Search results for: Salah Jellali
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 173

Search results for: Salah Jellali

23 Shear Behavior of Reinforced Concrete Beams Casted with Recycled Coarse Aggregate

Authors: Salah A. Aly, Mohammed A. Ibrahim, Mostafa M. khttab

Abstract:

The amount of construction and demolition (C&D) waste has increased considerably over the last few decades. From the viewpoint of environmental preservation and effective utilization of resources, crushing C&D concrete waste to produce coarse aggregate (CA) with different replacement percentage for the production of new concrete is one common means for achieving a more environment-friendly concrete. In the study presented herein, the investigation was conducted in two phases. In the first phase, the selection of the materials was carried out and the physical, mechanical and chemical characteristics of these materials were evaluated. Different concrete mixes were designed. The investigation parameter was Recycled Concrete Aggregate (RCA) ratios. The mechanical properties of all mixes were evaluated based on compressive strength and workability results. Accordingly, two mixes have been chosen to be used in the next phase. In the second phase, the study of the structural behavior of the concrete beams was developed. Sixteen beams were casted to investigate the effect of RCA ratios, the shear span to depth ratios and the effect of different locations and reinforcement of openings on the shear behavior of the tested specimens. All these beams were designed to fail in shear. Test results of the compressive strength of concrete indicated that, replacement of natural aggregate by up to 50% recycled concrete aggregates in mixtures with 350 Kg/m3 cement content led to increase of concrete compressive strength. Moreover, the tensile strength and the modulus of elasticity of the specimens with RCA have very close values to those with natural aggregates. The ultimate shear strength of beams with RCA is very close to those with natural aggregates indicating the possibility of using RCA as partial replacement to produce structural concrete elements. The validity of both the Egyptian Code for the design and implementation of Concrete Structures (ECCS) 203-2007 and American Concrete Institute (ACI) 318-2011Codes for estimating the shear strength of the tested RCA beams was investigated. It was found that the codes procedures gives conservative estimates for shear strength.

Keywords: construction and demolition (C&D) waste, coarse aggregate (CA), recycled coarse aggregates (RCA), opening

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22 Borderline Ovarian Tumor: Management of Recurrence After Conservative Surgical Treatment

Authors: Ghorbeli Eya, Naija Lamia, Khessairi Nayssem, Saadallah Fatma, Slimane Maher, Tarek Ben Dhiab

Abstract:

INTRODUCTION: Borderline ovarian tumors account for 15 to 20% of ovarian tumors. Prognostic factors of recurrence include the stage of the disease, presence of peritoneal implants, micropapillary pattern, microinvasion and intra-epithelial carcinoma. Fertility sparing constitutes a major therapeutic issue in young patients that leads to conservative surgical treatment in specific cases. METHODS: We conducted a retrospective descriptive study including patients treated at the Salah Azaiez Institute for Borderline Ovarian Tumor who underwent conservative surgical treatment from 2003 to 2018. RESULTS: Nine patients were included in our study. The median age was 33 years. Three patients were nulliparous. Given the age, conservative treatment was indicated in all these patients. Cystectomy without ovariectomy was indicated in 5 of the 9 women, which was within the margin of tumor resection on definitive anatomopathic examination in 3 of the 5 women. In contrast, given the impossibility of ovarian conservation, total annexectomy was carried out in 4 of all these women. All of the patients were followed regularly postoperatively; three had a carcinomatous transformation as an ovarian adenocarcinoma at an average interval of 18 months. Among these three patients, a single one presented intra-peritoneal metastases, requiring radical surgical treatment and adjuvant chemotherapy with 6 cures of Carbo-Taxol, with a good tolerance and a complete response. Moreover, one patient had a recurrence on the contralateral ovary as a Borderline mucinous ovarian tumor. For the remaining four women, after a median follow-up of 35 months, one patient fell spontaneously pregnant during follow-up, and three patients were in complete remission at 16 months. CONCLUSION: Borderline tumors of the ovary usually occur in young patients, which makes conservative treatment advisable if possible, but this always comes with a risk of recurrence and/or carcinomatous transformation, especially if the conservative surgical procedure was a cystectomy instead of a total annexectomy, and even more so if the resection margins were tumoral.

Keywords: ovarian tumor, conservative treatment, surgical management, borderline ovarian tumor, recurrence management

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21 Cannabis Sativa L as Natural Source of Promising Anti-Alzheimer Drug Candidates: A Comprehensive Computational Approach Including Molecular Docking, Molecular Dynamics, Admet and MM-PBSA Studies

Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

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20 Management of Severe Asthma with Omalizumab in United Arab Emirates

Authors: Shanza Akram, Samir Salah, Imran Saleem, Jassim Abdou, Ashraf Al Zaabi

Abstract:

Estimated prevalence of asthma in UAE is around 10% (900,000 people). Patients with persistent symptoms despite using high dose ICS plus a second controller +/- Oral steroids are considered to have severe asthma. Omalizumab (Xolair) is an anti-IgE monoclonal antibody approved as add-on therapy for severe allergic asthma. The objective of our study was to obtain baseline characteristics of our local cohort, to determine the efficacy of omalizumab based on clinical outcomes pre and post 52 weeks of treatment and to assess safety and tolerability. Medical records of patients receiving omalizumab therapy for asthma at Zayed Military Hospital, Abu Dhabi were retrospectively reviewed. Patients fulfilling the criteria for severe allergic asthma as per GINA guidelines were included. Asthma control over 12 months pre and post omalizumab were analyzed by taking into account the number of exacerbations, hospitalizations, maintenance of medication dosages, the need for reliever therapy and PFT’s. 21 patients (5 females) with mean age 41 years were included. The mean duration of therapy was 22 months. 19 (91%) patients had Allergic Rhinitis/Sinusitis. Mean serum total IgE level was 648 IU/ml (65-1859). 11 (52%) patients were on oral maintenance steroids pre-treatment. 7 patients managed to stop steroids on treatment while 4 were able to decrease the dosage. Mean exacerbation rate decreased from 5 per year pre-treatment to 1.36 while on treatment. The number of hospitalizations decreased from a mean of 2 per year to 0.9 per year. Reliever inhaler usage decreased from mean of 40 to 15 puffs per week.2 patients discontinued therapy, 1 due to lack of benefit (2 doses) and 2nd due to severe persistent side effects. Patient compliance was poor in some cases. Treatment with omalizumab reduced the number of exacerbations, hospitalizations, maintenance and reliever medications, and is generally well tolerated. Our results show that there is room for improved documentation in terms of symptom recording and use of rescue medication at our institution. There is also need for better patient education and counseling in order to improve compliance.

