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Walaa Y Elsabeeny, Nahla N Shehab, Mohamed A Wadod, Mostafa A Elkady Department of Anesthesia and Pain Management, National Cancer Institute, Cairo University, Cairo, EgyptCorrespondence: Walaa Y ElsabeenyDepartment of Anesthesia and Pain Management, National Cancer Institute, Kasr Al Eini Street, Fom El Khalig, Cairo 11796, EgyptTel +20 1007798466Email walaa.Elsabeeny@nci.cu.edu.egPurpose: Various analgesic modalities are adopted for perioperative analgesia in breast cancer surgeries. This study aimed to compare the efficacy of intravenous morphine versus serratus anterior plane block (SAPB) and erector spinae plane block (ESPB) in breast cancer surgeries.Patients and Methods: Seventy-five breast cancer patients undergoing modified radical mastectomy from January 2020 to June 2020 were randomly allocated into 3 groups; the morphine group received morphine 0.1 mg/kg, the SAPB group received ultrasound-guided SAPB with 25 mL bupivacaine 0.25% and the ESPB group received ultrasound-guided ESPB with 25 mL bupivacaine 0.25%. A visual analogue scale (VAS) 0– 10 was used to evaluate pain postoperatively, where 0 denotes no pain and 10 worst pain. If any patient in the 3 studied groups reported breakthrough pain with VAS ≥ 4 then a bolus of 3 mg morphine was given.Results: There was no difference in VAS scores between the 3 groups postoperatively. Morphine consumption was higher in the morphine group (9.19 ± 2.32 mg) than the SAPB group (4.00 ± 1.55 mg) and the ESPB group (4.20 ± 1.64 mg), respectively. First time to receive postoperative morphine was significantly longer for the ESPB and SAPB groups than the morphine group (20.40 ± 4.98 hours), (19.00 ± 5.9 hours), (5.00 ± 4.62 hours), respectively. Intraoperative hemodynamics and fentanyl consumption showed no difference between groups, whereas postoperative mean arterial blood pressure values at 2 and 4 hours were higher in the morphine group. Ramsay sedation score and postoperative nausea and vomiting values in the post anesthesia care unit were higher for the morphine group compared to the SAPB and ESPB groups. No complications related to the blocks were reported.Conclusion: SAPB and ESPB can be used as an effective and safe alternative to opioids with fewer side effects in breast cancer patients undergoing modified radical mastectomy.Trial Registration: This trial was prospectively registered at Clinical Trials.gov on 22 January 2020 with registration number NCT04248608 (https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009JS5&selectaction=Edit&uid=U0004LIG&ts=7&cx=− 81xkwa).Keywords: modified radical mastectomy, morphine, serratus plane block, erector spinae block

Mixing performance is commonly assessed using the Villermaux– –Dushman protocol. Mixing in passive mixers may need to be at very low Reynolds number (Re). This study is aimed at comparing the mixing performances of T, Y and arrow-shaped micromixers using the Villermaux–Dushman protocol at Re < 100. The mixing performance test was run at flow rates of 500 to 1 mL h-1 with the pressure drop measurement. Based on UV absorbance values and experimental mixing times of mixed fluids from the three micromixers, the order of mixing performance at Re > 26.5 was Y < T < arrow-shaped micromixers. At lower Re values, the order of performance based on the absorbance and the experimental mixing times, became inconsistent. However, the comparison of mixing performance based on predicted mixing time gave consistent order of performance at all Re values. The instability in UV absorbance of mixed reagents in Villermaux–Dushman protocol was noted as the major cause of the reported inconsistency at very low Re. The inadequacy of Villermaux– –Dushman protocol at low Re was verified via facile solvent extraction test. A more reliable technique should be used to assess the mixing performance of micromixers at very low Re and on-line UV measurement should be adopted for the Villermaux–Dushman experiment.

Self-sensing cement-based composite was used to monitor the flow of traffic volume. Composite material was prepared with numerous percentages of carbon black (CB) and activated granulated ground blast furnace slag (GGBFS). This economical and concrete friendly material having piezo resistive properties helped to detect the wheel pressure induced by the vehicles passing over it. Initially, the pressure sensitivity of different mix designs was investigated in the laboratory and the samples having more sensitivity to applied load were used on the real road test for vehicle detection. Mechanical and microstructural properties of hydrated cement composite filled with CB and GGBFS as an active filler were also explored. Scanning electron microscopy/Electron dispersive spectroscopy (SEM/EDS) and X-ray diffraction (XRD) analysis were carried out to characterize the microstructure and hydration product development of different specimens at different curing ages. The tested cement composite gives a remarkable response to both compressive and vehicular loading with excellent mechanical and microstructural properties. The results also showed that the self-sensitive cement composite has a great potential to use as a device for traffic monitoring.

