Search

To investigate effectiveness of the ABCDEF bundle to manage and prevent delirium., Background: ICU delirium is a common hospital problem that 80% of critically ill patients in the ICU experience. The ABCDEF bundle is one of the tools that included in Delirium guidelines to manage critically ill patients., Research Design: Pre- and post intervention a quasi-experimental design was utilized in the present study., Setting: This study was conducted in the intensive care units of Assiut University Hospital., Methods: A total of 60 mechanically ventilated patients were recruited using inclusion and exclusion criteria. The ABCDEF bundle was implemented every day for the first 7 days of ICU admission, and patient sedation and delirium status were assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Sedation instrument measures were utilized in data collection., Results: Significant differences were found in the incidence of delirium: 20% in the study group versus 70% in the control group. The increased mean of days without delirium ICU stay was 4.6333 in the study group and 1.1000 in the control group, with P value = .001., Conclusion: The mechanically ventilated patients exposed to the implementation of the ABCDE bundle experienced fewer delirium signs than before the ABCDE bundle was implemented., Competing Interests: The author has no conflicts of interest in the manuscript, including financial, consultant, institutional, and other relationships that might lead to bias or a conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Thoracoscopic sympathetic chain interruption is a definitive and effective therapy for severe primary palmar hyperhidrosis (PPH). Well-known methods include sympathectomy, sympathotomy, and clipping, but the occurrence of compensatory sweating offsets these methods. This study aims to report our experience with thoracoscopic sympathetic chain interruption in a large group of patients of age <18 years with PPH, focusing on surgical outcomes, complication rates, and patient satisfaction. Patients and Methods: This retrospective study included patients who underwent thoracoscopic sympathectomy, sympathotomy, or clipping for severe PPH between April 2008 and March 2023 at the Pediatric Surgery Department, Al-Azhar University Hospitals. Demographic and clinical data, operative steps, postoperative outcomes, complications, and patient satisfaction were reviewed from the patients' medical records. Results: During the 15-year study period, 420 children with PPH underwent bilateral thoracoscopic sympathetic chain interruption by either sympathectomy, sympathotomy, or clipping, with a sex ratio of 60% being females. The mean ages were 12 ± 3.48, 13 ± 2.45, and 13 ± 2.45 years, respectively. Sympathectomy was performed in 190 patients (45.2%), sympathotomy in 170 patients (40.5%), and clipping in 60 patients (14.3%). All patients had completed follow-up, with mean periods of ∼43 ± 5 months, 45 ± 3 months, and 42 ± 6 months, respectively. Complete palmar dryness was achieved in 405 patients (overall 96.4%) (97.8% after sympathectomy, 97.05% after sympathotomy, and 90% after clipping), whereas 2.1%, 2.9%, and 10% of patients experienced symptom recurrence, respectively, denoting significant statistical differences. Overall, 94 patients (22.4%) experienced compensatory sweating. Eventually, 409 patients (97.4%) were satisfied with the outcome, whereas 11 patients (2.6%) reported dissatisfaction, yet no significant differences found. Conclusion: The presented three modalities of thoracoscopic sympathetic chain interruption for PPH in children and adolescents are safe and effective, with overall very high postoperative satisfaction, despite a relatively high rate of compensatory sweating in sympathectomy group. Other major complications in this age population were scanty.

Long noncoding RNAs (lncRNAs) are crucial regulators of biological processes such as transcription interference and activation, chromatin remodeling, and mRNA translation. Uncontrolled gene expression could result from various epigenetic modifiers, like lncRNAs. So, this study aimed to evaluate the expression profiles of lncRNA GIAT4RA, lncRNA AATBC, lncRNA Sirt1-AS, and SMARCB1 in lung cancer. The current study included lung cancer patients (n = 50), patients with chronic inflammatory diseases (n = 30), and healthy volunteers (n = 20). The expression of blood genes and the concentration of serum neuron-specific enolase were determined by real-time PCR and electrochemiluminescence immunoassay, respectively. The receiver operating characteristic and Kaplan-Meier analyses assess the sensitivity of genes as diagnostic and prognostic biomarkers, respectively. LncRNA GIAT4RA and lncRNA AATBC were upregulated, while lncRNA Sirt1-AS was significantly downregulated in all patients compared to the control group. SMARCB1 expression was significantly downregulated in chronic inflammatory patients, while in those with lung cancer, it showed an insignificant difference. The expression of lncRNA GIAT4RA and lncRNA AATBC was significantly related to the stage of lung cancer. The survival analyses showed that lower lncRNA Sirt1-AS was linked to lung cancer patients' poorer disease-free survival and overall survival. Differences in lncRNA GIAT4RA, lncRNA AATBC, and lncRNA Sirt1-AS expression were detected in all patients. The consequent abnormal expression of lncRNAs could be crucial in lung cancer development. LncRNA GIAT4RA, lncRNA AATBC, and lncRNA Sirt1-AS may be utilized as promising diagnostic biomarkers. LncRNA AATBC, lncRNA Sirt1-AS, and SMARCB1 may be valuable prognostic biomarkers for lung cancer., (© 2024. The Author(s).)

A novel group of indolyl-1,2,4-triazole-chalcone hybrids was designed, synthesized, and assessed for their anticancer activity. The synthesized compounds exhibited significant antiproliferative activity. Compounds 9a and 9e exhibited significant cancer inhibition with GI 50 ranging from 3.69 to 20.40 µM and from 0.29 to >100 µM, respectively. Both compounds displayed a broad spectrum of anticancer activity with selectivity ratios ranging between 0.50-2.78 and 0.25-2.81 at the GI 50 level, respectively. The synthesized compounds were also screened for their cytotoxicity by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazol (MTT) assay and for inhibition of epidermal growth factor receptor (EGFR) and c-MET (mesenchymal-epithelial transition factor). Some of the tested compounds exhibited significant inhibition against EGFR and/or c-MET. Compound 9b showed the highest c-MET inhibition (IC 50  = 4.70 nM) compared to foretinib (IC 50  = 2.5 nM). Compound 9d showed equipotent activity compared with erlotinib against EGFR (IC 50  = 0.052 µM) and displayed significant c-MET inhibition with an IC 50 value of 4.90 nM., (© 2024 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

We developed and synthesized tetrahydropyrimidine derivatives as possible cytotoxic agents to inhibit EGFR and VEGFR-2 in the present study. Our study completely assesses the cytotoxic efficiency of pyrimidine-based derivatives 4-15 against various cancer cell lines, revealing derivatives 12 and 15 for their remarkable activity with GI 50 values of 37 and 35 nM, respectively, when compared to the reference erlotinib (33 nM). In vitro enzyme assays showed that target compounds, particularly 12 , 14 , and 15 , effectively inhibited EGFR and VEGFR-2. In vitro enzyme testing revealed that compound 15 was the most promising, with IC 50 values of 84 and 3.50 nM for EGFR and VEGFR-2, respectively. Additionally, an in vitro assessment of the novel targets' apoptotic potential revealed that both pro-apoptotic and antiapoptotic behaviors were promising, indicating that the apoptotic induction pathway is a strongly proposed action method for the newly developed targets. Finally, molecular docking experiments are elaborately discussed to corroborate the exact binding interactions of the most active hybrids 12 and 15 with the EGFR and VEGFR-2 active sites., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Benzimidazole scaffolds have potent anticancer activity due to their structure similarity to nucleoside. In addition, benzimidazoles could function as hydrogen donors or acceptors and bind to different drug targets that participate in cancer progression. The literature had many anticancer agents containing benzimidazole cores that gained much interest. Provoked by our endless interest in benzimidazoles as anticancer agents, we summarized the successful trials of the benzimidazole scaffolds in this concern. Moreover, we discuss the substantial opportunities in cancer treatment using benzimidazole-based drugs that may direct medicinal chemists for a compelling future design of more active chemotherapeutic agents with potential clinical applications. The uniqueness of this work lies in the highlighted benzimidazole scaffold hybridization with different molecules and benzimidazole-metal complexes, detailed mechanisms of action, and the IC 50 of the developed compounds determined by different laboratories after 2015., (© 2024. The Author(s).)