Keywords: asthma, exacerbations, omalizumab, IgE

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19 Cannabis Sativa L as Natural Source of Promising Anti-Alzheimer Drug Candidates: A Comprehensive Computational Approach Including Molecular Docking, Molecular Dynamics, ADMET and MM-PBSA Studies

Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

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18 Omalizumab Therapy Experience for Asthma, at Zayed Military Hospital (ZMH) in United Arab Emirates

Authors: Shanza Akram, Samir Salah, Imran Saleem, Ashraf Alzaabi, Jassim Abdou

Abstract:

Introduction: 300 million people worldwide are affected by asthma .In UAE, prevalence is around 10% (900,000 people).Patients with persistent symptoms despite using high dose ICS plus a second controller +/- OCS are considered to have severe asthma. Omalizumab (Xolaire) an IgE monoclonal antibody is approved as add on therapy for severe allergic asthma. Objective: To determine the efficacy of omalizumab based on clinical outcomes in our cohort of patient pre and post 52 weeks of treatment to assess safety and tolerability of treatment. Methods: Medical records of patients receiving omalizumab therapy for asthma at ZMH ,Abu Dhabi were retrospectively analyzed.Patients fulfilling the criteria of severe allergic asthma as per GINA guidelines were included. Asthma control over 12 months prior to and 12 months after commencement of omalizumab therapy was analysed by taking into account the number of exacerbations and hospitalizations in addition to maintenance of medication dosages, need for rescue reliever therapy and pulmonary function testing. Results: Total cohort of 21 patient (5 females), average age 41 years and av length of therapy 22 months were included. Seven patients (total 11/52%) managed to stop steroids on treatment while four were able to decrease the dosage. Mean exacerbation rate decreased from five/ year pre treatment to 1.36 while on treatment. Number of hospitalizations decreased from mean of two per year to 0.9 per year. Rescue reliever inhaler usage decreased from mean of 40 puffs to 15 puffs per week. 2 patients discontinued therapy, 1 due to lack of benefit (2 doses) and 2nd due to severe persistent side effects including local irritation, severe limb and joint pains after 6 months. Conclusion: Treatment with omalizumab showed effect in terms of reduced number of exacerbations, maintenance therapy and reliever medications. However, no improvement was seen in PFTs.There is room for improved documentation in terms of symptom recording and use of rescue medicationas as well as for better patient education and counselling in order to improve compliance.

Keywords: asthma, omalizumab, severe allergic asthma, UAE

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17 Ability of Bentonite-lactobacillus Rhamnosus GAF06 Mixture to Mitigate Aflatoxin M1 Damages in Balb/C Mice

Authors: Amina Aloui, Jalila Ben Salah-Abbès, Abdellah Zinedine, Amar Riba, Noel Durand, Catherine Brabet, Didier Montet, Samir Abbès

Abstract:

Mycotoxin contamination of food and feed-isa globaconcern, both economically and for public health. Aflatoxin M1 (AFM1) is the principal hydroxylated metabolite of aflatoxin B1. It is frequently found in milk and other dairy products. It is responsible for the development of hepatocellular carcinoma and immunotoxic in humans and animals. The reduction of its bioavailabilitybecomesa great demand in order to protect human and animal health. The use of probiotic bacteria and clay are demonstrated to be able to bind AFM1 in vitro. This study aimed to investigate, in vivo, the activity of two-component mixture: L. rhamnosusGAF06 (LR) and bentonite for reducing the oxidative stress and the histological alterationsinduced by AFM1 in the liver andkidneys. For the experiment, male mice were divided into 7 groups (6 mice/group) and treated, orally, by AFM1, alone or in combination with LR and/or bentonite, for 10 days as follows: group 1 control, group 2 treated with LR alone (2.108 CFU/ml), group 3 treated with bentonite alone (1g/kg), group 4 treated with AFM1 alone (100μg/kg), group 5 co-treated with LR+AFM1, group 6 co-treated with bentonite+AFM1, group 7 co-treated with bentonite+LR+AFM1. At the end of the treatment, the mice were sacrificed, and the livers and kidneys were collected for histological assays. Intracellular antioxidant activities and lipid peroxidation were also studied. The results showed that AFM1causeddamage in liver and kidney tissues, being evidence of hepatotoxicity and nephrotoxicity marked by necrotic cells. It increased the MDA level and decreased the antioxidant enzyme activities (SOD) in both organs. In contrast, the co-treatment with AFM1 plus LR and/or bentonitesignificantly improved the hepatic and renal tissues, regulated kidney, and liver antioxidant enzyme activities. This improvement was more remarkable with the administration of LR-bentonite mixture with AFM1.LR and bentonite alone showed to be safe during the treatment. This mixture can be a promising candidate for future applications in biotechnological processes that aimed to detoxify AFM1in food and feed.

Keywords: aflatoxin M1, bentonite, L. rhamnosus GAF06, oxidative stress, prevention

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16 Importance of Insect Crop Pests in the Diet of the Cattle Egret Bubulcus Ibis (Linnaeus, 1758)

Authors: Rachida Gherbi-Salmi, Abdelkarim Si Bachir, Salah Eddine Doumandji

Abstract:

The Cattle Egret is a predatory bird with an insectivorous diet. It feeds in open environments (wetlands, meadows, farmland and cultivated land). Few studies have determined the status of its prey (useful or harmful species for agriculture). Hence, our study was carried out in the Bejaia region (Algeria). It consisted of examining adult rejection pellets collected in a heronry located in the lower Soummam Valley (El-Kseur), which has been a permanent habitat for over 30 years. Field sampling was carried out during the juvenile rearing period in 1998 (wet spring) and 2020 (almost dry spring). Examination of 50 pellets at a rate of 10 per month (May - September) in 1998 revealed the presence of 2,661 prey belonging to 170 species, i.e., an average of 53.36 prey per pellet. The results reveal that the diet of this Ardeidae consists mainly of Insecta (95.09%). Arachnida was a distant second (4.05%). Vertebrates (Reptilia and Rodentia) (0.82%) and myriapods (0.04%) are rare prey. We counted 2,154 plant pests (80.27%), of which 2,138 were insects (99.27%) and 0.73% rodents (Mus spretus). Of the plant-pest insects identified, 1385 were Orthoptera (64.78%). Fourmicidae came second (13.05%), and Coleoptera third (12.82%). Dermaptera, on the other hand, accounted for only 7.86%. Analysis of 30 rejection pellets, 10 per month (May - July) in 2020, identified 1,330 prey belonging to 80 species, an average of 44.33 prey per pellet. The results reveal that its diet is essentially made up of Insecta (94.81%). These are followed by Vertebrata (3.01%) and Arachnida (2.18%). We counted 1156 plant pests (86.82%), of which 86.02% are Insecta. Orthoptera are the most frequent (45.72%). They are followed by Dermaptera (33.74%) and Coleoptera (18.44%). The present study highlighted the importance of plant pests consumed by the Cattle Egret (80.27% in 1998 and 86.82% in 2020), which are far more numerous and diverse than auxiliary prey and pollinators. This confirms the bird's status as a biological control agent in the lower Soummam valley. It is, therefore, worth pointing out that this species deserves to be protected.

