Since its first report in December 2019, the novel coronavirus virus, SARS-CoV-2, has caused an unprecedented global health crisis and economic loss imposing a tremendous burden on the worldwide ...finance, healthcare system, and even daily life. Even with the introduction of different preventive vaccines, there is still a dire need for effective antiviral therapeutics. Nature has been considered as the historical trove of drug discovery and development, particularly in cases of worldwide crises. Herein, a comprehensive
in silico
investigation of a highly focused chemical library of 34 pederin-structurally related marine compounds, belonging to four polyketides families, was initiated against the SARS-CoV-2 main protease, Mpro, being the key replicating element of the virus and main target in many drugs development programs. Two of the most potent SARS-CoV-2 Mpro co-crystallized inhibitors, O6K and N3, were added to the tested database as reference standards. Through molecular docking simulation, promising compounds including Pederin (
1
), Dihydro-onnamide A (
11
), Onnamide C (
14
), Pseudo-onnamide A (
17
), and Theopederin G (
29
) have been identified from different families based on their superior ligand-protein energies and relevant binding profiles with the key Mpro pocket residues. Thermodynamic behaviors of the identified compounds were investigated through 200 ns all-atom molecular dynamics simulation illustrating their significant stability and pocket accommodation. Furthermore, structural activity preferentiality was identified for the pederin-based marine compounds highlighting the importance of the terminal guanidine and cyclic hemiacetal linker, and the length of the sidechain. Our findings highlight the challenges of targeting SARS-CoV-2 Mpro as well as recommending further
in vitro
and
in vivo
studies regarding the examined marine products either alone or in combination paving the way for promising lead molecules.
Marine natural polyketides showed promising SARS-CoV-2 main protease inhibitory activities.
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Background
Defective cellular elements constitute an important challenge to achieve predictable periodontal regeneration. In an attempt to improve the cellularity of periodontal defects, gingival ...fibroblasts were implanted without their associated extracellular elements in periodontal defects to expose them to periodontal tissue mediators. In order to investigate the regenerative potential of gingival fibroblasts translocated into periodontal defects, the present study was designed to clinically and biochemically investigate the use of gingival fibroblasts (GF) and their associated mesenchymal stem cells (GMSC) in the treatment of intrabony periodontal defects.
Methods
A total of 20 subjects were randomly divided into two groups (n = 20). Group I: ten patients were included with ten intrabony periodontal defects that received β‐calcium triphosphate (β‐TCP) followed by collagen membrane defect coverage, while group II: (10 patients) ten periodontal defects received cultured gingival fibroblasts (GF) on the β‐TCP scaffold and covered by a collagen membrane. The clinical evaluation was carried out at the beginning and at 6 months. Gingival crevicular fluid (GCF) samples were collected directly from the test sites for the quantitative measurement of PDGF‐BB and BMP‐2 using the ELISA kit at 1, 7, 14, and 21 days after surgery.
Results
Group II reported a significantly greater reduction in vertical pocket depth (VPD) and CAL gain compared with group I after 6 months. Radiographic bone gain was statistically higher in group II compared with group I. A significantly higher concentration of PDGF‐BB was observed in group II on days 1, 3, and 7 compared with group I.
Conclusions
Translocation of gingival fibroblasts from gingival tissue to periodontal defects could be a promising option that increases cellular elements with regeneration potential. The concept of total isolation of gingival fibroblasts using occlusive membranes must be re‐evaluated.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
3.
Cancer Oral Tongue Abdel Aziz , Ahmed Hassan; El Wakiel , Hesham Mahmoud; El Sayed , Ahmed Gamal Ali ...
