Assessing the Predictive Accuracy of the aMAP Risk Score for Hepatocellular Carcinoma (HCC): Diagnostic Test Accuracy and Meta-analysis.

Purpose: We aimed to perform a meta-analysis with the intention of evaluating the reliability and test accuracy of the aMAP risk score in the identification of HCC. Methods: A systematic search was performed in PubMed, Scopus, Cochrane, Embase, and Web of Science databases from inception to September 2023, to identify studies measuring the aMAP score in patients for the purpose of predicting the occurrence or recurrence of HCC. The meta-analysis was performed using the meta package in R version 4.1.0. The diagnostic accuracy meta-analysis was conducted using Meta-DiSc software. Results: Thirty-five studies 102,959 participants were included in the review. The aMAP score was significantly higher in the HCC group than in the non-HCC group, with a mean difference of 6.15. When the aMAP score is at 50, the pooled sensitivity, specificity, negative likelihood ratio, and positive likelihood ratio with 95% CI was 0.961 (95% CI 0.936, 0.976), 0.344 (95% CI 0.227, 0.483), 0.114 (95% CI 0.087, 0.15), and 1.464 (95% CI 1.22, 1.756), respectively. At a cutoff value of 60, the pooled sensitivity, specificity, negative likelihood ratio, and positive likelihood ratio with 95% CI was 0.594 (95% CI 0.492, 0.689), 0.816 (95% CI 0.714, 0.888), 0.497 (95% CI 0.418, 0.591), and 3.235 (95% CI 2.284, 4.582), respectively. Conclusion: The aMAP score is a reliable, accurate, and easy-to-use tool for predicting HCC patients of all stages, including early-stage HCC. Therefore, the aMAP score can be a valuable tool for surveillance of HCC patients and can help to improve early detection and reduce mortality.

The effect of genetic polymorphisms in STIM1 and ORAI1 on erythropoietin resistance in Egyptian patients with end-stage renal disease.

Chronic renal failure (CRF) is an incurable disease with unique challenges. Anemia is a frequent complication affecting dialysis patients. Erythropoietin (EPO) is used to treat anemia, but a poor response may result. We investigated genetic polymorphisms of store-operated calcium channel (SOC) signaling, an important erythropoietin-activated pathway that may induce EPO resistance in patients with renal failure. A total of 108 end stage renal disease (ESRD) patients were selected for this study. Patients were divided into two groups according to their erythropoietin resistance index (ERI): 39 patients with an ERI>10 and 69 patients with an ERI<10. We selected four tagging single nucleotide polymorphisms (tSNPs) in STIM1 and five in ORAI1 in our study. A polymerase chain reaction was performed, and genotyping against EPO resistance was correlated. Patients with the AG genotype of rs1561876 in STIM1, the TC genotype of rs6486795 in ORAI1, and the TG or GG genotypes of rs12320939 in ORAI1 were associated with an increased risk of erythropoietin resistance. Overall, we reported a moderately significant relationship between genetic polymorphisms of STIM1 and EPO resistance. We also reported a highly significant relationship between genetic polymorphisms of ORAI1 and EPO resistance. The (A-A-G) haplotype of STIM1 and the (G-T-G-T-A, G-C-G-C-G, or G-T-T-C-G) haplotypes of ORAI1 were significantly associated with EPO resistance.

Attenuation of inflammation, oxidative stress and TGF-ß1/Smad3 signaling and upregulation of Nrf2/HO-1 signaling mediate the protective effect of diallyl disulfide against cadmium nephrotoxicity.

Heavy metals are toxic environmental pollutants with serious health effects on humans and animals. Cadmium (Cd) is known for its serious nephrotoxic effect and its toxicity involves oxidative stress (OS) and inflammation. Diallyl disulfide (DADS), a main constituent of garlic, exhibites cytoprotective and antioxidant activities. This study investigated the effect of DADS on OS, inflammation, and fibrosis induced by Cd in rat kidney, pointing to the involvement of transforming growth factor-ß (TGF-ß)/Smad3 and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling, and peroxisome proliferator-activated receptor gamma (PPARγ). Rats received DADS for 14 days and Cd on day 7 and blood and kidney samples were collected. Cd elevated serum creatinine, urea and uric acid, provoked kidney histopathological alterations and collagen deposition, increased kidney malondialdehyde (MDA) level, and decreased glutathione (GSH) and antioxidant enzymes. Nuclear factor-kappaB (NF-κB) p65, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1ß, and CD68 were upregulated in Cd-administered rat kidney. DADS prevented kidney injury, mitigated OS, suppressed NF-κB, CD68 and pro-inflammatory mediators, and boosted antioxidants. DADS downregulated TGF-ß1, Smad3 phosphorylation and Kelch-like ECH-associated protein-1 (Keap1), and increased Nrf2, HO-1, cytoglobin, and PPARγ. In conclusion, DADS protects the kidney against Cd toxicity by attenuating OS, inflammation, and TGF-ß1/Smad3 signaling, and enhancement of Nrf2/HO-1 signaling, antioxidants, and PPARγ.

