New Indole-6-Carboxylic Acid Derivatives as Multi-Target Antiproliferative Agents: Synthesis, in Silico Studies, and Cytotoxicity Evaluation.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are commonly overexpressed in cancers making them appealing targets for cancer therapeutics. Two groups of indole-6-carboxylic acid derivatives, hydrazone derivatives targeting EGFR and oxadiazole derivatives targeting VEGFR-2, were synthesized and characterized using FT-IR, 1 H-NMR, 13 CNMR, and HR-MS techniques. Binding patterns to potential molecular targets were studied using molecular docking and compared to standard EGFR and VEGFR-2 inhibitors. The newly synthesized compounds were cytotoxic to the three cancer cell lines tested (HCT-116, HeLa, and HT-29 cell lines) as evaluated by the MTT assay. Compound 3 b (EGFR-targeting) and compound 6 e (VEGFR-2-targeting) possessed the highest antiproliferation activity, were cancer-selective, arrested cancer cells in the G2/M phase, induced the extrinsic apoptosis pathway, and had the highest EGFR/VEGFR-2 enzyme inhibitory activity, respectively. The structure-activity relationships of the new compounds showed that the presence of an aryl or heteroaryl fragment attached to a linker is required for the anti-tumor activity. In conclusion, the findings of the current study suggest that compounds 3 b and 6 e are promising cytotoxic agents that act by inhibiting EGFR and VEGFR-2 tyrosine kinases, respectively.

Synthesis, docking study, and antitumor evaluation of benzamides and oxadiazole derivatives of 3-phenoxybenzoic acid as VEGFR-2 inhibitors.

Current chemotherapeutic agents have several limitations, including lack of selectivity, the development of undesirable side effects, and chemoresistance. As a result, there is an unmet need for the development of novel small molecules with minimal side effects and the ability to specifically target tumor cells. A new series of 3-phenoxybenzoic acid derivatives, including 1,3,4-oxadiazole derivatives (4a-d) and benzamides derivatives (5a-e) were synthesized; their chemical structures were confirmed by Fourier-transform infrared spectroscopy, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectra; and various physicochemical properties were determined. The antiproliferative activities of the new derivatives were evaluated by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Three compounds (4b, 4c, and 4d) exhibited cytotoxicity against two of the three cell lines tested, five compounds (3, 4a, 5a, 5b, and 5e) were toxic to one cell line, while two compounds (5c and 5d) were not cytotoxic to any of the three cell lines tested in the current study. Based on docking scores, MTT assay findings, and vascular endothelial growth factor receptor 2 (VEGFR-2) kinase activity data, Compound 4d was selected for further biological investigation. Flow cytometry was used to determine the mode of cell death (apoptosis vs. necrosis) and the effect on cell cycle progression. Compound 4d arrested HepG2 hepatocellular carcinoma cells in the G2/M phase and activated both the intrinsic and extrinsic apoptosis pathways. In conclusion, Compound 4d has shown promising results for future research as a potent VEGFR-2 tyrosine kinase inhibitor.

Novel 1,3,4-oxadiazole derivatives of naproxen targeting EGFR: Synthesis, molecular docking studies, and cytotoxic evaluation.

