Anti-Ribosomal-P Antibody Association with Neuropsychiatric Lupus in Sudanese Patients Attending Rheumatology Clinic in Omdurman Military Hospital.

Purpose: To assess and establish the relationship between neuropsychiatric systemic lupus erythematosus (NPSLE) involvement and serological biomarkers like antiribosomal-P antibodies. Patients and Methods: This is an analytical cross-sectional hospital-based study conducted on patients attending Omdurman Military Hospital from July 2019 to December 2019. A total of 90 patients were enrolled, 30 of whom had NPSLE compared with 60 SLE patients without NPSLE. SLE diagnosis was established based on the revised SLICC criteria (presence of at least 4 criteria) for SLE classification, with neuropsychiatric manifestations defined based on the ACR nomenclature. The immunological examination results have been performed by (ELISA immune-enzymatic method, immunofluorescence, and Western immunoblotting test). SPSS v 21.0 software was utilised for data analysis. Results: NPSLE patients exhibited +ve ANA in 96.7% vs 75% in non-NPSLE (P-value = 0.008), antiribosomal-P antibodies (46.7% vs 20%; P-value = 0.0001), anti-nucleosome antibodies (26.7% vs 5%; P-value = 0.005), and anti-histones antibodies (40% vs 20%; P-value = 0.04). ANA antibodies were significantly associated with neurological manifestations as ANA antibodies were common in epilepsy (n = 9; 91%) and stroke (n = 8; 27.6%) (P-value < 0.001). Conclusion: Neuropsychiatric manifestation of systemic lupus erythematosus exhibits variable clinical manifestations. Neuropsychiatric manifestations of SLE are strongly associated with the anti-ribosomal P antibody presence and can be employed as a powerful diagnostic tool.

Anticancer activity of chicken cathelicidin peptides against different types of cancer.

BACKGROUND: This study served as the pioneer in studying the anti-cancer role of chicken cathelicidin peptides. METHODS AND RESULTS: Chicken cathelicidins were used as anticancer agent against the breast cancer cell line (MCF-7) and human colon cancer cell line (HCT116). In addition, the mechanism of action of the interaction of cationic peptides with breast cancer cell line MCF-7 was also investigated. An in vivo investigation was also achieved to evaluate the role of chicken cathelicidin in Ehrlich ascites cell (EAC) suppression as a tumor model after subcutaneous implantation in mice. It was found during the study that exposure of cell lines to 40 µg/ml of chicken cathelicidin for 72 h reduced cell lines growth rate by 90-95%. These peptides demonstrated down-regulation of (cyclin A1 and cyclin D genes) of MCF-7 cells. The study showed that two- and three-fold expression of both of caspase-3 and - 7 genes in untreated MCF-7 cells compared to treated MCF-7 cells with chicken cathelicidin peptides. Our data showed that chicken (CATH-1) enhance releasing of TNFα, INF-γ and upregulation of granzyme K in treated mice groups, in parallel, the tumor size and volume was reduced in the treated EAC-bearing groups. Tumor of mice groups treated with chicken cathelicidin displayed high area of necrosis compared to untreated EAC-bearing mice. Based on histological analysis and immunohistochemical staining revealed that the tumor section in Ehrlich solid tumor exhibited a strong Bcl2 expression in untreated control compared to mice treated with 10 & 20 µg of cathelicidin. Interestingly, low expression of Bcl2 were observed in mice taken 40 µg/mL of CATH-1. CONCLUSIONS: This study drive intention in treatment of cancer through the efficacy of anticancer efficacy of chicken cathelicidin peptides.

Resource Oriented Decision Making for Treatment of Metastatic Colorectal Cancer (mCRC) in a Lower-Middle Income Country: Egyptian Foundation of Medical Sciences (EFMS) Consensus Recommendations 2020.

