Ashraf Abu-Seida

Objectives: This prospective, comparative and randomised clinical study evaluated the effectiveness of triple therapy regimen (hydrocortisone, thiamine and vitamin C) versus hydrocortisone alone in reducing the mortality rate and preventing progressive organ dysfunction in septic shock patients. Methods: A total of 94 patients were randomly assigned to one of two groups: the first group received hydrocortisone 50 mg/6-h IV for 7 days or till intensive care unit (ICU) discharge, if sooner, followed by tapering. The second group received hydrocortisone 50 mg/6-h IV for 7 days or ICU discharge followed by tapering, vitamin C 1.5 g/6-h IV for 4 days or till ICU discharge and thiamine 200 mg/12-h IV for 4 days or till ICU discharge. Results: The triple therapy regimen showed a non-significant reduction in 28-day mortality compared to hydrocortisone alone (17 [36.2%] vs. 21 [44.7%]; P =.4005), but it was significantly lower than the control group regarding shock time and the duration of vasopressor use in days (4.000 [3.000-7.000]; 5.000 [4.000-8.000], [P =.0100]). The patients in the control group were likely to get 0.59 more in SCr level than those in the intervention group by a linear regression model which was significant (P <.05). Also, the number of patients who developed a fever after 216 hours was significantly higher in the control group (P value =.0299). Conclusion: Vitamin C, thiamine, and hydrocortisone regimen for septic shock management showed non-significant efficacy in decreasing 28-day mortality when compared to hydrocortisone monotherapy. On the other hand, it showed significant efficacy in decreasing the shock time and duration on vasopressors. © 2021 John Wiley & Sons Ltd

Proton radioactivity and α-decay half-lives of neutron-deficient nuclei have been systematically studied. The proton-nucleus interaction potential is developed by single folding the density distribution of the daughter nuclei with the effective M3Y-Paris nucleon-nucleon (NN) interaction. The penetrability is calculated with the Wentzel-Kramers-Brillouin approximation. The applicability of the universal decay law on the proton decay half-lives has been examined and a new set of parameters has been identified. The competition between α-decay and proton radioactivity of neutron-deficient nuclei has been investigated. The proton radioactivity is found to be the dominant mode of decay for nuclides located very close to the proton drip-line. The effect of using different microscopic proton and neutron density distributions on the half-lives for these two decay modes is studied. It is found that the calculated half-lives with the microscopic densities that obtained from the self-consistent Hartree–Fock-Bogoliubov method successfully reproduce the experimental data. The impact of nuclear deformation on the half-lives is investigated for these two decay modes. The influence of nonlocality through the finite-range exchange part of the NN interaction on the α-decay process is elucidated. Our theoretical calculations have been confirmed experimentally and satisfactory agreement has been achieved.

SummaryCongenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

New SARS-CoV-2 variants emerged in the United Kingdom and South Africa in December 2020 in concomitant with the Brazillian variant in February 2021 (B.1.1.248 lineage) and currently sparking worldwide during the last few months. The new strain 501.V2 in South Africa bears three mutations in the spike receptor-binding domain (RBD); K417 N, E484K, and N501Y, while the Brazilian B.1.1.248 lineage has 12 mutations. In the current study, we simulate the complex ACE2-SARS-CoV-2 spike RBD system in which the RBD is in the wild-type and mutated isoforms. Additionally, the cell-surface Glucose Regulated Protein 78 (CS-GRP78) associated with the ACE2-SARS-CoV-2 spike RBD complex (ACE2-S RBD) is modeled at the presence of these mutant variants of the viral spike. The results showed that E484K and N501Y are critical in viral spike recognition through either ACE2 or CS-GRP78. The mutated variants (the UK, South African, and Brazilian) of the spike RBD tightly bind to GRP78 more than in the case of the wild-type RBD. These results point to the potent role of GRP78 with ACE2 in the attachment of the new variants, which could be a key for the design of inhibitors to block SARS-CoV-2 attachment and entry to the host cell. © 2021 Elsevier Inc.

Existence rectangles of positive eigenvalues with corresponding positive eigenfunctions of 2p-order and 2q-order nonlinear coupled multiparameter systems of ordinary differential equations are introduced. The boundary conditions are related to the Abel–Whittaker interpolation problem $$f^{(2k)}(1) =a_k,\,f^{(2k+1)}(0) =b_k,\,k\ge 0$$. The multiplicity of the eigenvalues are also investigated. Under standard conditions, we prove the existence of rectangles of non-simple eigenvalues with multiplicities greater than or equal to two.