Inoculation with Jeotgalicoccus sp. improves nutritional quality and biological value of Eruca sativa by enhancing amino acid and phenolic metabolism and increasing mineral uptake, unsaturated fatty acids, vitamins, and antioxidants.

Plant growth-promoting bacteria (PGPB) are considered a promising tool for triggering the synthesis of bioactive compounds in plants and to produce healthy foods. This study aimed to demonstrate the impact of PGPB on the growth, accumulation of primary and secondary metabolites, biological activities, and nutritional qualities of Eruca sativa (arugula), a key leafy vegetable worldwide. To this end, Jeotgalicoccus sp. (JW0823), was isolated and identified by using partial 16S rDNA-based identification and phylogenetic analysis. The findings revealed that JW0823 significantly boosted plant biomass production by about 45% (P<0.05) and enhanced pigment contents by 47.5% to 83.8%. JW0823-treated plants showed remarkable improvements in their proximate composition and vitamin contents, with vitamin E levels increasing by 161.5%. JW0823 induced the accumulation of bioactive metabolites including antioxidants, vitamins, unsaturated fatty acids, and essential amino acids, thereby improving the nutritional qualities of treated plants. An increase in the amounts of amino acids was recorded, with isoleucine showing the highest increase of 270.2%. This was accompanied by increased activity of the key enzymes involved in amino acid biosynthesis, including glutamine synthase, dihydrodipicolinate synthase, cystathionine γ-synthase, and phenylalanine ammonia-lyase enzymes. Consequently, the total antioxidant and antidiabetic activities of the inoculated plants were enhanced. Additionally, JW0823 improved antimicrobial activity against several pathogenic microorganisms. Overall, the JW0823 treatment is a highly promising method for enhancing the health-promoting properties and biological characteristics of E. sativa, making it a valuable tool for improving the quality of this important leafy vegetable.

A Rare Case of Gastric Phytobezoar (Diospyrobezoar) in a Healthy Adult.

Phytobezoars are solid masses of indigestible plant material and are a common type of gastrointestinal bezoar, with varying incidences globally. These bezoars typically form from the ingestion of high-fiber fruits and vegetables and are associated with factors such as decreased gastric acid production and delayed gastric emptying. We present a case of a 35-year-old healthy man with recurrent upper abdominal pain, nausea, a rolling ball sensation in the abdominal region, and a history of consuming unripe persimmons. Imaging revealed the presence of phytobezoars in the stomach, leading to unsuccessful endoscopic attempts at removal. Laparoscopic extraction was eventually performed successfully after failed conservative management. The case highlights the rarity of diospyrobezoars, a subtype of phytobezoars formed from persimmon ingestion, and the challenges in their management. Surgical intervention, particularly laparoscopic extraction, can be effective but carries risks such as surgical site infections. Comprehensive care involving diagnostic imaging, non-surgical interventions, and surgical techniques is crucial for the successful management of phytobezoars. Phytobezoars, though relatively common, present unique diagnostic and management challenges, especially when formed from specific dietary factors such as persimmons. Understanding their epidemiology, clinical manifestations, and treatment options, including the role of laparoscopic surgery, is essential for optimizing patient outcomes and minimizing complications such as surgical site infections.

Diverse applications of versatile quaternized chitosan salts: A review.

In the ever-evolving world of materials science, modifying natural polymers has garnered significant attention across diverse industries, driven by their inherent availability and cost-effectiveness. Among these, chitosan, a pseudo-natural cationic polymer, has emerged as a versatile player, finding applications in medical, pharmaceutical, filtration, and textile sectors, owing to its exceptional biodegradability, non-allergenicity, antimicrobial properties, and eco-friendly nature. However, the limitations of chitosan, such as low surface area, poor solubility at neutral to alkaline pH, and inadequate thermal-mechanical properties, have prompted researchers to explore innovative modification strategies, including graft copolymerization, quaternization, and cross-linking. This review delves into the remarkable potential of a specific chitosan derivative, N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan salts (N-HTCS), a quaternized form of chitosan. This review uniquely examines the properties and multifaceted applications of N-HTCS, spanning biomedical, textile, food packaging, and environmental domains. The outstanding features of N-HTCS, including antioxidant, anticancer, and antimicrobial bioactivity, as well as biocompatibility, biodegradability, hemostatic, piezoelectric, superparamagnetic, water solubility, and permeation-enhancing effects, offer novel solutions to the limitations of unmodified chitosan. Notably, while previous reviews have addressed the significance of chitosan, this work presents a groundbreaking focus on the N-HTCS derivative, providing a fresh perspective and paving the way for the design and engineering of cutting-edge N-HTCS-based devices and applications. The comprehensive coverage of this review aims to inspire researchers and industry professionals to explore the untapped potential of this remarkable chitosan derivative, unlocking new frontiers in material science and technology.