PURPOSE: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second cause of cancer related mortality. Treatment options for patients with metastatic CRC (mCRC) expanded during the last two decades, with introduction of new chemotherapeutic and targeted agents. Egypt is a lower middle-income country; Egyptian health care system is fragmented with wide diversity in drug availability and reimbursement policies across different health care providing facilities. We report the results of consensus recommendations for treatment of patients with metastatic colorectal cancer developed by Egyptian Foundation of Medical Sciences (EFMS), aiming to harmonize clinical practice through structured expert consensus-based recommendations consistent with the national status. EFMS recommendations could be utilized in other countries with similar economic status. METHODS: EFMS recommendations were developed using a modified Delphi process, with three rounds of voting till the final recommendations were approved. A non-systematic review of literature was conducted before generating the provisional statements. Content experts were asked to vote on some recommendations in two different resource groups (restricted resources and non-restricted resources). External review board of experts from a low income and lower-middle countries voted on the applicability of EFMS recommendations in their countries. RESULTS: The current recommendations highlighted the discrepancy in health care between restricted and non-restricted resources with expected survival loss and quality of life deterioration. Access to targeted agents in first line is very limited in governmental institutions, and no access to agents approved for third line in patients who failed oxaliplatin and irinotecan containing regimens for patients treated in restricted resource settings. CONCLUSION: Management of mCRC in developing countries is a challenge. The currently available resource-stratified guidelines developed by international cancer societies represent a valuable decision-making tool, adaptation to national status in each country based on healthcare system status is required.

High-throughput virtual screening of drug databanks for potential inhibitors of SARS-CoV-2 spike glycoprotein.

COVID-19, which is caused by a novel coronavirus known as SARS-CoV-2, has spread rapidly around the world, and it has infected more than 29 million individuals as recorded on 16 September 2020. Much effort has been made to stop the virus from spreading, and there are currently no approved pharmaceutical products to treat COVID-19. Here, we apply an in silico approach to investigate more than 3800 FDA approved drugs on the viral RBD S1-ACE2 interface as a target. The compounds were investigated through flexible ligand docking, ADME property calculations and protein-ligand interaction maps. Molecular dynamics (MD) simulations were also performed on eleven compounds to study the stability and the interactions of the protein-ligand complexes. The MD simulations show that bagrosin, chidamide, ebastine, indacaterol, regorafenib, salazosulfadimidine, silodosin and tasosartan are relatively stable near the C terminal domain (CTD1) of the S1 subunit of the viral S protein. The relative MMGBSA binding energies show that silodosin has the best binding to the target. The constant velocity steered molecular dynamics (SMD) simulations show that silodosin preferentially interacts with the RBD S1 and has potential to act as an interfering compound between viral spike-host ACE2 interactions. Communicated by Ramaswamy H. Sarma.

Discovery of potent inhibitors for SARS-CoV-2's main protease by ligand-based/structure-based virtual screening, MD simulations, and binding energy calculations.

COVID-19 has caused lockdowns all over the world in early 2020, as a global pandemic. Both theoretical and experimental efforts are seeking to find an effective treatment to suppress the virus. In silico drug design can play a vital role in identifying promising drug candidates against COVID-19. Herein, we focused on the main protease of SARS-CoV-2 that has crucial biological functions in the virus. We performed a ligand-based virtual screening followed by a docking screening for testing approved drugs and bioactive compounds listed in the DrugBank and ChEMBL databases. The top 8 docking results were advanced to all-atom MD simulations to study the relative stability of the protein-ligand interactions. MD simulations support that the catalytic residue, His41, has a neutral side chain with a protonated delta position. An absolute binding energy (ΔG) of -42 kJ mol-1 for the protein-ligand (Mpro-N3) complex has been calculated using the potential-of-mean-force (geometrical) approach. Furthermore, the relative binding energies were computed for the top docking results. Our results suggest several promising approved and bioactive inhibitors of SARS-CoV-2 Mpro as follows: a bioactive compound, ChEMBL275592, which has the best MM/GBSA binding energy; the second-best compound, montelukast, is an approved drug used in the treatment of asthma and allergic rhinitis; the third-best compound, ChEMBL288347, is a bioactive compound. Bromocriptine and saquinavir are other approved drugs that also demonstrate stability in the active site of Mpro, albeit their relative binding energies are low compared to the N3 inhibitor. This study provides useful insights into de novo protein design and novel inhibitor development, which could reduce the cost and time required for the discovery of a potent drug to combat SARS-CoV-2.