Background and Objectives: Parkinson's disease (PD) is a pathological state characterized by a combined set of abnormal movements including slow motion, resting tremors, profound stiffness of skeletal muscles, or obvious abnormalities in posture and gait, together with significant behavioral changes. Until now, no single therapeutic modality was able to provide a complete cure for PD. This work was a trial to assess the immunomodulatory effects of canagliflozin with or without levodopa/carbidopa on rotenone-induced parkinsonism in Balb/c mice. Materials and Methods: In a mouse model of PD, the effect of canagliflozin with or without levodopa/carbidopa was assessed at the behavioral, biochemical, and histopathological levels. Results: The combination of levodopa/carbidopa and canagliflozin significantly mitigated the changes induced by rotenone administration regarding the behavioral tests, striatal dopamine, antioxidant status, Nrf2 content, SIRT-1/PPAR-gamma axis, RAGE/HMGB1/NF-κB signaling, and mitochondrial dysfunction; abrogated the neuroinflammatory responses, and alleviated the histomorphologic changes induced by rotenone administration relative to the groups that received either levodopa/carbidopa or canagliflozin alone. Conclusions: Canagliflozin may represent a new adjuvant therapeutic agent that may add value to the combatting effects of levodopa/carbidopa against the pathological effects of PD.

Background: Bronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma., Methods: This study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs., Results: The current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

VEGFR-2 is a significant target in cancer treatment, inhibiting angiogenesis and impeding tumor growth. Utilizing the essential pharmacophoric structural properties, a new semi-synthetic theobromine analogue ( T-1-MBHEPA ) was designed as VEGFR-2 inhibitor. Firstly, T-1-MBHEPA 's stability and reactivity were indicated through several DFT computations. Additionally, molecular docking, MD simulations, MM-GPSA, PLIP, and essential dynamics (ED) experiments suggested T-1-MBHEPA 's strong binding capabilities to VEGFR-2. Its computational ADMET profiles were also studied before the semi-synthesis and indicated a good degree of drug-likeness. T-1-MBHEPA was then semi-synthesized to evaluate the design and the in silico findings. It was found that, T-1-MBHEPA inhibited VEGFR-2 with an IC 50 value of 0.121 ± 0.051 µM, as compared to sorafenib which had an IC 50 value of 0.056 µM. Similarly, T-1-MBHEPA inhibited the proliferation of HepG2 and MCF7 cell lines with IC 50 values of 4.61 and 4.85 µg/mL respectively - comparing sorafenib's IC 50 values which were 2.24 µg/mL and 3.17 µg/mL respectively. Interestingly, T-1-MBHEPA revealed a noteworthy IC 50 value of 80.0 µM against the normal cell lines exhibiting exceptionally high selectivity indexes (SI) of 17.4 and 16. 5 against the examined cell lines, respectively. T-1-MBHEPA increased the percentage of apoptotic MCF7 cells in early and late stages, respectively, from 0.71 % to 7.22 % and from 0.13 % to 2.72 %, while the necrosis percentage was increased to 11.41 %, in comparison to 2.22 % in control cells. Furthermore, T-1-MBHEPA reduced the production of pro-inflammatory cytokines TNF-α and IL-2 in the treated MCF7 cells by 33 % and 58 %, respectively indicating an additional anti-angiogenic mechanism. Also, T-1-MBHEPA decreased significantly the potentialities of MCF7 cells to heal and migrate from 65.9 % to 7.4 %. Finally, T-1-MBHEPA 's oral treatment didn't show toxicity on the liver function (ALT and AST) and the kidney function (creatinine and urea) levels of mice., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: VEGFR-2 is one of the most effective targets in cancer treatment. Aim: The design and semi-synthesis of new theobromine derivatives as potential VEGFR-2 inhibitors. Methods: In vitro and in silico evaluation of the synthesized compounds. Results: Compound 5b demonstrated excellent antiproliferative and VEGFR-2 inhibitory effects with significant apoptotic activity. It modulated the immune response by increasing IL-2 and reducing TNF-α levels. Docking and molecular dynamics simulations revealed the compound's binding affinity with VEGFR-2. Lastly, computational absorption, distribution, metabolism, excretion and toxicity studies indicated the high potential of compound 5b for drug development. Conclusion: Compound 5b could be a promising anticancer agent targeting VEGFR-2.