Discovery of novel diaryl urea-oxindole hybrids as BRAF kinase inhibitors targeting BRAF and KRAS mutant cancers.

In the current study, a novel series of diaryl urea incorporating oxindole moiety was rationally designed as type II BRAF inhibitors targeting BRAF and KRAS mutant cancers. Molecular hybridization between the diaryl urea scaffold which binds to the inactive conformation of protein kinases on one side and the oxindole core which exhibit adenine mimic properties to be settled in the hinge region on the other side was performed. Studying the antiproliferative activity of the synthesized candidates 9a-t on NCI cancer cell lines showed that they exhibit potent and broad spectrum of antiproliferative activity on the tested cancer cell lines with compounds 9c, 9p, 9q, 9s, and 9t demonstrating potent GI50 reaching 0.01 µM. Noteworthy, compound 9s demonstrated a potent GI50 on cell lines expressing mutant KRAS and those express BRAFV600E with GI50 ranges of 1.79 and 7.94 µM and 1.68 to 2.0 µM, respectively. Further analysis on A375 and Mel501 cell lines expressing BRAFV600E revealed that compound 9s has a potent growth inhibitory activity with IC50 of 0.7 and 1.5 µM, respectively, in reference to sorafenib (IC50 = 8.7 and 0.3 µM, respectively). Additionally, nearly all the target candidates did not show any cytotoxic effect on the normal fibroblast cell line BJ-1 with compound 9s showing IC50 of 20.2 µM in reference to sorafenib (IC50 = 6.1 µM). Further cellular assays on A375 cell line, revealed the ability of compound 9s to halt the cell cycle progression at the G2 phase besides its ability to induce apoptosis. In parallel, all the synthesized candidates 9a-t were biochemically evaluated for their inhibitory activity on BRAFWT and compounds 9b, 9c, and 9n revealed a sub-micromolar IC50 of 0.11, 0.84 and 0.80 µM, respectively. Further investigation of selected compounds on BRAFV600E showed that compounds 9c, 9n, 9s, and 9t exhibit a sub-micromolar IC50 range of 0.17 to 0.89 µM. Noteworthy, the examined candidates demonstrated a higher selectively towards BRAFV600E over BRAFWT highlighting their promising optimization for treating BRAFV600E expressing cancers. Molecular docking and molecular dynamics simulations in the inactive DFG-out kinase domain of BRAFWT/V600E protein kinases confirmed the planned design strategy.

Role of interleukin 6 polymorphism and inflammatory markers in outcome of pediatric Covid- 19 patients.