Molecular level investigation of curcumin self-assembly induced by trigonelline and nanoparticle formation.

Nanoparticle-facilitated drug delivery forms the core of medicine nowadays with the drug being delivered right at the target, reducing side effects and enhancing therapeutic value. Nanoparticles derived from natural compounds are further a point of focus being biocompatible and safe by and large. In this study, we have performed HF/6-31G calculations coupled with intermolecular interaction calculations and nanoscale molecular dynamics simulations to investigate self-assemblage in curcumin induced by trigonelline. Similar to recently reported self-assemblage in curcumin induced by sugar, trigonelline, a natural antidiabetic derived from fenugreek, can also induce auto-catalyzed self-assemblage in curcumin to form nanoparticles. It has been shown that these nanoparticles may be utilized for the delivery of drugs with severe side effects especially for diabetic patients with triple benefit of being antidiabetic, biocompatible and safe. As an example, carriage of antidiabetic drug pioglitazone and anticancer drug taxol have been depicted utilizing nanoparticles of curcumin and trigonelline. Twenty five taxol molecules could be comfortably carried in a 50 nm nanoparticle with an average overall root mean square deviation of 2.89 Å with reference to initial positions. For the first time, this study shows the possibility of developing antidiabetic nanoparticles with plethora of opportunities for diabetic patients. The study is expected to motivate experimental verification and has a long lasting impact in medicinal chemistry.

Screening for thyroid diseases among students of applied medical sciences at King Abdulaziz University, Saudi Arabia.

OBJECTIVES: To identify the occurrence rate of thyroid ultrasound abnormalities in asymptomatic subjects, and describe the features of detected nodules among university students. METHODS: The study is based on an observational research design that was conducted from April 2015 to May 2015. The study included 166 individuals, aged between 19 and 23 years. The subjects had their glands examined by ultrasound (US) scanning, using Philips ultrasound machine (5-12 MHz linear transducer). RESULTS: We recruited 90 (57.8%) females and 76 (42.2%) males without any indications of thyroid disease. Data estimated that 41 (24.7%) subjects had positive results on thyroid disease screening, 24 (70.6%) participants had solitary nodules, and 10 (29.4%) had multiple nodules. Thirty-four subjects revealed nodular presentation in the screening, among which 24 (70.6%) indicated solitary nodules and 10 (29.4%) had multiple nodules. Among 3 subjects, who indicated hypoechoic nodules, 2 (66.7%) underwent US-fine needle aspiration biopsy and received histological confirmation that they had papillary carcinomas. CONCLUSION: Ultrasonography is a useful and effective technique for screening thyroid related diseases, and can be utilized as a routine practice for general population screening.

Chemical fractionation of radium-226 in NORM contaminated soil from oilfields.

Contamination of soil with 226Ra is a common problem in the oilfields, leading to costly remediation and disposal programmes. The present study focuses on the chemical fractionation and mobility of 226Ra in contaminated soils collected from an oilfield using a three-step sequential extraction procedure (BCR). The total activity concentrations of 226Ra in contaminated soils were measured and found to be in the range from 1030 ± 90 to 7780 ± 530 Bq kg-1, with a mean activity concentration of 2840 ± 1840 Bq kg-1. The correlation between the total concentration of 226Ra and soil properties, mainly pH, LOI, Corg, clay and Ca, was investigated using the principal component analysis method (PCA). The chemical fractionation of 226Ra was studied using the sequential extraction method (BCR). The highest fraction of 226Ra (27-65%) was found to be in the acid-reducible fraction, which suggests that 226Ra is mainly bound to FeMn oxides. The BCR method showed that high percentages of 226Ra were found to be in mobile soil phases (between 45 and 99%). Consequently, groundwater contamination could occur due to the remobilization of 226Ra from soils under normal environmental conditions. However, the obtained results could be useful to reduce the volume of NORM wastes generated from the oilfields and decision-making process for final treatment and disposal of NORM-contaminated soil.