The close association between inflammation and cancer inspired the synthesis of a series of 1,3,4-oxadiazole derivatives (compounds H4-A-F) of 6-methoxynaphtalene. The chemical structures of the new compounds were validated utilizing Fourier-transform infrared, proton nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance spectroscopic techniques and CHN analysis. Computer-aided drug design methods were used to predict the compounds biological target, ADMET properties, toxicity, and to evaluate the molecular similarities between the design compounds and erlotinib, a standard epidermal growth factor receptor (EGFR) inhibitor. The antiproliferative effects of the new compounds were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, cell cycle analysis, apoptosis detection by microscopy, quantitative reverse transcription-polymerase chain reaction, and immunoblotting, and EGFR enzyme inhibition assay. In silico analysis of the new oxadiazole derivatives indicated that these compounds target EGFR, and that compounds H4-A, H4-B, H4-C, and H4-E show similar molecular properties to erlotinib. Additionally, the results indicated that none of the synthesized compounds are carcinogenic, and that compounds H4-A, H4-C, and H4-F are nontoxic. Compound H4-A showed the best-fit score against EGFR pharmacophore model, however, the in vitro studies indicated that compound H4-C was the most cytotoxic. Compound H4-C caused cytotoxicity in HCT-116 colorectal cancer cells by inducing both apoptosis and necrosis. Furthermore, compounds H4-D, H4-C, and H4-B had potent inhibitory effect on EGFR tyrosine kinase that was comparable to erlotinib. The findings of this inquiry offer a basis for further investigation into the differences between the synthesized compounds and erlotinib. However, additional testing will be needed to assess all of these differences and to identify the most promising compound for further research.

Dietary flaxseed cake influences on performance, quality, and sensory attributes of eggs, serum, and egg trace minerals of laying hens.

Nowadays, there is a global shortage in feed supply for animal nutrition; however, there are a considerable amount of agro-industrial co- and by-products that may offer a reasonable solution. Flaxseed cake (FSC) is a by-product of flaxseed for oil extraction rich in n-3 α-linolenic acid (ALA). Thus, the dietary inclusion of FSC on laying performance, egg quality, and serum and egg trace elements (Se, Zn, and Fe) was evaluated using Hisex White hens. The hens were distributed to three equal experimental treatments and provided diets including 0%, 5%, or 10% FSC from 48 to 58 weeks of age. Findings clarified that up to 10% FSC in the laying hen diet had no detrimental effect on laying rate, egg mass, and feed utilization. It was found that FSC resulted in a valuable source of protein, energy, macro- (Ca and P), micro- (Se, Zn and Fe) elements, and essential amino acids, with arginine being the highest. Dietary FSC did not negatively influence the egg quality traits, as well as egg sensory attributes. Including 5% or 10% FSC in diet did not significantly affect serum total protein and renal function in terms of creatinine, uric acid, and uric acid-to-creatinine ratio. Different FSC levels did not influence the chemical composition of eggs and trace elements in serum and eggs. It could be concluded that FSC is a valuable feedstuff that can provide a good source of energy, protein, amino acids, and macro- and micro-elements for hens' nutrition. The inclusion of up to 10% of FSC in hens diet did not adversely influence egg laying performance, egg quality of both fresh and stored eggs, sensory attributes, and nutritional composition, as well as Se, Zn, and Fe in serum and eggs due to balanced nutrient profile of FSC.

Primary retrograde urinary drainage using image and endoscopy guidance via urostomies.

AIM: To report the technical success of image and endoscopy-guided retrograde trans-urostomy urinary drainage as a primary catheter placement method performed by interventional radiology (IR). MATERIALS AND METHODS: Nine patients (15 attempted drain placements) with ureteric obstruction following radical cystectomy and urostomy creation were included. The patients were referred to IR for urinary drainage. All patients underwent primary image and endoscopy-guided retrograde trans-urostomy urinary drainage. RESULTS: Primary image and endoscopy-guided retrograde trans-urostomy urinary drainage was successful in 13/15 (86.6%) attempts. The proposed technique had a limited complication rate omitting the percutaneous nephrostomy access step. CONCLUSION: Primary image and endoscopy guided retrograde trans-urostomy urinary drainage should be considered before percutaneous nephrostomy in all patients with a urostomy.

Sensitivity analysis and reduction of a dynamic model of a bioproduction of fructo-oligosaccharides.

