Search

IntroductionInfluenza A virus (IAV) infection can cause the often-lethal acute respiratory distress syndrome (ARDS) of the lung. Concomitantly, acute kidney injury (AKI) is frequently noticed during IAV infection, correlating with an increased mortality. The aim of this study was to elucidate the interaction of IAV with human kidney cells and, thereby, to assess the mechanisms underlying IAV-mediated AKI.MethodsTo investigate IAV effects on nephron cells we performed infectivity assays with human IAV, as well as with human isolates of either low or highly pathogenic avian IAV. Also, transcriptome and proteome analysis of IAV-infected primary human distal tubular kidney cells (DTC) was performed. Furthermore, the DTC transcriptome was compared to existing transcriptomic data from IAV-infected lung and trachea cells.ResultsWe demonstrate productive replication of all tested IAV strains on primary and immortalized nephron cells. Comparison of our transcriptome and proteome analysis of H1N1-type IAV-infected human primary distal tubular cells (DTC) with existing data from H1N1-type IAV-infected lung and primary trachea cells revealed enrichment of specific factors responsible for regulated cell death in primary DTC, which could be targeted by specific inhibitors.DiscussionIAV not only infects, but also productively replicates on different human nephron cells. Importantly, multi-omics analysis revealed regulated cell death as potential contributing factor for the clinically observed kidney pathology in influenza.

Background: One of the most dangerous problems that the world faced recently is viral respiratory pathogens. Marine creatures, including Echinodermata, specially Asteroidea class (starfish) have been extensively studied due to their miscellaneous bioactivities, excellent pharmacological properties, and complex secondary metabolites, including steroids, steroidal glycosides, anthraquinones, alkaloids, phospholipids, peptides, and fatty acids. These chemical constituents show antiviral activities against a wide range of viruses, including respiratory viruses. Results: The present study aimed at the identification of potential antiviral compounds from some starfish species. The bioactive compounds from Pentaceraster cumingi, Astropecten polyacanthus, and Pentaceraster mammillatus were extracted using two different solvents (ethyl acetate and methanol). The antiviral activity against influenza A/H1N1 virus showed that ethyl acetate extract from Pentaceraster cumingi has the highest activity, where the selective index was 150.8. The bioactive compounds of this extract were identified by GC/MS analysis. The molecular docking study highlighted the virtual mechanism of binding of the identified compounds towards polymerase basic protein 2 and neuraminidase for H1N1 virus. Interestingly, linoleic acid showed promising binding energy of −10.12 Kcal/mol and −24.20 Kcal/mol for the selected two targets, respectively, and it formed good interactive modes with the key amino acids inside both proteins. Conclusion: The molecular docking analysis showed that linoleic acid was the most active antiviral compound from P. cumingi. Further studies are recommended for in-vitro and in-vivo evaluation of this compound against influenza A/H1N1 virus.

Following virus recognition of host cell receptors and viral particle/genome internalization, viruses replicate in the host via hijacking essential host cell machinery components to evade the provoked antiviral innate immunity against the invading pathogen. Respiratory viral infections are usually acute with the ability to activate pattern recognition receptors (PRRs) in/on host cells, resulting in the production and release of interferons (IFNs), proinflammatory cytokines, chemokines, and IFN-stimulated genes (ISGs) to reduce virus fitness and mitigate infection. Nevertheless, the game between viruses and the host is a complicated and dynamic process, in which they restrict each other via specific factors to maintain their own advantages and win this game. The primary role of the non-structural protein 1 (NS1 and Nsp1) of influenza A viruses (IAV) and the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively, is to control antiviral host-induced innate immune responses. This review provides a comprehensive overview of the genesis, spatial structure, viral and cellular interactors, and the mechanisms underlying the unique biological functions of IAV NS1 and SARS-CoV-2 Nsp1 in infected host cells. We also highlight the role of both non-structural proteins in modulating viral replication and pathogenicity. Eventually, and because of their important role during viral infection, we also describe their promising potential as targets for antiviral therapy and the development of live attenuated vaccines (LAV). Conclusively, both IAV NS1 and SARS-CoV-2 Nsp1 play an important role in virus–host interactions, viral replication, and pathogenesis, and pave the way to develop novel prophylactic and/or therapeutic interventions for the treatment of these important human respiratory viral pathogens.