VKORC1 and CYP2C9 genotypes in Egyptian patients with warfarin resistance.

Warfarin is the most commonly prescribed anticoagulant drug; however, a narrow therapeutic range and a high risk of bleeding or stroke complicate its clinical use. Warfarin resistance was defined as prolonged warfarin requirements of more than 15 mg/day to achieve therapeutic anticoagulation or failure to achieve therapeutic anticoagulation with more than 20 mg/day. The resistance is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex (VKORC1) and cytochrome P450-2C9 (CYP2C9) genes, which affect warfarin pharmacodynamics and pharmacokinetics, respectively. Identification of the VKORC1 -1639 (A/G) and CYP2C9 (*1/*2/*3) allelic variants was performed using the PGX-Thrombo Strip in 41 patients with warfarin resistance compared with 30 patients with normal warfarin response out of 352 diagnosed cases of deep vein thrombosis. In warfarin-resistant patients, the VKORC1-1639 genotype frequencies were GG 0.756, GA 0.244 and AA 0.0, whereas in warfarin responder patients, they were: GG 0.333, GA 0.400 and AA 0.276 with P ≤ 0.001. The CYP2C9 genotype frequencies showed nonsignificant difference in both group of patients (P = 0.31). Our results suggest that the VKORC1-1639 GG and the wild type CYP2C9*1*1genotypes are associated with the high-dose requirement for warfarin therapy, and that VKORC1-1639 GG is responsible for warfarin resistance and failure in Egyptian patients.

Mechanical integrity of a carbon nanotube/copper-based through-silicon via for 3D integrated circuits: a multi-scale modeling approach.

Carbon nanotube (CNT)/copper (Cu) composite material is proposed to replace Cu-based through-silicon vias (TSVs) in micro-electronic packages. The proposed material is believed to offer extraordinary mechanical and electrical properties and the presence of CNTs in Cu is believed to overcome issues associated with miniaturization of Cu interconnects, such as electromigration. This study introduces a multi-scale modeling of the proposed TSV in order to evaluate its mechanical integrity under mechanical and thermo-mechanical loading conditions. Molecular dynamics (MD) simulation was used to determine CNT/Cu interface adhesion properties. A cohesive zone model (CZM) was found to be most appropriate to model the interface adhesion, and CZM parameters at the nanoscale were determined using MD simulation. CZM parameters were then used in the finite element analysis in order to understand the mechanical and thermo-mechanical behavior of composite TSV at micro-scale. From the results, CNT/Cu separation does not take place prior to plastic deformation of Cu in bending, and separation does not take place when standard thermal cycling is applied. Further investigation is recommended in order to alleviate the increased plastic deformation in Cu at the CNT/Cu interface in both loading conditions.

Transition from 2D conventional to 3d conformal radiation therapy in patients with brain gliomas: clinical outcome (Mansoura University).

BACKGROUND AND OBJECTIVES: Radiotherapy became an important component in the treatment of brain gliomas either high grade or low grade. This study was conducted to evaluate the efficacy and safety of the three-dimensional conformal radiotherapy and compare this results with two-dimensional conventional radiotherapy in patients with brain gliomas. PATIENTS AND METHODS: Sixty patients with histologically proven brain gliomas between November 2007 and december 2009, were enrolled in this study. They were 25 with low grade and 35 with high grade, treated in our department according to a three-dimensional conformal radiotherapy; patients received a total irradiation dose of 54-60 GY, 2 GY/day, 5 days/week, were enrolled prospectively (arm I). The patients under study were compared to 120 patients (44 low grade and 76 high grade) who received irradiation with 2 D-conventional radiotherapy and were served as a retrospective study (arm II). The overall survival and progression free survival times were estimated using Kaplan-Meier method and the prognostic factors were analyzed with log-rank test. Acute and late toxicity evaluated using the Swog Scoring. RESULTS: During the follow-up period (median 12.5 months ranged 8-24 months) the median overall survival and progression free survival times were 14 and 6 months respectively. There was no statistically significant differences as regard survival between both arms. In univariate analysis, age, grade of the tumors and type of surgery were important prognostic factorsr. Regarding late complication of radiotherapy, there were significant differences in MRI encephalomalcia between both groups (30%Vs. 69.2%) in arm I and arm II respectively. CONCLUSION: Concerning the tumor control and survival rate, the three-dimensional treatment planning shows no advantages compared to the standard two dimensional conventional methods. The main advantage of the 3-DCRT is the possibility to spare normal brain tissue.