Starting from a relatively detailed model of a bioprocess producing fructo-oligosaccharides, a set of experimental data collected in batch and fed-batch experiments is exploited to estimate the unknown model parameters. The original model includes the growth of the fungus Aureobasidium pullulans which produces the enzymes responsible for the hydrolysis and transfructosylation reactions, and as such contains 25 kinetic parameters and 16 pseudo-stoichiometric coefficients, which are not uniquely identifiable with the data at hand. The aim of this study is, therefore, to show how sensitivity analysis and quantitative indicators based on the Fisher information matrix can be used to reduce the detailed model to a practically identifiable model. Parametric sensitivity analysis can indeed be used to progressively simplify the model to a representation involving 15 kinetic parameters and 8 pseudo-stoichiometric coefficients. The reduced model provides satisfactory prediction and can be convincingly cross validated.

Prospective associations of C-reactive protein (CRP) levels and CRP genetic risk scores with risk of total knee and hip replacement for osteoarthritis in a diverse cohort.

OBJECTIVE: To examine associations of high-sensitivity C-reactive protein (CRP) levels and polygenic CRP genetic risk scores (GRS) with risk of end-stage hip or knee osteoarthritis (OA), defined as incident total hip (THR) or knee replacement (TKR) for OA. DESIGN: This study included a cohort of postmenopausal white, African American, and Hispanic women from the Women's Health Initiative. Women were followed from baseline to date of THR or TKR, death, or December 31, 2014. Medicare claims data identified THR and TKR. Hs-CRP and genotyping data were collected at baseline. Three CRP GRS were constructed: 1) a 4-SNP GRS comprised of genetic variants representing variation in the CRP gene among European populations; 2) a multilocus 18-SNP GRS of genetic variants significantly associated with CRP levels in a meta-analysis of genome-wide association studies; and 3) a 5-SNP GRS of genetic variants significantly associated with CRP levels among African American women. RESULTS: In analyses conducted separately among each race and ethnic group, there were no significant associations of ln hs-CRP with risk of THR or TKR, after adjusting for age, body mass index, lifestyle characteristics, chronic diseases, hormone therapy use, and non-steroidal anti-inflammatory drug use. CRP GRS were not associated with risk of THR or TKR in any ethnic group. CONCLUSIONS: Serum levels of ln hs-CRP and genetically-predicted CRP levels were not associated with risk of THR or TKR for OA among a diverse cohort of women.

Prevalence of human papillomavirus in benign and malignant laryngeal lesions in Egyptian patients: Cross-sectional study.

OBJECTIVE: To assess the prevalence of human papillomavirus (HPV) in benign and malignant laryngeal lesions among Egyptian patients. DESIGN: Observational analytical cross-sectional study. SETTING: Ain Shams University hospital, Otorhinolaryngology department PARTICIPANTS: Formalin-fixed paraffin-embedded specimens of 126 patients (70 benign laryngeal lesions and 56 squamous cell carcinoma lesions) were assessed for the presence of HPV DNA using MY09/11 PCR-based DNA detection. MAIN OUTCOME MEASURES: Percentage of positive samples was calculated. RESULTS: All 70 benign laryngeal lesion specimens were negative for the HPV DNA, while 2 of the 56 squamous cell carcinoma lesions (3.6%) were positive. CONCLUSIONS: The presence of HPV DNA in only two specimens in our study suggests that the proportion of laryngeal squamous cell carcinomas attributable to infection by HPV seems to be very low in Egypt.

Genetic risk factors affecting mitochondrial function are associated with kidney disease in people with Type 1 diabetes.

AIM: To evaluate the association with diabetic kidney disease of single nucleotide polymorphisms (SNPs) that may contribute to mitochondrial dysfunction. METHODS: The mitochondrial genome and 1039 nuclear genes that are integral to mitochondrial function were investigated using a case (n = 823 individuals with diabetic kidney disease) vs. control (n = 903 individuals with diabetes and no renal disease) approach. All people included in the analysis were of white European origin and were diagnosed with Type 1 diabetes before the age of 31 years. Replication was conducted in 5093 people with similar phenotypes to those of the discovery collection. Association analyses were performed using the plink genetic analysis toolset, with adjustment for relevant covariates. RESULTS: A total of 25 SNPs were evaluated in the mitochondrial genome, but none were significantly associated with diabetic kidney disease or end-stage renal disease. A total of 38 SNPs in nuclear genes influencing mitochondrial function were nominally associated with diabetic kidney disease and 16 SNPS were associated with end-stage renal disease, secondary to diabetic kidney disease, with meta-analyses confirming the same direction of effect. Three independent signals (seven SNPs) were common to the replication data for both phenotypes with Type 1 diabetes and persistent proteinuria or end-stage renal disease. CONCLUSIONS: Our results suggest that SNPs in nuclear genes that influence mitochondrial function are significantly associated with diabetic kidney disease in a white European population.