There is still a great global need for efficient treatments for the management of SARS-CoV-2 illness notwithstanding the availability and efficacy of COVID-19 vaccinations. Olive leaf is an herbal remedy with a potential antiviral activity that could improve the recovery of COVID-19 patients. In this work, the olive leaves major metabolites were screened in silico for their activity against SARS-CoV-2 by molecular docking on several viral targets such as methyl transferase, helicase, Plpro, Mpro, and RdRp. The results of in silico docking study showed that olive leaves phytoconstituents exhibited strong potential antiviral activity against SARS-CoV-2 selected targets. Verbacoside demonstrated a strong inhibition against methyl transferase, helicase, Plpro, Mpro, and RdRp (docking scores = -17.2, -20, -18.2, -19.8, and -21.7 kcal/mol.) respectively. Oleuropein inhibited 5rmm, Mpro, and RdRp (docking scores = -15, -16.6 and -18.6 kcal/mol., respectively) respectively. Apigenin-7-O-glucoside exhibited activity against methyl transferase and RdRp (docking score = -16.1 and -19.4 kcal/mol., respectively) while Luteolin-7-O-glucoside inhibited Plpro and RdRp (docking score = -15.2 and -20 kcal/mol., respectively). The in vitro antiviral assay was carried out on standardized olive leaf extract (SOLE) containing 20% oleuropein and IC50 was calculated. The results revealed that 20% SOLE demonstrated a moderate antiviral activity against SARS-CoV-2 with IC50 of 118.3 μg /mL. Accordingly, olive leaf could be a potential herbal therapy against SARS-CoV-2 but more in vivo and clinical investigations are recommended.

Lung infections in Influenza-Like Illness (ILI) are triggered by a variety of respiratory viruses. All human pandemics have been caused by the members of two major virus families, namely Orthomyxoviridae (influenza A viruses (IAVs); subtypes H1N1, H2N2, and H3N2) and Coronaviridae (severe acute respiratory syndrome coronavirus 2, SARS−CoV−2). These viruses acquired some adaptive changes in a known intermediate host including domestic birds (IAVs) or unknown intermediate host (SARS-CoV-2) following transmission from their natural reservoirs (e.g. migratory birds or bats, respectively). Verily, these acquired adaptive substitutions facilitated crossing species barriers by these viruses to infect humans in a phenomenon that is known as zoonosis. Besides, these adaptive substitutions aided the variant strain to transmit horizontally to other contact non-human animal species including pets and wild animals (zooanthroponosis). Herein we discuss the main zoonotic and reverse-zoonosis events that occurred during the last two pandemics of influenza A/H1N1 and SARS-CoV-2. We also highlight the impact of interspecies transmission of these pandemic viruses on virus evolution and possible prophylactic and therapeutic interventions. Based on information available and presented in this review article, it is important to close monitoring viral zoonosis and viral reverse zoonosis of pandemic strains within a One-Health and One-World approach to mitigate their unforeseen risks, such as virus evolution and resistance to limited prophylactic and therapeutic interventions.

Aim: Migraine is a neurological disorder characterized by recurring and often severe headaches. The aim of this study was to evaluate the effectiveness of coenzyme Q10 (CoQ10) in episodic migraine prophylaxis. Material and Methods: In a prospective follow-up study, 80 patients with episodic migraine were enrolled according to the International Classification of Headache Disorders 3rd edition and divided into two groups. One group consisted of 40 patients who received CoQ10 oral 200 mg twice daily as monotherapy for three months, while the other group consisted of 40 patients who received CoQ10 as an adjunct therapy in combination with other prophylactic antimigraine drugs. The Migraine Disability Assessment (MIDAS) questionnaire was administered to both groups before and after three months of therapy. Throughout the three-month therapy period, patients recorded daily symptoms, allowing for observation of changes in symptom severity, number, and duration of attacks from baseline. Results: Both groups that received CoQ10 supplementation exhibited positive responses. The group receiving adjunct therapy showed a statistically more significant reduction in the MIDAS (p

Abstract Background Low back pain (LBP) is one of the most common musculoskeletal complaints and considered as the most disabling condition among general population. Magnetic resonance imaging (MRI) is the preferred modality in imaging of LBP. Diffusion tensor imaging (DTI) is a version of MRI that can detect tissue microstructure changes occurring in different pathologies. The commonly used parameters are fractional anisotropy (FA) and mean diffusivity (MD). We aimed in this study to evaluate the role of DTI in the assessment of back muscles in young adults with chronic LBP with no major neurological or orthopedic disorders. Results There was a statistically significant difference in MD values of back muscles between patients and control groups. At the ROC curve, for psoas muscle, the AUC was 0.906 with a cutoff point of 0.951. Sensitivity and specificity were 89.2% and 90.9% with accuracy 89.8%. For multifidus muscle, the AUC was 0.919 with a cutoff point of 1.29. Sensitivity and specificity were 91.9% and 90.9% with accuracy 91.4%. For erector spinae muscle, the AUC was 0.834 with a cutoff point of 1.224. Sensitivity and specificity were 81.1% and 72.7% with accuracy 77.9%. There was a statistically significant difference in FA values of back muscles between the patients and control groups. At the ROC curve, for psoas muscle, the AUC was 0.840 with a cutoff point of 0.546. Sensitivity and specificity were 81.1% and 72.7% with accuracy 77.97%. For multifidus muscle, the AUC was 0.875 with a cutoff point of 0.415. Sensitivity and specificity were 81.1% and 90.9% with accuracy 84.7%. For erector spinae muscle, the AUC was 0.805 with a cutoff point of 0.437. Sensitivity and specificity were 81.1% and 77.3% with accuracy 79.7%. Conclusions DTI is a valuable promising noninvasive tool in the assessment of back muscles quality in patient with chronic low back pain, with no detected neurological or orthopedic pathologies. This is due to its sensitivity to microscopic intracellular changes that could not be detected on conventional imaging, allowing better tissue characterization.