Keywords: bubulcus ibis, diet, lower soummam valley, insect crop pests

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15 Mineralogy and Fluid Inclusion Study of the Kebbouch South Pb-Zn Deposit, Northwest Tunisia

Authors: Imen Salhi, Salah Bouhlel, Bernrd Lehmann

Abstract:

The Kebbouch South Pb-Zn deposit is located 20 km to the east of El Kef (NW) in the southeastern part of the Triassic diapir belt in the Tunisian Atlas. The deposit is composed of sulfide and non-sulfide zinc-lead ore bodies. The aim of this study is to provide petrographic results, mineralogy, as well as fluid inclusion data of the carbonate-hosted Pb-Zn Kebbouch South deposit. Mineralization forms two major ore types: (1) lenticular dolostones and clay breccias in the contact zone between Triassic and Upper Cretaceous strata;, it consists of small-scale lenticular, strata-or fault-controlled mineralization mainly composed of marcasite, galena, sphalerite, pyrite, and (2) stratiform mineralization in the Bahloul Formation (Upper Cenomanian-Lower Turonian) consisting of framboidal and cubic pyrite, disseminated sphalerite and galena. Non-metalliferous and/or gangue minerals are represented by dolomite, calcite, celestite and quartz. Fluid inclusion petrography study has been carried out on calcite and celestite. Fluid inclusions hosted in celestite are less than 20 µm large and show two types of aqueous inclusions: monophase liquid aqueous inclusions (L), abundant and very small, generally less than 15 µm and liquid-rich two phase inclusions (L+V). The gas phase forms a mobile vapor bubble. Microthermometric analyses of (L+V) fluid inclusions for celestite indicate that the homogenization temperature ranges from 121 to 156°C, and final ice melting temperatures are in the range of – 19 to -9°C corresponding to salinities of 12 to 21 wt% NaCl eq. (L+V) fluid inclusions from calcite are frequently localized along the growth zones; their homogenization temperature ranges from 96 to 164°C with final ice melting temperatures between -16 and -7°C corresponding to salinities of 9 to 19 wt% NaCl eq. According to mineralogical and fluid inclusion studies, mineralization in the Pb – Zn Kebbouch South deposit formed between 96 to 164°C with salinities ranging from 9 to 21 wt% NaCl eq. A contribution of basinal brines in the ore formation of the kebbouch South Pb–Zn deposit is likely. The deposit is part of the family of MVT deposits associated with the salt diapir environment.

Keywords: fluid inclusion, Kebbouch South, mineralogy, MVT deposits, Pb-Zn

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14 Biodegradable Polymeric Vesicles Containing Magnetic Nanoparticles, Quantum Dots and Anticancer Drugs for Drug Delivery and Imaging

Authors: Fei Ye, Åsa Barrefelt, Manuchehr Abedi-Valugerdi, Khalid M. Abu-Salah, Salman A. Alrokayan, Mamoun Muhammed, Moustapha Hassan

Abstract:

With appropriate encapsulation in functional nanoparticles drugs are more stable in physiological environment and the kinetics of the drug can be more carefully controlled and monitored. Furthermore, targeted drug delivery can be developed to improve chemotherapy in cancer treatment, not only by enhancing intracellular uptake by target cells but also by reducing the adverse effects in non-target organs. Inorganic imaging agents, delivered together with anti-cancer drugs, enhance the local imaging contrast and provide precise diagnosis as well as evaluation of therapy efficacy. We have developed biodegradable polymeric vesicles as a nanocarrier system for multimodal bio-imaging and anticancer drug delivery. The poly (lactic-co-glycolic acid) PLGA) vesicles were fabricated by encapsulating inorganic imaging agents of superparamagnetic iron oxide nanoparticles (SPION), manganese-doped zinc sulfide (MN:ZnS) quantum dots (QDs) and the anticancer drug busulfan into PLGA nanoparticles via an emulsion-evaporation method. T2-weighted magnetic resonance imaging (MRI) of PLGA-SPION-Mn:ZnS phantoms exhibited enhanced negative contrast with r2 relaxivity of approximately 523 s-1 mM-1 Fe. Murine macrophage (J774A) cellular uptake of PLGA vesicles started fluorescence imaging at 2 h and reached maximum intensity at 24 h incubation. The drug delivery ability PLGA vesicles was demonstrated in vitro by release of busulfan. PLGA vesicles degradation was studied in vitro, showing that approximately 32% was degraded into lactic and glycolic acid over a period of 5 weeks. The biodistribution of PLGA vesicles was investigated in vivo by MRI in a rat model. Change of contrast in the liver could be visualized by MRI after 7 min and maximal signal loss detected after 4 h post-injection of PLGA vesicles. Histological studies showed that the presence of PLGA vesicles in organs was shifted from the lungs to the liver and spleen over time.

Keywords: biodegradable polymers, multifunctional nanoparticles, quantum dots, anticancer drugs

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13 Contribution of Artificial Intelligence in the Studies of Natural Compounds Against SARS-COV-2

Authors: Salah Belaidi

Abstract:

We have carried out extensive and in-depth research to search for bioactive compounds based on Algerian plants. A selection of 50 ligands from Algerian medicinal plants. Several compounds used in herbal medicine have been drawn using Marvin Sketch software. We determined the three-dimensional structures of the ligands with the MMFF94 force field in order to prepare these ligands for molecular docking. The 3D protein structure of the SARS-CoV-2 main protease was taken from the Protein Data Bank. We used AutoDockVina software to apply molecular docking. The hydrogen atoms were added during the molecular docking process, and all the twist bonds of the ligands were added using the (ligand) module in the AutoDock software. The COVID-19 main protease (Mpro) is a key enzyme that plays a vital role in viral transcription and mediating replication, so it is a very attractive drug target for SARS-CoV-2. In this work, an evaluation was carried out on the biologically active compounds present in these selected medicinal plants as effective inhibitors of the protease enzyme of COVID-19, with an in-depth computational calculation of the molecular docking using the Autodock Vina software. The top 7 ligands: Phloroglucinol, Afzelin, Myricetin-3-O- rutinosidTricin 7-neohesperidoside, Silybin, Silychristinthat and Kaempferol are selected among the 50 molecules studied which are Algerian medicinal plants, whose selection is based on the best binding energy which is relatively low compared to the reference molecule with binding affinities of -9.3, -9.3, -9, -8.9, -8 .5, 8.3 and -8.3 kcal mol-1 respectively. Then, we analyzed the ADME properties of the best7 ligands using the web server SwissADME. Two ligands (Silybin, Silychristin) were found to be potential candidates for the discovery and design of novel drug inhibitors of the protease enzyme of SARS-CoV-2. The stability of the two ligands in complexing with the Mpro protease was validated by molecular dynamics simulation; they revealed a stable trajectory in both techniques, RMSD and RMSF, by showing molecular properties with coherent interactions in molecular dynamics simulations. Finally, we conclude that the Silybin ligand forms a more stable complex with the Mpro protease compared to the Silychristin ligand.

