Berberine protects against sepsis-related acute lung injury in rats via PPAR-γ signaling pathway upregulation and improvement at the cellular level: Functional, biochemical, and immunohistochemistry study.

This study aimed to assess the prophylactic effects of Berberine on experimentally induced lung sepsis and examine its effects on selected cytokines, genes, and protein expression besides the histopathological evaluation. Berberine significantly reduced the wet/dry lung ratio, the broncho-alveolar lavage fluid (BALF) protein, cells, neutrophils percentage, and cytokines levels. In addition, pretreatment with Berberine decreased the myeloperoxidase (MPO) and malondialdehyde (MDA) levels and decreased gene expression of nuclear factor kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and the intracellular adhesion molecule 1 (ICAM-1) by RT-qPCR analysis, revealing Berberine's antioxidant and anti-inflammatory mode of action. Western blot analysis revealed increased peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in the Berberine pretreated group compared to the cecal ligation and puncture (CLP) group, in which the histopathological examination evidenced this improvement. In conclusion, Berberine improved lung sepsis via its PPAR-γ mediated antioxidant and anti-inflammatory effects.

Nicotine promotes e-cigarette vapour-induced lung inflammation and structural alterations.

BACKGROUND: Electronic cigarette (e-cigarette) vapour is gaining popularity as an alternative to tobacco smoking and can induce acute lung injury. However, the specific role of nicotine in e-cigarette vapour and its long-term effects on the airways, lung parenchyma and vasculature remain unclear. RESULTS: In vitro exposure to nicotine-containing e-cigarette vapour extract (ECVE) or to nicotine-free e-cigarette vapour extract (NF ECVE) induced changes in gene expression of epithelial cells and pulmonary arterial smooth muscle cells (PASMCs), but ECVE in particular caused functional alterations (e.g. a decrease in human and mouse PASMC proliferation by 29.3±5.3% and 44.3±8.4%, respectively). Additionally, acute inhalation of nicotine-containing e-cigarette vapour (ECV) but not nicotine-free e-cigarette vapour (NF ECV) increased pulmonary endothelial permeability in isolated lungs. Long-term in vivo exposure of mice to ECV for 8 months significantly increased the number of inflammatory cells, in particular lymphocytes, compared to control and NF ECV in the bronchoalveolar fluid (BALF) (ECV: 853.4±150.8 cells·mL-1; control: 37.0±21.1 cells·mL-1; NF ECV: 198.6±94.9 cells·mL-1) and in lung tissue (ECV: 25.7±3.3 cells·mm-3; control: 4.8±1.1 cells·mm-3; NF ECV: 14.1±2.2 cells·mm-3). BALF cytokines were predominantly increased by ECV. Moreover, ECV caused significant changes in lung structure and function (e.g. increase in airspace by 17.5±1.4% compared to control), similar to mild tobacco smoke-induced alterations, which also could be detected in the NF ECV group, albeit to a lesser degree. In contrast, the pulmonary vasculature was not significantly affected by ECV or NF ECV. CONCLUSIONS: NF ECV components induce cell type-specific effects and mild pulmonary alterations, while inclusion of nicotine induces significant endothelial damage, inflammation and parenchymal alterations.

Epidemiological characterization of viral etiological agents of the central nervous system infections among hospitalized patients in Egypt between 2016 and 2019.

Viral infections of the central nervous system (CNS) are common worldwide and result in considerable morbidity and mortality associated with neurologic illness. Until now, there have been no epidemiologic data regarding viruses causing aseptic meningitis, encephalitis, and CNS infections in Egypt. We investigated 1735 archived cerebrospinal fluid samples collected from Egyptian patients between 2016 and 2019 and performed molecular characterization for infection for12 different viruses: herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesviruses 6 and 7 (HHV-6 and HHV-7), human enteroviruses (HEVs), human parechovirus (HPeV), parvovirus B19 (B19V), adenovirus (AdV), and mumps virus (MuV). All included samples were negative for bacterial infection. Our results indicated a relatively high prevalence of viral infection, with HEVs being the most prevalent viruses, followed by HSV-1, EBV, and then HSV-2. The highest prevalence was among male patients, peaking during the summer. Data obtained from this study will contribute to improving the clinical management of viral infections of the CNS in Egypt.