High inhibition of Paenibacillus larvae and Listeria monocytogenes by Enterococcus isolated from different sources in Tunisia and identification of their bacteriocin genes.

UNLABELLED: A total of 300 isolates of Enterococcus, from different sources including faeces of poultry, cow and sheep, raw milk, ricotta cheese and water, in Tunisia, were screened for their antibacterial activity. Amongst them, 59 bacteriocin-producing strains were detected and identified by molecular methods. Genes encoding for entA, entP, entB, entL50A/B, AS-48 and bac31 bacteriocins were targeted by PCR. The bacteriocin-producing strains were assigned to the species Enterococcus faecium, Enterococcus faecalis, Enterococcus hirae, Enterococcus mundtii and Enterococcus durans, respectively, 34, 19, 3, 2 and 1 isolates. Antimicrobial activity was specifically observed against different spoilage and pathogenic micro-organisms, such as Listeria monocytogenes, Listeria innocua, Listeria ivanovii, Escherichia coli, Ent. faecalis, Staphylococcus aureus, Salmonella enterica serovar Enteritidis and Paenibacillus larvae. The inhibitory activity was totally lost after proteinase K treatment, thereby revealing the proteinaceous nature of the antimicrobial compound. Only three bacteriocin genes, namely entP, entA and entL50A/B were detected in the isolates included in this study. Enterocins A and P were the most frequent genes and they were found in 55 (93.2%) and 39 isolates (66.1%), respectively, followed by enterocin L50A/B present in 27 isolates (45.7%). These newly identified bacteriocin-producing enterococci have the potential to be used in bio-preservation of food as well as biological control of foulbrood disease. SIGNIFICANCE AND IMPACT OF THE STUDY: Enterococci possess interesting properties not only for the food industry, but also for animal and human health. The antimicrobial potential of these bacteria includes principally bacteriocin-like molecules. With the aim of identifying bacteriocinogenic strains, a collection of 300 enterococci isolated from different origins were screened and their spectrum of action, as well as the gene encoding the bacteriocin, was determined. Fifty-nine bacteriocin-producing Enterococcus showed high activity against Listeria monocytogenes and Paenibacillus larvae, the causative agent of American foulbrood. Enterocins A, P and L50A/B were found in various combinations. The most important finding of this study is the growth inhibition of P. larvae due to bacteriocin-producing Enterococcus, which opens up the possibility to use these strains to control the disease in honeybees.

Can laparoscopic removal of Essure device before embryo transfer correct poor reproductive outcome pattern in IVF? A case report.