Background: Histone deacetylase (HDAC) inhibitors have good contributions in cancer management. Aim: To introduce new active HDAC inhibitors. Methods: Design and synthesis of 16 thiouracil derivatives with deep biological and computational investigation. Results: Compounds 7a , 7c , 7d , 7e , 8a and 8f showed the highest antiproliferative effects against MCF7, HepG2 and HCT116 cell lines. Compound 7e exhibited the highest activities against HDAC1 and HDAC4. Compound 7e arrested the cell cycle of HCT116 cells at G0-G1 with significant apoptotic effect. In addition, treatment with compound 7e was associated with a significant increase in the levels of caspase-3 and caspase-8. The docking studies gave good insight about the binding patterns of the synthesized compounds against HDAC1. Conclusion: Compound 7e has a promising anticancer activity targeting HDAC.

Weaning is the most crucial period associated with increased stress and susceptibility to diseases in rabbits. Methicillin-resistant Staphylococcus aureus (MRSA), a historic emergent pathogen related to post weaning stressors, adversely affects rabbit's growth rate and productive cycle. Since MRSA is rapidly evolving antibiotics resistance, natural products are desperately required to tackle the public health threats posed by antimicrobial resistance. Thus, this study aimed to screen the iin vitro antibacterial activity of Nigella sativa extract (NSE) and its interactions with antibiotics against MRSA isolates. Moreover, 200 weaned rabbits were divided into 4 groups to investigate the iin vivo superiority of NSE graded levels towards growth performance, tight junction integrity, immune responsiveness and resistance against MRSA. Herein, NSE showed promising antimicrobial activities against MRSA isolates from animal (77.8%) and human (64.3%) origins. Additionally, MRSA isolates exposed to NSE became sensitive to all antimicrobials to which they were previously resistant. Our results described that the growth-promoting functions of NSE, especially at higher levels, were supported by elevated activities of digestive linked enzymes. Post-NSE feeding, rabbits' sera mediated bactericidal activities against MRSA. Notably, upregulated expression of occludin, CLDN-1 , MUC-2 and JAM-2 genes was noted post NSE supplementation with maximum transcriptional levels in 500 mg/kg NSE fed group. Our data described that NSE constitutively motivated rabbits' immune responses and protected them against MRSA-induced experimental infection. Our results suggest the antimicrobial, growth stimulating and immunomodulation activities of NSE to maximize the capability of rabbits for disease response.

Escherichia coli ( E.coli) found in retail chicken meat could be causing a wide range of infections in humans and constitute a potential risk. This study aimed to evaluate 60 E. coli isolates from retail chicken meat ( n = 34) and human urinary tract infections (UTIs, n = 26) for phylogenetic diversity, presence of pathogenicity island (PAI) markers, antimicrobial susceptibility phenotypes, and antimicrobial resistance genes, and to evaluate their biofilm formation capacity. In that context, confirmed E.coli isolates were subjected to phylogrouping analysis using triplex PCR, antimicrobial susceptibility testing using the Kirby-Bauer disc diffusion method; PAI distribution was investigated by using two multiplex PCRs. Most of the chicken isolates (22/34, 64.7%) were identified as commensal E. coli (A and B1), while 12 isolates (35.3%) were classified as pathogenic virulent E. coli (B2 and D). Similarly, the commensal group dominated in human isolates. Overall, 23 PAIs were detected in the chicken isolates; among them, 39.1% (9/23) were assigned to group B1, 34.8% (8/23) to group A, 4.34% (1/23) to group B2, and 21.7% (5/23) to group D. However, 25 PAIs were identified from the human isolates. PAI IV536 was the most prevalent (55.9%, 69.2%) PAI detected in both sources. In total, 37 (61.7%) isolates of the chicken and human isolates were biofilm producers. Noticeably, 100% of E. coli isolates were resistant to penicillin and rifamycin. Markedly, all E. coli isolates displayed multiple antibiotic resistance (MAR) phenotypes, and the multiple antibiotic resistance index (MARI) among E. coli isolates ranged between 0.5 and 1. Several antibiotic resistance genes (ARGs) were identified by a PCR assay; the sul 2 gene was the most prevalent (38/60, 63.3%) from both sources. Interestingly, a significant positive association ( r = 0.31) between biofilm production and resistance to quinolones by the qnr gene was found by the correlation analysis. These findings were suggestive of the transmission of PAI markers and antibiotic resistance genes from poultry to humans or humans to humans through the food chain. To avoid the spread of virulent and multidrug-resistant E. coli , intensive surveillance of retail chicken meat markets is required.