Keywords: COVID-19, medicinal plants, molecular docking, ADME properties, molecular dynamics

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12 Computational Approach to Cyclin-Dependent Kinase 2 Inhibitors Design and Analysis: Merging Quantitative Structure-Activity Relationship, Absorption, Distribution, Metabolism, Excretion, and Toxicity, Molecular Docking, and Molecular Dynamics Simulations

Authors: Mohamed Moussaoui, Mouna Baassi, Soukayna Baammi, Hatim Soufi, Mohammed Salah, Rachid Daoud, Achraf EL Allali, Mohammed Elalaoui Belghiti, Said Belaaouad

Abstract:

The present study aims to investigate the quantitative structure-activity relationship (QSAR) of a series of Thiazole derivatives reported as anticancer agents (hepatocellular carcinoma), using principally the electronic descriptors calculated by the density functional theory (DFT) method and by applying the multiple linear regression method. The developed model showed good statistical parameters (R²= 0.725, R²ₐ𝒹ⱼ= 0.653, MSE = 0.060, R²ₜₑₛₜ= 0.827, Q²𝒸ᵥ = 0.536). The energy of the highest occupied molecular orbital (EHOMO) orbital, electronic energy (TE), shape coefficient (I), number of rotatable bonds (NROT), and index of refraction (n) were revealed to be the main descriptors influencing the anti-cancer activity. Additional Thiazole derivatives were then designed and their activities and pharmacokinetic properties were predicted using the validated QSAR model. These designed molecules underwent evaluation through molecular docking (MD) and molecular dynamic (MD) simulations, with binding affinity calculated using the MMPBSA script according to a 100 ns simulation trajectory. This process aimed to study both their affinity and stability towards Cyclin-Dependent Kinase 2 (CDK2), a target protein for cancer disease treatment. The research concluded by identifying four CDK2 inhibitors - A1, A3, A5, and A6 - displaying satisfactory pharmacokinetic properties. MDs results indicated that the designed compound A5 remained stable in the active center of the CDK2 protein, suggesting its potential as an effective inhibitor for the treatment of hepatocellular carcinoma. The findings of this study could contribute significantly to the development of effective CDK2 inhibitors.

Keywords: QSAR, ADMET, Thiazole, anticancer, molecular docking, molecular dynamic simulations, MMPBSA calculation

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11 Clinical Outcomes of Toric Implantable Collamer Lens (T-ICL) and Toric Implantable Phakic Contact Lens (IPCL) for Correction of High Myopia with Astigmatism: Comparative Study

Authors: Mohamed Salah El-Din Mahmoud, Heba Radi Atta Allah

Abstract:

Background: Our study assesses the safety profile and efficacy of toric Implantable Collamer Lens (T-ICL) and toric implantable phakic contact lens (IPCL) for the correction of high myopia with astigmatism. Methods: A prospective interventional randomized comparative study included 60 myopic eyes divided into 2 groups, group A including 30 eyes that were implanted with T-ICL, and group B including 30 eyes that were implanted with toric IPCL. The refractive results, visual acuity, corneal endothelial cell count, and intraocular pressure (IOP) were evaluated at baseline and at 1, 6, and 9 months post-surgery. Any complications either during or after surgery were assessed. Results: A significant reduction in both spherical and cylindrical refractive errors with good predictability was reported in both groups compared with preoperative values. Regarding the predictability, In T-ICL group (A), the median spherical and cylindrical errors were significantly improved from (-10 D & -4.5 D) pre-operatively to (-0.25 D & - 0.3 D) at the end of 9 months follow up period. Similarly, in the toric IPCL group (B), the median spherical and cylindrical errors were significantly improved from (-11 D & -4.5 D) pre-operatively to (-0.25 D & - 0.3 D) at the end of 9 months follow up period. A statistically significant improvement of UCDVA at 9 months postoperatively was found in both groups, as median preoperative Log Mar UCDVA was 1.1 and 1.3 in groups A and B respectively, which was significantly improved to 0.2 in both groups at the end of follow-up period. Regarding IOP, no significant difference was found between both groups, either pre-operatively or during the postoperative period. Regarding the endothelial count, no significant differences were found during the pre-operative and postoperative follow-up periods between the two groups. Fortunately, no intra or postoperative complications as cataract, keratitis or lens decentration had occurred. Conclusions: Toric IPCL is a suitable alternative to T-ICL for the management of high myopia with astigmatism, especially in developing countries, as it is cheaper and easier for implantation than T-ICL. However, data over longer follow-up periods are needed to confirm its safety and stability.

Keywords: T-ICL, Toric IPCL, IOP, corneal endothelium

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10 An Overview of the Porosity Classification in Carbonate Reservoirs and Their Challenges: An Example of Macro-Microporosity Classification from Offshore Miocene Carbonate in Central Luconia, Malaysia

Authors: Hammad T. Janjuhah, Josep Sanjuan, Mohamed K. Salah

Abstract:

Biological and chemical activities in carbonates are responsible for the complexity of the pore system. Primary porosity is generally of natural origin while secondary porosity is subject to chemical reactivity through diagenetic processes. To understand the integrated part of hydrocarbon exploration, it is necessary to understand the carbonate pore system. However, the current porosity classification scheme is limited to adequately predict the petrophysical properties of different reservoirs having various origins and depositional environments. Rock classification provides a descriptive method for explaining the lithofacies but makes no significant contribution to the application of porosity and permeability (poro-perm) correlation. The Central Luconia carbonate system (Malaysia) represents a good example of pore complexity (in terms of nature and origin) mainly related to diagenetic processes which have altered the original reservoir. For quantitative analysis, 32 high-resolution images of each thin section were taken using transmitted light microscopy. The quantification of grains, matrix, cement, and macroporosity (pore types) was achieved using a petrographic analysis of thin sections and FESEM images. The point counting technique was used to estimate the amount of macroporosity from thin section, which was then subtracted from the total porosity to derive the microporosity. The quantitative observation of thin sections revealed that the mouldic porosity (macroporosity) is the dominant porosity type present, whereas the microporosity seems to correspond to a sum of 40 to 50% of the total porosity. It has been proven that these Miocene carbonates contain a significant amount of microporosity, which significantly complicates the estimation and production of hydrocarbons. Neglecting its impact can increase uncertainty about estimating hydrocarbon reserves. Due to the diversity of geological parameters, the application of existing porosity classifications does not allow a better understanding of the poro-perm relationship. However, the classification can be improved by including the pore types and pore structures where they can be divided into macro- and microporosity. Such studies of microporosity identification/classification represent now a major concern in limestone reservoirs around the world.