OBJECTIVE: This report describes a successful surgical approach to multiple in vitro fertilization (IVF) failures in the setting of hydrosalpinges, which had been previously treated with Essure inserts. MATERIALS AND METHODS: A non-smoking 33-year-old Caucasian G2 P0020 (body mass index: BMI = 22) attended for second opinion. Her history was significant for bilateral hydrosalpinges having been noted on hysterosalpingogram two years earlier. This was managed by hysteroscopic placement of Essure inserts bilaterally. One year later, and now with Essure in situ, the patient completed three IVF cycles elsewhere. Her first and third IVF attempts resulted in biochemical pregnancy, while human chorionic gonadotropin (hCG) was negative after the second cycle. Upon presentation at the authors' center and before beginning a fourth IVF cycle, further testing and surgical removal of the Essure devices was recommended. RESULTS: Repeat hysteroscopy was unremarkable; laparoscopic bilateral salpingectomy and extirpation of Essure implants was accomplished without difficulty. Following menses, the patient initiated IVF with three embryos transferred. At day 60, a single intrauterine pregnancy was identified with positive cardiac activity (rate > 100/min). Her obstetrical course was uneventful; a healthy 4,195 gram male infant was delivered (breech) by Cesarean at 40 weeks' gestation. CONCLUSION: Essure inserts comprise inner fibers of polyethylene terephthalate, a stainless steel coil, and a nickel-titanium coil. The product received FDA approval as a contraceptive in 2002 although its use for hydrosalpinx remains off-label. While successful outcomes with IVF following Essure placement have been reported, this is the first description of pregnancy and delivery from IVF after Essure removal. Essure may be considered for sterilization when laparoscopy is contraindicated, but experience with its use specifically for treating hydrosalpinges before IVF is limited. This observed association between prior poor IVF outcomes and Essure with subsequent delivery after surgical Essure removal is the first of its kind to be reported, and warrants further investigation.

Characterization of residual debris on packaged hip arthroplasty stems demonstrates the dominance of less than 10 µm sized particulate: Updated USP788 guidelines for orthopedic implants.

Past evaluation of particle contamination on packaged implants has typically been conducted using US Pharmacopeia (USP) 788, a 1970s pharmaceutical guideline created to evaluate contaminant particles in injectable fluids and syringes. Our objective was to reestablish relevant acceptance criteria for residual orthopedic and other implant debris, including smaller particles (i.e., <10 µm in diameter). Packaged total hip arthroplasty (THA) titanium (Ti6Al4V)-alloy femoral stems were used (hydroxyapatite [HA]-coated and non-coated stems). Short-term ultrasonication and longer-term 24-hour soak/agitation methods were used to elute surface-bound contaminant particles, and released particles were analyzed via scanning electron microscopy, energy-dispersive x-ray analysis, image analysis, and particle characterization. For HA-coated THA-stems, >99% of eluted particles were calcium phosphate. For plain non-coated THA-stems, >99% of eluted particles were titanium-alloy-based. The number-based median size of particles in both groups was approximately 1.5 µm in diameter despite being composed of different materials. The total volume of particulate removed from HA-coated stems was 0.037 mm3 (671 × 103 particles total), which was approximately >50-fold more volume than that on plain non-coated stems at 0.0006 mm3 (89 × 103 particles total). Only non-coated THA stems passed reestablished USP788 acceptance criteria, compared by using equivalent total volumes of contaminant particulate within new and legacy guideline ranges of >10 and >25 µm ECD, that is, <1.0 × 107 particles for <1 µm diameter in size, <600,000 for <1-10 µm, <6000 for 10-25 µm and <600 for >25 µm. These results fill a knowledge gap on how much residual debris can be expected to exist on packaged implants and can be used as a basis for updating acceptance criteria (i.e., termed USP788-Implant [USP788-I]). Residual implant particulate assessment is critical given the increasing implant complexity and new manufacturing techniques (e.g., additive manufacturing).

Using a Disposable Flexible Fiberoptic Scope as a Bougie for Difficult Intubation.

In this case report, we describe two difficult intubations in which an endotracheal tube was threaded over a fiberoptic bronchoscope that was acting as a bougie. Our patients initially presented with limited neck extension, narrow mouth opening, and restricted view of the glottic region. A fiberoptic bronchoscope was guided through while the patient was oxygenated through a laryngeal mask. After the scope provided an unrestricted view of the vocal cords, the digital module was removed by cutting the fiberoptic thread, and an endotracheal tube was passed through. After proper confirmation of the endotracheal tube position, the intubation was deemed successful and thereby, we share our experience with the novel technique. This technique may potentially improve critical patient outcomes whether in trauma or an unexpectedly difficult intubation.

New Carbothioamide and Carboxamide Derivatives of 3-Phenoxybenzoic Acid as Potent VEGFR-2 Inhibitors: Synthesis, Molecular Docking, and Cytotoxicity Assessment.