BACKGROUND: IL-6 polymorphisms were associated to viral infection outcomes through affection of IL-6 production and it is an early indicator of tissue injury and systemic inflammatory response. The study aimed to determine whether genetic IL-6 polymorphisms, serum interleukin-6 level and inflammatory markers (Presepsin, CXCL-10, C3, and C4) are associated with the prediction of disease severity in pediatric COVID-19 patients and its possible use as a prognostic tool in pediatric patients admitted to hospital. METHODS: This prospective cohort study was conducted on 150 children with COVID-19. Patients were divided according to the severity of infection into four groups: group I (mild) 67 cases; group II (moderate) 53 cases, group III (severe) 17 cases and group IV (critical) 14 cases. Serum Interleukin 6, CXCL-10, Presepsin, renal and liver functions, electrolytes, C3, C4, ferritin, and D dimer serum levels were assessed in all patients. The Kruskal Wallis test used to compare parametric quantitative data between studied groups and Mann Whitney test for each pair of groups. Non-parametric quantitative data was compared between studied groups using a one-way ANOVA test and post-hoc Bonferroni analysis for each pair of groups. RESULTS: Group I: 35 males and 32 females with a median age of 16 months. Group II: 17 males and 35 females with a median age of 13 months. Group III: 6 males and 11 females with a median age of 12 months and group IV: 3 males and 11 females with a median age of 12 months. There was no statistical difference between the studied groups regarding gender and age. Serum levels of IL- 6, serum ferritin; D-dimer, Presepsin and CXCL 10 were significantly higher in both severe and critical groups than the other 2 groups (mild and moderate). ROC curve analysis showed that interleukin-6 and Presepsin were good markers for prediction of severity of COVID-19 among the diseased children. For severe cases, the sensitivity of interleukin-6 was 76.47% and specificity was 92.31%. For critical cases, the sensitivity of interleukin-6 was 71.43% and specificity was 82.35%. The sensitivity of Presepsin was 76.47% and specificity was 88.46% in severe cases. For critical cases, the sensitivity of Presepsin was 78.57% and specificity of 91.2%. There was significant difference in IL-6 572 allelic among moderate cases with the most frequent 42.3% for genotype (GC) and allelic among severe cases with the most frequent 47.1% for genotype (GC). Significant difference in IL-6 174 allelic among critical cases with the most frequent 78.6% for genotype (CC). CONCLUSIONS: Children whom expressed GC genotypes of IL6 (-572G > C) polymorphism are at a considerably higher risk of developing a severe disease. This risk is significantly larger in the severe group of children than in children in critical condition who have GC genotypes of IL6 (-174 G > C) polymorphism. While IL6 (-597G > A) polymorphism has no role in COVID 19 severity in children.

Prevalence, Determinants, and Coping Strategies of Preoperative Anxiety Among Surgical Patients: A Cross-Sectional Study in Jazan, Saudi Arabia.

BACKGROUND: Preoperative anxiety is a prevalent concern among surgical patients, significantly impacting their well-being and recovery. Common sources of anxiety include fears related to pain, anesthesia, and surgical outcomes. Despite the importance of addressing this issue, there is limited research on preoperative anxiety in Jazan, Saudi Arabia. This study explores the prevalence, determinants, and coping strategies for preoperative anxiety among surgical patients in this region. METHODS: A cross-sectional study was conducted using an online survey distributed to patients scheduled for surgery at healthcare facilities in Jazan. The survey collected data on demographics, surgical history, anxiety symptoms, sources of anxiety, and coping strategies. Descriptive statistics were used to analyze the data. RESULTS: The study included 312 participants, primarily young adults aged 18-24 years. The majority reported experiencing anxiety symptoms such as nausea (47.8%), sweating (47.8%), and irritability (41.3%). Pain (54.2%), surgical outcomes (49.0%), and anesthesia (32.4%) were the most common sources of anxiety. Support from family and friends (66.7%) and relaxation techniques (26.6%) were identified as the most effective coping strategies. A significant proportion (71.8%) expressed a need for additional support. CONCLUSION: Preoperative anxiety is common among surgical patients in Jazan, driven mainly by concerns about pain, anesthesia, and surgical outcomes. Effective coping strategies include support from family and friends and relaxation techniques. There is a need for additional support resources to improve patient care and reduce anxiety.

Safety and efficacy of platelet-rich plasma injection for treatment of erectile dysfunction: a prospective randomized controlled study.

BACKGROUND: Affected sexual relationships affect both the quality of life of men and women. Platelet-derived therapies are becoming increasingly popular in various medical and surgical fields because of their ability to aid in tissue healing and vascular remodeling. This study aimed to assess the safety and effectiveness of platelet-rich plasma (PRP) injections in treating patients with erectile dysfunction (ED). RESULTS: Fifty-two participants with mild to moderate ED were divided into two groups: group A, who received three PRP penile injections, and group B, who received three saline injections (5 ml for each injection site). The International Index of Erectile Function (IIEF) was used to evaluate all participants. A month after the last injection, the PRP group's IIEF was 16.12 ± 1.25, while the placebo group's was 15.99 ± 1.21 (p = 0.683). Following a 3-month period, the IIEF for the PRP group was 16.44 ± 1.17, while the placebo group's was 16.31 ± 1.06 (p value = 0.653). Following a 6-month period, the IIEF for the PRP group was 16.35 ± 1.45, while that for the placebo group's was 16.23 ± 1.19 (p = 0.727). In terms of IIEF, there was no significant difference between the two groups after one, three, and six months of treatment. CONCLUSION: In brief, our research revealed no data to support the application of PRP injections in the management of mild-to-moderate ED.

