of KC. The control group included 48 eyes of normal subjects with no topographic evidence of KC. All of the participants underwent full cycloplegic refraction, spectacle best-corrected distance visual acuity, comprehensive slit-lamp biomicroscopy and fundoscopy. All participants underwent corneal topography by Pentacam HR and AS-OCT. RESULTS: There were highly significant differences between the studied groups as regarding BCVA, intraocular pressure and CCT measurements which were found to be lower among KC group compared to the control one. There were highly significant differences between the studied groups regarding TCT measurement detected by Pentacam HR and AS-OCT which was found to be lower among the keratoconus group compared to the control one (470.9, 455.7 versus 541.9 and 518.7 respectively). CONCLUSION: Both Scheimpflug-based imaging and AS-OCT provide comparable readings with a good agreement regarding corneal pachymetry in keratoconus group with accurate identification of KC eyes and healthy ones. However, there was a significant difference in K readings between both devices in Keratoconus and control group.

Interplay between cross sectional analysis of risk factors associated with Toxoplasma gondii infection in pregnant women and their domestic cats.

Toxoplasmosis is a global zoonotic disease caused by Toxoplasma gondii (T. gondii). The primary aim of this study was to identify hygienic and cat management practices that could affect the occurrence of T. gondii in cats and their owners in Sharqia Governorate, Egypt. T. gondii infection was evaluated in 80 pregnant women and 29 domestic cats using Real-time PCR. A questionnaire was administered to obtain information regarding the risk factors associated with T. gondii infection. Blood samples were collected from enrolled pregnant women, and fecal samples were collected from their pet cats. Firth logistic regression model complemented with random forest (RF) analysis was used to evaluate the association of different hygiene and cat management practices with T. gondii infection in pregnant women. T. gondii infection was identified in 27.5% of pregnant women and 17% of domestic cats. Drinking raw milk and contacting stray and pet cats were significantly associated with higher odds of T. gondii infection. The proportion of T. gondii-positive women who ate raw meat (60.0%) was higher than those ate heat-cooked meat (25.3%). Moreover, women who did not wash their hands after contact with cats were 6 times (OR 6.12; CI: 3.03-9.21) more likely to experience T. gondii infection than those washed their hands after cat contact. The RF analysis showed that washing hands constitute a serious yet preventable public health concern that requires targeted, community-specific efforts. Cat owners, particularly pregnant women, need to be aware about the risk of T. gondii infection, while handling cat and pet's owner should be advised to take necessary hygienic measures to prevent its infection.

The Outcomes of Diffuse Large B-cell Lymphoma Patients with Synchronous and Early Central Nervous System Involvement: A Single-Center Experience.

BACKGROUND: Diffuse large B cell lymphoma (DLBCL) is the most commonly diagnosed subtype of non-Hodgkin's lymphoma (NHL). R-CHOP has significantly improved clinical outcomes in patients with DLBCL, however, its indication in the prevention of CNS relapse and recurrence is still inconsistent. Moreover, prophylactic methotrexate and/or cytarabine have been used prophylactically for DLBCL patients is at high risk of CNS relapse and to treat CNS DLBCL, however, their efficacy remains unclear. METHODS: The aim of our retrospective study was to determine the incidence of CNS in-volvement in patients with DLBCL and to describe its risk factors and survival outcomes. RESULTS: A total of 406 patients with DLBCL were identified, and 17 (4.2%) of DLBCL patients had CNS involvement i.e. 9 (2.2 %) at diagnosis and 8 (~2%) at relapse. The patients were younger, had advanced stage, high CNS-IPI, and had extra nodal involvement. Seven out of the 17 patients who survived received chemotherapy and a prophylactic methotrexate. Considering the CNS-IPI, of the 146 patients with high CNS-IPI at presentation, 18 received the prophylactic HDMTX and 3 (16.7%) of them had CNS relapse. Two (1.6%) out of 128 who did not receive the prophylactic HDMTX had CNS relapse. On the other hand, of the 223 patients with intermediate CNS-IPI, 25 received the prophylactic HDMTX and 2 (8%) of them had CNS relapse and in 198 patients who did not receive the prophylactic HDMTX, 2 (1.01%) had CNS relapse. The 5-year progression-free survival and overall survival rates for the entire cohort were 73% and 84%, respectively. The median OS for those who had CNS involvement was 17 months and the 2-year OS was 40%. CONCLUSION: CNS involvement in DLBCL has a poor prognosis, thus, aggressive CNS-directed therapy should be considered, especially in young patients.

Computational analysis and in vitro evaluation of TMF 104, for its antioxidant, antimicrobial, and anticancer efficacies.

Benzylidene chromanones are small molecules, structurally similar to active phytochemicals. Herein, we report one novel benzylidene chromanone, TMF 104, for its bio-efficacies. Its computational docking for Vanin-1, antioxidant, free radical scavenging capacities, antimicrobial effects, and anticancer efficacy were analyzed. TMF 104 predicated strong binging to Vanin-1 protein with a docking energy of -8.1 kcal/mol. The compound dose-dependently exhibited free-radical scavenging and antioxidant activities when tested in vitro. The compound also had remarkable activity against Salmonella typhimurium, Enterococcus faecalis, Staphylococcus aureus, and Escherichia coli with minimum inhibitory concentration values of 1.5, 2.0, 12.5, and 13.5 µg/ml, respectively. The compound was also effective against Bacillus cereus and Pseudomonas aeruginosa albeit at higher concentrations. TMF 104 dose-dependently inhibited the proliferation of MCF-7, NCI H460, and Caki-1 cells with respective GI50 values of 24.51, 21.95, and 32.95 µg/ml, whereas the compound was toxic to normal Vero cells at much higher concentration of 264.70 µg/ml. The compound also aided in apoptosis and increased the sub G0 /G1 phase of the cell cycle in all three cancer cells tested. Our study identified a novel, potent benzylidene analogue with potent antioxidant, antimicrobial, and anticancer activities, which drives further attention for further research.

