BACKGROUND: Galectin-3 (Gal-3) signaling protein is a unique member of lectin family present at the cell surface, intracellularly in both the nucleus and cytoplasm and extracellularly in the general circulation. Circulating Gal-3 is present in both normal and cancer cells. High levels of circulating Gal-3 have been proven to be associated with inflammation and fibrosis in several acute and chronic conditions, which include neurological degeneration, inflammatory and immune responses, autoimmune diseases, diabetes, heart failure, atherosclerosis, response to infection, wound healing, liver, lung, and kidney disease. Gal-3 is known to regulate many biological activities including cell adhesion, angiogenesis, growth, apoptosis, migration, and metastasis. Rapamycin has been examined alone or in combination with other drugs for treatment of various cancers in clinical studies. Although it has shown promising therapeutic effects, its clinical development was interrupted by poor aqueous solubility and limited preferential distribution. To overcome these limitations, RA has been chemically modified to hydrophilic analogues, such as everolimus (EV). However, all these approaches can only partially increase the solubility, but has little effect on the blood distribution and pharmacokinetics. Therefore, it is necessary to explore other RA conjugates to improve aqueous solubility and tissue distribution profile. Recently we reported that RP-MPEG inhibits the growth of various cancer cell lines by acting on mammalian target of RP (mTOR) receptor site and it can be used for gastric cancer.
OBJECTIVE: To construct various molecular weight RP-MPEG by replacing MPEG chain in 40-O-(2- hydroxyethyl) position of the EV and analyze their binding affinity to Gal-3.
METHODS: The chemical structures of various molecular weight RP-MPEG were built using ChemSketch software. The molecular docking study was performed to find the best probable structure of RP-MPEG for competitive inhibition of the CRD, based on the interaction score. For that purpose, the 3D structures of RP and EV were obtained from NCBI PubChem compound database, where the structural protein-co-crystallized ligand complex of Gal-3 (TD2, as a native ligand) was retrieved from RCSB Protein Data Bank. All structures of the selected compounds, served as molecules for molecular modeling, were optimized through MOE.2014 software before docking. Hydrogen atoms and partial charges were added to the protein. Protein minimization was performed in gas solvation with the side chains, keeping it rigid and the ligand flexible. The selected site was isolated and minimized, followed by protonating the protein. The 3D ligands were minimized using MMFF94x with cutoffs of 10 to 12 Å. The hydrogens and charges were fixed, and the RMS gradient was set to 0.001 kcal/mol. The docking results were analyzed to identify and assess the binding affinity of these compounds to CRD using drug discovery software.
RESULTS: Our results indicated that RP-MPEG with MW 1178.51 g/mol has a logP value of 3.79 and has possessed the strongest binding affinity toward CRD of Gal-3 with a docking score of -6.87. Compared with TD2, there were additional close contacts for RP-MPEG (MW 1178.51 g/mol), coming from three hydrogen bonds with Asp148, Arg162, and Arg144 which suggest that this ligand is a strong competitive inhibitor among the other molecules for Gal-3.
CONCLUSION: RP-MPEG with the MW 1178.51 g/mol could be a promising blocker for various biological action of Gal-3 includes profibrotic activity, modulation of immune responses and inflammatory responses to cancer that contributes to neoplastic transformation, angiogenesis and metastasis. Other: The 95% confidence intervals (CIs) of the binding affinity (according to their mean and standard errors) were estimated with 2.5 and 97.5 percentile as the lower and upper bounds.
Aim: This study aimed to investigate the mediating effect of model-based learning on nurses' attitudes toward nurses' pain management awareness during the COVID 19 pandemic in Saudi Arabia government hospitals.
Method: The Heath Beliefs Model was used, with a quasi-experimental design, with per experimental one group pre-test post-test design, and a quantitative approach using self-administered questionnaires obtained from 330 nurses working with patients suffering from pain. IBM SPSS V23 and Analysis of Moment Structures (AMOS)V23 were applied to analyze the causal relationships between the variables.
Results: A two-step approach to analyze the study: the first step was to test the measurement models' constructs' reliability and validity. The second step was to test research hypotheses in the structural models. The results show a significant positive relationship between model-based learning and pain management awareness among nurses during COVID 19 pandemic. Furthermore, model-based learning fully mediated the relationship between nurses' attitudes and pain management awareness.
Conclusions: The study successfully improved nurses' attitudes toward pain management awareness among nurses during COVID 19 pandemic. These findings will help strengthen the debate in the existing literature, and this is a new development window in the pain management area.
Graphical abstract:
PURPOSE: To investigate the mediating effect of patient safety culture between the relationship of transformational leadership and safety practices among nurses.
METHODS: The data in this cross-sectional study were gathered from a survey targeted clinical nurses using a random sampling technique. The study was conducted in a medical city in Saudi Arabia, and two hundred nurses were surveyed. The Multifactor Leadership, Hospital Survey on Patient Safety Culture, and Nursing Safety Practice questionnaires were used in the study.
RESULTS: The results revealed significant positive associations between transformational leadership, patient safety culture, and nursing safety practices. Moreover, patient safety culture mediates the association between transformational leadership and safety practices among nurses.
CONCLUSION: Enhancing transformational leadership capabilities among nurse managers should be considered in order to improve nursing safety practices. Additionally, patient safety culture should be measured and improved periodically to ensure better nursing safety practices.
DESIGN: The study was conducted using the quantitative descriptive method with a cross-sectional design. Data were collected using an FFQ and sociodemographic, sedentary behaviour and physical activity questionnaires. Anthropometric measurements and blood analyses were also conducted.
SETTING: The study population included all Palestinian female adolescents enrolled in secondary schools in the academic years 2015-2016. Five female secondary schools were selected randomly from five governorates of the Gaza Strip.
SUBJECTS: Female adolescents (n 330) aged 15-19 years in the selected secondary schools were enrolled randomly.
RESULTS: Prevalence of anaemia, ID and IDA among female adolescents in the Gaza Strip, Palestine, was 35·8, 40·3 and 26·0 %, respectively. A significant association (P<0·05) existed between ID, anaemia and IDA and dietary habits, including skipping breakfast and amount of junk food intake. Also, low consumption of fruits and vegetables was associated with IDA in the female adolescents. A statistically significant association was found between mother's education and ID but not with the other sociodemographic factors.
CONCLUSIONS: The study shows that there is an alarming problem of anaemia and IDA in the Gaza Strip, Palestine. This may indicate that there are insufficient nutrition education programmes, particularly inside schools or by the mass media.
METHODS: From the databases of endoscopic endonasal skull base and rhinological surgical procedures maintained by our groups, all cases with isolated sphenoid sinus fungal mucoceles were retrieved and included in the study. Clinical and radiological findings, histopathologic evidence of fungal rhinosinusitis, culture results, clinicopathological designation, treatment details, and outcome of CN neuropathies were analyzed.
RESULTS: Headache was the most common symptom (seven cases). Oculomotor (three cases) and abducens (two cases) nerve palsies were encountered in five out of eight patients. Visual loss was seen in two cases. Hypopituitarism was seen in one case. All patients underwent endoscopic endonasal wide bilateral sphenoidectomy. CN palsies improved in four out of five cases.
CONCLUSION: Endoscopic endonasal wide sphenoidectomy is the surgical treatment of choice and should be performed in a timely manner to prevent permanent sequelae. Histopathological and microbiological examination findings should both be obtained as they dictate the next steps of therapeutic intervention.