A novel series of dihydropyrimidine/sulphonamide hybrids 3a-j with anti-inflammatory properties have been developed and tested as dual mPGES-1/5-LOX inhibitors. In vitro assay, results showed that compounds 3c , 3e , 3h , and 3j were the most effective dual inhibitors of mPGES-1 and 5-LOX activities. Compound 3j was the most potent dual inhibitor with IC 50 values of 0.92 µM and 1.98 µM, respectively. In vivo, anti-inflammatory studies demonstrated that compounds 3c , 3e , 3h, and 3e had considerable anti-inflammatory activity, with EI% ranging from 29% to 71%. Compounds 3e and 3j were equivalent to celecoxib after the first hour but exhibited stronger anti-inflammatory effects than celecoxib after the third and fifth hours. Moreover, compounds 3e and 3j significantly reduced the levels of pro-inflammatory cytokines (PGE 2 , TNF-α, and IL-6) with gastrointestinal safety profiles. Molecular docking simulations explored the most potent derivatives' binding affinities and interaction patterns within mPGES-1 and 5-LOX active sites. This study disclosed that compound 3j is a promising anti-inflammatory lead with dual mPGES-1/5-LOX inhibition that deserves further preclinical investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Al-Wahaibi, Elshamsy, Ali, Youssif, Bräse, Abdel-Aziz and El-Koussi.)

Two new series of quinazoline-chalcone hybrids were designed, synthesized as histone deacetylase (HDAC)/epidermal growth factor receptor (EGFR) dual inhibitors, and screened in vitro against the NCI 60 human cancer cell line panel. The most potent derivative, compound 5e bearing a 3,4,5-trimethoxyphenyl chalcone moiety, showed the most effective growth inhibition value against the panel of NCI 60 human cancer cell lines. Thus, it was selected for further investigation for NCI 5 log doses. Interestingly, this trimethoxy-substituted analog inhibited the proliferation of Roswell Park Memorial Institute (RPMI)-8226 cells by 96%, at 10 µM with IC 50  = 9.09 ± 0.34 µM and selectivity index = 7.19 against normal blood cells. To confirm the selectivity of this compound, it was evaluated against a panel of tyrosine kinase enzymes. Mechanistically, it successfully and selectively inhibited HDAC6, HDAC8, and EGFR with IC 50  = 0.41 ± 0.015, 0.61 ± 0.027, and 0.09 ± 0.004 µM, respectively. Furthermore, the selected derivative induced apoptosis via the mitochondrial apoptotic pathway by raising the Bax/Bcl-2 ratio and activating caspases 3, 7, and 9. Also, the flow cytometry analysis of RPMI-8226 cells showed that the trimethoxy-substituted analog produced cell cycle arrest in the G1 and S phases at 55.82%. Finally, an in silico study was performed to explore the binding interaction of the most active compound within the zinc-containing binding site of HDAC6 and HDAC8., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

The relentless pursuit of novel therapeutic agents against cancer has led to the identification of multiple molecular targets, among which Sirtuin 2 (SIRT2) has garnered significant attention. This study presents an extensive SAR study of our reported trityl scaffold-based SIRT2 inhibitors. This study encompasses a range of different medicinal chemistry approaches to improve the activity of the lead compounds TH-3 and STCY1. The rationally designed and synthesized structures were confirmed using NMR and high-resolution mass spectroscopy before performing SIRT2 inhibition assay, NCI60 cytotoxicity test, and cell cycle analysis. Indeed, our strategies afforded hitherto unreported SIRT2 inhibitors with high activity, particularly 2a, 4a, 7c, and 7f. Remarkably, the presence of a lipophilic para substitution on the phenyl group of a freely rotating or a locked trityl moiety enhanced activity SIRT2 inhibition. Concomitantly, the synthesized compounds showed prominent activity against different cancer lines from the NCI60 assay. Of interest, compound 7c stands out as a potent and highly selective antiproliferative agent against leukemia and colon cancer panels. Furthermore, 7c treatment resulted in cell cycle arrest in MCF-7 cells at G2 phase and did not cause in vitro DNA cleavage., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The eradication of multifactorial diseases, such as cancer, requires the design of drug candidates that attack multiple targets that contribute to the progression and proliferation of such diseases. Here, 1,5-diarylpyrazole derivatives bearing vanillin or sulfanilamide are developed as potential dual inhibitors of epidermal growth factor receptor (EGFR)/c-Jun N-terminal kinase 2 (JNK-2) for possible anticancer activity. These derivatives inhibited the growths of DLD-1, HeLa, K-562, SUIT-2 and HepG2 cancer cell lines, with minimum concentration required to inhibit half of the cellular growth (IC 50 ) values of 2.7-63 μM. The tests confirmed that 5b and 5d were potent JNK-2 inhibitors, with IC 50 of 2.0 and 0.9 μM, respectively, whereas 6 h selectively inhibited EGFR protein kinase (EGFR-PK) (IC 50  = 1.7 μM). Notably, 6c inhibited both kinases, with IC 50 values of 2.7 and 3.0 μM against EGFR-PK and JNK-2, respectively, offering a reference for designing mutual inhibitors of EGFR/JNK-2. The docking studies revealed the ability of the pyrazole ring to bind to the hinge region of the ATP binding site, thereby supporting the experimental inhibitory results. Furthermore, the developed compounds could induce apoptosis and induce cell cycle arrest at different cell phases., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Diseases in fish due to helminth parasites, especially Philometra species, are the primary worry in aquaculture. Philometra are responsible for health problem in fishes they directly affect fish growth and population parameters. A comprehensive survey was conducted involving the examination of the marine fish species Terapon jarbua, gathered from the coastal waters of Sindh, Pakistan In this research different Philometra species from marine fish Terapon jarbua during 2021 and 2022. Philometra nematodes, belonging to the family Philometridae, are common parasitic organisms inhabiting both marine and freshwater environments. Their prevalence, particularly when existing in high numbers within host organisms, can lead to severe and potentially lethal consequences. Employing light microscopy techniques, diverse species of Philometra were identified, including Philometra teraponi, P. jarbuai, P. arabiai, P. karachii, and P. awarii, localized primarily within the ovaries of the host fish. A total of 140 fish samples were examined and 76 were infected. The intensity of infected fish was 54.28%. The identification process encompassed meticulous analysis of crucial parameters, such as body size, esophagus length, positioning of the nerve ring, dimensions of the ventriculus, and ligament size. Intriguingly, the parasites were found in varying contexts; while some were free within the ovaries, others were embedded within tissues, inducing severe muscular dystrophy. This research presents novel findings of Philometra nematodes in the marine waters of Pakistan, extending their host and geographical distribution records. Future studies are needed to better evaluate and describe the dynamics and the epidemiology of Philometra infection in wild and cultured fish species.

A new class of benzimidazole-based derivatives ( 4a - j , 5 , and 6 ) with potential dual inhibition of EGFR and BRAF V600E has been developed. The newly synthesized compounds were submitted for testing for antiproliferative activity against the NCI-60 cell line. All newly synthesized compounds 4a - j , 5 , and 6 were selected for testing against a panel of sixty cancer cell lines at a single concentration of 10 µM. Some compounds tested demonstrated remarkable antiproliferative activity against the cell lines tested. Compounds 4c , 4e , and 4g were chosen for five-dose testing against 60 human tumor cell lines. Compound 4c demonstrated strong selectivity against the leukemia subpanel, with a selectivity ratio of 5.96 at the GI 50 level. The most effective in vitro anti-cancer assay derivatives ( 4c , 4d , 4e , 4g , and 4h ) were tested for EGFR and BRAF V600E inhibition as potential targets for antiproliferative action. The results revealed that compounds 4c and 4e have significant antiproliferative activity as dual EGFR/BRAF V600E inhibitors. Compounds 4c and 4e induced apoptosis by increasing caspase-3, caspase-8, and Bax levels while decreasing the anti-apoptotic Bcl2 protein. Moreover, molecular docking studies confirmed the potential of compounds 4c and 4e to act as dual EGFR/BRAF V600E inhibitors.