Background: It remains essential for non-alcoholic fatty liver (NAFLD) patients, to develop a sensitive and specific diagnostic model. Data regarding the use of micro (mi)RNA-34 for NAFLD diagnosis are few. Routine clinical assessment, laboratory tests were done for Egyptian individuals (n = 314) were included (100 healthy individuals and 214 NAFLD patients). Quantification of miRNA-34 was done using real-time PCR. Extremely significant variables were entered into stepwise logistic regression. The diagnostic power of variables was estimated by the area under the ROC (AUC)., Results: MiRNA-34 levels were higher in NAFLD patients than healthy individuals with a significant difference (P< 0.0001). The multivariate analysis was used to evaluate the NAFLD-associated variables (CRP, cholesterol, body mass index (BMI), ALT had p< 0.0001 while mRNA-34 had (p=0.0004). The AUCs (CI) of candidate NAFLD markers were in the order of miRNA-34 0.72 (0.66-0.77) < ALT 0.73 (0.67-0.79) < BMI 0.81 (0.76-0.86) < cholesterol < 0.85 (0.79-0.90) < CRP 0.88 (0.84-0.92). We developed a novel index for discriminating patients with NAFLD named NAFLD Mark. AUC was jumped to 0.98 (0.93-0.99) when five markers were combined. The AUC of NAFLD mark for NAFLD detection was higher than the AUCs of seven common NAFLD indexes (0.44-0.86)., Conclusions: The NAFLD mark is a non-invasive and highly sensitive and specific model for NAFLD diagnosis., (© 2021. The Author(s).)

MicroRNA-567 (miR-567) plays a decisive role in cancers whereas its role in non-small cell lung cancer (NSCLC) is still unexplored. This study was therefore planned to explore the regulatory function of miR-567 in A549 NSCLC cells and investigate its possible molecular mechanism that may help in NSCLC treatment. In the current study, miR-567 expression was examined by quantitative real time-polymerase chain reaction (qRT-PCR) in different NSCLC cell lines in addition to normal cell line. A549 NSCLC cells were transfected by miR-567 mimic, miR-567 inhibitor, and negative control siRNA. Cell proliferation was evaluated by MTT and 5-bromo-2'deoxyuridine assays. Cell cycle distribution and apoptosis were studied by flow cytometry. Bioinformatics analysis programs were used to expect the putative target of miR-567. The expression of cyclin-dependent kinase 8 (CDK8) gene at mRNA and protein levels were evaluated by using qRT-PCR and western blotting. Our results found that miR-567 expressions decreased in all the studied NSCLC cells as compared to the normal cell line. A549 cell proliferation was suppressed by miR-567 upregulation while cell apoptosis was promoted. Also, miR-567 upregulation induced cell cycle arrest at sub-G1 and S phases. CDK8 was expected as a target gene of miR-567. MiR-567 upregulation decreased CDK8 mRNA and protein expression while the downregulation of miR-567 increased CDK8 gene expression. These findings revealed that miR-567 may be a tumor suppressor in A549 NSCLC cells through regulating CDK8 gene expression and may serve as a novel therapeutic target for NSCLC treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Background. The prognostic value of cardiopulmonary exercise testing (CPET) is known, but the predictive value of 6MWT in patients with heart failure (HF) and patients undergoing coronary artery bypass grafting (CABG) is not established yet. Objective. We conducted a systematic review exploring the prognostic value of 6MWT in HF patients undergoing cardiac surgery. The aim was to find out whether the change in the distance walked during follow-up visits was associated with prognosis. Data Source. We searched "PubMed" from January 1990 to December 2012 for any review articles or experimental studies investigating the prognostic value of 6MWT in HF patients and patients undergoing cardiac surgery. Results. 53 studies were included in the review, and they explored the role of 6MWT in cardiology, cardiac surgery, and rehabilitation. The results did not show the relation between the six-minute walk distance and adverse events after CABG. The predictive power of the distance walked for death in HF patients undergoing cardiac surgery was not found. It is not yet proved if the change in the six-minute walk distance is associated with prognosis. The predictive power of the six-minute walk distance for death in HF patients undergoing cardiac surgery remains unclear.