INTRODUCTION/BACKGROUND: Because of the well-established link between angiogenesis and tumor development, the use of antiangiogenic therapeutics, such as those targeting VEGFR-2, presents a promising approach to cancer treatment. In the current study, a set of five hydrazine-1-- carbothioamide (compounds 3a-e) and three hydrazine-1-carboxamide derivatives (compounds 4a-c) were successfully synthesized from 3-phenoxybenzoic acid. These compounds were specially created as antiproliferative agents with the goal of targeting cancer cells by inhibiting VEGFR-2 tyrosine kinase. MATERIALS AND METHODS: The new derivatives were synthesized by conventional organic methods, and their structure was versified by IR, 1HNMR, 13CNMR, and mass spectroscopy. In silico investigation was carried out to identify the compounds' target, molecular similarity, ADMET, and toxicity profile. The cytotoxic activity of the prepared compounds was evaluated in vitro against three human cancer cell lines (DLD1 colorectal adenocarcinoma, HeLa cervical cancer, and HepG2 hepatocellular carcinoma). The effects of the leading compound on cell cycle progression and apoptosis induction were investigated by flow cytometry, and the specific apoptotic pathway triggered by the treatment was evaluated by RT-PCR and immunoblotting. Finally, the inhibitory activities of the new compounds against VEGFR-2 was measured. RESULTS: The designed derivatives exhibited comparable binding positions and interactions to the VEGFR-2 binding site to that of sorafenib (a standard VEGFR-2 tyrosine kinase inhibitor), as determined by molecular docking analysis. Compound 4b was the most cytotoxic compound, achieving the lowest IC50 against HeLa cells. Compound 4b, a strong representative of the synthesized series, induced cell cycle arrest at the G2/M phase, increased the proportion of necrotic and apoptotic HeLa cells, and activated caspase 3. The EC50 value of compound 4b against VEGFR-2 kinase activity was comparable to sorafenib's. CONCLUSION: Overall, the findings suggest that compound 4b has a promising future as a starting point for the development of new anticancer drugs.

Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors.

INTRODUCTION: Allosteric inhibition of EGFR Tyrosine Kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies. METHOD: A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy. Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. RESULT: All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity. CONCLUSION: Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

Non-overlapping activities of ADF and cofilin-1 during the migration of metastatic breast tumor cells.

BACKGROUND: ADF/cofilin proteins are key modulators of actin dynamics in metastasis and invasion of cancer cells. Here we focused on the roles of ADF and cofilin-1 individually in the development of polarized migration of rat mammary adenocarcinoma (MTLn3) cells, which express nearly equal amounts of each protein. Small interference RNA (siRNA) technology was used to knockdown (KD) the expression of ADF and cofilin-1 independently. RESULTS: Either ADF KD or cofilin KD caused cell elongation, a reduction in cell area, a decreased ability to form invadopodia, and a decreased percentage of polarized cells after 180 s of epidermal growth factor stimulation. Moreover, ADF KD or cofilin KD increased the rate of cell migration and the time of lamellipodia protrusion but through different mechanisms: lamellipodia protrude more frequently in ADF KD cells and are more persistent in cofilin KD cells. ADF KD cells showed a significant increase in F-actin aggregates, whereas cofilin KD cells showed a significant increase in prominent F-actin bundles and increased cell adhesion. Focal adhesion area and cell adhesion in cofilin KD cells were returned to control levels by expressing exogenous cofilin but not ADF. Return to control rates of cell migration in ADF KD cells was achieved by expression of exogenous ADF but not cofilin, whereas in cofilin KD cells, expression of cofilin efficiently rescued control migration rates. CONCLUSION: Although ADF and cofilin have many redundant functions, each of these isoforms has functional differences that affect F-actin structures, cell adhesion and lamellipodial dynamics, all of which are important determinants of cell migration.

c-ANCA-associated vasculitis with predominant CNS demyelination after COVID-19.