Objective: This study aims to explore underlying molecular variations in the expression of miRNAs in kidney tissues of ginger-treated and non-treated cyclophosphamide (CP)-intoxicated rats., Materials and Methods:   A total of 40 adult male Wistar rats were randomly divided into four groups of 10 each: Group I (control: received normal food and water), Group II (received ginger at a dose of 300 mg/kg), Group III (received CP 75 mg/kg, i.p.), and Group IV (received the same dose of CP and ginger extract).  Rats received a single injection of 75 mg/kg CP on days 3, 4, 5, 19, 20, and 21. In CP-intoxicated rats, the treatment with ginger extract at a dose of 300 mg/kg was received by oral gavage starting seven days before CP and continuing throughout the duration of the experiment for four weeks. Molecular variations in the expression of miRNAs, apoptotic genes, histological kidney damage, and abnormal kidney function in control, ginger, and CP-intoxicated rats were identified by using real-time RT-PCR Analysis, immunohistochemical, and colorimetric assays. In addition, HPLC analysis and liquid chromatography spectrophotometry analysis using Diphenyl-1-picrylhydrazyl (DPPH) radical, and Β-Carotene-linoleic acid reagents were applied respectively for in-vitro screening of phytoconstituents and antioxidant activity for ginger extract., Results: The kidney tissues of CP-intoxicated rats displayed an increase in lipid peroxidation marker malonaldehyde (MDA), DNA damage, and fibrosis markers like hyaluronic acid (HA) and hydroxyproline Hypx) with a decrease in the superoxide dismutase (SOD) and total antioxidant capacity (TAC). In addition, molecular expressions of mRNA fibrotic genes such as collagen, type 1, alpha 1 (COL1A1), and α-smooth muscle actin (αSMA). Molecular expressions of levels of B-cell lymphoma 2 (BCl-2) mRNA gene were down-regulated, and the expression of mRNA apoptotic; BCL2 associated X gene (Bax), caspase-3, Bax/BCl-2 ratio genes were significantly up-regulated respectively. Moreover, cellular oxidative genes, erythroid 2-related factor (Nrf2), and heme oxygenase-1 (HO-1) were down-regulated, respectively. The miR-155-5p, miR-34a-5p, miR-21-5p significantly increased while the miR-193b-3p, miR-455-3p, and miR-342-3p significantly decreased. Ginger also increased the expression of Nrf2, HO-1, and BCl-2 genes in the kidneys of rats induced with CP. In addition, active phytoconstituents, particularly 6]]-shogaol and 6]]-gingerol, were significantly identified in ginger extract using HPLC analysis. Antioxidant activity of these active metabolites were shown to be higher against in vitro free radicals (DPPH and Β-Carotene-linoleic acid), suggesting the potential antioxidant and antiapoptotic properties of ginger against CP-toxicity., Conclusions: Treatment with ginger in rats induced with CP resulted in significant improvement in the expression of certain molecular miRNAs. The kidney tissues of these rats showed a marked decrease in the expression of miR-155-5p, miR-34a-5p, and miR-21-5p, while the levels of miR-193b-3p, miR-455-3p, and miR-342-3p were observed to increase significantly. In conclusion, ginger can protect rats from CP-induced nephrotoxicity.

A novel series of hybrid compounds comprising quinazolin-4-one and 3-cyanopyridin-2-one structures has been developed, with dual inhibitory actions on both EGFR and BRAF V600E . These hybrid compounds were tested in vitro against four different cancer cell lines. Compounds 8 , 9 , 18 , and 19 inhibited cell proliferation significantly in the four cancer cells, with GI 50 values ranging from 1.20 to 1.80 µM when compared to Doxorubicin (GI 50 = 1.10 µM). Within this group of hybrids, compounds 18 and 19 exhibited substantial inhibition of EGFR and BRAF V600E . Molecular docking investigations provided confirmation that compounds 18 and 19 possess the capability to inhibit EGFR and BRAF V600E . Moreover, computational ADMET prediction indicated that most of the newly synthesized hybrids have low toxicity and minimal side effects.

Histone deacetylase (HDAC) inhibitors are well-established multifaceted bioactive agents against tumors and neurodegenerative disorders. Pyrimidine and its fused and substituted derivatives were employed as a surface recognition moiety of HDAC inhibitors. De facto, the literature was loaded with different success stories of pyrimidine-based HDAC inhibitors that garnered much interest. Provoked by our continuous interest in HDAC inhibitors, we summarized and elaborated on the successful harnessing of the pyrimidine scaffold in this regard. Furthermore, we dissect our perspective that may guide medicinal chemists for an effective future design of more active chemotherapeutic agents with potential clinical applications., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

Purpose: Adenoidectomy, either alone or with tonsillectomy, is a common surgical procedure in the field of pediatric otorhinolaryngology. Resonance function may be altered postoperatively in the form of hypernasality, which is usually transient. This study aimed to investigate the effect of adenoid size on post-adenoidectomy hypernasality in children with a normal palate., Methods: Seventy-one children with different degrees of adenoid hypertrophy were included in this prospective observational study. Endoscopic assessment of the adenoid size and preoperative and postoperative evaluation of speech (at 1 and 3 months) with auditory perceptual assessment (APA) and nasometry were performed., Results: APA showed preoperative hyponasality in 59.1% of children and was found to be significantly related to the adenoid size, with more hyponasality in grades 3 and 4. One month postoperatively, hypernasality was detected in 26.7% of patients and was found to be related to the preoperative adenoid size with higher hypernasality in grades 3 and 4. Three months postoperatively, all patients had gained normal nasality except one (1.4%) who was subjected to a longer follow-up period. Nasometric assessment showed significant differences at the three visits (pre, 1, and 3 months postoperatively), with a negative correlation between the grade of adenoid size and nasalance scores preoperatively and a significant positive correlation between them at 1 month postoperatively. However, no significant correlation was detected at 3 months postoperatively., Conclusion: Transient hypernasality may develop in some patients after adenoidectomy, especially in children with a larger preoperative adenoid size. However, transient hypernasality generally resolves spontaneously within 3 months., (© 2023. The Author(s).)

Introduction: One of the most robust global challenges and difficulties in the 21st century is cancer. Treating cancer is a goal which continues to motivate researchers to innovate in design and development of new treatments to help battle the disease., Objectives: Our objective was developing new antiapoptotic hybrids based on biologically active heterocyclic motifs "benzimidazole?oxadiazole-chalcone hybrids'' that had shown promising ability to inhibit EGFR and induce apoptosis. We expected these scaffolds to display anticancer activity via inhibition of BRAF, EGFR, and Bcl-2 and induction of apoptosis through activation of caspases., Methods: The new hybrids 7a-x were evaluated for their anti-proliferative, EGFR & BRAF V600E inhibitory, and apoptosis induction activities were detected. Docking study & dynamic stimulation into EGFR and BRAF V600E were studied., Results: All hybrids exhibited remarkable cell growth inhibition on the four tested cell lines with IC 50 ranging from 0.95 μM to 12.50 μM. which was comparable to Doxorubicin. Compounds 7k-m had the most potent EGFR inhibitory activity. While, compounds 7e, 7g, 7k and 7l showed good inhibitory activities against BRAF V600E . Furthermore, Compounds 7k, 7l, and 7m increased Caspases 3,8 & 9, Cytochrome C and Bax levels and decreased Bcl-2 protein levels. Compounds 7k-m received the best binding scores and showed binding modes that were almost identical to each other and comparable with that of the co-crystalized Erlotinib in EGFR and BRAF active sites., Conclusion: Compounds 7k-m could be used as potential apoptotic anti-proliferative agents upon further optimization., (© 2023. Springer Nature Switzerland AG.)

BACKGROUND A central venous catheter (CVC) is an indwelling catheter that is inserted into a large central vein for different purposes, including hemodynamic monitoring and administration of fluids and medications. This report is of a 47-year-old woman with a retained CVC line guidewire presenting with a large right atrial thrombus requiring removal during open heart surgery. CVC insertion is one of the most frequently attempted procedures in intensive care units, emergency departments, and operation rooms, especially for critically ill patients. Possible complications range from failure to place the catheter to cardiac arrest. One of the rarest complications is missing the guidewire after insertion, which is usually discovered early after inserting it. CASE REPORT We report the case of a 47-year-old woman who had a CVC line inserted following complicated open cholecystectomy. A few years later, she developed shortness of breath, with an incidental finding of a huge right atrial thrombus and a wire shown on transthoracic echocardiography. The right atrial thrombus required open heart surgery to excise the thrombus and the wire, which was done successfully. The thrombus was histopathologically and clinically proven to be an organized right atrial thrombus formed around the CVC guidewire. CONCLUSIONS This case report presents a rare complication of CVC insertion. Because this procedure is increasingly used, clinicians should be aware of the potential complications of retained CVC lines. Moreover, this report outlines different techniques to prevent such fatal complications and emphasizes the significance of radiography after insertion.