Detection of MET gene somatic mutations in hepatocellular carcinoma of Egyptian patients using next-generation sequencing.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer worldwide and fourth in Egypt. Liquid biopsy is important to get cell-tumour DNA (ctDNA), for subsequent utilisation as a biomarker for cancer diagnosis, prognosis, and treatment. In clinical oncology, ctDNA analysis is utilised in cancer screening. METHODS: The collected 48 blood samples from HCC patients were classified according to Barcelona Clinic Liver Cancer (BCLC) staging, in addition to Hepatitis C Virus (HCV) group and normal group. After the liquid biopsy, ctDNA and genomic DNA (gDNA) of the same individual were extracted. Next-generation sequencing (NGS) was conducted using a Hot spot panel, and data analysis via different cancer databases was performed. RESULTS: There were no significant differences in the detected mutation frequency between groups. The frequency of mutations was higher in ctDNA than in the gDNA samples from the same patients. Hence, it can be concluded that these mutations are somatic mutations, rather than germline mutations. CONCLUSION: Screening of the targeted genes such as c-MET for potential mutations is very important in the determination of the appropriate therapy. Therefore, it can be used as a biomarker in the prognosis of HCC. Such screenings are also of paramount importance in the development of personalised medicine.

Comparison of SARS-Cov-2 omicron variant with the previously identified SARS-Cov-2 variants in Egypt, 2020-2022: insight into SARS-Cov-2 genome evolution and its impact on epidemiology, clinical picture, disease severity, and mortality.

BACKGROUND: The o severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic has killed millions of people and caused widespread concern around the world. Multiple genetic variants of SARS-CoV-2 have been identified as the pandemic continues. Concerns have been raised about high transmissibility and lower vaccine efficacy against omicron. There is an urgent need to better describe how omicron will impact clinical presentation and vaccine efficacy. This study aims at comparing the epidemiologic, clinical, and genomic characteristics of the omicron variant prevalent during the fifth wave with those of other VOCs between May 2020 and April 2022. METHODS: Epidemiological data were obtained from the National Electronic Diseases Surveillance System. Secondary data analysis was performed on all confirmed COVID-19 patients. Descriptive data analysis was performed for demographics and patient outcome and the incidence of COVID-19 was calculated as the proportion of SARS-CoV-2 confirmed patients out of the total population of Egypt. Incidence and characteristics of the omicron cohort from January- April 2022, were compared to those confirmed from May 2020-December 2021. We performed the whole-genome sequencing of SARS-CoV-2 on 1590 specimens using Illumina sequencing to describe the circulation of the virus lineages in Egypt. RESULTS: A total of 502,629 patients enrolled, including 60,665 (12.1%) reported in the fifth wave. The incidence rate of omicron was significantly lower than the mean of incidences in the previous subperiod (60.1 vs. 86.3/100,000 population, p < 0.001). Symptoms were reported less often in the omicron cohort than in patients with other variants, with omicron having a lower hospitalization rate and overall case fatality rate as well. The omicron cohort tended to stay fewer days at the hospital than did those with other variants. We analyzed sequences of 2433 (1590 in this study and 843 were obtained from GISAID platform) Egyptian SARS-CoV-2 full genomes. The first wave that occurred before the emergence of global variants of concern belonged to the B.1 clade. The second and third waves were associated with C.36. Waves 4 and 5 included B.1.617.2 and BA.1 clades, respectively. CONCLUSIONS: The study indicated that Omicron-infected patients had milder symptoms and were less likely to be hospitalized; however, patients hospitalized with omicron had a more severe course and higher fatality rates than those hospitalized with other variants. Our findings demonstrate the importance of combining epidemiological data and genomic analysis to generate actionable information for public health decision-making.