Unusual vascular access for hemodialysis: transposed venae comitante of the brachial artery.

The National Kidney Foundation Dialysis Outcomes Quality Initiative guidelines favor autogenous vein for arteriovenous fistulas. This report describes our technique and results of arteriovenous fistulas between brachial artery and its transposed venae comitantes. The procedure was done in two stages, first anastomosis between brachial artery at the elbow and one of its venae comitantes and, 1 month later, transposition of the vein to a subcutaneous tunnel. The study included 21 patients (15 males, six females), nine of whom were diabetic, with a mean age of 53 years. The cumulative primary patency rate was (75.89%) at 1 year and (55.34%) at 2 years. Complications developed in 11/21 fistulas, including thrombosis, infection, aneurysm formation, and nonmaturation of the vein. Brachial artery to its transposed venae comitante fistula is an alternative access which can be used as a tertiary autogenous access.

Primary gastric lymphoma: a clinicopathologic study.

BACKGROUND/AIMS: This study aims to define the clinicopathologic criteria of primary gastric lymphoma in view of MALT concept and to present the outcome after different treatment modalities. METHODOLOGY: Seventy-six cases of primary gastric lymphoma treated between January 1980 and December 2001 were reviewed. All tissue specimens (endoscopic or surgically resected) were re-examined. Tumors were staged according to Ann Arbor staging system and the Musshoff modification (IE in 30.3%, IIE in 39.4% and IIIE in 30.3%). Sixty patients underwent gastrectomy (partial or total) with postoperative chemotherapy for 32 patients. Sixteen patients were treated by chemotherapy only. The mean follow-up period was 15 years (range, 6 months to 21 years). RESULTS: Primary gastric lymphoma represented 69.1% of cases of gastrointestinal lymphoma and 16.2% of all gastric malignancy. The mean age was 45 years and male to female ratio was 2.3:1. Epigastric pain was the commonest symptom (in 88.2%). Ulcer-like lesions were the commonest (65.8%) and the most commonly involved site was the lower third (48.7%). The resectability rate was 80%. The operative mortality rate was 2.7%. Another 2 cases died after partial gastrectomy and chemotherapy. Four cases in the chemotherapy group (25%) died. Tumor recurrence occurred in 4 cases (out of 32) after gastrectomy and chemotherapy (12.5%), 2 of them died and 2 were cured by chemotherapy. The mean overall survival was 18.49 years, survival was 20.28 years after gastrectomy, 15.48 years after gastrectomy with chemotherapy and 5.76 years after chemotherapy (p=0.0056). CONCLUSIONS: Primary gastric lymphoma is not an uncommon tumor. Gastritis-like lesions are rare. If the tumor is resectable, gastrectomy will provide the most accurate means of diagnosis, staging and locoregional control of the disease.

A highly efficient photochemical bromination as a new method for preparation of mono, bis and fused pyrazole derivatives.

N-Bromosuccinimide (NBS) was found to afford photochemical bromination of N-substituted 3-methyl-2-pyrazolin-5-one in chloroform solution. The nature of the products formed was found to be highly dependent on the photolysis time and on the type of N-substituted 3-methyl-2-pyrazolin-5-one. The reaction of substituted 2-pyrazolin-5-ones with NBS in the absence of light yielded in all cases a mixture of N-substituted 3-methyl-4-bromo- (and -4,4-dibromo-) 2-pyrazolin-5-ones. The mechanism of photobromination was illustrated. Separation of all of the products was achieved using column chromatography. The chemical structure of all of the products was assigned by elemental analysis, IR, 1H NMR and GC-MS measurements.