Background: Advanced magnetic resonance imaging (MRI) technique called diffusion tensor imaging (DTI) can assess tissue microstructure. It's challenging to identify sensorineural hearing loss (SNHL) cause suing CT or MRI without significant gross disruption. Objectives: to assess microstructural integrity of auditory neural pathway SNHL patients with or without tinnitus by DTI. Patients and methods: This prospective, case-control study included 55 subjects in three groups: 30 healthy volunteers in control group (GI), 12 patients in bilateral SNHL without tinnitus group (GII), and 13 patients in bilateral SNHL with tinnitus group (GIII) were MRI-assessed using 1.5 Tesla GE machine. Ordinary one-way ANOVA test was used to compare groups with normal distributions, Kroskal Wallis test: compares groups with abnormally distributed data; post-hoc test: determines significance between pairs. Results: ANOVA test revealed statistically significant difference at Lateral lemniscus(LL), Inferior colliculus(IC), medial geniculate body (MGB), auditory radiation(AR), Superior temporal gyrus(STG), Hippocampus, amygdala, Superior longitudinal fasciculus(SLF), genu and splenium of corpus callosum (CC) with P value ≤0.05. Post-hoc test: group II had lower FA comparing to group I at LL, MGB, IC, AR, STG, genu and splenium of CC. In group III the forementioned regions were affected besides hippocampus and amygdala. Group III had statistically significant lower FA values compared to group II at LL, IC, MGB, hippocampus, amygdala, SLF, genu and splenium of CC. Conclusion: Using DTI to assess microstructural integrity of auditory pathway, SNHL is associated with white matter microstructure affection as proved by the current study, and presence of tinnitus is associated with limbic system affection.

Background: Cannabis is a versatile plant in conventional medicine, and intera-peritoneal infusion of its hydroalcoholic extract reduced sperm motility substantially over time. Seminiferous tubule diameter and sperm count both significantly reduced when as opposed to the control group. The reproductive system of animals undergoes morphological and physiological alterations as a result of chronic ethanol intake. Vitamin C has a crucial part in the male reproductive system and plays an antioxidant role in organisms by scavenging reactive oxygen species [ROS] created by oxidizing agents.Aim of the work: Evaluation of effects of ethanol and cannabis consumption on adult albinos' reproductive hormones together with histopathological changes.Patients and Methods: The forty animals were divided into four groups: group I, which received only normal saline; group II, which was given oral ethanol [30% [v/v]] at a dose of 2 g/kg; group III, which obtained oral cannabis at an amount of 1.5 mg/kg; and group IV, which acquired ethanol and cannabis by way of ingestion and at the dose indicated above for 28 days. 24 hours after the last dose had been administered, rats were killed, blood was taken, and the resulting serum chemical profile was evaluated. Testes were gathered and measured. Glutathione, catalase, superoxide dismutase peroxidase inhibitor glutathione, malondialdehyde, and histology [hematoxylin and eosin] levels in the testis were measured.Results: In comparison to controls, all experimental groups had significantly lower testosterone levels and testicular glutathione, catalase, superoxide dismutase [SOD], and peroxidase glutathione levels. Malondialdehyde, on the other hand, was markedly elevated in each group of experiments as compared to controls. Alcohol and/or cannabis produced structural abnormalities in the testicles.Conclusion: Ethanol and cannabis abuse had comparable, additive, and synergistic effects that were detrimental to male reproductive health. These effects may be related to how they damaged the body's antioxidant protection mechanism.