Resurgence of influenza and respiratory syncytial virus in Egypt following two years of decline during the COVID-19 pandemic: outpatient clinic survey of infants and children, October 2022.

INTRODUCTION: Two years after unprecedented low rates of circulation of most common respiratory viruses (SARS-CoV-2), the Egyptian ARI surveillance system detected an increase in acute respiratory infections (ARIs) with a reduced circulation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially among school children. A national survey was conducted to estimate the burden and identify the viral causes of ARIs among children < 16 years of age. METHODS: A one-day survey was carried out in 98 governmental outpatient clinics distributed all over Egypt 26 governorates. The four largest referral hospitals in each governorate where most influenza-like illness (ILI) patients seek care were selected. Using the WHO case definition, the first five patients < 16 years of age with ILI symptoms visiting the selected outpatient clinics on the survey day were enrolled. Basic demographic and clinical data of patients were collected using a linelist. Patients were swabbed and tested for SARS-CoV-2, influenza, and Respiratory Syncytial virus (RSV) by RT-PCR at the Central Laboratory in Cairo. RESULTS: Overall, 530 patients enrolled, their mean age was 5.8 ± 4.2, 57.1% were males, and 70.2% reside in rural or semi-rural areas. Of all patients, 134 (25.3%) had influenza, 111 (20.9%) RSV, and 14 (2.8%) coinfections. Influenza-positive children were older compared to RSV, (7.2 ± 4.1, 4.3 ± 4.1, p < 0.001), with more than half of them (53.0%) being school students. Dyspnea was reported in RSV more than in influenza (62.2% vs. 49.3%, p < 0.05). Among RSV patients, children < 2 years had a higher rate of dyspnea than others (86.7% vs. 53.1%, < 0.001). CONCLUSIONS: A resurgence of influenza and RSV was detected in Egypt in the 2022-2023 winter season. Influenza caused a higher rate of infection than RSV, while RSV caused more severe symptoms than influenza. Monitoring a broader range of respiratory pathogens is recommended to estimate the ARI burden and risky groups for severe disease in Egypt.

Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers.

A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines. In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised. The targets and the SeNP derivatives were examined for their cytotoxicity towards five cancer cell lines. The inhibitory potencies of the best members against Topo I and Topo II were also assayed besides their DNA intercalation abilities. Compound 7d NPs exhibited the best inhibition against Topo I and Topo II enzymes with IC50 of 0.042 and 1.172 µM, respectively. The ability of compound 7d NPs to arrest the cell cycle and induce apoptosis was investigated. It arrested the cell cycle in the A549 cell at the S phase and prompted apoptosis by 41.02% vs. 23.81% in the control. In silico studies were then performed to study the possible binding interactions between the designed members and the target proteins.

A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines.In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised.Cytotoxicity, Topo I and Topo II inhibitory assays, and DNA intercalation abilities were evaluated.Compound 7d NPs showed the best Topo I and Topo II inhibition.Cell cycle arrest, apoptosis induction, and molecular docking studies were performed.

Design and synthesis of novel rigid dibenzo[b,f]azepines through ring closure technique as promising anticancer candidates against leukaemia and acting as selective topoisomerase II inhibitors and DNA intercalators.

