Plenum-to-plenum heat transfer characteristics under natural circulation in a scaled-down prismatic modular reactor

“Gas-cooled reactor (GCR) is being developed under the Next Generation Nuclear Plant Program (NGNP) in nuclear engineering studies. As the world searches for an energy source with high energy density, clean, abundant, and storable nature to avoid global warming issues, GCR seems to be a promising solution, particularly the possibility of producing hydrogen. Studying and developing the safety analysis and GCR technologies are required for the optimum design and safety of GCR system. Multiphase Reactors Engineering and Applications Laboratory (mReal) at Missouri University of Science and Technology (S&T) has developed a natural convection heat transfer test facility with one riser and one downcomer between two plena to investigate loss of flow accident scenario (LOFA) for a prismatic very high temperature reactor (VHTR). Using advanced heat transfer coefficient probe and T-thermocouples. The facility represents a scaled down prismatic modular reactor with a reference to High-Temperature Test Facility at Oregon State University (OSU-HTTF). The natural circulation heat transfer in terms of temperature fields and heat transfer coefficients across the core of current facility (i.e., channels) has been investigated at different conditions to understand the passive safety features of prismatic modular reactors (PMR). This dissertation advance knowledge and understanding of the intra core natural circulation phenomenon in the PMRs. Moreover, fill the gaps in the open literature and understanding of the natural circulation heat transfer and gaseous dynamics in the prismatic VHTR and provide experimental benchmark data, which is much needed and is missing in the literature for verification and validation”--Abstract, page iii

Prevalence and correlates of diastolic dysfunction in patients with hypertension: a cross-sectional study from in The Kingdom of Saudi Arabia

Introduction: diastolic dysfunction refers to impaired ventricular relaxation or filling regardless of ejection fraction and symptoms. It accounts for 8% and 25% in the hospitalized and general population, respectively. The present study was conducted to determine the prevalence and correlates of diastolic dysfunction in hypertensive patients living in Saudi Arabia. Methods: a multicentric, cross-sectional study was conducted from February 2019 to February 2020 at King Khalid Hospital and Prince Sultan Center for Health Services, Prince Sattam Bin Abdulaziz University hospital in Al Kharj, and Al Kharj Military Industries Corporation hospital, KSA. All patients with hypertension who underwent an echocardiography were included in the study. Logistic regression analysis was performed to determine factors associated with left ventricular diastolic dysfunction (LVDD). Results: the study included a total of 104 participants, where 51.9% were females andthe mean age of the patients was 48.01±12.81 years.Most patients had an abnormal echocardiography finding (64.4%, n = 67). The most common abnormalities were left ventricular (LV) hypertrophy (44.2%, n = 46), and diastolic dysfunction, (35.6%, n = 37). The study revealed that age (aOR: 6.1, 95% CI 1.17-31.3; p = 0.032) and dyslipidemia (aOR: 3.45, 95% CI 1.16-10.24; p = 0.026) have significant association with LVDD in the patients with hypertension. Conclusion: in conclusion, diastolic dysfunction is prevalent among older hypertensive patients and those with dyslipidaemia. Age and dyslipidaemia were non-modifiable and modifiable factors associated with LVDD in hypertensive patients, respectively

Combining Ability and Gene Action Controlling Agronomic Traits for Cytoplasmic Male Sterile Line, Restorer Lines, and New Hybrids for Developing of New Drought-Tolerant Rice Hybrids

This study aimed to identify new rice lines and hybrids that are tolerant to water deficit and produce high yields under water stress conditions. A line × tester mating design was used to study the lines and testers’ general combining ability (GCA) effects. The specific combining ability (SCA) of the hybrid rice combinations was measured under three different irrigation regimes; 6, 9, and 12 days. The study was carried out at the experimental farm of Sakha Agricultural Research Station, Sakha, Kafr El-Sheikh, Egypt, during the 2018 and 2019 rice growing seasons. Due to the genotypes and their partitions to the parents and the crosses, the mean squares were highly significant for all studied traits under the three irrigation regimes. The additive gene effects play an important role in expressing most of the studied traits. Therefore, the selection procedures based on the accumulation of the additive effect would be successful at improving these traits and the grain yield. The cytoplasmic male sterile (CMS) line G46A (L1) was the best combiner for most yield component traits in the three irrigation regimes. The newly devolved restorer lines T11, T1, T2, T5, T4, and T3, as well as the new hybrids L2 × T10, L2 × T6, L1 × T7, L1 × T5, L1 × T3, L2 × T7, L2 × T9, L2 × T8, L2 × T4, L1 × T4, L2 × T2, L1 × T8, L1 × T9, and L2 × NRL 10, showed good, desirable values of the studied traits such as earliness of flowering, short plant height, number of panicles/plant, panicle length, number of spikelets/panicle, number of filled grains/panicle, panicle weight, 1000-grain weight, hulling percentage, milling percentage, head rice percentage, and grain yield under the irrigation regimes of 6, 9, and 12 days. The hybrids L2 × T10, L2 × T6, L1 × T7, and L1 × T5, showed significant positive SCA effects for grain yield, under all three irrigation regimes