Keywords: overview of porosity classification, reservoir characterization, microporosity, carbonate reservoir

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9 Phosphate Tailings in View of a Better Waste Disposal And/or Valorization: Case of Tunisian Phosphates Mines

Authors: Mouna Ettoumi, Jouini Marouen, Carmen Mihaela Neculita, Salah Bouhlel, Lucie Coudert, Mostafa Benzaazoua, Y. Taha

Abstract:

In the context of sustainable development and circular economy, waste valorization is considered a promising alternative to overcome issues related to their disposal or elimination. The aim of this study is to evaluate the potential use of phosphate sludges (tailings) from the Kef Shfeir mine site (Gafsa, Tunisia) as an alternative material in the production of fired bricks. To do so, representative samples of raw phosphate treatment sludges were collected and characterized for their physical, chemical, mineralogical and environmental characteristics. Then, the raw materials were baked at different temperatures (900°C, 1000°C, and 1100°C) for bricks making. Afterward, fired bricks were characterized for their physical (particle size distribution, density, and plasticity), chemical (XRF and digestion), mineralogical (XRD) and mechanical (flexural strength) properties as well as for their environmental behavior (TCLP, SPLP, and CTEU-9) to ensure whether they meet the required construction standards. Results showed that the raw materials had low density (2.47g/cm 3), were non-plastic and were mainly composed of fluoroapatite (15.6%), calcite (23.1%) and clays (22.2% - mainly as heulandite, vermiculite and palygorskite). With respect to the environmental behavior, all metals (e.g., Pb, Zn, As, Cr, Ba, Cd) complied with the requirements set by the USEPA. In addition, fired bricks had varying porosity (9-13%), firing shrinking (5.2-7.5%), water absorption (12.5-17.2%) and flexural strength (3.86-13.4 MPa). Noteworthy, an improvement in the properties (porosity, firing shrinking, water absorption, and flexural strength) of manufactured fired bricks was observed with the increase of firing temperature from 900 to 1100°C. All the measured properties complied with the construction norms and requirements. Moreover, regardless of the firing temperature, the environmental behavior of metals obeyed the requirements of the USEPA standards. Finally, fired bricks could be produced at high temperatures (1000°C) based on 100% of phosphate sludge without any substitution or addition of either chemical agents or binders. This sustainable brick-making process could be a promising approach for the Phosphate Company to partially manage these wastes, which are considered “non-profitable” for the moment and preserve soils that are exploited presently.

Keywords: phosphate treatment sludge, mine waste, backed bricks, waste valorization

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8 Methodological Deficiencies in Knowledge Representation Conceptual Theories of Artificial Intelligence

Authors: Nasser Salah Eldin Mohammed Salih Shebka

Abstract:

Current problematic issues in AI fields are mainly due to those of knowledge representation conceptual theories, which in turn reflected on the entire scope of cognitive sciences. Knowledge representation methods and tools are driven from theoretical concepts regarding human scientific perception of the conception, nature, and process of knowledge acquisition, knowledge engineering and knowledge generation. And although, these theoretical conceptions were themselves driven from the study of the human knowledge representation process and related theories; some essential factors were overlooked or underestimated, thus causing critical methodological deficiencies in the conceptual theories of human knowledge and knowledge representation conceptions. The evaluation criteria of human cumulative knowledge from the perspectives of nature and theoretical aspects of knowledge representation conceptions are affected greatly by the very materialistic nature of cognitive sciences. This nature caused what we define as methodological deficiencies in the nature of theoretical aspects of knowledge representation concepts in AI. These methodological deficiencies are not confined to applications of knowledge representation theories throughout AI fields, but also exceeds to cover the scientific nature of cognitive sciences. The methodological deficiencies we investigated in our work are: - The Segregation between cognitive abilities in knowledge driven models.- Insufficiency of the two-value logic used to represent knowledge particularly on machine language level in relation to the problematic issues of semantics and meaning theories. - Deficient consideration of the parameters of (existence) and (time) in the structure of knowledge. The latter requires that we present a more detailed introduction of the manner in which the meanings of Existence and Time are to be considered in the structure of knowledge. This doesn’t imply that it’s easy to apply in structures of knowledge representation systems, but outlining a deficiency caused by the absence of such essential parameters, can be considered as an attempt to redefine knowledge representation conceptual approaches, or if proven impossible; constructs a perspective on the possibility of simulating human cognition on machines. Furthermore, a redirection of the aforementioned expressions is required in order to formulate the exact meaning under discussion. This redirection of meaning alters the role of Existence and time factors to the Frame Work Environment of knowledge structure; and therefore; knowledge representation conceptual theories. Findings of our work indicate the necessity to differentiate between two comparative concepts when addressing the relation between existence and time parameters, and between that of the structure of human knowledge. The topics presented throughout the paper can also be viewed as an evaluation criterion to determine AI’s capability to achieve its ultimate objectives. Ultimately, we argue some of the implications of our findings that suggests that; although scientific progress may have not reached its peak, or that human scientific evolution has reached a point where it’s not possible to discover evolutionary facts about the human Brain and detailed descriptions of how it represents knowledge, but it simply implies that; unless these methodological deficiencies are properly addressed; the future of AI’s qualitative progress remains questionable.