The Egyptian journal of hospital medicine,
04/2020, Volume:
79, Issue:
1
Journal Article
Open access
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction Blood parasites pose a significant threat to livestock production in southern Egypt, yet there is a scarcity of information regarding their circulation and epidemiology in sheep in this ...region. This study aimed to investigate the seroprevalence of blood parasite infections in sheep in Assiut governorate, Upper Egypt. Methods A total of 400 blood samples were collected from sheep of varying ages and genders. The preliminary screening for the presence of piroplasms, mainly Babesia and Theileria spp., via microscopic examination, followed by investigation of the potential risk factors linked with the exposure to infection. Moreover, molecular identification of both parasites on some of positive samples was performed using PCR targeting Babesia 18S rRNA and Theileria annulata Tams1 gene. Results The microscopic examination revealed that among the examined sheep, there was an overall prevalence of blood parasites at 44% (176 out of 400), with Babesia spp. observed in 14% (56 out of 400) and Theileria spp. in 30% (120 out of 400). Furthermore, the infection rate was non-significantly higher in young animals (50%) compared to adults (38.5%) ( P = 0.246). Male sheep exhibited a significantly higher vulnerability to both parasites' infection (63.3%) compared to females (35.7%) ( P = 0.011). Interestingly, the prevalence of both blood parasites was significantly higher during the cold season (66.1%) compared to the hot season (15.9%) ( P = < 0.001). The molecular analysis identified the presence of Babesia ovis and Theileria annulata among a subsample of the positive sheep's bloods films. The identified species were recorded in the GenBank™ databases and assigned specific accession numbers (OQ360720 and OQ360719 for B. ovis ), and (OP991838 for T. annulata ). Conclusions Taken together, this study confirms a high prevalence of piroplasmosis and offers epidemiological and molecular insights into blood parasites in sheep from Upper Egypt, highlighting the importance of detecting these parasites in various hosts and their competent vectors (ticks).
Background
Perforated barrier membranes (PBM) were suggested to enhance periodontal regeneration by allowing positive charity of wanted elements from the gingival tissue side. The present study was ...designed to evaluate clinically and biochemically the use of PBM combined with simvastatin (SMV) gel with and without an associated EDTA gel root surface etching as a suggested option that could improve SMV availability and clinical outcomes of PBM.
Methods
Forty patients having moderate‐to‐severe chronic periodontitis with 40 intrabony defects were randomly divided into four treatment groups (10 sites each). Patients in group 1 received 1.2% SMV gel and covering the defect with occlusive membrane (OM). Patients in group 2 received 1.2% SMV gel and covering the defect with PBM. Group 3 received 24% EDTA root surface etching, 1.2% SMV gel, and defect coverage with OM (eOM). Patients in group 4 were treated as in group 3 but the defect was covered with PBM (ePBM). Clinical parameters were recorded at baseline before surgical procedures and were reassessed at 6 and 9 months after therapy. The mean concentration of SMV in gingival crevicular fluid (GCF) was estimated by reverse‐phase high‐performance liquid chromatography at days 1, 7, 14, 21, and 30.
Results
At 6‐ and 9‐month observation periods, groups 3 and 4 showed a statistically significant improvement in PD reduction and CAL gain compared with groups 1 and 2. Group 4 showed a statistically significant more defect fill compared with groups 1, 2, and 3 (P ≤ .05). Group 2 showed statistically significant higher defect fill compared with group 1 and group 3 (P < .05). Bone density was significantly increased with no significant difference between the four groups at 6‐ and 9‐month observation periods. SMV‐GCF concentration in group 4 showed the highest mean concentration with no significant difference than that of group 3.
Conclusion
The use of perforated barrier membranes in association with SMV enhances the clinical hard tissue parameters compared with occlusive ones in treating intrabony periodontal defects. Moreover, EDTA root surface treatment could enhance SMV availability in the defect area.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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.
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.
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.
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.
The current research looks into magnetohydrodynamics Casson nanofluid flow and suction/injection implications for a nonlinearly stretched interface. To improve heat transport, joules of heat, ...radiation impacts and thermal stratification are used. A Darcy-Forchheimer porous media is used to conduct fluid flow. Chemical reactions involving energies of activation and solutal stratum are additionally considered. The Keller-box technique is used to solve the resulting non-linear set of ordinary differential equations. The impacts of a number of variables are examined employing diagrams of quantity, velocity, and heat. Increased assessments of porousness, Darcy-Forchheimer, and Casson fluid characteristics result in a decrease in velocity trends. For improved measurements of Lewis number and solutal fractionated factors, the intensity pattern reduces. The skin friction factor increases with increasing Casson parameter estimate. In the instance of the porous and nonlinear stretching parameters, the Nusselt number rises. For increasing levels of the Lewis number and Brownian motion factors, the Sherwood number drops. Furthermore, Nusselt number ratios are estimated with Prandtl numbers with regard to current information available, which shows remarkable consistency. For varied incorporated parameters, streamlines, heatlines, and masslines additionally displayed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Background
Ultrasound imaging is currently a well-known, now frequently used method in the diagnosis of Rheumatoid arthritis. In recent years, it has become an essential supplement of ...physical examination in Rheumatologist practice. B-mode US & PDUS are very sensitive in detecting synovial hypertrophy, joint effusion, activity, tenosynovitis and any early bony erosions.