Abstract Background SARS-CoV-2 infection involves disturbing multiple molecular pathways related to immunity and cellular functions. PIM1 is a serine/threonine-protein kinase found to be involved in the pathogenesis of several viral infections. One PIM1 substrate, Myc, was reported to interact with TMPRSS2, which is crucial for SARS-CoV-2 cell entry. PIM1 inhibitors were reported to have antiviral activity through multiple mechanisms related to immunity and proliferation. This study aimed to evaluate the antiviral activity of 2-pyridone PIM1 inhibitor against SARS-CoV-2 and its potential role in hindering the progression of COVID-19. It also aimed to assess PIM1 inhibitor’s effect on the expression of several genes of Notch signaling and Wnt pathways. In vitro study was conducted on Vero-E6 cells infected by SARS-CoV-2 “NRC-03-nhCoV” virus. Protein–protein interaction of the study genes was assessed to evaluate their relation to cell proliferation and immunity. The effect of 2-pyridone PIM1 inhibitor treatment on viral load and mRNA expression of target genes was assessed at three time points. Results Treatment with 2-pyridone PIM1 inhibitor showed potential antiviral activity against SARS-CoV-2 (IC50 of 37.255 µg/ml), significantly lowering the viral load. Functional enrichments of the studied genes include negative regulation of growth rate, several biological processes involved in cell proliferation, and Interleukin-4 production, with interleukin-6 as a predicted functional partner. These results suggest an interplay between study genes with relation to cell proliferation and immunity. Following in vitro SARS-CoV-2 infection, Notch pathway genes, CTNNB1, SUMO1, and TDG, were found to be overexpressed compared to uninfected cells. Treatment with 2-pyridone PIM1 inhibitor significantly lowers the expression levels of study genes, restoring Notch1 and BCL9 to the control level while decreasing Notch2 and CTNNB1 below control levels. Conclusion 2-pyridone PIM1 inhibitor could hinder cellular entry of SARS-CoV-2 and modulate several pathways implicated in immunity, suggesting a potential benefit in the development of anti-SARS-CoV-2 therapeutic approach.

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a life-saving treatment for various hematological disorders. The success of allo-HSCT depends on the engraftment of donor cells and the elimination of recipient cells monitored through chimerism testing. We aimed to validate a next-generation sequencing (NGS)-based chimerism assay for engraftment monitoring and to emphasize the importance of including the most prevalent cell subsets in proficiency testing (PT) programs. We evaluated the analytical performance of NGS-based chimerism testing (AlloSeq-HCT and CareDx) with a panel of targeted 202 informative single-nucleotide polymorphisms (SNPs) (i.e., linearity and precision, analytical sensitivity and specificity, system accuracy, and reproducibility). We further compared the performance of our NGS panel with conventional short tandem repeat (STR) analysis in unfractionated whole blood and cell-subset-enriched CD3 and CD66. Our NGS-based chimerism monitoring assay has an impressive detection limit (0.3% host DNA) for minor alleles and analytical specificity (99.9%). Pearson’s correlation between NGS- and STR-based chimerism monitoring showed a linear relationship with a slope of 0.8 and r = 0.973. The concordance of allo-HSCT patients using unfractionated whole blood, CD3, and CD66 was 0.95, 0.96, and 0.54, respectively. Utilization of CD3+ cell subsets for mixed chimerism detection yielded an average of 7.3 ± 7-fold higher donor percentage detection compared to their corresponding unfractionated whole blood samples. The accuracy of the NGS assay achieved a concordance of 98.6% on blinded external quality control STR samples. The reproducibility series showed near 100% concordance with respect to inter-assay, inter-tech, inter-instrument, cell flow kits, and AlloSeq-HCT software versions. Our study provided robust validation of NGS-based chimerism testing for accurate detection and monitoring of engraftment in allo-HSCT patients. By incorporating the cell subsets (CD3 and CD66), the sensitivity and accuracy of engraftment monitoring are significantly improved, making them an essential component of any PT program. Furthermore, the implementation of NGS-based chimerism testing shows potential to streamline high-volume transplant services and improve clinical outcomes by enabling early relapse detection and guiding timely interventions.

Next-Generation Sequencing (NGS) has transformed clinical histocompatibility laboratories through its capacity to provide accurate, high-throughput, high-resolution typing of Human Leukocyte Antigen (HLA) genes, which is critical for transplant safety and success. As this technology becomes widely used for clinical genotyping, histocompatibility laboratories now have an increased capability to identify novel HLA alleles that previously would not be detected using traditional genotyping methods. Standard guidelines for the clinical verification and reporting of novelties in the era of NGS are greatly needed. Here, we describe the experience of a clinical histocompatibility laboratory’s use of NGS for HLA genotyping and its management of novel alleles detected in an ethnically-diverse population of British Columbia, Canada. Over a period of 18 months, 3,450 clinical samples collected for the purpose of solid organ or hematopoietic stem cell transplantation were sequenced using NGS. Overall, 29 unique novel alleles were identified at a rate of ∼1.6 per month. The majority of novelties (52%) were detected in the alpha chains of class II (HLA-DQA1 and -DPA1). Novelties were found in all 11 HLA classical genes except for HLA-DRB3, -DRB4, and -DQB1. All novelties were single nucleotide polymorphisms, where more than half led to an amino acid change, and one resulted in a premature stop codon. Missense mutations were evaluated for changes in their amino acid properties to assess the potential effect on the novel HLA protein. All novelties identified were confirmed independently at another accredited HLA laboratory using a different NGS assay and platform to ensure validity in the reporting of novelties. The novel alleles were submitted to the Immuno Polymorphism Database-Immunogenetics/HLA (IPD-IMGT/HLA) for official allele name designation and inclusion in future database releases. A nationwide survey involving all Canadian HLA laboratories confirmed the common occurrence of novel allele detection but identified a wide variability in the assessment and reporting of novelties. In summary, a considerable proportion of novel alleles were identified in routine clinical testing. We propose a framework for the standardization of policies on the clinical management of novel alleles and inclusion in proficiency testing programs in the era of NGS-based HLA genotyping.