Crop plants are continuously exposed to abiotic and biotic constraints like salt, drought, heat, heavy metal, ultraviolet, fungi, bacteria, pathogens etc. Plants respond to them by altering their physiology and metabolism. The response is initiated at molecular, cellular and at whole plant level. Plants undergo alterations in growth, photosynthesis, yield and quality attributes when exposed to stresses. Nevertheless, these complex processes are modulated by the application of different kinds of nanoparticles (NPs). In the current times, nanotechnology, as a broad interdisciplinary area of research, finds potential in agriculture regarding plant disease management, pathogen detection and imparting stress tolerance. Nanoparticles at particular concentrations control growth, morpho-physiology and yield attributes under stress conditions. In the present chapter, we attempt to discuss various response alterations initiated by crop plants towards abiotic and biotic stresses, vis-à-vis controlling nature of various NPs doses in protecting these processes under these stress conditions.

A novel human coronavirus prompted considerable worry at the end of the year 2019. Now, it represents a significant global health and economic burden. The newly emerged coronavirus disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the primary reason for the COVID-19 global pandemic. According to recent global figures, COVID-19 has caused approximately 243.3 million illnesses and 4.9 million deaths. Several human cell receptors are involved in the virus identification of the host cells and entering them. Hence, understanding how the virus binds to host-cell receptors is crucial for developing antiviral treatments and vaccines. The current work aimed to determine the multiple host-cell receptors that bind with SARS-CoV-2 and other human coronaviruses for the purpose of cell entry. Extensive research is needed using neutralizing antibodies, natural chemicals, and therapeutic peptides to target those host-cell receptors in extremely susceptible individuals. More research is needed to map SARS-CoV-2 cell entry pathways in order to identify potential viral inhibitors. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Background and aim: Rifaximin is an oral antibiotic with promising efficacy in the reduction of hepatic encephalopathy (HE) recurrence. Development of microbial resistance to rifaximin is not studied yet in HE. The study aim was to assess the microbial resistance, safety and efficacy of rifaximin as secondary prophylaxis of HE. Method: In this open-label parallel, prospective interventional study, 100 patients were randomly allocated either to receive 400 mg rifaximin 3 times/d plus 30-45 mL lactulose 3 times/d (intervention group) or to receive the standard of care only which is lactulose alone (control group) for 6 months. The primary outcome of the study was the difference between minimum inhibitory concentration (MIC) of rifaximin among the two studied groups at the end of treatment. The secondary outcomes included the time to first episode of HE, time to first hospitalisation, and patient's survival. Results: The MIC did not differ significantly after treatment exposure compared with baseline either between groups or within the same group. The time to new episode of HE was 18.84 ± 6.49 weeks (mean ± SD) in the intervention group and was significantly longer (P =.002) than that in the control group 14 ± 7.52 weeks. Moreover, only 23 (46%) patients developed overt HE in the intervention group compared with 35 patients (70%) in the control group (P =.005). Also, there was an observed 32% reduction in the risk of hospitalisation in intervention group compared with control group. Conclusion: Rifaximin succeeded to maintain remission from new episodes of HE in hepatitis C virus cirrhotic patients with limited potential for development of microbial resistance over the study period. ClinicalTrials.gov Identifier: NCT04736836. © 2021 John Wiley & Sons Ltd

INTRODUCTION: Numerous surgical techniques regarding cesarean section performance were assessed. The usefulness of cervical dilatation during cesarean section, are still based on restricted research obtained data. PURPOSE: To assess the impact of intraoperative digital dilatation of cervix on postoperative pain. MATERIAL AND METHODS: The current research study is a Prospective parallel group randomized controlled double blind research trial that was conducted in obstetrics and gynecology hospital, Faculty of Medicine, Cairo University and Algezeera Hospital, Egypt from the period May 2018 until February 2018. RESULTS: The visual analog scale scoring level was statistically significantly higher in noncervical dilatation research group at 8th, 30th, 48 hours and 7th day postoperative (p values <.001, .001, .001, and .001, respectively). On the other hand at the 4th day postoperative, there was no statistical significant difference concerning VAS scoring level. CONCLUSIONS: Manual cervical dilatation during cesarean section is an innovative procedure to reduce postoperative pain in obese women. We thought that according to the results of the present study, cervical dilatation leads to proper continuous adequate evacuation and drainage of the intracavitary contents that leads to decrease the uterine subinvolution, retained blood and so, decreased postoperative pain and postoperative blood loss. CLINICALTRIALS.GOV ID: NCT03513237.