In this research, two novel series of dibenzo[b,f]azepines (14 candidates) were designed and synthesised based on the rigidification principle and following the reported doxorubicin's pharmacophoric features. The anti-proliferative activity was evaluated at the NCI against a panel of 60 cancer cell lines. Further, the promising candidates (5a-g) were evaluated for their ability to inhibit topoisomerase II, where 5e was noticed to be the most active congener. Moreover, its cytotoxicity was evaluated against leukaemia SR cells. Also, 5e arrested the cell cycle at the G1 phase and increased the apoptosis ratio by 37.34%. Furthermore, in vivo studies of 5e showed the inhibition of tumour proliferation and the decrease in its volume. Histopathology and liver enzymes were examined as well. Besides, molecular docking, physicochemical, and pharmacokinetic properties were carried out. Finally, a SAR study was discussed to open the gate for further optimisation of the most promising candidate (5e).HighlightsTwo novel series of dibenzo[b,f]azepines were designed and synthesised based on the rigidification principle in drug design.The anti-proliferative activity was evaluated at the NCI against a panel of 60 cancer cell lines.5e was the most active anti-topo II congener (IC50 = 6.36 ± 0.36 µM).5e was evaluated against leukaemia SR cells and its cytotoxic effect was confirmed (IC50 = 13.05 ± 0.62 µM).In vivo studies of 5e significantly inhibited tumour proliferation by 62.7% and decreased tumour volume to 30.1 mm3 compared to doxorubicin treatment.

Biochemical alterations in cotton leafworm, Spodoptera littoralis (Boisd.) related to emamectin benzoate and fipronil compared to their joint action.

Cotton leafworm, Spodoptera littoralis (Boisduval), is one of the major destructive pests of ornamental, industrial, and vegetable crops. The efficacy of technical emamectin benzoate (EMB) and fipronil (FPR) was assessed against the 4th larval instar using leaf-dip bioassay method. EMB was more efficient than FPR based on 96 h LC50 values of 0.004 and 0.023 µg/ml, respectively. Joint toxic action of the dual exposure in sequence with time interval 24 h and in mix were evaluated at LC10:LC10, LC25:LC25 and LC50:LC50 after 96 h posttreatment, as well. Their impacts on detoxification enzymes, esterases (ESTs); alkaline phosphatase (ALP); and glutathione S-transferase (GST) as well as acetylcholine esterase (AChE) were also determined. The sequential exposure of EMB after FPR (S1) produced antagonism, potentiation, and potentiation effects, respectively while sequential exposure of FPR after EMB (S2) interacted as addition, potentiation, and potentiation respectively. The rest of binary mixtures (Mix) revealed antagonistic effect regardless of concentration. Orthogonal contrast analysis showed that the highest elevations of AChE, α-EST, ß- EST and ALP enzymes were obtained from Mix at LC50:LC50 (181.6%, 288.4, 229.2 and 460.9%, respectively), LC25:LC25 (131.5%, 252.8, 205.60 and 252.0, respectively) and LC10:LC10 (106.6%, 215.6%, 201.8% and 170.0%, respectively). Differently, the greatest elevation of GST activity (157.7%) resulted from S1 at LC50:LC50, while it was significantly lower at LC25:LC25 and LC10:LC10 as well as Mix and S2 at all concentrations than corresponding concentrations of FPR. These findings shed some light on the role of GST in FPR toxicity and clarified the risk of these dual exposures in elevating detoxification enzymes dangerously compared to their individual insecticides. These dual exposures should be carefully handled. Although rotational exposure at low concentrations may enhance performance and mitigate resistance risk, rotational exposure at high concentrations and Mix may indirectly contribute to the evolution of cross-resistance to other insecticides.

New Supramolecular Hypoxia-Sensitive Complexes Based on Azo-Thiacalixarene.

Hypoxia accompanies many human diseases and is an indicator of tumor aggressiveness. Therefore, measuring hypoxia in vivo is clinically important. Recently, complexes of calix[4]arene were identified as potent hypoxia markers. The subject of this paper is new hypoxia-sensitive host-guest complexes of thiacalix[4]arene. We report a new high-yield synthesis method for thiacalix[4]arene with four anionic carboxyl azo fragments on the upper rim (thiacalixarene L) and an assessment of the complexes of thiacalixarene L with the most widespread cationic rhodamine dyes (6G, B, and 123) sensitivity to hypoxia. Moreover, 1D and 2D NMR spectroscopy data support the ability of the macrocycles to form complexes with dyes. Rhodamines B and 123 formed host-guest complexes of 1:1 stoichiometry. Complexes of mixed composition were formed with rhodamine 6G. The association constant between thiacalixarene L and rhodamine 6G is higher than for other dyes. Thiacalixarene L-dye complexes with rhodamine 6G and rhodamine B are stable in the presence of various substances present in a biological environment. The UV-VIS spectrometry and fluorescence showed hypoxia responsiveness of the complexes. Our results demonstrate that thiacalixarene L has a stronger binding with dyes compared with the previously reported azo-calix[4]arene carboxylic derivative. Thus, these results suggest higher selective visualization of hypoxia for the complexes with thiacalixarene L.