Abstract Exchange of viral segments between one or more influenza virus subtypes can contribute to a shift in virulence and adaptation to new hosts. Among several influenza subtypes, H9N2 is widely circulating in poultry populations worldwide and has the ability to infect humans. Here, we studied the reassortant compatibility between chicken H9N2 with N1–N9 gene segments of wild bird origin, either with an intact or truncated stalk. Naturally occurring amino acid deletions in the NA stalk of the influenza virus can lead to increased virulence in both mallard ducks and chickens. Our findings show extended genetic compatibility between chicken H9Nx gene segments and the wild-bird NA with and without 20 amino acid stalk deletion. Replication kinetics in avian, mammalian and human cell lines revealed that parental chH9N2 and rH9N6 viruses with intact NA-stalk replicated significantly better in avian DF1 cells compared to human A549 cells. After introducing a stalk deletion, an enhanced preference for replication in mammalian and human cell lines could be observed for rH9N2Δ(H6), rH9N6Δ and rH9N9Δ compared to the parental chH9N2 virus. This highlights the potential emergence of novel viruses with variable phenotypic traits, warranting the continuous monitoring of H9N2 and co-circulating subtypes in avian hosts.

Background Hospital-acquired infections (HAIs) are increasing due to the spread of multi-drug-resistant organisms. Gut dysbiosis in an intensive care unit (ICU) patients at admission showed an altered abundance of some bacterial genera associated with the occurrence of HAIs and mortality. In the present study, we investigated the pattern of the gut microbiome in ICU patients at admission to correlate it with the development of HAIs during ICU stay. Methods Twenty patients admitted to an ICU with a cross-matched control group of 30 healthy subjects of matched age and sex. Quantitative SYBR green real-time polymerase chain reaction was done for the identification and quantitation of selected bacteria. Results Out of those twenty patients, 35% developed ventilator-associated pneumonia during their ICU stay. Gut microbiome analysis showed a significant decrease in Firmicutes and Firmicutes to Bacteroidetes ratio in ICU patients in comparison to the control and in patients who developed HAIs in comparison to the control group and patients who did not develop HAIs. There was a statistically significant increase in Bacteroides in comparison to the control group. There was a statistically significant decrease in Bifidobacterium and Faecalibacterium prausnitzii and an increase in Lactobacilli in comparison to the control group with a negative correlation between Acute Physiology and Chronic Health Evaluation (APACHE) II score and Firmicutes to Bacteroidetes and Prevotella to Bacteroides ratios. Conclusions Gut dysbiosis of patients at the time of admission highlights the importance of identification of the microbiome of patients admitted at the ICU as a target for preventing of HAIs.

Abstract Background Cervical incompetence is a failure of the cervix to retain the products of conception throughout pregnancy, which results into cervical dilatation and preterm delivery. Many methods are conducted for early detection of cervical shortening, ripening and eventually dilatation to lessen the incidence of the preterm delivery, which is responsible for about 75% of neonatal comorbidities. Ultrasound plays an important role in the diagnosis and early detection of cervical incompetence. Elastography is a relatively new technique, which investigates into another important factor for cervical insufficiency which is “tissue stiffness”. The process of early cervical ripening, which is an important and main step in spontaneous preterm delivery, precedes cervical shortening and renders the human cervix soft which can be diagnosed through the color-coding method of the sonoelastography technique. The aim of this study is to determine the value of cervical elastography as a predictor of spontaneous preterm labor and validate the role of strain ratio in such technique. Results In our study, we examined the pregnant females by transvaginal conventional B-mode ultrasound and complementary elastography technique and recorded the elastography index of their cervix, internal os and external os together with measuring the amount of strain and strain ratio at internal and external os. Conclusions We concluded that women who had preterm delivery did have higher strain and elastography index as their cervices were softer than those who had full-term deliveries. Elastography therefore can be a reliable method for the prediction of preterm delivery.