RéSUMé: CONTEXTE: Une altération des relations sexuelles affecte à la fois la qualité de vie des hommes et des femmes. Les thérapies dérivées des plaquettes deviennent de plus en plus populaires dans divers domaines médicaux et chirurgicaux, en raison de leur capacité à aider à la guérison des tissus et au remodelage vasculaire. La présente étude visait à évaluer l'innocuité et l'efficacité d'injections de plasma riche en plaquettes (PRP) dans le traitement des patients atteints de dysfonction érectile (DE). RéSULTATS: Fifty-two participants atteints de dysfonction érectile légère à modérée ont été divisés en deux groupes: le groupe A, qui a reçu trois injections de PRP dans le pénis, et le groupe B, qui a reçu trois injections de solution saline (5 ml pour chaque site d'injection). L'indice international de la fonction érectile (IIEF) a été utilisé pour évaluer tous les participants. Un mois après la dernière injection, l'IIEF du groupe PRP était de 16,12 ± 1,25, tandis que celui du groupe placebo était de 15,99 ± 1,21 (p = 0,68). Trois mois après la dernière injection, l'IIEF pour le groupe PRP était de 16,44 ± 1,17, tandis que celui du groupe placebo était de 16,31 ± 1,06 (valeur p = 0,65). Enfin, 6 mois après la dernière injection, l'IIEF pour le groupe PRP était de 16,35 ± 1,45, tandis que celui du groupe placebo était de 16,23 ± 1,19 (p = 0,73). En ce qui concerne l'IIEF, il n'y avait pas de différence significative entre les deux groupes après un, trois et six mois de traitement. CONCLUSION: En bref, notre recherche n'a révélé aucune donnée en faveur de l'application des injections de PRP dans la prise en charge de la dysfonction érectile légère à modérée.

Neuroprotective effects of punicalagin and/or micronized zeolite clinoptilolite on manganese-induced Parkinson's disease in a rat model: Involvement of multiple pathways.

BACKGROUND: Manganism, a central nervous system dysfunction correlated with neurological deficits such as Parkinsonism, is caused by the substantial collection of manganese chloride (MnCl2) in the brain. OBJECTIVES: To explore the neuroprotective effects of natural compounds, namely, micronized zeolite clinoptilolite (ZC) and punicalagin (PUN), either individually or in combination, against MnCl2-induced Parkinson's disease (PD). METHODS: Fifty male albino rats were divided into 5 groups (Gps). Gp I was used as the control group, and the remaining animals received MnCl2 (Gp II-Gp V). Rats in Gps III and IV were treated with ZC and PUN, respectively. Gp V received both ZC and PUN as previously reported for the solo-treated plants. RESULTS: ZC and/or PUN reversed the depletion of monoamines in the brain and decreased acetyl choline esterase activity, which primarily adjusted the animals' behavior and motor coordination. ZC and PUN restored the balance between glutamate/γ-amino butyric acid content and markedly improved the brain levels of brain-derived neurotrophic factor and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and decreased glycogen synthase kinase-3 beta activity. ZC and PUN also inhibited inflammatory and oxidative markers, including nuclear factor kappa-light-chain-enhancer of activated B cells, Toll-like receptor 4, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 and caspase-1. Bcl-2-associated X-protein and B-cell leukemia/lymphoma 2 protein (Bcl-2) can significantly modify caspase-3 expression. ZC and/or PUN ameliorated PD in rats by decreasing the levels of endoplasmic reticulum (ER) stress markers (p-protein kinase-like ER kinase (PERK), glucose-regulated protein 78, and C/EBP homologous protein (CHOP)) and enhancing the levels of an autophagy marker (Beclin-1). DISCUSSION AND CONCLUSION: ZC and/or PUN mitigated the progression of PD through their potential neurotrophic, neurogenic, anti-inflammatory, antioxidant, and anti-apoptotic activities and by controlling ER stress through modulation of the PERK/CHOP/Bcl-2 pathway.

Chemical composition and biological activities of nine essential oils obtained from Algerian plants.

The essential oils (EOs) from nine species (Artemisia campestris, A. herba-alba, Juniperus foetidissima, Laurus nobilis, Mentha pulegium, M. spicata, Rosmarinus officinalis, Salvia officinalis, and Thymus vulgaris) of the Algerian flora have been hydrodistilled, analysed, and tested for their antioxidant and antiproliferative properties. A. campestris EO showed a higher content of terpene hydrocarbons; A. herba-alba EO was mainly rich in their oxygenated derivatives. Sesquiterpenes were the most abundant compounds in J. foetidissima EO, while oxygenated monoterpenes and phenylpropanoids prevailed in L. nobilis EO. The other EOs were rich in oxygenated monoterpenes, with quality-quantitative differences. T. vulgaris and L. nobilis performed better in all the antioxidant assays, respectively with IC50 values ranging from 0.0002 and 0.0012 mg/mL in the CUPRAC assay to 2.83 and 3.50 mg/mL in the FRAP assay. T. vulgaris was also the only EO exhibiting an antiproliferative activity towards the human breast (MCF-7) and lung (A549) cancer cell lines.