Loss-of-function variants in SRRM2 cause a neurodevelopmental disorder.

PURPOSE: SRRM2 encodes the SRm300 protein, a splicing factor of the SR-related protein family characterized by its serine- and arginine-enriched domains. It promotes interactions between messenger RNA and the spliceosome catalytic machinery. This gene, predicted to be highly intolerant to loss of function (LoF) and very conserved through evolution, has not been previously reported in constitutive human disease. METHODS: Among the 1000 probands studied with developmental delay and intellectual disability in our database, we found 2 patients with de novo LoF variants in SRRM2. Additional families were identified through GeneMatcher. RESULTS: Here, we report on 22 patients with LoF variants in SRRM2 and provide a description of the phenotype. Molecular analysis identified 12 frameshift variants, 8 nonsense variants, and 2 microdeletions of 66 kb and 270 kb. The patients presented with a mild developmental delay, predominant speech delay, autistic or attention-deficit/hyperactivity disorder features, overfriendliness, generalized hypotonia, overweight, and dysmorphic facial features. Intellectual disability was variable and mild when present. CONCLUSION: We established SRRM2 as a gene responsible for a rare neurodevelopmental disease.

Topo II inhibition and DNA intercalation by new phthalazine-based derivatives as potent anticancer agents: design, synthesis, anti-proliferative, docking, and in vivo studies.

This research presents the design and synthesis of a novel series of phthalazine derivatives as Topo II inhibitors, DNA intercalators, and cytotoxic agents. In vitro testing of the new compounds against HepG-2, MCF-7, and HCT-116 cell lines confirmed their potent cytotoxic activity with low IC50 values. Topo II inhibition and DNA intercalating activities were evaluated for the most cytotoxic members. IC50 values determination demonstrated Topo II inhibitory activities and DNA intercalating affinities of the tested compounds at a micromolar level. Amongst, compound 9d was the most potent member. It inhibited Topo II enzyme at IC50 value of 7.02 ± 0.54 µM with DNA intercalating IC50 of 26.19 ± 1.14 µM. Compound 9d was then subjected to an in vivo antitumor examination. It inhibited tumour proliferation reducing solid tumour volume and mass. Additionally, it restored liver enzymes, proteins, and CBC parameters near-normal, indicating a remarkable amelioration in their functions along with histopathological examinations.

Discovery of new nicotinamides as apoptotic VEGFR-2 inhibitors: virtual screening, synthesis, anti-proliferative, immunomodulatory, ADMET, toxicity, and molecular dynamic simulation studies.

A library of modified VEGFR-2 inhibitors was designed as VEGFR-2 inhibitors. Virtual screening was conducted for the hypothetical library using in silico docking, ADMET, and toxicity studies. Four compounds exhibited high in silico affinity against VEGFR-2 and an acceptable range of the drug-likeness. These compounds were synthesised and subjected to in vitro cytotoxicity assay against two cancer cell lines besides VEGFR-2 inhibitory determination. Compound D-1 showed cytotoxic activity against HCT-116 cells almost double that of sorafenib. Compounds A-1, C-6, and D-1 showed good IC50 values against VEGFR-2. Compound D-1 markedly increased the levels of caspase-8 and BAX expression and decreased the anti-apoptotic Bcl-2 level. Additionally, compound D-1 caused cell cycle arrest at pre-G1 and G2-M phases in HCT-116 cells and induced apoptosis at both early and late apoptotic stages. Compound D-1 decreased the level of TNF-α and IL6 and inhibited TNF-α and IL6. MD simulations studies were performed over 100 ns.