A series of novel 3-cyanopyridone/pyrazoline hybrids ( 21-30 ) exhibiting dual inhibition against EGFR and BRAF V600E has been developed. The synthesized target compounds were tested in vitro against four cancer cell lines. Compounds 28 and 30 demonstrated remarkable antiproliferative activity, boasting GI 50 values of 27 nM and 25 nM, respectively. These hybrids exhibited dual inhibitory effects on both EGFR and BRAF V600E pathways. Compounds 28 and 30 , akin to Erlotinib, displayed promising anticancer potential. Compound 30 emerged as the most potent inhibitor against cancer cell proliferation and BRAF V600E . Notably, both compounds 28 and 30 induced apoptosis by elevating levels of caspase-3 and -8 and Bax, while downregulating the antiapoptotic Bcl2 protein. Molecular docking studies confirmed the potential of compounds 28 and 30 to act as dual EGFR/BRAF V600E inhibitors. Furthermore, in silico ADMET prediction indicated that most synthesized 3-cyanopyridone/pyrazoline hybrids exhibit low toxicity and minimal adverse effects.

New 1,5-diarylpyrazole oxime hybrid derivatives (scaffolds A and B ) were designed, synthesized, and then their purity was verified using a variety of spectroscopic methods. A panel of five cancer cell lines known to express EGFR and JNK-2, including human colorectal adenocarcinoma cell line DLD-1, human cervical cancer cell line Hela, human leukemia cell line K562, human pancreatic cell line SUIT-2, and human hepatocellular carcinoma cell line HepG2, were used to biologically evaluate for their in vitro cytotoxicity for all the synthesized compounds 7a - j , 8a - j , 9a - c , and 10a - c . The oxime containing compounds 8a-j and 10a-c were more active as antiproliferative agents than their non-oxime congeners 7a-j and 9a-c. Compounds 8d , 8g , 8i , and 10c inhibited EGFR with IC 50 values ranging from 8 to 21 µM when compared with sorafenib. Compound 8i inhibited JNK-2 as effectively as sorafenib, with an IC 50 of 1.0 µM. Furthermore, compound 8g showed cell cycle arrest at the G2/M phase in the cell cycle analysis of the Hela cell line, whereas compound 8i showed combined S phase and G2 phase arrest. According to docking studies, oxime hybrid compounds 8d , 8g , 8i , and 10c exhibited binding free energies ranging from -12.98 to 32.30 kcal/mol at the EGFR binding site whereas compounds 8d and 8i had binding free energies ranging from -9.16 to -12.00 kcal/mol at the JNK-2 binding site.

Lung cancer is the second most common cause of morbidity and mortality among cancer types worldwide, with non-small cell lung cancer (NSCLC) representing the majority of most cases. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are among the most commonly used targeted therapy to treat NSCLC. Recent years have seen the evaluation of many synthetic EGFR TKIs, most of which showed therapeutic activity in pertinent models and were classified as first, second, and third-generation. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S. Because second- and third-generation EGFR TKIs are irreversible inhibitors, they are ineffective against C797S containing EGFR triple mutations (Del19/T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism. This review covers the fourth-generation EGFR-TKIs' most recent design with their essential binding interactions, the clinical difficulties, and the potential outcomes of treating patients with EGFR mutation C797S resistant to third-generation EGFR-TKIs was also discussed. Moreover, the utilization of various therapeutic strategies, including multi-targeting drugs and combination therapies, has also been reviewed., Competing Interests: The authors affirm that they have no known financial or interpersonal conflicts that would have appeared to impact the research presented in this paper., (This journal is © The Royal Society of Chemistry.)

Introduction: The main objective of this study was to assess the cost of prostate cancer over a 1-year period from a societal perspective., Methods: We constructed a cost-of-illness model to assess the cost of different health states of prostate cancer, metastatic or nonmetastatic, among Egyptian men. Population data and clinical parameters were extracted from the published literature. We relied on different clinical trials to extract clinical data. We considered all direct medical costs, including the costs of treatment and required monitoring, in addition to the indirect costs. The unit costs were captured from Nasr City Cancer Center and Egyptian Authority for Unified Procurement, Medical Supply, and Management of Medical Technology, and resource utilization were collected from clinical trials and validated by the Expert Panel. One-way sensitivity analysis was conducted to ensure model robustness., Results: The number of targeted patients with nonmetastatic hormone-sensitive prostate cancer, hormone-sensitive prostate cancer, and metastatic castration-resistant prostate cancer was 215,207, 263,032, and 116,732, respectively. The total costs, in Egyptian pounds (EGP) and US dollars (USD), for the targeted patients, including drug costs and nondrug costs over a time horizon of 1 year, were EGP 41.44 billion (USD 9.010 billion) for localized prostate cancer; for metastatic prostate cancer, they doubled to EGP 85.14 billion (USD 18.510 billion), which reflects a huge burden on the Egyptian healthcare system. The drug costs for localized and metastatic prostate cancer are EGP 41,155,038,137 (USD 8.946 billion) and EGP 81,384,796,471 (USD 17.692 billion), respectively. A significant difference in nondrug costs between localized and metastatic prostate cancer was demonstrated. Nondrug costs were estimated at EGP 293,187,203 (USD 0.063 billion) for localized prostate cancer and EGP 3,762,286,092 (USD 0.817 billion) for metastatic prostate cancer. This significant difference in nondrug costs highlights the importance of early treatment due to the increased costs of progression and the burden of follow-up and productivity loss associated with metastatic prostate cancer., Conclusion: Metastatic prostate cancer has a huge economic burden on the Egyptian healthcare system compared with localized prostate cancer owing to the increased costs of progression, follow-up, and productivity loss. This highlights the necessity of early treatment of these patients to save costs and lighten the burden of the disease on the patient, society, and economy., Competing Interests: Conflict of Interest: None.

Some new Bis-pyrazoline hybrids 8-17 with dual EGFR and BRAF V600E inhibitors have been developed. The target compounds were synthesized and tested in vitro against four cancer cell lines. Compounds 12 , 15 , and 17 demonstrated strong antiproliferative activity with GI 50 values of 1.05 µM, 1.50 µM, and 1.20 µM, respectively. Hybrids showed dual inhibition of EGFR and BRAF V600E . Compounds 12 , 15 , and 17 inhibited EGFR-like erlotinib and exhibited promising anticancer activity. Compound 12 is the most potent inhibitor of cancer cell proliferation and BRAF V600E . Compounds 12 and 17 induced apoptosis by increasing caspase 3, 8, and Bax levels, and resulted in the downregulation of the antiapoptotic Bcl2. The molecular docking studies verified that compounds 12 , 15 , and 17 have the potential to be dual EGFR/BRAF V600E inhibitors. Additionally, in silico ADMET prediction revealed that most synthesized bis-pyrazoline hybrids have low toxicity and adverse effects. DFT studies for the two most active compounds, 12 and 15 , were also carried out. The values of the HOMO and LUMO energies, as well as softness and hardness, were computationally investigated using the DFT method. These findings agreed well with those of the in vitro research and molecular docking study.

As dual EGFR and BRAF V600E inhibitors, 2-(3-cyano-4,6-bis(aryl)-2-oxo-1,2-dihydropyridine-1-yl)-N-(4-cinnamoylphenyl) acetamide derivatives 8-20 were developed. Compounds 8, 12, and 13 showed strong antiproliferative activity when the target compounds were synthesized and tested in vitro against four cancer cell lines. These hybrids have a dual inhibition activity on EGFR and BRAF V600E , according to in vitro studies. The EGFR was inhibited by compounds 8, 12, and 13 with IC 50 values between 89 and 110 nM, which were equivalent to those of erlotinib (IC 50  = 80 nm). Compound 13 was found to be an effective inhibitor of the proliferation of cancer cells (GI 50  = 0.72 µM) and demonstrated hopeful inhibitory activity of BRAF V600E (IC 50  = 58 nm), which is superior to erlotinib (IC 50  = 65 nm). Compound 13 caused apoptosis and showed cell cycle arrest in the G0/G1phase in a study on the MCF-7 cell line. The new compounds can fit tightly into the active sites of EGFR and BRAF V600E kinases, according to molecular docking analyses., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Conducting poly orthophenylene diamine polymer (PoPDA) was synthesized via the oxidative polymerization route. A poly(o-phenylene diamine) (PoPDA)/titanium dioxide nanoparticle mono nanocomposite [PoPDA/TiO 2 ] MNC was synthesized using the sol-gel method. The physical vapor deposition (PVD) technique was successfully used to deposit the mono nanocomposite thin film with good adhesion and film thickness ≅ 100 ± 3 nm. The structural and morphological properties of the [PoPDA/TiO 2 ] MNC thin films were studied by X-ray diffraction (XRD) and scanning electron microscope (SEM). The measured optical properties of the [PoPDA/TiO 2 ] MNC thin films such as reflectance (R) in the UV-Vis-NIR spectrum, absorbance (Abs), and transmittance (T) were employed to probe the optical characteristics at room temperatures. As well as the calculations of TD-DFT (time-dependent density functional theory), optimization through the TD-DFTD/Mol 3 and Cambridge Serial Total Energy Bundle (TD-DFT/CASTEP) was employed to study the geometrical characteristics. The dispersion of the refractive index was examined by the single oscillator Wemple-DiDomenico (WD) model. Moreover, the single oscillator energy (Eo), and the dispersion energy (Ed) were estimated. The obtained results show that thin films based on [PoPDA/TiO 2 ] MNC can be utilized as a decent candidate material for solar cells and optoelectronic devices. The efficiency of the considered composites reached 19.69%.