Immune Checkpoints and Cellular Landscape of the Tumor Microenvironment in Non-Melanoma Skin Cancer (NMSC).

Non-melanoma skin cancer (NMSC) is primarily categorized into basal cell carcinoma (BCC), the most prevalent form of skin cancer, and cutaneous squamous cell carcinoma (cSCC), the second most common type. Both BCC and cSCC represent a significant health burden, particularly in immunocompromised individuals and the elderly. The immune system plays a pivotal role in the development and progression of NMSC, making it a critical focus for therapeutic interventions. This review highlights key immunological targets in BCC and cSCC, with a focus on immune checkpoint molecules such as PD-1/PD-L1 and CTLA-4, which regulate T cell activity and contribute to immune evasion. This review also highlights anti-tumor immune cell subsets within the tumor microenvironment (TME), such as tumor-infiltrating lymphocytes (TILs) and dendritic cells. Additionally, it examines the immunosuppressive elements of the TME, including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs), as well as their roles in NMSC progression and resistance to therapy. Emerging strategies targeting these immune elements, such as monoclonal antibodies, are also discussed for their potential to enhance anti-tumor immune responses and improve clinical outcomes. By elucidating the immunological landscape of BCC and cSCC and drawing comparisons to melanoma, this review highlights the transformative potential of immunotherapy in treating these malignancies.

Design, synthesis and mechanistic study of N-4-Piperazinyl Butyryl Thiazolidinedione derivatives of ciprofloxacin with Anticancer Activity via Topoisomerase I/II inhibition.

A new group of thiazolidine-2,4-dione derivatives of ciprofloxacin having butyryl linker 3a-l was synthesized via an alkylation of thiazolidine-2,4-diones with butyryl ciprofloxacin with yield range 48-77% andfully characterized by various spectroscopic and analytical tools. Anti-cancer screening outcomes indicated that 3a and 3i possess antiproliferative activities against human melanoma LOX IMVI cancer cell line with IC50 values of 26.7 ± 1.50 and 25.4 ± 1.43 µM, respectively, using doxorubicin and cisplatin as positive controls with an IC50 of 7.03 ± 0.40 and 5.07 ± 0.29 µM, respectively. Additionally, compound 3j showed promising anticancer activity against human renal cancer A498 cell line with IC50 value of 33.9 ± 1.91 µM while doxorubicin and cisplatin showed IC50 values of 3.59 ± 0.20 and 7.92 ± 0.45, respectively. On the other hand, compound 3i did not show considerable anti-bacterial activity against S. aureus, E. coli and P. aeruginosa, and only moderate activity against K. pneumoniae with only a tenth of the activity of ciprofloxacin, confirming the cytotoxicity observed. Mechanistically, compound 3i inhibited both topoisomerase I and II with IC50 of 4.77 ± 0.26 and 15 ± 0.81 µM. Furthermore, it induced cell cycle arrest at S phase in melanoma LOX IMVI cells. Moreover, 3i provoked substantial levels of early, late apoptosis and necrosis in melanoma LOX IMVI cell line comparable to that induced by doxorubicin. Furthermore, compound 3i increased the expression level of active caspase-3 by 49 folds higher in LOX IMVI cell, increased protein expression level of Bax more than the control by 3 folds and inhibited PARP-1by 33% in LOX IMVI. All results were supported by theoretical docking studies on both tested enzymes confirming potential cytotoxicity for the synthesized hybrids.

Is Migraine Surgery Financially Viable for the Hospital and Surgeon? A Single-Surgeon, Ten-Year Study at an Academic Institution.