Keywords: cognitive sciences, knowledge representation, ontological reasoning, temporal logic

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7 Predicting Provider Service Time in Outpatient Clinics Using Artificial Intelligence-Based Models

Authors: Haya Salah, Srinivas Sharan

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Healthcare facilities use appointment systems to schedule their appointments and to manage access to their medical services. With the growing demand for outpatient care, it is now imperative to manage physician's time effectively. However, high variation in consultation duration affects the clinical scheduler's ability to estimate the appointment duration and allocate provider time appropriately. Underestimating consultation times can lead to physician's burnout, misdiagnosis, and patient dissatisfaction. On the other hand, appointment durations that are longer than required lead to doctor idle time and fewer patient visits. Therefore, a good estimation of consultation duration has the potential to improve timely access to care, resource utilization, quality of care, and patient satisfaction. Although the literature on factors influencing consultation length abound, little work has done to predict it using based data-driven approaches. Therefore, this study aims to predict consultation duration using supervised machine learning algorithms (ML), which predicts an outcome variable (e.g., consultation) based on potential features that influence the outcome. In particular, ML algorithms learn from a historical dataset without explicitly being programmed and uncover the relationship between the features and outcome variable. A subset of the data used in this study has been obtained from the electronic medical records (EMR) of four different outpatient clinics located in central Pennsylvania, USA. Also, publicly available information on doctor's characteristics such as gender and experience has been extracted from online sources. This research develops three popular ML algorithms (deep learning, random forest, gradient boosting machine) to predict the treatment time required for a patient and conducts a comparative analysis of these algorithms with respect to predictive performance. The findings of this study indicate that ML algorithms have the potential to predict the provider service time with superior accuracy. While the current approach of experience-based appointment duration estimation adopted by the clinic resulted in a mean absolute percentage error of 25.8%, the Deep learning algorithm developed in this study yielded the best performance with a MAPE of 12.24%, followed by gradient boosting machine (13.26%) and random forests (14.71%). Besides, this research also identified the critical variables affecting consultation duration to be patient type (new vs. established), doctor's experience, zip code, appointment day, and doctor's specialty. Moreover, several practical insights are obtained based on the comparative analysis of the ML algorithms. The machine learning approach presented in this study can serve as a decision support tool and could be integrated into the appointment system for effectively managing patient scheduling.

Keywords: clinical decision support system, machine learning algorithms, patient scheduling, prediction models, provider service time

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6 From Victim to Ethical Agent: Oscar Wilde's The Ballad of Reading Gaol as Post-Traumatic Writing

Authors: Mona Salah El-Din Hassanein

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Faced with a sudden, unexpected, and overwhelming event, the individual's normal cognitive processing may cease to function, trapping the psyche in "speechless terror", while images, feelings and sensations are experienced with emotional intensity. Unable to master such situation, the individual becomes a trauma victim who will be susceptible to traumatic recollections like intrusive thoughts, flashbacks, and repetitive re-living of the primal event in a way that blurs the distinction between past and present, and forecloses the future. Trauma is timeless, repetitious, and contagious; a trauma observer could fall prey to "secondary victimhood". Central to the process of healing the psychic wounds in the aftermath of trauma is verbalizing the traumatic experience (i.e., putting it into words) – an act which provides a chance for assimilation, testimony, and reevaluation. In light of this paradigm, this paper proposes a reading of Oscar Wilde's The Ballad of Reading Gaol, written shortly after his release from prison, as a post-traumatic text which traces the disruptive effects of the traumatic experience of Wilde's imprisonment for homosexual offences and the ensuing reversal of fortune he endured. Post-traumatic writing demonstrates the process of "working through" a trauma which may lead to the possibility of ethical agency in the form of a "survivor mission". This paper draws on fundamental concepts and key insights in literary trauma theory which is characterized by interdisciplinarity, combining the perspectives of different fields like critical theory, psychology, psychiatry, psychoanalysis, history, and social studies. Of particular relevance to this paper are the concepts of "vicarious traumatization" and "survivor mission", as The Ballad of Reading Gaol was written in response to Wilde's own prison trauma and the indirect traumatization he experienced as a result of witnessing the execution of a fellow prisoner whose story forms the narrative base of the poem. The Ballad displays Wilde's sense of mission which leads him to recognize the social as well as ethical implications of personal tragedy. Through a close textual analysis of The Ballad of Reading Gaol within the framework of literary trauma theory, the paper aims to: (a) demonstrate how the poem's thematic concerns, structure and rhetorical figures reflect the structure of trauma; (b) highlight Wilde's attempts to come to terms with the effects of the cataclysmic experience which transformed him into a social outcast; and (c) show how Wilde manages to transcend the victim status and assumes the role of ethical agent to voice a critique of the Victorian penal system and the standards of morality underlying the cruelties practiced against wrong doers and to solicit social action.

Keywords: ballad of reading of reading, post-traumatic writing, trauma theory, Wilde

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5 Predictors of Response to Interferone Therapy in Chronic Hepatitis C Virus Infection

Authors: Ali Kassem, Ehab Fawzy, Mahmoud Sef el-eslam, Fatma Salah- Eldeen, El zahraa Mohamed

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Introduction: The combination of interferon (INF) and ribavirin is the preferred treatment for chronic hepatitis C viral (HCV) infection. However, nonresponse to this therapy remains common and is associated with several factors such as HCV genotype and HCV viral load in addition to host factors such as sex, HLA type and cytokine polymorphisms. Aim of the work: The aim of this study was to determine predictors of response to (INF) therapy in chronic HCV infected patients treated with INF alpha and ribavirin combination therapy. Patients and Methods: The present study included 110 patients (62 males, 48 females) with chronic HCV infection. Their ages ranged from 20-59 years. Inclusion criteria were organized according to the protocol of the Egyptian National Committee for control of viral hepatitis. Patients included in this study were recruited to receive INF ribavirin combination therapy; 54 patients received pegylated NF α-2a (180 μg) and weight based ribavirin therapy (1000 mg if < 75 kg, 1200 mg if > 75 kg) for 48 weeks and 53 patients received pegylated INF α-2b (1.5 ug/kg/week) and weight based ribavirin therapy (800 mg if < 65 kg, 1000 mg if 65-75 kg and 1200 mg if > 75kg). One hundred and seven liver biopsies were included in the study and submitted to histopathological examination. Hematoxylin and eosin (H&E) stained sections were done to assess both the grade and the stage of chronic viral hepatitis, in addition to the degree of steatosis. Modified hepatic activity index (HAI) grading, modified Ishak staging and Metavir grading and staging systems were used. Laboratory follow up including: HCV PCR at the 12th week to assess the early virologic response (EVR) and at the 24th week were done. At the end of the course: HCV PCR was done at the end of the course and tested 6 months later to document end virologic response (ETR) and sustained virologic response (SVR) respectively. Results One hundred seven patients; 62 males (57.9 %) and 45 females (42.1%) completed the course and included in this study. The age of patients ranged from 20-59 years with a mean of 40.39±10.03 years. Six months after the end of treatment patients were categorized into two groups: Group (1): patients who achieved sustained virological response (SVR). Group (2): patients who didn't achieve sustained virological response (non SVR) including non-responders, breakthrough and relapsers. In our study, 58 (54.2%) patients showed SVR, 18 (16.8%) patients were non-responders, 15 (14%) patients showed break-through and 16 (15 %) patients were relapsers. Univariate binary regression analysis of the possible risk factors of non SVR showed that the significant factors were higher age, higher fasting insulin level, higher Metavir stage and higher grade of hepatic steatosis. Multivariate binary regression analysis showed that the only independent risk factor for non SVR was high fasting insulin level. Conclusion: Younger age, lower Metavir stage, lower steatosis grade and lower fasting insulin level are good predictors of SVR and could be used in predicting the treatment response of pegylated interferon/ribavirin therapy.