Exploring the Binding Pattern of Geraniol with Acetylcholinesterase through In Silico Docking, Molecular Dynamics Simulation, and In Vitro Enzyme Inhibition Kinetics Studies

Acetylcholinesterase (AChE) inhibition is a key element in enhancing cholinergic transmission and subsequently relieving major symptoms of several neurological and neuromuscular disorders. Here, the inhibitory potential of geraniol and its mechanism of inhibition against AChE were elucidated in vitro and validated via an in silico study. Our in vitro enzyme inhibition kinetics results show that at increasing concentrations of geraniol and substrate, Vmax did not change significantly, but Km increased, which indicates that geraniol is a competitive inhibitor against AChE with an IC50 value 98.06 ± 3.92 µM. All the parameters of the ADME study revealed that geraniol is an acceptable drug candidate. A docking study showed that the binding energy of geraniol (−5.6 kcal mol−1) was lower than that of acetylcholine (−4.1 kcal mol−1) with AChE, which exhibited around a 12.58-fold higher binding affinity of geraniol. Furthermore, molecular dynamics simulation revealed that the RMSD of AChE alone or in complex with geraniol fluctuated within acceptable limits throughout the simulation. The mean RMSF value of the complex ensures that the overall conformation of the protein remains conserved. The average values of Rg, MolSA, SASA, and PSA of the complex were 3.16 Å, 204.78, 9.13, and 51.58 Å2, respectively. We found that the total SSE of AChE in the complex was 38.84% (α-helix: 26.57% and β-sheets: 12.27%) and remained consistent throughout the simulation. These findings suggest that geraniol remained inside the binding cavity of AChE in a stable conformation. Further in vivo investigation is required to fully characterize the pharmacokinetic properties, optimization of dose administration, and efficacy of this plant-based natural compound

Formulation and Evaluation of Topical Nano-Lipid-Based Delivery of Butenafine: In Vitro Characterization and Antifungal Activity

The present research work was designed to prepare butenafine (BN)-loaded bilosomes (BSs) by the thin-film hydration method. BN is a sparingly water-soluble drug having low permeability and bioavailability. BSs are lipid-based nanovesicles used to entrap water-insoluble drugs for enhanced permeation across the skin. BSs were prepared by the thin-film hydration method and optimized by the Box–Behnken design (BBD) using lipid (A), span 60 (B), and sodium deoxycholate (C) as independent variables. The selected formulation (BN-BSo) was converted into the gel using Carbopol 940 as a gelling agent. The prepared optimized gel (BN-BS-og) was further evaluated for the gel characterization, drug release, drug permeation, irritation, and anti-fungal study. The optimized bilosomes (BN-BSo) showed a mean vesicle size of 215 ± 6.5 nm and an entrapment efficiency of 89.2 ± 1.5%. The DSC study showed that BN was completely encapsulated in the BS lipid matrix. BN-BSog showed good viscosity, consistency, spreadability, and pH. A significantly (p < 0.05) high release (81.09 ± 4.01%) was achieved from BN-BSo compared to BN-BSog (65.85 ± 4.87%) and pure BN (17.54 ± 1.37 %). The permeation study results revealed that BN-BSo, BN-BSog, and pure BN exhibited 56.2 ± 2.7%, 39.2 ± 2.9%, and 16.6 ± 2.3%. The enhancement ratio of permeation flux was found to be 1.4-fold and 3.4-fold for the BN-BS-og and pure BN dispersion. The HET-CAM study showed that BN-BSog was found to be nonirritant as the score was found within the limit. The antifungal study revealed a significant (p < 0.05) enhanced antifungal activity against C. albicans and A. niger. The findings of the study revealed that BS is an important drug delivery system for transdermal delivery

Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study

Neurodegenerative disorders involve various pathophysiological pathways, and finding a solution for these issues is still an uphill task for the scientific community. In the present study, a combination of molecular docking and dynamics approaches was applied to target different pathways leading to neurodegenerative disorders such as Alzheimer’s disease. Initially, abrineurin natural inducers were screened using physicochemical properties and toxicity assessment. Out of five screened compounds, a pentacyclic triterpenoid, i.e., Soyasapogenol B appeared to be the most promising after molecular docking and simulation analysis. Soyasapogenol B showed low TPSA (60.69), high absorption (82.6%), no Lipinski rule violation, and no toxicity. Docking interaction analysis revealed that Soyasapogenol B bound effectively to all of the targeted proteins (AChE, BuChE MAO-A, MAO-B, GSK3β, and NMDA), in contrast to other screened abrineurin natural inducers and inhibitors. Importantly, Soyasapogenol B bound to active site residues of the targeted proteins in a similar pattern to the native ligand inhibitor. Further, 100 ns molecular dynamics simulations analysis showed that Soyasapogenol B formed stable complexes against all of the targeted proteins. RMSD analysis showed that the Soyasapogenol B–protein complex exhibited average RMSD values of 1.94 Å, 2.11 Å, 5.07 Å, 2.56 Å, 3.83 Å and 4.07 Å. Furthermore, the RMSF analysis and secondary structure analysis also indicated the stability of the Soyasapogenol B–protein complexes

Radiation Dose Optimization Based on Saudi National Diagnostic Reference Levels and Effective Dose Calculation for Computed Tomography Imaging: A Unicentral Cohort Study

Few studies have reviewed the reduction of doses in Computed tomography (CT), while various diagnostic procedures use ionizing radiation to explore the optimal dose estimate using multiple exposure quantities, including milliampere-seconds, kilovoltage peak, and pitch factors while controlling the CT dose index volume (CTDIvol) and dose length product (DLP). Therefore, we considered optimizing CT protocols to reduce radiation and organ doses during head, chest, abdominal, and pelvic CT examinations. For establishing institutional diagnostic reference levels as a benchmark to correlate with national diagnostic reference levels (NDRLs) in KSA conforming to international guidelines for radiation exposure, 3000 adult-patients underwent imaging of organs. Dose parameters were obtained using Monte Carlo software and adjusted using the Siemens Teamplay™ software. CTDIvol, DLP, and effective dose were 40.67 ± 3.8, 757 ± 63.2, and 1.74 ± 0.19, for head; 14.9 ± 1.38, 547 ± 42.9, and 7.27 ± 0.95 for chest; and 16.84 ± 1.45, 658 ± 53.4, and 10.2 ± 0.66 for abdomen/pelvis, respectively. The NDRL post-optimization comparison showed adequate CT exposure. Head CT parameters required additional optimization to match the NDRL. Therefore, calculations were repeated to assess radiation doses. In conclusion, doses could be substantially minimized by selecting parameters per clinical indication of the study, patient size, and examined body region. Additional dose reduction to superficial organs requires a shielding material

Radiation Dose Optimization Based on Saudi National Diagnostic Reference Levels and Effective Dose Calculation for Computed Tomography Imaging: A Unicentral Cohort Study

Few studies have reviewed the reduction of doses in Computed tomography (CT), while various diagnostic procedures use ionizing radiation to explore the optimal dose estimate using multiple exposure quantities, including milliampere-seconds, kilovoltage peak, and pitch factors while controlling the CT dose index volume (CTDIvol) and dose length product (DLP). Therefore, we considered optimizing CT protocols to reduce radiation and organ doses during head, chest, abdominal, and pelvic CT examinations. For establishing institutional diagnostic reference levels as a benchmark to correlate with national diagnostic reference levels (NDRLs) in KSA conforming to international guidelines for radiation exposure, 3000 adult-patients underwent imaging of organs. Dose parameters were obtained using Monte Carlo software and adjusted using the Siemens Teamplay™ software. CTDIvol, DLP, and effective dose were 40.67 ± 3.8, 757 ± 63.2, and 1.74 ± 0.19, for head; 14.9 ± 1.38, 547 ± 42.9, and 7.27 ± 0.95 for chest; and 16.84 ± 1.45, 658 ± 53.4, and 10.2 ± 0.66 for abdomen/pelvis, respectively. The NDRL post-optimization comparison showed adequate CT exposure. Head CT parameters required additional optimization to match the NDRL. Therefore, calculations were repeated to assess radiation doses. In conclusion, doses could be substantially minimized by selecting parameters per clinical indication of the study, patient size, and examined body region. Additional dose reduction to superficial organs requires a shielding material