BACKGROUND: Data exists to demonstrate that migraine surgery is cost-effective for the long-term treatment of headaches, but no data exists regarding its financial viability for healthcare institutions. The goals of the current study are to demonstrate that (1) migraine surgery is financially viable for an academic institution with a net-positive profitability and (2) migraine surgery is a sought-after therapy that can draw patients into the healthcare system. METHODS: A retrospective chart review of migraine and bilateral breast reduction (BBR) consults seen in clinic between 05/01/2011-05/30/2020 was conducted. Patient age, sex, payor information, and distance from the hospital was collected. Profit margin, percentage profit, collection percentage, and conversion rate to surgery from clinic was calculated. RESULTS: 407 new migraine consults and 119 new BBR consults were included from which, 150 underwent migraine surgeries and 117 underwent BBR respectively. Migraine surgery group came from a further distance for the initial consult (P-value<0.001) and for surgery (P-value<0.001). There were also more migraine surgery patients from out-of-state (P-value=0.012). Migraine clinic patients had a larger ratio of private insurers (P-value<0.001). Migraine surgery patients had a greater total charge (P-value<0.001), estimated reimbursement (P-value=0.001), and total cost (P-value<0.001). CONCLUSIONS: This study provides evidence that migraine surgery is financially viable for hospitals and while performing similarly to bilateral breast reduction in profit margin, it brought in more patients from outside the catchment area of our institution. These findings may encourage hospitals to recruit migraine surgeons to improve care for this underserved patient population.

Novel benzenesulfonamide derivatives as potential selective carbonic anhydrase IX, XII inhibitors with anti-proliferative activity: Design, synthesis and in silico studies.

As inhibitors of carbonic anhydrases (CAs) IX and XII, a novel series of 1,2,3-triazole benzenesulfonamide derivatives 17a-l containing pyrazolyl-thiazole moiety was designed, synthesized, and tested for anti-proliferative activity. Compounds 17e-h demonstrated more effective inhibitory activity than acetazolamide (IC50 63 nM CA IX and IC50 92 nM CA XII), with IC50 range of 25-52 nM against CA IX and IC50 range of 31-80 nM against CA XII. To verify selectivity against CA IX and CA XII, carbonic anhydrase inhibitory activity of compounds 17e-h against the physiological CA I and CA II isoforms was carried out. The results showed that compounds 17e-h induced lower inhibitory activity against CA I and CA II with IC50 range of 0.428-0.638 µM (CA I) and 0.095-0.164 µM (CA II), in addition to higher selectivity indices (CA I/CA IX S.I. 8.9-19.92, CA I/CA XII S.I. 5.78-16.06) and (CA II/CA IX S.I. 2.83-4.35, CA II/CA XII S.I. 2.05-3.15) when compared to that of acetazolamide, IC50 of 0.199 µM (CA I), 0.133 µM (CA II) (CA I/CA IX S.I. 3.15, CA I/CA XII S.I. 2.16) and (CA II/CA IX S.I. 2.11, CA II/CA XII S.I. 1.44). Concerning anti-proliferative activity of compounds 17e-h, investigations were done on HEPG-2 cell line with IC50 ranges of 3.44-15.03 µM in comparison, 5-FU and doxorubicin showed IC50 values of 11.80 and 9.53 µM, respectively. Furthermore IC50 of MCF-7 and MDA-MB-231 were determined under both normoxic and hypoxic conditions with IC50 values ranging from 3.18-8.26 µM MCF-7 (normoxic), 1.39-6.05 µM MCF-7 (hypoxic), 7.13-26.3 µM MDA-MB-231 (normoxic), 0.76-16.3 µM MDA-MB-231 (hypoxic) using acetazolamide and SLC-0111 as selective CA inhibition references. Moreover, compounds 17e-h demonstrated greater safety against the normal cell line, MCF-10A, with IC50 of 23.06-99.50 µM in comparison to 5-FU and doxorubicin IC50 of 59.8 and 71.8 µM respectively. They also demonstrated (MCF-7 S.I. range of 3.77-31.28) in contrast to doxorubicin (S.I. 13.72) and (HepG-2 S.I. range of 3.60-6.95) in comparison to doxorubicin (S.I. 7.53). In relation to CA IX, XII inhibition, molecular docking of and ADME studies of sulfonamide derivatives 17a-l with CA IX (PDB: 5FL6) and CA XII (PDB: 1JD0) was carried out. Additionally, molecular dynamic simulation was carried out for compounds 17e and 17g which maintained good stability inside the active sites of both enzymes, with average RMSDs of 2.3 Å and 2.1 Å, respectively.

Pediatric Eyelid Cutaneous Horns: A Case Series and Literature Review.