COVID-19 infection may trigger the presentation or exacerbation of autoimmune diseases. c-Antineutrophil cytoplasmic antibody (c-ANCA)-associated vasculitis after COVID-19 mainly involves the kidneys and lungs, and is rarely reported. We describe the case of a 13-year-old girl with a history of chronic immunologic thrombocytopenic purpura who presented with transverse myelitis and central nervous system demyelination, and was subsequently diagnosed with c-ANCA-associated vasculitis following COVID-19. The patient's condition improved after pulse therapy with methylprednisolone and rituximab. To our knowledge, this is the first reported pediatric case of ANCA-associated vasculitis with predominant central nervous system involvement after COVID-19 infection.

Synthesis of bee venom loaded chitosan nanoparticles for anti-MERS-COV and multi-drug resistance bacteria.

This study aims to fully exploit the natural compound; bee venom (BV) as a substance that can kill and inhibit the growth of microbes and viruses. For this target, BV was loaded onto a safe, natural, and economically inexpensive polymer; chitosan (Ch) in its nano-size form prepared using ionic gelation method in the presence of chemical crosslinking agent (sodium tripolyphosphate; TPP). The findings illustrated that chitosan nanoparticles (ChNPs) were prepared thru this method and exhibited spherical shape and average hydrodynamic size of 202 nm with a polydispersity index (PDI = 0.44). However, the size was increased to 221 nm with PDI (0.37) when chitosan nanoparticles were loaded with BV (ChNC). In addition, the particles of BV appeared as a core and chitosan nanoparticles as a shell implying the successful preparation of nanocomposite (ChNC). Encapsulation of BV into ChNPs with significantly small size distribution and good stability that protect these formed nanocomposites from agglomeration. The cytopathic effect (CPE) inhibition assay was used to identify potential antivirals for Middle East respiratory syndrome coronavirus (MERS-CoV). The response of the dose study was designed to influence the range of effectiveness for the chosen antiviral, i.e., the 50 % inhibitory concentration (IC50), as well as the range of cytotoxicity (CC50). However, our results indicated that crude BV had mild anti-MERS-COV with selective index (SI = 4.6), followed by ChNPs that exhibited moderate anti-MERS-COV with SI = 8.6. Meanwhile. The nanocomposite of ChNC displayed a promising anti-MERS-COV with SI = 12.1. Additionally, the synthesized nanocomposite (ChNC) had greater antimicrobial activity against both Gram-positive and Gram-negative bacteria when compared with ChNPs, BV or the utilized model drug.

Do internship students do well in a clinical environment? A qualitative naturistic study.

Background: The internship year marks the culmination of the nursing program across all Saudi universities, bridging theoretical learning and practical application. The significance of the internship year lies in the application of skills acquired during the preceding years of study. Understanding interns' experiences, identifying influences, and sharing their recommendations for best practices become crucial. Objective: This study aimed to explore the experiences of internship students and address the challenges they encountered in a clinical environment. Methods: A qualitative naturistic descriptive approach was employed, involving 20 purposively selected participants from internship students in two regions in Saudi Arabia. Data were collected in January 2023 through semi-structured interviews, focus group discussions, and observation. A conventional content analysis approach was used for data analysis. Results: Four major themes were generated: 1) Transferring Shock, 2) Self-Learning, 3) Supportive Environments, and 4) Factors Facilitating Learning. Transferring Shock comprised two subthemes: feeling lost and feeling left out. Conclusion: Internship students acknowledged the utility of orientation and mentorship programs in advancing the practical skills of new nurses and enhancing patient safety. The findings also indicated that those with prior preparation and robust communication skills reported a positive experience. Consequently, integrating communication courses into the nursing education curriculum could be beneficial. Establishing a supportive learning environment for nursing interns is imperative to address challenges and ensure the delivery of safe and effective patient care.

Corrigendum: The impact of multi-enzyme fortification on growth performance, intestinal morphology, nutrient digestibility, and meat quality of broiler chickens fed a standard or low-density diet.

[This corrects the article DOI: 10.3389/fvets.2022.1012462.].