A series of new 1,3,4-oxadiazole-chalcone/benzimidazole hybrids 9a-o and 10a-k were designed and synthesized as potential antiproliferative agents. Hybrids 9a-o exhibited remarkable antiproliferative activities on different NCI-60 cell lines in a single-dose assay. The antiproliferative activities of the newly synthesized compounds were evaluated against a panel of four human cancer cell lines (A-549, MCF-7, Panc-1, and HT-29). Compounds 9g-i and their oxygen isosteres, 10f-h, exhibited promising antiproliferative activities with IC 50 values ranging from 0.80 to 2.27 µM compared to doxorubicin (IC 50 ranging from 0.90 to 1.41 µM). Furthermore, the inhibitory potency of these compounds against the epidermal growth factor receptor (EGFR) and BRAF V600E kinases was evaluated using erlotinib as a reference drug. Molecular modeling studies were done to investigate the binding mode of the most active hybrids in the ATP binding site of EGFR., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Background: Children with cleft palate are more liable to have obstructive sleep apnea than children with normal palate due to narrow airways. Tonsillar hypertrophy is a common cause of pediatric obstructive sleep apnea; hence, it is not surprising to be encountered during cleft palate repair. The aim of this study was to evaluate the feasibility of tonsillectomy and Furlow palatoplasty performed as a 1-stage operation in patients presenting with submucous cleft palate (SMCP) and tonsillar hypertrophy., Materials and Methods: Eleven pediatric patients with SMCP and hypertrophied tonsils were included in this case series study. Furlow palatoplasty and tonsillectomy were performed for the patients in 1 sitting. The evaluation of velopharyngeal function was done preoperatively and postoperatively via auditory-perceptual-assessment, nasometry, and flexible nasopharyngoscopy. In addition, the Epworth sleepiness scale for children/adolescents was administered to the parents to assess daytime sleepiness of their children., Results: The speech improved postoperatively. Auditory-perceptual-assessment showed significant reductions in hypernasal speech, nasal air escape, and weak pressure consonants. In addition, nasometry revealed significantly decreased nasalance scores for nasal and oral sentences. A postoperative increased velar movement was observed with a significant improvement in velopharyngeal closure. The preoperative Epworth sleepiness scale for children/adolescents assessment revealed excessive daytime sleepiness in 8 patients, with significant improvement of scores postoperatively., Conclusions: Removal of hypertrophied tonsils during the repair of SMCP with Furlow palatoplasty did not negatively affect speech outcome or velar movement postoperatively. It is logical to perform both procedures simultaneously in 1 sitting to avoid postoperative sleep-related breathing disorder, which may necessitate a second stage operation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: Quinazolinone scaffolds have drawn international attention due to their potent anticancer activity and therapeutic applications. Furthermore, Chalcone and Oxime are special chemical templates with a wide range of biological activities, including anti-cancer activity. As a result, the purpose of this research is to synthesize and develop a new series of 2-thioxo-3-substituted quinazolin-4-one/chalcone analogues and 2-thioxo-3-substituted quinazolin-4-one/oximes analogues in order to obtain a new cytotoxic agent that can target epidermal growth factor (EGFR) and/or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF V600E ) oncogene., Objective: All synthesised compounds were tested for anticancer activity against four human cancer cell lines. The new hybrids' potential anti-cancer mechanism was evaluated using EGFR and BRAF enzymatic tests. The most active molecules within the target enzyme's active site were studied using molecular docking. Apoptosis and cell cycle analysis were also investigated., Methods: The target compounds 7a-j (series I) are obtained in high yields by alkylation of 2-mercapto-3-ethyl-(3H)- quinazolin-4-one 3a with acylated chalcones 6a-j. Alkylation of compounds 3b-c with N-(4-acetylphenyl)-2- bromoacetamide 8, the corresponding ketones intermediates 9b-c was produced in high yields. Compounds 7a-j, 9b-c, and 10b-c were tested for their antiproliferative activity against four human cancer cell lines using the MTT assay and doxorubicin as a control drug. The EGFR and BRAF assay tests were used to assess the inhibitory potency against EGFR and BRAF., Results: Compounds 7c, 7d, 7f and 10c exhibited high proliferative activity and inhibited EGFR, which could serve as a potential target for antiproliferative activity. The most active hybrid, 7c, primarily caused cell cycle arrest in G0/G1 phase and S phase as well as cell apoptosis. Finally, the most active hybrids were docked well to the EGFR active site., Conclusion: 2-thioxo-3-substituted quinazolin-4-one/chalcone derivatives have significant apoptotic and antiproliferative properties., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The traditional method of obtaining fresh water for drinking is by burning fossil fuels, emitting greenhouse gases into the atmosphere. However, renewable energy is gaining more traction since it is available free of cost for producing fresh water. In this study, Al 2 O 3 nanoparticles were distributed in a phase change material (paraffin wax) that had been fixed at a hemispherical distiller water basin. Three scenarios with three hemispherical distillers were examined. A conventional hemispherical distiller (CHD), a conventional hemispherical distiller with paraffin wax as a phase change material (CHD-PCM), and a conventional hemispherical distiller with PCM partially filled with Al 2 O 3 nanoparticles (CHD-N-PCM) were tested under the same climatic conditions. The experimental results showed that CHD gave a daily yield of 4.85 L/m 2 /day, while CHD-PCM increased the yield to up to 6.2 L/m 2 /day with a 27.84% daily yield enhancement. The addition of Al 2 O 3 nanoparticles to paraffin wax CHD-N-PCM improved hemispherical distillate yield up to 8.3 L/m 2 /day with a 71.13% increase over CHD yield.

A series of ciprofloxacin-uracil conjugates 5a-t were synthesized and identified by 1 H NMR, 13 C NMR, mass spectroscopy and elemental analyses. The antibacterial results revealed that the new derivatives exhibited better activity against Gram-positive than the Gram-negative strains; most of the target compounds exhibited good activities against S. aureus ATCC 6538. Compounds 5b and 5g possess the highest activities with MICs of 1.25 and 2.37 µM, respectively, which are more potent than the parent drug ciprofloxacin, MIC, 7.58 µM. In addition, they also exhibited potent activities against MRSA AUMC 261 with MICs, 0.031 and 0.046 µM respectively, higher than ciprofloxacin with MIC, 0.57 µM. Moreover, compounds 5b and 5g showed potent inhibitory activities against DNA gyrase (IC 50  = 1.72 and 5.72 µM) and topoisomerase IV (4.36 and 7.77 µM) compared to ciprofloxacin with IC 50 values 0.66 and 8.16 µM, respectively. The molecular docking study revealed that compounds 5b and 5g may formed stable interaction with the active sites of DNA gyrase and topoisomerase IV similar to ciprofloxacin. Hence, 5b and 5g are considered promising antibacterial candidated against MRSA AUMC 261 strains that requires further optimization., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Synthesis of thiazolidinone based on quinolone moiety was established starting from 4-hydroxyquinol-2-ones. The strategy started with the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding N , N -disubstituted thioureas. Finally, on subjecting the N , N -disubstituted thioureas with dialkyl acetylenedicarboxylates, cyclization occurred, and thiazolidinone derivatives were obtained in good yields. The two series based on quinolone moiety, one containing N , N -disubstituted thioureas and the other containing thiazolidinone functionalities, were screened for their in vitro urease inhibition properties using thiourea and acetohydroxamic acid as standard inhibitors. The inhibition values of the synthesized thioureas and thiazolidinones exhibited moderate to good inhibitory effects. The structure-activity relationship revealed that N -methyl quinolonyl moiety exhibited a superior effect, since it was proved to be the most potent inhibitor in the present series achieving (IC 50 = 1.83 ± 0.79 µM). The previous compound exhibited relatively much greater activity, being approximately 12-fold more potent than thiourea and acetohydroxamic acid as references. Molecular docking analysis showed a good protein-ligand interaction profile against the urease target (PDBID: 4UBP), emphasizing the electronic and geometric effect of N , N -disubstituted thiourea.