PURPOSE: To describe the clinical and histopathologic features of pediatric eyelid cutaneous horns. DESIGN: Retrospective observational case series and review of literature. SUBJECTS: Five pediatric patients with eyelid cutaneous horns Methods: Five cases with eyelid cutaneous horns were retrospectively identified using departmental databases. Patients' records were analyzed for demographic data, clinical appearance, histologic findings, and clinical course. An excisional biopsy of the lesion was performed in 3 patients. The remaining 2 patients were managed conservatively. MAIN OUTCOME MEASURES: Clinical outcome and histopathologic evaluation with emphasis on excluding malignancy. RESULTS: All 5 cutaneous horn lesions resolved surgically or conservatively. The average age at presentation was 6.6 years (range 5-11 years). Clinically, 4 lesions were preceded by a hordeolum or chalazion and all excised lesions had benign features on histologic examination. Mitotic figures or atypia were not observed. None of the patients developed recurrence during the follow-up period ranging from 1 to 96 months. Five previous reports of five cases were found on review of the literature. Our case series doubles this number to support the benign nature of these lesions in children. CONCLUSIONS: Pediatric eyelid cutaneous horns are closely related to eyelid margin inflammatory disease and appear to follow a benign course. This contrasts with the adult population where cutaneous horns are frequently associated with neoplasia.

HYBRID APPROACH OF MASSIVE LIPOLYMPHEDEMA OF THE THIGH: A NOVEL SURGICAL TECHNIQUE.

OBJECTIVES: The goal of this study was to test the hybrid technique of combined tumescent liposuction and surgical excision in patients with advanced lipolymphedema of the thigh after compression therapy as a golden standard for treatment. PATIENTS AND METHODS: Between January 2016 and April 2020, 18 females and one male patient with massive thigh lipolymphedema were treated with complete decongestive therapy (CDT) for the whole thigh followed by selective decongestive therapy to the upper and lower thigh to make a lump on the mid-medial region, then, the patient was prepared for surgery. Skin is refashioned and sutured in a manner that leaves no furrows and a cosmetic contour is obtained. Compression therapy is maintained from the day of the surgery starting by compression bandage till full healing of the wound, followed by will fitted garments. RESULTS: This study was conducted on 18 female patients and one male patient presented with massive lipolymphedema of the thigh. The age of the patients ranged from 46 to 65 years old with mean age 51.38. All patients in this study underwent compression therapy as a preparatory stage to turn the massive lipolymphedema into lumpedema, followed by hybrid technique which consisted of combined liposuction and surgical excision. CONCLUSION: Conversion of massive thigh lipolymphedema into lumpedema followed by tumescent liposuction and surgical excision had proven to be safe and effective treatment option with a marvelous cosmetic result with low wound morbidity and should be considered as a solution for all patients with this disorder.

Biosynthesis of metal/metal oxide nanoparticles via Deverra tortuosa: characterization, GC/MS profiles, and biological potential.

Since the beginning of humanity, people have used wild medicinal plants for the treatment of various diseases. Nowadays, researchers and scientists pay attention to exploring new tools to maximize the efficacy of natural products from natural resources, and among these tools formulation of nanoparticles is very promising. The green synthesis of metal/metal oxide nano-solutions using the Deverra tortuosa extract has still not been explored well. This study aims to prepare many metal/metal oxide nanoparticle solutions such as ZnO-NPs, SeO2-MNPs, and Ag-NPs via the methanol extract of D. tortuosa as safe, easy, green, and economic approach as well as characterize the chemical components of D. tortuosa plant by GC-MS spectroscopy analysis. The synthesized M-NPs solutions were characterized by UV-visible (UV-Vis) spectroscopy, Transmission Electron Microscope (TEM), zeta potential, Fourier Transform Infrared (FT-IR) spectroscopy, and phytochemical analyses. The potential antioxidant capacity was estimated for the methanol extract of this plant along with the metal/metal oxide nanoparticles solutions by DPPH assay. In addition, the cytotoxic activity was in vitro assessed for the inspected samples against various tumor and normal cell lines applying MTT assay. The application of the D. tortuosa methanolic extract resulted in NPs with a range of 11.79-85.9 nm which was characterized by UV-Vis spectroscopy, TEM, zeta potential, and FT-IR spectroscopy that revealed various functional groups of the tested samples. The GC-MS analysis of the D. tortuosa methanolic extract showed the presence of 31 chemical compounds with 2-methyl-3-oxocyclopent-1-ene-1-carboxylic acid, methyl oleate, and 6-allyl-4,5-dimethoxybenzo[d][1,3]-dioxole as major constituents. The extract showed considerable antioxidant activity as well as antimicrobial activity that was assessed also against varied bacterial and fungal species. Remarkable potencies for the investigated metal/metal oxide nanoparticle solutions hinder the growth of the tumor cell lines, in addition to the growth of the microbial species. Based on the determined biological activities of the produced NPs, future study is recommended to characterize the pure authentic compounds that are identified within the D. tortuosa as major compounds as well as evaluate their modes of action.