Abstract The persistent evolution of drug-resistant influenza strains represents a global concern. The innovation of new treatment approaches through drug screening strategies and investigating the antiviral potential of bioactive natural-based chemicals may address the issue. Herein, we screened the anti-influenza efficacy of some biologically active indole and β-carboline (βC) indole alkaloids against two different influenza A viruses (IAV) with varied host range ranges; seasonal influenza A/Egypt/NRC098/2019(H1N1) and avian influenza A/chicken/Egypt/N12640A/2016(H5N1). All compounds were first assessed for their half-maximal cytotoxic concentration (CC50) in MDCK cells and half-maximal inhibitory concentrations (IC50) against influenza A/H5N1. Intriguingly, Strychnine sulfate, Harmalol, Harmane, and Harmaline showed robust anti-H5N1 activities with IC50 values of 11.85, 0.02, 0.023, and 3.42 µg/ml, respectively, as compared to zanamivir and amantadine as control drugs (IC50 = 0.079 µg/ml and 17.59 µg/ml, respectively). The efficacy of the predefined phytochemicals was further confirmed against influenza A/H1N1 and they displayed potent anti-H1N1 activities compared to reference drugs. Based on SI values, the highly promising compounds were then evaluated for antiviral efficacy through plaque reduction assay and consistently they revealed high viral inhibition percentages at non-toxic concentrations. By studying the modes of antiviral action, Harmane and Harmalol could suppress viral infection via interfering mainly with the viral replication of the influenza A/H5N1 virus, whilst Harmaline exhibited a viricidal effect against the influenza A/H5N1 virus. Whereas, Strychnine sulfate elucidated its anti-influenza potency by interfering with viral adsorption into MDCK cells. Consistently, chemoinformatic studies showed that all studied phytochemicals illustrated HB formations with essential peptide cleft through the NH of indole moiety. Among active alkaloids, harmalol displayed the best lipophilicity metrics including ligand efficiency (LE) and ligand lipophilic efficiency (LLE) for both viruses. Compounds geometry and their ability to participate in HB formation are very crucial.

Background: Large-volume therapeutic thoracocentesis may be associated with pulmonary congestion or a more serious complication; re-expansion pulmonary edema (RPE). We investigated whether monitoring pleural pressure with manometry during thoracocentesis would prevent these pulmonary symptoms/RPE and allow larger volume drainage. Methods: We did a randomized controlled trial involving 110 patients with large malignant pleural effusions. Patients were randomly allocated to obtain thoracocentesis with or without pleural manometry. We measured the incidence of pulmonary congestion symptoms, total fluid aspirated, and pleural pressures in both groups. This trial is listed on ClinicalTrials.gov as NCT04420663. Results: The mean amount of total thoracocentesis fluid withdrawn from the control group was 945.4±78.9 (mL) and 1690.9±681.0 (mL) from the intervention group (P

Occurrence of multi-class antibiotics in edible fish species from the Saudi market was investigated. A fast and sensitive UPLC-MS/MS method for simultaneous determination of selected fluoroquinolones, sulfonamides and macrolides in fish muscle was developed and validated. Sample clean up was performed using solid-phase extraction on Oasis HLB cartridges. The greenness profile of the developed method was evaluated using three assessment tools: analytical Eco-scale assessment method, green analytical procedure index and analytical greenness metric. Detection limits ranged from 0.008 to 0.35 μg/kg. The recovery ranged from 80.1 % to 98.6 % with RSDs ≤ 12.1 %. The mean and maximum concentrations of the detected antibiotics in fish samples ranged between 0.28 and 19.15 and 3.50–112.00 µg/kg, respectively. Human antibiotics (clarithromycin and roxithromycin) were detected in 50 % and 27.5 % of the samples, respectively. The estimated daily intake for the detected antibiotics ranged from 0.10 to 6.61 ng/kg/ BW/day for Saudi adults. The health risk associated with fish consumption was evaluated. The results suggested that fish consumption may not pose a serious risk to consumers in Saudi Arabia. The developed method was fast, sensitive, cost-effective and environmentally friendly.

Objectives: Varicocele is the most common correctable cause of male infertility that always has been a debatable subject as regards how it affects fertility and the best way to treat it. Proper assessment of the disease bilaterality is crucial not to miss one side and not to jeopardize treatment outcome. This study aimed to objectively assess varicocele bilaterality in infertile men aiming to improve treatment outcome in this cohort of patients. Methods: This prospective study was conducted between January 2019 and January 2022 including infertile males with varicoceles. Assessment of missed concomitant contralateral varicocele done pre-operatively by Color Doppler Ultrasound and intraoperatively by intraoperative Doppler device and measurement of maximal vein diameter of contralateral side. Results: A total of 329 cases completed the study. A hundred cases (30.4%) were initially referred as unilateral varicoceles and 229 (69.6%) as bilateral varicoceles. After reassessment of the study population, bilaterality of varicocele was found to be as high as 98.5% (324/329). Repeat CDUS strongly correlated with the intraoperative measured varicocele diameter (r = 0.9, p < 0.001). Moreover, sperm parameters showed significant improvement 3 and 6 months post varicocelectomy. Normal pregnancy after 1 year of surgery occurred in 118 cases (35.9%). Conclusions: Varicocele bilaterality in infertile men is underreported. Thorough assessment by expert radiologists and andrologists is of paramount importance not to miss significant pathology or hazard treatment outcome.