New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and in silico studies.

A new series of benzoxazole derivatives were designed and synthesised to have the main essential pharmacophoric features of VEGFR-2 inhibitors. Cytotoxic activities were evaluated for all derivatives against two human cancer cell lines, MCF-7 and HepG2. Also, the effect of the most cytotoxic derivatives on VEGFR-2 protein concentration was assessed by ELISA. Compounds 14o, 14l, and 14b showed the highest activities with VEGFR-2 protein concentrations of 586.3, 636.2, and 705.7 pg/ml, respectively. Additionally, the anti-angiogenic property of compound 14b against human umbilical vascular endothelial cell (HUVEC) was performed using a wound healing migration assay. Compound 14b reduced proliferation and migratory potential of HUVEC cells. Furthermore, compound 14b was subjected to further biological investigations including cell cycle and apoptosis analyses. Compound 14b arrested the HepG2 cell growth at the Pre-G1 phase and induced apoptosis by 16.52%, compared to 0.67% in the control (HepG2) cells. The effect of apoptosis was buttressed by a 4.8-fold increase in caspase-3 level compared to the control cells. Besides, different in silico docking studies were also performed to get better insights into the possible binding mode of the target compounds with VEGFR-2 active sites.

Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluation.

In this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (12d, 12f, 12i, 12l, and 13a) displayed high growth inhibitory activities against HepG2 and MCF-7 cell lines and were further investigated for their VEGFR-2 inhibitory activities. The most potent anti-proliferative member 12 l (IC50 = 10.50 µM and 15.21 µM against HepG2 and MCF-7, respectively) had the most promising VEGFR-2 inhibitory activity (IC50 = 97.38 nM). A further biological evaluation revealed that compound 12l could arrest the HepG2 cell growth mainly at the Pre-G1 and G1 phases. Furthermore, compound 12l could induce apoptosis in HepG2 cells by 35.13%. likely, compound 12l exhibited a significant elevation in caspase-3 level (2.98-fold) and BAX (3.40-fold), and a significant reduction in Bcl-2 level (2.12-fold). Finally, docking studies indicated that 12l exhibited interactions with the key amino acids in a similar way to sorafenib.

Incidence of major complications from embolo-sclerotherapy of head and neck vascular malformations in a single specialist centre.

OBJECTIVE: Current data on the nature and rate of major complications for embolo-sclerotherapy (EST) of vascular malformations are scarce. However, even fewer studies focus on vascular malformations specific to the head and neck, which confer an increased specific risk of airway compromise, neurologic and ophthalmologic injury. More understanding is required surrounding the type and incidence of complications to improve treatment planning and informed consent. Therefore, this study aimed to review major complications secondary to EST of head and neck vascular malformations over a 5-year period in a single specialized multidisciplinary centre for vascular anomalies. METHODS: All interventions were decided by the multidisciplinary team. Demographic, procedural and complication data between 1st January 2013 and 31st December 2017 were prospectively documented in a dedicated database and analysed. EST of high-flow vascular malformations (HFVMs) was performed by selective catheter angiography or direct injection, and by direct injection only for low-flow vascular malformations (LFVMs). Major complications were defined as any tissue or functional damage caused by direct injection, distal embolization or tissue reaction and were decided by the multidisciplinary team. RESULTS: Forty-eight patients (median age of 35 years; range of 14-70 years; 18 men and 30 women) had 100 EST procedures for head and neck vascular malformation. Of these, 14 patients had EST for HFVM and 34 patients for LFVM, total 43 and 57 procedures, respectively. Overall, five patients with HFVM developed major complications from EST when compared with two patients with LFVM (p = 0.0167). Two patients required pre-emptive tracheostomy due to risk of post-operative airway compromise. Overall, seven (14.6%) patients experienced major complication from EST. In the HFVM group, major complications from EST occurred in five patients; four cases of tissue ulceration and necrosis (two needed debridement, one healed with resultant fibrosis that impeded speech and one resolved spontaneously) and one post-procedural airway compromise requiring tracheostomy. Meanwhile, in the LFVM group, major complications occurred in two patients; one case of severe necrosis involving the alar cartilage, lip and cheek requiring debridement and reconstruction under plastics and one simple cellulitis. No patients sustained stroke or vision impairment. CONCLUSIONS: EST is relatively safe for head and neck vascular malformations in a high-volume experienced centre. Our major complication rate of 14.6% per patient (35.7% for HFVM; 5.9% for LFVM) or 7% per procedure (11.6% for HFVM; 3.5% LFVM) compares favourably with published data from other centres. These data will improve treatment planning and informed consent for EST for both HFVM and LFVM of the head and neck.