Aim of the Work
to demonstrate the role of Ultrasonography and Power Doppler in proper detection of activity of rheumatoid arthritis in the wrist and small hands joints among different aged population, compared with the laboratory results.
Patients and Methods
A prospective study was conducted on 40 patients (35 females & 5 males). They were referred from the Rheumatology Department to Ultrasound Unit at Ain Shams University hospitals for US examination of hand and wrist joints mainly.
Results
In our study, most of the 40 patients enrolled showed one or more of the B-mode or PDUS findings for Rheumatoid Arthritis or its activity. On adding the findings of US & PD to the clinical examination and laboratory protocol of Rheumatoid Arthritis, sensitivity and specificity for diagnosis of disease and disease activity raises.
Conclusion
Ultrasound and Power Doppler have additional value to clinical examination both in improving early detection of RA and defining true RA remission. B-mode US & PDUS are very sensitive in detecting synovial hypertrophy, joint effusion, activity, tenosynovitis and any early bony erosions.
Abstract The world is currently facing a severe economic crisis and the rational consumption and reuse of products, including waste are necessary. Agriculture wastes have importance containing ...beneficial and economic value matters, which unutilized may lead to environmental pollution. Date seed is one of these viable wastes with high nutritional value. Mass rearing of peach fruit flies is important to produce parasitoids for use in biological control programs or sterile insect techniques. In this study powder of date seeds were evaluated as an alternative diet for mass rearing of peach fruit fly Bactrocera zonata. The nutrient composition of the tested diet that contained date seed powder was rich in crude proteins (13.1%), crude carbohydrates (40.41), crude fats (4.6), crude fibers (8.4), and ashes (0.29). The results indicated that the date seed powder produced insects with quality parameters equivalent to FAO, IAEA/USDA standards, without differences with those reared on yeast. The histology of the reproductive system of B. zonata reveals that the female ovariole is of meristic-polytrophic type with successive stages of egg chambers. The male testis has a single long follicle with successive stages of spermatogenesis. Thus, date seed powder is a potential alternative diet for use in the mass rearing of the peach fruit fly.
Aim
The aim of this study was to explore the effectiveness and safety of pentoxifylline as an adjuvant to risperidone in mitigating the negative symptoms in patients with chronic schizophrenia.
...Methods
In this randomized, placebo‐controlled study, eighty outpatients with chronic schizophrenia were given risperidone for 8 weeks along with either pentoxifylline or a placebo. The positive and negative syndrome scale (PANSS) was used to assess patients at the start of the trial, as well as at 2, 4, 6, and 8 weeks. Pre‐ and posttreatment serum levels of cAMP, TNF‐α‐, and IL‐6 were measured.
Results
The pentoxifylline group revealed a significant effect for time‐treatment interaction on PANSS‐negative subscale scores (p < 0.001), PANSS general psychopathology subscale scores (p < 0.001), and PANSS total scores (p < 0.001), but not on PANSS‐positive subscale scores (p = 0.169). Additionally, when compared to the placebo group, the pentoxifylline group demonstrated a statistically significant increase in cAMP serum level and a statistically significant decrease in TNF‐α and IL‐6 serum levels.
Conclusion
Pentoxifylline adjunctive therapy with risperidone for 8 weeks was found to be promising in mitigating the negative symptoms in patients with chronic schizophrenia. Trial registration number: NCT04094207.
Phosphodiesterases and inflammation play a role in the pathophysiology of schizophrenia negative symptoms. Treatment with the PDE inhibitor pentoxifylline improve the expression of cAMP and decreases the expression of inflammatory cytokines including TNF‐α and IL‐6. Upregulation of cAMP/PKA signaling triggers the synthesis of dopamine at dopaminergic synapse, blocks the dopamine D2‐receptor, and activates dopamine D1‐receptor in striatonigral neurons. Pentoxifylline adjunctive therapy with risperidone for 8‐weeks demonstrated a favorable efficacy and safety profile in improving the negative symptoms in patients with chronic schizophrenia.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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