Background: In cases of large-angle horizontal strabismus, standard two-horizontal muscle surgery is insufficient. Utilizing supramaximal recession and resection techniques would result in limited duction. True muscle transplantations have been explored in this scenario as a potential solution for this large angle deviation. Objectives: to evaluate the long-term effects of muscle transplantation on patients with large-angle horizontal strabismus, assessing success rate, ocular alignment improvement, and patient satisfaction post-surgery. Patients and methods: This prospective case series with 30 cases, divided into Group A (large-angle esotropia) and Group B (large-angle exotropia). The surgical procedure involved muscle transplantation using a recession technique. Preoperative evaluations, including comprehensive ophthalmic examinations, were conducted to determine the angle of deviation, visual acuity, and ocular motility. The participants underwent follow-up visits post-surgery. Results: In Group A, the mean preoperative distance angle of deviation, measured in prism diopters (PD), was 80.67±11.63. The mean preoperative adduction and abduction restriction was -0.07±0.26, -0.73±0.96, respectively. The amount of lateral rectus (LR) resection, and medial rectus (MR) recession ranged from 6 to 9 mm, and 2 to 5 mm, respectively. In Group B, the mean preoperative distance angle of deviation, measured in prism diopters (PD), was 75.67±13.61. The mean preoperative adduction and abduction restriction was -1.47±1.36, - 0.53±0.74, respectively. The amount of medial rectus (MR) resection, and lateral rectus (LR) recession ranged from 6 to 8 mm, and 3 to 10 mm, respectively. Conclusion: Muscle transplantation is an effective surgical technique for large angle horizontal strabismus. It leads to significant improvements in ocular alignment and movement restrictions.

The global outbreak of the COVID-19 pandemic provokes scientists to make a prompt development of new effective therapeutic interventions for the battle against SARS-CoV-2. A new series of N-(5-nitrothiazol-2-yl)-carboxamido derivatives were designed and synthesised based on the structural optimisation principle of the SARS-CoV Mpro co-crystallized WR1 inhibitor. Notably, compound 3b achieved the most promising anti-SARS-CoV-2 activity with an IC50 value of 174.7 µg/mL. On the other hand, compounds 3a, 3b, and 3c showed very promising SARS-CoV-2 Mpro inhibitory effects with IC50 values of 4.67, 5.12, and 11.90 µg/mL, respectively. Compound 3b docking score was very promising (−6.94 kcal/mol) and its binding mode was nearly similar to that of WR1. Besides, the molecular dynamics (MD) simulations of compound 3b showed its great stability inside the binding pocket until around 40 ns. Finally, a very promising SAR was concluded to help to design more powerful SARS-CoV-2 Mpro inhibitors shortly.

Mediastinal lymph node assessment is a crucial step in non-small cell lung cancer staging. Positron emission tomography (PET) has been the gold standard for the assessment of mediastinal lymphadenopathy, though it has limited specificity. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is quick, accurate, and a less invasive method for obtaining a diagnostic sample in contrast to mediastinoscopy. We performed a retrospective chart analysis of 171 patients to assess the adequacy of tissue obtained by EBUS for diagnosis and molecular profiling as well as the assessment of staging and lymph node (LN) stations diagnostic yield, in correlation to PET scan and the operator’s level of experience. A significantly increased tissue adequacy was observed based on the operators’ experience, with the highest adequacy noted in trained Interventional Pulmonologist (IP) (100%), followed by >5 years of experience (93.33%), and 88.89% adequacy with p = 0.0019). PET-CT scan 18F-fluorodeoxyglucose (FDG) uptake in levels 1, 2, and 3 LN had a tissue adequacy of 76.67%, 54.64%, and 35.56%, respectively (p = 0.0009). EBUS bronchoscopy method could be used to achieve an accurate diagnosis, with IP-trained operators yielding the best results. There is no correlation with PET scan positivity, indicating that both PET and EBUS are complementary methods needed for staging.

Abstract Background Recent studies and reports have documented the ability of the co-circulating seasonal influenza A/H1N1 (ancestor: 2009 pandemic H1N1) and A/H3N2 to exchange their genetic segments, generating a novel H1N2 strain in different geographical localities around the world with an ability to infect human. This raises concerns and triggers alarms to develop a multivalent vaccine that can protect against the documented H1- and H3-type human influenza A viruses (IAVs). Results Here, we generated a PR8-based vaccine strain that carries the HA gene segment from the contemporary H1N1 virus while the NA gene segment was derived from a currently circulating influenza A/H3N2 strain. A recombinant PR8-based H1N2 vaccine strain (rgH1N2), engineered by reassortment between influenza A/H1N1 and A/H3N2 to mimic the documented human influenza A/H1N2, was used for immunization to provoke immunogenicity and cross-antigenicity against the H1- and H3-type human IAVs and was evaluated for its immunogenicity and effectiveness in mice. Following challenge infection of rgH1N2-vaccinated mice with contemporary influenza A/H1N1 and A/H3N2, results revealed that rgH1N2-vaccinated mice showed less viral shedding, more survival, and less body weight loss compared to control unvaccinated groups and vaccinated mice with rgH1N1 and rgH3N2. Conclusions This study highlights the applicability of the PR8-based H1N2 vaccine strain to protect against seasonal IAVs and emphasizes the role of both surface proteins, HA and NA, to stimulate protective and neutralizing antibodies against circulating influenza A/H1N1 and A/H3N2 strains.