In machine learning, searching for the optimal feature subset from the original datasets is a very challenging and prominent task. The metaheuristic algorithms are used in finding out the relevant, important features, that enhance the classification accuracy and save the resource time. Most of the algorithms have shown excellent performance in solving feature selection problems. A recently developed metaheuristic algorithm, gaining-sharing knowledge-based optimization algorithm (GSK), is considered for finding out the optimal feature subset. GSK algorithm was proposed over continuous search space; therefore, a total of eight S-shaped and V-shaped transfer functions are employed to solve the problems into binary search space. Additionally, a population reduction scheme is also employed with the transfer functions to enhance the performance of proposed approaches. It explores the search space efficiently and deletes the worst solutions from the search space, due to the updation of population size in every iteration. The proposed approaches are tested over twenty-one benchmark datasets from UCI repository. The obtained results are compared with state-of-the-art metaheuristic algorithms including binary differential evolution algorithm, binary particle swarm optimization, binary bat algorithm, binary grey wolf optimizer, binary ant lion optimizer, binary dragonfly algorithm, binary salp swarm algorithm. Among eight transfer functions, V4 transfer function with population reduction on binary GSK algorithm outperforms other optimizers in terms of accuracy, fitness values and the minimal number of features. To investigate the results statistically, two non-parametric statistical tests are conducted that concludes the superiority of the proposed approach.

Background: Postpartum hemorrhage (PPH) is a direct cause of maternal death all over the world. A Bakri balloon is recommended by American College of Obstetricians and Gynecologists (ACOG) and World Health Organization (WHO) as a treatment line for PPH unresponsive to uterotonics. We carried out a systematic review to assess the safety and effectiveness of Bakri balloon in the management of PPH.Methods: We searched PubMed, SCOPUS, central Cochrane, and Web of Science, from 2001 to 2018 for randomized controlled trials (RCTs) and observational studies to assess the safety and effectiveness of Bakri balloon on refractory PPH.Results: Twenty-eight articles were included for analysis. The primary indication for the use of a Bakri balloon tamponade was PPH. Only 67.9% (19/28) quantified the estimate blood loss necessary to use the balloon. Uterine atony was the underlying cause of PPH in 75% (21/28) of studies. Most of the studies on Bakri balloon are followed by vaginal birth (3/4). Bakri balloon displacement from the uterine cavity was reported by five publications, with the overall rate being 9% (95% CI: 5-15%). Hysterectomy was necessary for 1% (95% CI: 0-8%) of the women who required the balloon.Conclusions: Bakri balloon seems to be a less effective tool for management of PPH either after vaginal or cesarean delivery.

Introduction: SARS-CoV-2 replication in cell cultures has been shown to be inhibited by ivermectin. However, ivermectin's low aqueous solubility and bioavailability hinders its application in COVID-19 treatment. Also, it has been suggested that best outcomes for this medication can be achieved via direct administration to the lung. Objectives: This study aimed at evaluating the safety of a novel ivermectin inhalable formulation in rats as a pre-clinical step. Methods: Hydroxy propyl-β-cyclodextrin (HP-β-CD) was used to formulate readily soluble ivermectin lyophilized powder. Adult male rats were used to test lung toxicity for ivermectin-HP-β-CD formulations in doses of 0.05, 0.1, 0.2, 0.4 and 0.8 mg/kg for 3 successive days. Results: The X-ray diffraction for lyophilized ivermectin-HP-β-CD revealed its amorphous structure that increased drug aqueous solubility 127-fold and was rapidly dissolved within 5 s in saline. Pulmonary administration of ivermectin-HP-β-CD in doses of 0.2, 0.4 and 0.8 mg/kg showed dose-dependent increase in levels of TNF-α, IL-6, IL-13 and ICAM-1 as well as gene expression of MCP-1, protein expression of PIII-NP and serum levels of SP-D paralleled by reduction in IL-10. Moreover, lungs treated with ivermectin (0.2 mg/kg) revealed mild histopathological alterations, while severe pulmonary damage was seen in rats treated with ivermectin at doses of 0.4 and 0.8 mg/kg. However, ivermectin-HP-β-CD formulation administered in doses of 0.05 and 0.1 mg/kg revealed safety profiles. Conclusion: The safety of inhaled ivermectin-HP-β-CD formulation is dose-dependent. Nevertheless, use of low doses (0.05 and 0.1 mg/kg) could be considered as a possible therapeutic regimen in COVID-19 cases. © 2021 Elsevier B.V.