The indole moiety is one of the most widespread heterocycles found in both natural products and biological systems. Indoles have important biological activities including anticancer, antioxidant, anti-inflammatory, antifungal, anticholinesterase, and antibacterial properties. Scientists are therefore interested in the synthesis of biologically active indole-based hybrids such as indole-coumarin, indole-chalcone, indole-isatin, indole-pyrimidine and so on, with the aim of improving activity, selectivity, and mitigating side effects. This review will discuss the newly synthesized indole-based hybrids along with their biological activity which will be useful in drug discovery and development., (© 2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Background: Keratosis pilaris (KP) is a common disorder of keratinization with different therapeutic modalities; however, none of them is completely satisfactory., Objective: Assess and compare the efficacy of trichloroacetic acid (TCA) 20% and long-pulsed 1,064-nm Nd:YAG laser in the treatment of KP., Materials and Methods: Twenty patients with symmetrically distributed areas of KP were enrolled in this study. In each patient, 2 symmetrical KP areas were randomly assigned to receive 4 sessions of either long-pulsed Nd:YAG laser or TCA 20%. Clinical evaluation by Investigator Global Assessment (IGA) was done by 2 blinded physicians after treatment. Dermoscopic assessment was done at baseline and at the end point of the study., Results: Investigator Global Assessment of laser-treated area showed that 2 patients (10%) had moderate improvement, 10 patients (50%) had marked improvement, and 8 patients (40%) had excellent improvement. Investigator Global Assessment of TCA-treated area showed that 9 patients (45%) had marked improvement and 11 patients (55%) had excellent improvement. Dermoscopic score of KP showed a significant reduction with both modalities. The IGA and reduction in dermoscopic scores were comparable between the 2 modalities., Conclusion: Both long-pulsed 1,064-nm Nd:YAG laser and 20% TCA are effective in the treatment of KP., Clinical Trial Registration: Name of the trial register: clinicaltrial.gov . Registration number: NCT04797663., (Copyright © 2022 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Polypyrrole (PPy) is a conducting polymer with attractive thermoelectric (TE) properties. It is simple to fabricate and modify its morphology for enhanced electrical conductivity. However, such improvement is still limited to considerably enhancing TE performance. In this case, a single-wall carbon nanotube (SWCNT), which has ultrathin diameters and exhibits semi-metallic electrical conductivity, might be a proper candidate to be combined with PPy as a core shell one-dimensional (1D) nanocomposite for higher TE power generation. In this work, core shell nanocomposites based on SWCNT/PPy were fabricated. Various amounts of pyrrole (Py), which are monomer sources for PPy, were coated on SWCNT, along with methyl orange (MO) as a surfactant and ferric chloride as an initiator. The optimum value of Py for maximum TE performance was determined. The results showed that the SWCNT acted as a core template to direct the self-assembly of PPy and also to further enhance TE performance. The TE power factor, PF , and figure of merit, zT, values of the pure PPy were initially recorded as ~1 µW/mK 2 and 0.0011, respectively. These values were greatly increased to 360 µW/mK 2 and 0.09 for the optimized core shell nanocomposite sample. The TE power generation characteristics of the fabricated single-leg module of the optimized sample were also investigated and confirmed these findings. This enhancement was attributed to the uniform coating and good interaction between PPy polymer chains and walls of the SWCNT through π-π stacking. The significant enhancement in the TE performance of SWCNT/PPy nanocomposite is found to be superior compared to those reported in similar composites, which indicates that this nanocomposite is a suitable and scalable TE material for TE power generation.

A 95-day feeding study was carried out to evaluate the impact of complete replacement of fish oil by plant oils in the growth performance, feed consumption fatty acid and body composition of juvenile rabbitfish, Siganus rivulatus. There were four treatments i.e., A (fish oil diet), (linseed oil diet), C (soybean meal oil diet) and D (sunflower oil diet). The experimental trial was conducted in twelve 1.5-m3 fiber glass tanks (n=3). Spinefoot rabbitfish juveniles had an average initial weight of 0.948 g ± 0.124 g and they were stocked at 50 fish per tank. Fish fed diet A showed significantly better growth rate, final body weight, and total body weight than fish fed on the other diets. Moreover, the best FCR was observed for diet A followed by diet C and diets B and D had the worst FCR. Fish body composition for crude protein, dry matter, ashes and gross energy at the end of the trial had not differed between the treatments. The highest polyunsaturated fatty acids (PUFA) was found in fish fed diet A followed in decreasing order by diets D, B, and C. Fish oil is a better dietary lipid source for Spinefoot rabbitfish juveniles, Siganus rivulatus, than plant oils. Among plant oils, soybean oil was better than linseed oil and sunflower oil as the main dietary fat source.

Statement of Problem: Polyetheretherketone (PEEK) can be used as a framework material for removable and fixed dental prostheses. However, information about the use of PEEK as a post-and-core restoration is scarce., Purpose: The purpose of this in vitro study was to evaluate the effect of different surface treatments on the push-out bond strength of milled polyetheretherketone posts to resin cement., Material and Methods: Sixty intact human maxillary central incisors were selected and endodontically treated, and standardized post spaces were prepared. Sixty PEEK posts were milled from a prefabricated PEEK blank by using a computer-aided design and computer-aided manufacturing (CAD-CAM) system and divided into 3 groups (n=15) according to the surface treatment: acid etching by using 98% sulfuric acid (AE); airborne-particle abrasion by using 50-μm Al 2 O 3 (AA); nonthermal plasma treatment (NTP); in addition, PEEK posts (n=15) received no treatment (NT) and served as a control. All posts were bonded by using a self-adhesive resin cement. Three sections (coronal, middle, and apical) were obtained for each specimen. Push-out bond strength measurements (MPa) for each section were recorded by using a universal testing machine at a crosshead speed of 0.5 mm/min until failure occurred. The post-cement interfaces and failure modes were evaluated by using scanning electron microscopy. The data obtained were statistically analyzed by using 1-way ANOVA and the pair-wise Tukey (HSD) test to study the difference between group mean values (α=.05)., Results: The overall mean ±standard deviation of the push-out bond strength was 11 ±2 MPa for AE group, 6 ±1 MPa for AA group, 5 ±1 MPa for NTP group, and 3 ±1 MPa for NT group. A statistically significant difference was found among all groups subjected to different surface treatments as indicated by the ANOVA test (P<.001). The pair-wise Tukey honestly significant difference (HSD) test showed a significant difference among the AE group and all groups (P<.001); however, no significant difference was observed between the AA and NTP groups (P>.05). Moreover, a significant difference was observed among all root sections (P<.001)., Conclusions: Surface treatment of PEEK posts with 98% sulfuric acid for 60 seconds showed significantly higher bond strength values than those in other groups. The bond strength of PEEK posts to resin cement was significantly higher in the coronal section than that in other sections., (Copyright © 2020 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

In this study anodic oxidation of Cr 2 (SO 4 ) 3 was carried out in an air-sparged divided parallel plate cell. Variables studied were current density, Cr 2 (SO 4 ) 3 concentration, and superficial air velocity. The rate constant of Cr 2 (SO 4 ) 3 oxidation was found to increase with increasing current density and Cr 2 (SO 4 ) 3 concentration. The effect of air sparging was found to depend on Cr 2 (SO 4 ) 3 concentrations, at high Cr 2 (SO 4 ) 3 concentration (> 0.1 M) air sparging does not affect the rate constant of the reaction denoting that the reaction is charge transfer controlled. As Cr 2 (SO 4 ) 3 concentration decreases below 0.1 M the reaction becomes under mixed diffusion and chemical control and the rate constant increases with increasing air superficial velocity, the lower Cr 2 (SO 4 ) 3 concentration the higher the contribution of diffusion to the reaction rate. The current efficiency of the process ranged from 20 to 85% depending on current density and Cr 2 (SO 4 ) 3 concentration. Electrical energy consumption which ranged from 1.8 to 14.4 kW h/kg of Cr 6+ was found to increase with increasing current density and decreases with increasing Cr 2 (SO 4 ) 3 concentration. Air sparging was found to decrease electrical energy consumption in the case of dilute solutions << 0.1 M Cr 2 (SO 4 ) 3 .