على الرغم من الجهود الكبيرة التي تبذلها الجهات الحكومية السعودية لتجنب تأخير وتعثر مشاريع التشييد، الا ان أغلب الدراسات المعاصرة أظهرت أنه مازال هناك نسبة كبيرة من المشاريع متأخرة ومتعثرة نتيجة لعوامل متعددة منها ضعف إعداد الجدول الزمني للمشروع، وذلك على الرغم من توافر العديد من التقنيات الرقمية التي يمكنها دعم تطوير وإحكام هذه الجداول لتحقيق أهداف المشاريع، وهو ما يمثل الإشكالية الرئيسية لهذه الدراسة التي تستهدف دراسة الإتجاهات المعاصرة للتقنيات الرقمية ذات العلاقة بالجداول الزمنية لمشاريع التشييد، والتحديات التي تواجه تطبيقها، والوصول إلى إطار لتوظيفها في إحكام الجداول الزمنية لمشاريع التشييد. ولتحقيق هذه الأهداف تبنت الدراسة المنهج البحثي الوصفي التحليلي اعتماداً على المراجعات الأدبية للإتجاهات والتحديات التي تواجه تطبيق هذه التقنيات. وناقشت الدراسة أربعة من الإتجاهات المعاصرة لإحكام الجداول الزمنية وثلاثة من أهم التحديات التي تواجهها وخلصت إلى إطار العمل المستهدف وعدد من النتائج والتوصيات المهمة لمعالجة إشكالية الدراسة ودعم جهود المملكة ورؤيتها تجاه التحول الرقمي واستخدام التقنيات الحديثة في جميع المجالات. Abstract: Despite the great efforts made by Saudi government to avoid construction projects delays, most contemporary studies have shown that the phenomena of construction projects delays are spread with high percentage due to multiple factors, including poor project schedules. With the availability of many digital technologies that could enhance these schedules to achieve projects’ objectives, this is considered the main problem of this research, aiming to study the contemporary trends of digital technologies related to construction schedules and the challenges facing their application to reach a framework to utilize its capabilities to enhance construction schedules. To achieve these goals, the study adopted the analytical descriptive method through an literature-based reviews of the related trends and challenges. The study discussed four of the contemporary trends to enhance schedules and three of the most important challenges they face during application, and concluded the target framework and a number of important results and recommendations to handle the research problem and support the Kingdom's efforts and vision towards digital transformation and the use of modern technologies in all fields.

Net Zero Energy Buildings (NZEB) are becoming more and more important with the global sustainability movements and energy crisis which increase the need to reduce carbon emissions and energy consumption. The development of Building Information Modelling (BIM) and Building Energy Modelling (BEM) techniques and applications increase its capabilities to support designers in their trials to cope with such movements during the design process and proved its benefits in the Architecture, Engineering and Construction (AEC) industry and used in multiple purposes efficiently. However, the status of the documented trials to achieve a NZE is in its modest situation. This represents a research gap and the intensive for this study that aim to invest the capabilities of BIM and BEM applications to reach a NZE house model in Riyadh, Saudi Arabia. The study adopted a descriptive and experimental approach to apply the NZE concepts on a house model using Revit, Green Building Studio and Insight applications. The reached model could reduce the normal yearly energy combined consumption by about 40% and proved that the building could produce more energy than it consumes.

With the emerging technologies of the fourth industrial revolution (4th IR), there are more possibilities to enhance the facility management (FM). Despite the increasing tendencies to integrate new technologies in the process of FM, its potentials in enhancing the BIM-based FM decision making process is not yet totally explored and its application is facing many challenges that should be considered. This paper aims to explore the benefits and challenges of integrating the Internet of Things (IoT), Virtual Reality (VR) and Augmented Reality (AR) in the Facility Management (FM) process to enhance the decision making; and to conclude a framework for integrating of such technologies in the BIM-based FM Process. The paper adopted a descriptive methodology through a comprehensive literature and case-based review to achieve its objectives. The conclusion shows that integrating the IoT, VR & AR in the FM process and handling its related challenges from the early stages could greatly enhance and support the FM team and the FM related parties in making quick, accurate and effective decisions, saving energy & cost and optimizing the use of resources.