Keywords: chronic HCV infection, interferon ribavirin combination therapy, predictors to antiviral therapy, treatment response

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4 Encapsulation of Venlafaxine-Dowex® Resinate: A Once Daily Multiple Unit Formulation

Authors: Salwa Mohamed Salah Eldin, Howida Kamal Ibrahim

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Introduction: Major depressive disorder affects high proportion of the world’s population presenting cost load in health care. Extended release venlafaxine is more convenient and could reduce discontinuation syndrome. The once daily dosing also reduces the potential for adverse events such as nausea due to reduced Cmax. Venlafaxine is an effective first-line agent in the treatment of depression. A once daily formulation was designed to enhance patient compliance. Complexing with a resin was suggested to improve loading of the water soluble drug. The formulated systems were thoroughly evaluated in vitro to prove superiority to previous trials and were compared to the commercial extended release product in experimental animals. Materials and Methods: Venlafaxine-resinates were prepared using Dowex®50WX4-400 and Dowex®50WX8-100 at drug to resin weight ratio of 1: 1. The prepared resinates were evaluated for their drug content, particle shape and surface properties and in vitro release profile in gradient pH. The release kinetics and mechanism were evaluated. Venlafaxine-Dowex® resinates were encapsulated using O/W solvent evaporation technique. Poly-ε-caprolactone, Poly(D, L-lactide-co-glycolide) ester, Poly(D, L-lactide) ester and Eudragit®RS100 were used as coating polymers alone and in combination. Drug-resinate microcapsules were evaluated for morphology, entrapment efficiency and in-vitro release profile. The selected formula was tested in rabbits using a randomized, single-dose, 2-way crossover study against Effexor-XR tablets under fasting condition. Results and Discussion: The equilibrium time was 30 min for Dowex®50WX4-400 and 90 min for Dowex®50WX8-100. The percentage drug loaded was 93.96 and 83.56% for both resins, respectively. Both drug-Dowex® resintes were efficient in sustaining venlafaxine release in comparison to the free drug (up to 8h.). Dowex®50WX4-400 based venlafaxine-resinate was selected for further encapsulation to optimize the release profile for once daily dosing and to lower the burst effect. The selected formula (coated with a mixture of Eudragit RS and PLGA in a ratio of 50/50) was chosen by applying a group of mathematical equations according to targeted values. It recorded the minimum burst effect, the maximum MDT (Mean dissolution time) and a Q24h (percentage drug released after 24 hours) between 95 and 100%. The 90% confidence intervals for the test/reference mean ratio of the log-transformed data of AUC0–24 and AUC0−∞ are within (0.8–1.25), which satisfies the bioequivalence criteria. Conclusion: The optimized formula could be a promising extended release form of the water soluble, short half lived venlafaxine. Being a multiple unit formulation, it lowers the probability of dose dumping and reduces the inter-subject variability in absorption.

Keywords: biodegradable polymers, cation-exchange resin, microencapsulation, venlafaxine hcl

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3 Decreasing the Oxidative Stress in Autistic Children: A Randomized Double-Blind Controlled Study With Palm Dates Fruit

Authors: Ammal Mokhtar Metwally, Amal Elsaied, Ghada A. Abdel-Latef, Ebtissam M. Salah El-Din, Hanaa R. M. Attia

Abstract:

The link between various diet therapies and autism is controversial and limited. Nutritional interventions aim to increase antioxidant levels suggesting a positive effect on the improvement of autism severity. In this study, the effectiveness of a 90-day Dates fruits consumption fruits (a non-pharmacological and risk-free option) on alleviating autism severity symptoms in individuals with ASD was investigated. The study examined also whether the baseline or improvements of some of the clinical and laboratory characteristics of the subjects affected their response to dates fruits intake on the severity of ASD symptoms. Methodology: This study involved a randomized controlled, double-blind 3-month dates fruits intake. 131 Egyptian children aged 3-12 years with confirmed ASD were enrolled in the study. cases were randomized in one of the three groups as follows; 1st regimen: Group I on 3 dates’ fruits/day (47 cases), 2nd regimen: Group II on 5 dates’ fruits/day (42 cases), and 3rd regimen: group III; nondates group (42 cases). ASD severity was assessed using both the Diagnostic and statistical manual of mental disorders, 5th ed. (DSM-V) criteria and the Childhood Autism Rating Scale (CARS) analysis. The following measures were assessed before and after the regimens: blood levels of three oxidative markers; Malondialdehyde (MDA), glutathione peroxidase (GPX1), and superoxide dismutase (SOD), nutritional, dietary assessment & anthropometric measurements Results: A significant reduction in the mean score of autism was detected based on CARS scores for those on dates’ regimens compared to those on non-dates (p < 0.01). Participants on 5 dates’ fruits/day for three months showed the highest improvement for autism severity based on both CARS and DSM5 compared to those in 3 dates’ fruits/day and non-dates groups. Responders to dates fruits intake as reflected on the Improvement of autism severity based on CARS diagnosis was detected among 78.7 % and 62.9 % based on CARS and DSM5 diagnosis, respectively. Responders had significant improvement in BMI z score and in the ratio levels of both MDA/SOD and MDA/GPX. Conclusion: The positive results of this study suggest that palm dates fruits could be recommended for children with ASD as adjuvant therapy on a daily regular basis to achieve consistent improvement of autism symptoms Objective: Investigate the effectiveness of a 90-day Dates fruits consumption fruits on alleviating autism severity symptoms in individuals with ASD and explore the clinical and laboratory characteristics of the subjects affected their response to dates fruits intake. Methodology: The study was a randomized controlled, double-blind for 3-month. 131 autistic Egyptian children aged 3-12 years were enrolled in one of the three groups; 1st: on 3 dates’ fruits/day (47 cases), 2nd: Group II on 5 dates’ fruits/day (42 cases), and 3rd: group III; nondates group (42 cases). Conclusion: The positive results of this study suggest that palm dates fruit (a non-pharmacological and risk-free option) could be recommended for children with ASD as adjuvant therapy on a daily regular basis to achieve consistent improvement of autism symptoms.