Nanoplatform for the Delivery of Topotecan in the Cancer Milieu: An Appraisal of its Therapeutic Efficacy

Chemotherapy has been the predominant treatment modality for cancer patients, but its overall performance is still modest. Difficulty in penetration of tumor tissues, a toxic profile in high doses, multidrug resistance in an array of tumor types, and the differential architecture of tumor cells as they grow are some of the bottlenecks associated with the clinical usage of chemotherapeutics. Recent advances in tumor biology understanding and the emergence of novel targeted drug delivery tools leveraging various nanosystems offer hope for developing effective cancer treatments. Topotecan is a topoisomerase I inhibitor that stabilizes the transient TOPO I-DNA cleavable complex, leading to single-stranded breaks in DNA. Due to its novel mechanism of action, TOPO is reported to be active against various carcinomas, namely small cell lung cancer, cervical cancer, breast cancer, and ovarian cancer. Issues of cross-resistance with numerous drugs, rapid conversion to its inactive form in biological systems, appended adverse effects, and higher water solubility limit its therapeutic efficacy in clinical settings. Topotecan nanoformulations offer several benefits for enhancing the therapeutic action of this significant class of chemotherapeutics. The likelihood that the target cancer cells will be exposed to the chemotherapeutic drug while in the drug-sensitive s-phase is increased due to the slow and sustained release of the chemotherapeutic, which could provide for a sustained duration of exposure of the target cancer cells to the bioavailable drug and result in the desired therapeutic outcome. This article explores nanoenabled active and passive targeting strategies and combinatorial therapy employing topotecan to ameliorate various cancers, along with a glimpse of the clinical studies utilizing the said molecule

Global, regional, and national burden of low back pain, 1990–2020, its attributable risk factors, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

Background: Low back pain is highly prevalent and the main cause of years lived with disability (YLDs). We present the most up-to-date global, regional, and national data on prevalence and YLDs for low back pain from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021. Methods: Population-based studies from 1980 to 2019 identified in a systematic review, international surveys, US medical claims data, and dataset contributions by collaborators were used to estimate the prevalence and YLDs for low back pain from 1990 to 2020, for 204 countries and territories. Low back pain was defined as pain between the 12th ribs and the gluteal folds that lasted a day or more; input data using alternative definitions were adjusted in a network meta-regression analysis. Nested Bayesian meta-regression models were used to estimate prevalence and YLDs by age, sex, year, and location. Prevalence was projected to 2050 by running a regression on prevalence rates using Socio-demographic Index as a predictor, then multiplying them by projected population estimates. Findings: In 2020, low back pain affected 619 million (95% uncertainty interval 554–694) people globally, with a projection of 843 million (759–933) prevalent cases by 2050. In 2020, the global age-standardised rate of YLDs was 832 per 100 000 (578–1070). Between 1990 and 2020, age-standardised rates of prevalence and YLDs decreased by 10·4% (10·9–10·0) and 10·5% (11·1–10·0), respectively. A total of 38·8% (28·7–47·0) of YLDs were attributed to occupational factors, smoking, and high BMI. Interpretation: Low back pain remains the leading cause of YLDs globally, and in 2020, there were more than half a billion prevalent cases of low back pain worldwide. While age-standardised rates have decreased modestly over the past three decades, it is projected that globally in 2050, more than 800 million people will have low back pain. Challenges persist in obtaining primary country-level data on low back pain, and there is an urgent need for more high-quality, primary, country-level data on both prevalence and severity distributions to improve accuracy and monitor change. Funding: Bill and Melinda Gates Foundation