The mental health of healthcare workers in GCC countries during the COVID-19 pandemic: A systematic review and meta-analysis.

Objectives: The aim of this study was to summarize the available evidence on the prevalence of stress, burnout, anxiety and depression among healthcare providers in the Gulf Cooperation Council (GCC) countries (KSA, Bahrain, Kuwait, Oman, Qatar, and the United Arab Emirates) during the COVID-19 pandemic. Methods: We searched PubMed, PsycINFO, Scopus, and Google scholar for related studies published between January 2020 and April 2021 and conducted a systematic review and meta-analysis. Results: Of the 1815 identified studies, 29 met the inclusion criteria, and 19 studies were included in the meta-analysis. The pooled estimate of prevalence for moderate to severe anxiety as reported using GAD-7 was 34.57% (95% CI = 19.73%, 51.12%), that for moderate to severe depression using PHQ-9 was 53.12% (95% CI = 32.76%, 72.96%), and that for moderate to severe stress using the 10-item Perceived Stress Scales was 81.12% (95% CI = 72.15%, 88.70%). Meta-analysis was not performed for burnout due to the small number of identified studies and the different tools used; however, the highest prevalence was reported at 76% (95% CI = 64%, 85%). Overall, a positive trend was observed over time for moderate to severe anxiety and depression, p = 0.0059 and 0.0762, respectively. Of note, the heterogeneity was significant among the studies, and many studies were of poor quality. Conclusion: The prevalence of mental health disorders during the current pandemic among healthcare workers in GCC countries is high. However, the results could be affected by the high heterogeneity and low quality studies.

Comparative study between ultra-mini-percutaneous nephrolithotomy versus stented extracorporeal shock wave lithotripsy for treatment of renal stones in Egypt.

Objectives: The purpose of this study is to compare results, safety and outcome of ultra-mini-percutaneous nephrolithotomy (PCNL) versus stented shock wave lithotripsy (SWL) for the management of renal calculi sized 10-20 mm. Methods: This study was conducted at Urology Department, Faculty of Medicine, Ain Shams University. After meeting inclusion and exclusion criteria, 90 patients were randomized to either ultra-mini-PCNL group or stented SWL group through the closed-envelope technique, with 45 patients in each group. Patient data were collected preoperatively, immediately postoperatively and 2 and 4 weeks postoperatively assessing operative time, hospital stay, complications including haematuria, fever, the need for blood transfusion, residual stones and the need for retreatment. Results: Stone-free rate (SFR) was higher in the ultra-mini-PCNL group compared to the stented SWL group, with no statistically significant difference with P-value = 0.316. As for the need for retreatment, it was slightly higher in the stented SWL group compared to the ultra-mini-PCNL group, yet this difference was statistically insignificant with P-value = 0.681.We found no statistically significant difference between both groups regarding post-operative complications including fever, haematuria and need for blood transfusion, respectively.Operative time and hospital stay were significantly higher in the ultra-mini-PCNL group compared to the stented SWL group with P-value < 0.001 for both. Conclusion: Both stented SWL and ultra-mini-PCNL are good treatment choices for renal stones sized less than 2 cm with low complication rates. Stone size indices were significant predictor for the need for retreatment. Further studies to compare SFR based on stone size in both interventions are needed.

Tackling strong biofilm and multi-virulent vancomycin-resistant Staphylococcus aureus via natural alkaloid-based porous nanoparticles: perspective towards near future eradication.

Introduction: As a growing direction, nano-based therapy has become a successful paradigm used to address the phytogenic delivery-related problems in overcoming multivirulent vancomycin-resistant Staphylococcus aureus (VRSA) infection. Methods: Hence, our aim was to develop and assess a novel nanocarrier system (mesoporous silica nanoparticles, MPS-NPs) for free berberine (Free-BR) as an antimicrobial alkaloid against strong biofilm-producing and multi-virulent VRSA strains using in vitro and in vivo mouse model. Results and discussion: Our outcomes demonstrated vancomycin resistance in 13.7% of Staphylococcus aureus (S. aureus) strains categorized as VRSA. Notably, strong biofilm formation was observed in 69.2% of VRSA strains that were all positive for icaA gene. All strong biofilm-producing VRSA strains harbored a minimum of two virulence genes comprising clfA and icaA with 44.4% of them possessing all five virulence genes (icaA, tst, clfA, hla, and pvl), and 88.9% being multi-virulent. The study findings affirmed excellent in vitro antimicrobial and antibiofilm properties of BR-loaded MPS-NPs. Real-time quantitative reverse transcription PCR (qRT-PCR) assay displayed the downregulating role of BR-loaded MPS-NPs on strong biofilm-producing and multi-virulent VRSA strains virulence and agr genes in both in vitro and in vivo mice models. Additionally, BR-loaded MPS-NPs supplementation has a promising role in attenuating the upregulated expression of pro-inflammatory cytokines' genes in VRSA-infected mice with attenuation in pro-apoptotic genes expression resulting in reduced VRSA-induced apoptosis. In essence, the current study recommends the future scope of using BR-loaded MPS-NPs as auspicious alternatives for antimicrobials with tremendous antimicrobial, antibiofilm, anti-quorum sensing (QS), and anti-virulence effectiveness against problematic strong biofilm-producing and multi-virulent VRSA-associated infections.