Postoperative morbidity risk factors after conservative surgery of hydatic cyst of the liver: a retrospective study of 151 hydatic cysts of the liver.

BACKGROUND: The purpose of the present paper is to assess the morbidity specifics risk factors of hepatic hydatid cyst after conservative surgery. METHODS: We conducted a retrospective study of 102 patients over a period of 13 years, from 2006 to 2019. We included all patients operated on hydatid cyst of the liver, complicated and uncomplicated, in the Department of General Surgery in Tahar Sfar hospital, Mahdia, Tunisia. We excluded patients who received an exclusive medical treatment and those who have other hydatic cyst localizations. RESULTS: The cohort was composed of 102 patients with a total of 151 cysts operated on using conservative surgery, among them there was 75 women (73.5%) and 27 men (26.5%). The median age was 43, with extremes ranging from 12 to 88 years. The majority of patients (94.1%) were from rural areas. The cysts were uncomplicated in about half of the cases (48%), elsewhere complications such as compression of neighboring organs (25.5%), opening in the bile ducts (16.7%), infection (9.8%), and rupture in the peritoneum (2%) were found. Conservative surgery was the mainstay of treatment with an overall mortality rate of 1.9%. The overall morbidity rate was 22%: 14% specific morbidity and 8% non-specific morbidity. External biliary fistula was the most common postoperative complication (9%). The predictive factors of morbidity in univariate analysis were: preoperative hydatid cyst infection (P = 0.01), Compressive cysts (P = 0.05), preoperative fever and jaundice, (respectively P = 0.03 and P = 0.02), no one achieved statistical significance in the multivariate model. CONCLUSIONS: Preoperative hydatid cyst infection, compressive cysts and preoperative fever and jaundice could be predictor factors of morbidity after conservative surgery for liver hydatid cyst. They must be considered in the treatment and the surgical decision for patients with hydatid cyst.

Synthesis of Cyano-Benzylidene Xanthene Synthons Using a Diprotic Brønsted Acid Catalyst, and Their Application as Efficient Inhibitors of Aluminum Corrosion in Alkaline Solutions.

Novel cyano-benzylidene xanthene derivatives were synthesized using one-pot and condensation reactions. A diprotic Brønsted acid (i.e., oxalic acid) was used as an effective catalyst for the promotion of the synthesis process of the new starting xanthene-aldehyde compound. Different xanthene concentrations (ca. 0.1-2.0 mM) were applied as corrosion inhibitors to control the alkaline uniform corrosion of aluminum. Measurements were conducted in 1.0 M NaOH solution using Tafel extrapolation and linear polarization resistance (LPR) methods. The investigated xanthenes acted as mixed-type inhibitors that primarily affect the anodic process. Their inhibition efficiency values were enhanced with inhibitor concentration, and varied according to their chemical structures. At a concentration of 2.0 mM, the best-performing studied xanthene derivative recorded maximum inhibition efficiency values of 98.9% (calculated via the Tafel extrapolation method) and 98.4% (estimated via the LPR method). Scanning electron microscopy (SEM) was used to examine the morphology of the corroded and inhibited aluminum surfaces, revealing strong inhibitory action of each studied compound. High-resolution X-ray photoelectron spectroscopy (XPS) profiles validated the inhibitor compounds' adsorption on the Al surface. Density functional theory (DFT) and Monte Carlo simulations were applied to investigate the distinction of the anticorrosive behavior among the studied xanthenes toward the Al (111) surface. The non-planarity of xanthenes and the presence of the nitrile group were the key players in the adsorption process. A match between the experimental and theoretical findings was evidenced.