Keywords: autism spectrum disorders, palm dates fruits, CARS, DSM5, oxidative markers

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2 Implementation of Cord- Blood Derived Stem Cells in the Regeneration of Two Experimental Models: Carbon Tetrachloride and S. Mansoni Induced Liver Fibrosis

Authors: Manal M. Kame, Zeinab A. Demerdash, Hanan G. El-Baz, Salwa M. Hassan, Faten M. Salah, Wafaa Mansour, Olfat Hammam

Abstract:

Cord blood (CB) derived Unrestricted Somatic Stem Cells (USSCs) with their multipotentiality hold great promise in liver regeneration. This work aims at evaluation of the therapeutic potentiality of USSCs in two experimental models of chronic liver injury induced either by S. mansoni infection in balb/c mice or CCL4 injection in hamsters. Isolation, propagation, and characterization of USSCs from CB samples were performed. USSCs were induced to differentiate into osteoblasts, adipocytes and hepatocyte-like cells. Cells of the third passage were transplanted in two models of liver fibrosis: (1) Twenty hamsters were induced to liver fibrosis by repeated i. p. injection of 100 μl CCl4 /hamster for 8 weeks. This model was designed as; 10 hamsters with liver fibrosis and treated with i.h. injection of 3x106 USSCs (USSCs transplanted group), 10 hamsters with liver fibrosis (pathological control group), and 10 hamsters with healthy livers (normal control group). (2) Murine chronics S.mansoni model: twenty mice were induced to liver fibrosis with S. mansoni ceracariae (60 cercariae/ mouse) using the tail immersion method and left for 12 weeks. This model was designed as; 10 mice with liver fibrosis were transplanted with i. v. injection of 1×106 USCCs (USSCs transplanted group). Other 2 groups were designed as in hamsters model. Animals were sacrificed 12 weeks after USSCs transplantation, and their liver sections were examined for detection of human hepatocyte-like cells by immunohistochemistry staining. Moreover, liver sections were examined for fibrosis level, and fibrotic indices were calculated. Sera of sacrificed animals were tested for liver functions. CB USSCs, with fibroblast-like morphology, expressed high levels of CD44, CD90, CD73 and CD105 and were negative for CD34, CD45, and HLA-DR. USSCs showed high expression of transcripts for Oct4 and Sox2 and were in vitro differentiated into osteoblasts, adipocytes. In both animal models, in vitro induced hepatocyte-like cells were confirmed by cytoplasmic expression of glycogen, alpha-fetoprotein, and cytokeratin18. Livers of USSCs transplanted group showed engraftment with human hepatocyte-like cells as proved by cytoplasmic expression of human alpha-fetoprotein, cytokeratin18, and OV6. In addition, livers of this group showed less fibrosis than the pathological control group. Liver functions in the form of serum AST & ALT level and serum total bilirubin level were significantly lowered in USSCs transplanted group than pathological control group (p < 0.001). Moreover, the fibrotic index was significantly lower (p< 0.001) in USSCs transplanted group than pathological control group. In addition liver sections, of i. v. injection of 1×106 USCCs of mice, stained with either H&E or sirius red showed diminished granuloma size and a relative decrease in hepatic fibrosis. Our experimental liver fibrosis models transplanted with CB-USSCs showed liver engraftment with human hepatocyte-like cells as well as signs of liver regeneration in the form of improvement in liver function assays and fibrosis level. These data provide hope that human CB- derived USSCs are introduced as multipotent stem cells with great potentiality in regenerative medicine & strengthens the concept of cellular therapy for the treatment of liver fibrosis.

Keywords: cord blood, liver fibrosis, stem cells, transplantation

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1 Effect of Cerebellar High Frequency rTMS on the Balance of Multiple Sclerosis Patients with Ataxia

Authors: Shereen Ismail Fawaz, Shin-Ichi Izumi, Nouran Mohamed Salah, Heba G. Saber, Ibrahim Mohamed Roushdi

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Background: Multiple sclerosis (MS) is a chronic, inflammatory, mainly demyelinating disease of the central nervous system, more common in young adults. Cerebellar involvement is one of the most disabling lesions in MS and is usually a sign of disease progression. It plays a major role in the planning, initiation, and organization of movement via its influence on the motor cortex and corticospinal outputs. Therefore, it contributes to controlling movement, motor adaptation, and motor learning, in addition to its vast connections with other major pathways controlling balance, such as the cerebellopropriospinal pathways and cerebellovestibular pathways. Hence, trying to stimulate the cerebellum by facilitatory protocols will add to our motor control and balance function. Non-invasive brain stimulation, both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), has recently emerged as effective neuromodulators to influence motor and nonmotor functions of the brain. Anodal tDCS has been shown to improve motor skill learning and motor performance beyond the training period. Similarly, rTMS, when used at high frequency (>5 Hz), has a facilitatory effect on the motor cortex. Objective: Our aim was to determine the effect of high-frequency rTMS over the cerebellum in improving balance and functional ambulation of multiple sclerosis patients with Ataxia. Patients and methods: This was a randomized single-blinded placebo-controlled prospective trial on 40 patients. The active group (N=20) received real rTMS sessions, and the control group (N=20) received Sham rTMS using a placebo program designed for this treatment. Both groups received 12 sessions of high-frequency rTMS over the cerebellum, followed by an intensive exercise training program. Sessions were given three times per week for four weeks. The active group protocol had a frequency of 10 Hz rTMS over the cerebellar vermis, work period 5S, number of trains 25, and intertrain interval 25s. The total number of pulses was 1250 pulses per session. The control group received Sham rTMS using a placebo program designed for this treatment. Both groups of patients received an intensive exercise program, which included generalized strengthening exercises, endurance and aerobic training, trunk abdominal exercises, generalized balance training exercises, and task-oriented training such as Boxing. As a primary outcome measure the Modified ICARS was used. Static Posturography was done with: Patients were tested both with open and closed eyes. Secondary outcome measures included the expanded Disability Status Scale (EDSS) and 8 Meter walk test (8MWT). Results: The active group showed significant improvements in all the functional scales, modified ICARS, EDSS, and 8-meter walk test, in addition to significant differences in static Posturography with open eyes, while the control group did not show such differences. Conclusion: Cerebellar high-frequency rTMS could be effective in the functional improvement of balance in MS patients with ataxia.

Keywords: brain neuromodulation, high frequency rTMS, cerebellar stimulation, multiple sclerosis, balance rehabilitation

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