Background: The intrauterine device (IUD), being a reversible and effective contraception method, is the most widely used worldwide. This study aims to demonstrate the efficacy of IUD insertion during elective lower segment cesarean section (LSCS) versus its insertion six weeks postpartum., Methods: A cohort study was conducted on 200 women planned for elective cesarean delivery and desired IUD as a contraceptive method. They were allocated into two groups; group I, in which IUD was inserted during LSCS, and group II, in which IUD was inserted six weeks or more after LSCS. Both groups were compared regarding failed insertion, post-insertion pain, and uterine perforation. They were followed for one year for the incidence of menorrhagia, vaginal infection, IUD displacement/expulsion, missed threads, or unintended pregnancy., Results: Women in the second group showed a significantly higher incidence of failed insertion and uterine perforation than women in the first group. On the contrary, women in the first group showed a significantly higher incidence of missed threads than women in the second group. Regarding other consequences, there were no significant differences between both groups concerning menorrhagia, vaginal infection, IUD displacement/expulsion, or unintended pregnancy., Conclusion: IUD insertion during elective LSCS showed a significantly lower incidence of failed insertion and uterine perforation than its insertion six weeks postoperative., (© 2022. The Author(s).)

Hybrid polymer films of polyvinyl pyrrolidone (PVP)/polyvinyl alcohol (PVA) embedded with gradient levels of Bi-powder were prepared using a conventional solution casting process. XRD, FTIR, and SEM techniques have been used to examine the micro/molecular structure and morphology of the synthesized flexible films. The intensities of the diffraction peaks and transmission spectrum of the PVP/PVA gradually declined with the introduction of Bi-metal. In addition, filler changes the microstructure surface of the pure film. The modification in the microstructure leads to an enhancement in the optical absorption characteristic of the blend films. The indirect allowed transition energy was calculated via Tauc's and ASF (Absorption Spectra Fitting) models. The decrease in the hybrid film's bandgap returns to the localized states in the forbidden region, which led the present films to be suitable for photo-electric, solar cell, etc., applications. The relation between the transition energy and the refractive index was studied. The enhancement in the refractive index with Bi-metal concentrations led to use the as-prepared films in optical sensors. The rise of Bi-metal concentrations leads also to the improvement of the nonlinear susceptibility and refractive parameters. The optical limiting characteristics revealed that the higher concentration dopant films reduce the light transmission intensity which is appropriate for laser attenuation and optical limiting in photonic devices. The results suggest that hybrid films are promising materials in a wide range of opto-electronic applications.

Abstract: Children with down syndrome (DS) are more liable to develop obstructive sleep apnea (OSA) which is usually treated with adenotonsillectomy. However, OSA may persist in many of those patients after the procedure. The aim of this study was to assess the efficacy of drug-induced sleep endoscopy (DISE)-directed treatment in management of DS children with persistent OSA after adenotonsillectomy. Sixteen DS children with persistent OSA after adenotonsillectomy were evaluated. DISE was done in the operating theatre to identify the site of obstruction, and surgical intervention was performed according to the finding. Polysomnographic study was used pre- and post-operatively to measure the outcome. DISE revealed obstruction in different sites of the airway. DISE-directed treatment was done according to the site of obstruction. Polysomnographic study showed postoperative significant changes for all parameters. The authors achieved improvement of overall apnea-hypopnea index which was normalized in seven patients (44%). In conclusion, DISE-directed treatment is an effective procedure for persistent OSA in DS children who underwent adenotonsillectomy. However, residual obstruction in those children may be due to many characteristic features that cause narrowing of the airway., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Trichinella spiralis larvae have very special characters that make them able to completely transform the function of the affected muscle cells towards a self-serving environment, offering them nourishment and protection via what is known as "nurse cells". This setting may be affected by drugs that are used for the treatment of co-morbidities and co-infections as calcium channel blockers, which are widely used in clinical practice. In the present study, the effects of verapamil, ivermectin (IVM), and their combined administration on the parasitic burden, immuno-pathology and angiogenesis were investigated during experimental trichinellosis. Estimation of intestinal adult parasitic stages and muscle larvae was done. VEGF gene expression and CD31 immunohistochemical local expression were measured to investigate angiogenesis, in addition to histopathological examination to explore the extent of inflammation. Although verapamil did not have an effect on the adult worm count during the intestinal phase, it induced an anti-inflammatory effect on intestinal pathology. During the muscle phase, it was very effective in reducing the larval count by 93.78%. IVM effectively reduced the worm count by 85.34%, and the muscle larval count by 97.84%, while combined verapamil and IVM administration resulted in a significant reduction in both adult parasites by 69.5% and larval stages by 99%. Both verapamil and IVM and their combination induced a potent decrease in local CD31 protein expression and VEGF gene expression. The important role of calcium and calcium channels during the pathology of trichinellosis, in addition to the pivotal role of calcium on biological processes such as immunity and angiogenesis, make calcium-channel blockers promising candidates for drug repurposing in the management of helminthic infection., Competing Interests: The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (© 2022 The Authors.)

Keratitis is a global health issue that claims the eye sight of millions of people every year. Dry eye, contact lens wearing and refractive surgeries are among the most common causes. The resistance rate among fluoroquinolone antibiotics is >30%. This study aims at formulating a newly synthesized ciprofloxacin derivative (2b) niosomes and Solulan C24-, sodium cholate- and deoxycholate-modified niosomes. The prepared niosomal dispersions were characterized macroscopically and microscopically (SEM) and by percentage entrapment efficiency, in vitro release and drug release kinetics. While the inclusion of Solulan C24 produced something discoidal-shaped with a larger diameter, both cholate and deoxycholate were unsuccessful in forming niosomes dispersions. Conventional niosomes and discomes (Solulan C24-modified niosomes) were selected for further investigation. A corneal ulcer model inoculated with colonies of Pseudomonas aeruginosa in rabbits was developed to evaluate the effectiveness of keratitis treatment of the 2b-loaded niosomes and 2b-loaded discomes compared with Ciprocin ® (ciprofloxacin) eye drops and control 2b suspension. The histological documentation and assessment of gene expression of the inflammatory markers (IL-6, IL1B, TNFα and NF-κB) indicated that both 2b niosomes and discomes were superior treatments and can be formulated at physiological pH 7.4 compatible with the ocular surface, compared to both 2b suspension and Ciprocin ® eye drops.

Heterocycles containing thienopyrimidine moieties have attracted attention due to their interesting biological and pharmacological activities. In this research article, we reported the synthesis of a series of new hybrid molecules through merging the structural features of chalcones and pyridothienopyrimidinones. Our results indicated that the synthesis of chalcone-thienopyrimidine derivatives from the corresponding thienopyrimidine and chalcones proceeded in a relatively short reaction time with good yields and high purity. Most of these novel compounds exhibited moderate to robust cytotoxicity against HepG2 and MCF-7 cancer cells similar to that of 5-fluorouracil (5-FU). The results indicated that IC 50 of the two compounds ( 3b and 3g ) showed more potent anticancer activities against HepG2 and MCF-7 than 5-FU. An MTT assay and flow cytometry showed that only 3b and 3g had anticancer activity and antiproliferative activities at the G1 phase against MCF-7 cells, while six compounds ( 3a - e and 3g ) had cytotoxicity and cell cycle arrest at different phases against HepG2 cells. Their cytotoxicity was achieved through downregulation of Bcl-2 and upregulation of Bax, caspase-3, and caspase-9. Although all tested compounds increased oxidative stress via increment of MDA levels and decrement of glutathione reductase (GR) activities compared to control, the 3a , 3b , and 3g in HepG2 and 3b and 3g in MCF-7 achieved the target results. Moreover, there was a positive correlation between cytotoxic efficacy of the compound and apoptosis in both HepG2 ( R 2 = 0.531; P = 0.001) and MCF-7 ( R 2 = 0.219; P = 0.349) cell lines. The results of molecular docking analysis of 3a-g into the binding groove of Bcl-2 revealed relatively moderate binding free energies compared to the selective Bcl-2 inhibitor, DRO. Like venetoclax, compounds 3a-g showed 2 violations from Lipinski's rule. However, the results of the ADME study also revealed higher drug-likeness scores for compounds 3a-g than for venetoclax. In conclusion, the tested newly synthesized chalcone-pyridothienopyrimidinone derivatives showed promising antiproliferative and apoptotic effects. Mechanistically, the compounds increased ROS production with concomitant cell cycle arrest and apoptosis. Therefore, regulation of the cell cycle and apoptosis are possible targets for anticancer therapy. The tested compounds could be potent anticancer agents to be tested in future clinical trials after extensive pharmacodynamic, pharmacokinetic, and toxicity profile investigations., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Ghada M. Safwat et al.)