Discovery of New VEGFR-2 Inhibitors: Design, Synthesis, Anti-Proliferative Evaluation, Docking, and MD Simulation Studies.

Four new nicotinamide-based derivatives were designed as antiangiogenic VEGFR-2 inhibitors. The congeners were synthesized possessing the pharmacophoric essential features to bind correctly with the VEGFR-2 active pocket. All members were evaluated for their cytotoxic and VEGFR-2 inhibitory potentialities. Compound 6 was the most potent showingIC50 values of 9.3 ± 0.02 and 7.8 ± 0.025 µM against HCT-116 and HepG-2 cells, respectively, and IC50 of 60.83 nM regarding VEGFR-2 enzyme inhibition. Compound 6 arrested the growth of HCT-116 cells at the pre-G1 and G2-M phases. Further, it induced both early and late apoptosis. Additionally, compound 6 caused a significant decrease in TNF-α and IL6 by 66.42% and 57.34%, respectively. The considered compounds had similar docking performances to that of sorafenib against the VEGFR-2 (PDB ID: 2OH4). The correct binding of compound 6 with VEGFR-2 was validated using MD simulations, and MM-GPSA calculations.

Genome-wide association screening and verification of potential genes associated with root architectural traits in maize (Zea mays L.) at multiple seedling stages.

BACKGROUND: Breeding for new maize varieties with propitious root systems has tremendous potential in improving water and nutrients use efficiency and plant adaptation under suboptimal conditions. To date, most of the previously detected root-related trait genes in maize were new without functional verification. In this study, seven seedling root architectural traits were examined at three developmental stages in a recombinant inbred line population (RIL) of 179 RILs and a genome-wide association study (GWAS) panel of 80 elite inbred maize lines through quantitative trait loci (QTL) mapping and genome-wide association study. RESULTS: Using inclusive composite interval mapping, 8 QTLs accounting for 6.44-8.83 % of the phenotypic variation in root traits, were detected on chromosomes 1 (qRDWv3-1-1 and qRDW/SDWv3-1-1), 2 (qRBNv1-2-1), 4 (qSUAv1-4-1, qSUAv2-4-1, and qROVv2-4-1), and 10 (qTRLv1-10-1, qRBNv1-10-1). GWAS analysis involved three models (EMMAX, FarmCPU, and MLM) for a set of 1,490,007 high-quality single nucleotide polymorphisms (SNPs) obtained via whole genome next-generation sequencing (NGS). Overall, 53 significant SNPs with a phenotypic contribution rate ranging from 5.10 to 30.2 % and spread all over the ten maize chromosomes exhibited associations with the seven root traits. 17 SNPs were repeatedly detected from at least two growth stages, with several SNPs associated with multiple traits stably identified at all evaluated stages. Within the average linkage disequilibrium (LD) distance of 5.2 kb for the significant SNPs, 46 candidate genes harboring substantial SNPs were identified. Five potential genes viz. Zm00001d038676, Zm00001d015379, Zm00001d018496, Zm00001d050783, and Zm00001d017751 were verified for expression levels using maize accessions with extreme root branching differences from the GWAS panel and the RIL population. The results showed significantly (P < 0.001) different expression levels between the outer materials in both panels and at all considered growth stages. CONCLUSIONS: This study provides a key reference for uncovering the complex genetic mechanism of root development and genetic enhancement of maize root system architecture, thus supporting the breeding of high-yielding maize varieties with propitious root systems.