Protein kinases have grown over the past few years as a crucial target for different cancer types. With the multifactorial nature of cancer, and the fast development of drug resistance for conventional chemotherapeutics, a strategy for designing multi-target agents was suggested to potentially increase drug efficacy, minimize side effects and retain the proper pharmacokinetic properties. Kinase inhibitors were used extensively in such strategy. Different kinase inhibitor agents which target EGFR, VEGFR, c-Met, CDK, PDK and other targets were merged into hybrids with conventional chemotherapeutics such as tubulin polymerization and topoisomerase inhibitors. Other hybrids were designed gathering kinase inhibitors with targeted cancer therapy such as HDAC, PARP, HSP 90 inhibitors. Nitric oxide donor molecules were also merged with kinase inhibitors for cancer therapy. The current review presents the hybrids designed in the past five years discussing their design principles, results and highlights their future perspectives., Competing Interests: Declaration of competing interest 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., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

A 70-day rearing trial was done to determine the optimal frequency of feeding on growth performance (GP), feed conversion rate (FCR), cannibalism, survival rate (SR), body chemical composition and economic efficiency of the Asian sea bass. This study tested four different treatments of feeding frequencies (FF), once (T1), twice (T2), three times (T3), and four times (T4) per day. An average initial weight of Asian sea bass fry was 0.2 g (SD = ±0.12) were stocked 10 individuals per m 3 (9.14 m × 1.82 m × 1.22 m, L × W × H; water depth 0.61 m) with two replicates per treatment (4 × 2 = 8). Fry were fed a mixture of larval commercial feed and shrimp with a pellet diet containing (46% CP). Initially, the feeding rate of 8% biomass per day was further adjusted according to fish biomass on a weekly basis. Results showed that, the FF significantly affected ( p  < 0.05) on growth indictors and survival rate (SR). Specifically fry fed three times a day (T3) had the best FBW, FL, SGR, ADWG and FCR followed by T4 and T2 while fry fed one time a day was the lowest in these parameters. Also, VSI, HSI and CF (k) significantly differed among the treatments. The fish whole body content of protein, moisture and ash did not significantly ( p  < 0.05) be affected by feeding frequency, but lipid content differed and both T3, T4 were the highest. It could be concluded that, increasing FF up to three times a day had a positive effect on weight gain, survival rate and feed utilization of Lates calcarifer . The second degree polynomial regression indicates that fed three times a day is optimum for best growth performance and survival for Asian sea bass., 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).)

Src kinase activity controls diverse cellular functions, including cell growth, migration, adhesion, and survival. It is de-regulated in several cancers, including breast cancer, where it is highly expressed and phosphorylated. Thus, targeting Src by a small molecule is a feasible strategy for managing different breast cancer types. Several Src kinase inhibitors are available, including the FDA-approved drug (dasatinib). However, they are primarily ATP-competitive inhibitors that have been reported to lack specificity towards Src. We have a long-time interest in discovering protein kinase inhibitors that are non-competitive for ATP. In this project, three groups of 2'-aminospiro[pyrano[3,2-c]quinoline]-3'-carbonitrile derivatives were designed and synthesized, hypothesizing that small molecules with a spiro scaffold appended to a pyrano[3,2-c]quinoline analog could act as non-ATP competitive Src kinase inhibitors. 3b, 3c, and 3d inhibited Src kinase activity with IC50s of 4.9, 5.9, and 0.9 μM, respectively. At the same time, they did not impact the MDM2/p53 interaction in HEK293 cells, which has been reported to be affected by some spirocyclic compounds. 25 µM of 3b, 3c, or 3d did not inhibit the kinase activity of ERK2, JNK1, or p38-alpha in an in-vitro kinase assay. Steady-state kinetic studies for the effect of 3d on the ability of recombinant Src to phosphorylate its substrate (Srctide) revealed a non-ATP competitive inhibition mechanism. 1.6 µM of 3d was enough to diminish Src, Fak, and paxillin phosphorylation in the breast cancer cell lines MDA-MB-231 and MCF7. In the NCI screening, 3d induced broad tumor cytotoxicity for the NCI-60 cell lines, including all the breast cancer cell lines. The potency of 3b, 3c, and 3d to inhibit migration, proliferation, and colony formation of MDA-MB-231 and proliferation of MCF7 cells correlates with their potency to suppress Src kinase activity in the same cell line. Noticeably, the cell growth suppression and apoptosis induction in the tested cell lines can be attributed to the ability of the new derivatives to suppress the ERK and Akt survival pathways downstream of Src., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Data of 651 lambs (68 Romanov, 49 Rahmani, 151 [♀1/2 Rahmani X ♂1/2 Romanov) and 383 (♀3/4 Rahmani and 1/4♂ Romanov]) were collected from Mehalet Mousa Farm, belonging to Animal Production Research Institute from the period of 2009 to 2016 to estimate phenotypic and genetic parameters. The traits studied were birth weight (BW), body weight at four week (BW4), body weight at eight weeks (BW8) and body weight at twelve weeks (BW12) or weaning weight. Least squares analysis of variance shows significance of the effects of breed groups, gender of lambs, birth type; month of birth and year of birth on all traits studied. Rahmani lambs had heavier BW, BW4, BW8 and BW12 while Romanov lambs had the lowest ones. The first generation (♀1/2 Rhamani X ♂1/2 Romanov) had heavier body weights than Romanov and the second generation (♀3/4 Rahmani X ♂1/4 Roamnov). Gender of lambs had highly significant effect on body weights. Males were significantly (p < 0.01) heavier than females for all traits studied. Least square means of BW, BW4, BW8 and BW12 for single lambs were 2.69, 10.43, 13.53 and 16.10 kg, respectively. Least square means of BW, BW4, BW8 and BW12 for twin lambs were 2.50, 9.37, 12.5 and 15.16 kg, respectively, while least square means of BW, BW4, BW8 and BW12 for triple lambs were 2.09, 7.86, 10.83 and 13.67 kg, respectively. Estimates of direct heritability measured by single trait animal model were 0.14, 0.23, 0.25 and 0.26 for BW, BW4, BW8 and BW12, respectively, and the corresponding measured by multi trait animal model were 0.17, 0.24, 0.32 and 0.36 for the same traits, respectively. All genetic and phenotypic correlations among different traits studied are positive and significant., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2021 Korean Society of Animal Science and Technology.)

Abstract: Acute invasive fungal rhinosinusitis (mucormycosis) is a rare, highly fatal disease. This opportunistic fungal infection causes angioinvasion and ischemic tissue necrosis. It mainly affects immunocompromised patients. Since the coronavirus disease 2019 (COVID-19) outbreak, many case reports have described the rhino-orbital-cerebral mucormycosis associated with COVID-19. However, the underlying predisposing factors are unknown. Several factors, other than diabetes, which is the most well-known contributing factor, may be involved in causing this severe fungal infection in COVID-19 patients. These factors may include steroid therapy, which is being used in severely dyspneic patients, the use of broad-spectrum antibiotics that may cause fungal flare-ups, and hospitalization with possible nosocomial infections. In addition, increased serum ferritin levels, possible endothelial damage, and pancreatic islets affection among COVID-19 patients may be implicated. Head and neck surgeons should be aware of the increasing prevalence of craniofacial mucormycosis among COVID-19 patients, as early diagnosis and prompt treatment are essential to improve the outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)