Assessing the Predictive Accuracy of the aMAP Risk Score for Hepatocellular Carcinoma (HCC): Diagnostic Test Accuracy and Meta-analysis.

Purpose: We aimed to perform a meta-analysis with the intention of evaluating the reliability and test accuracy of the aMAP risk score in the identification of HCC. Methods: A systematic search was performed in PubMed, Scopus, Cochrane, Embase, and Web of Science databases from inception to September 2023, to identify studies measuring the aMAP score in patients for the purpose of predicting the occurrence or recurrence of HCC. The meta-analysis was performed using the meta package in R version 4.1.0. The diagnostic accuracy meta-analysis was conducted using Meta-DiSc software. Results: Thirty-five studies 102,959 participants were included in the review. The aMAP score was significantly higher in the HCC group than in the non-HCC group, with a mean difference of 6.15. When the aMAP score is at 50, the pooled sensitivity, specificity, negative likelihood ratio, and positive likelihood ratio with 95% CI was 0.961 (95% CI 0.936, 0.976), 0.344 (95% CI 0.227, 0.483), 0.114 (95% CI 0.087, 0.15), and 1.464 (95% CI 1.22, 1.756), respectively. At a cutoff value of 60, the pooled sensitivity, specificity, negative likelihood ratio, and positive likelihood ratio with 95% CI was 0.594 (95% CI 0.492, 0.689), 0.816 (95% CI 0.714, 0.888), 0.497 (95% CI 0.418, 0.591), and 3.235 (95% CI 2.284, 4.582), respectively. Conclusion: The aMAP score is a reliable, accurate, and easy-to-use tool for predicting HCC patients of all stages, including early-stage HCC. Therefore, the aMAP score can be a valuable tool for surveillance of HCC patients and can help to improve early detection and reduce mortality.

The effect of genetic polymorphisms in STIM1 and ORAI1 on erythropoietin resistance in Egyptian patients with end-stage renal disease.

Chronic renal failure (CRF) is an incurable disease with unique challenges. Anemia is a frequent complication affecting dialysis patients. Erythropoietin (EPO) is used to treat anemia, but a poor response may result. We investigated genetic polymorphisms of store-operated calcium channel (SOC) signaling, an important erythropoietin-activated pathway that may induce EPO resistance in patients with renal failure. A total of 108 end stage renal disease (ESRD) patients were selected for this study. Patients were divided into two groups according to their erythropoietin resistance index (ERI): 39 patients with an ERI>10 and 69 patients with an ERI<10. We selected four tagging single nucleotide polymorphisms (tSNPs) in STIM1 and five in ORAI1 in our study. A polymerase chain reaction was performed, and genotyping against EPO resistance was correlated. Patients with the AG genotype of rs1561876 in STIM1, the TC genotype of rs6486795 in ORAI1, and the TG or GG genotypes of rs12320939 in ORAI1 were associated with an increased risk of erythropoietin resistance. Overall, we reported a moderately significant relationship between genetic polymorphisms of STIM1 and EPO resistance. We also reported a highly significant relationship between genetic polymorphisms of ORAI1 and EPO resistance. The (A-A-G) haplotype of STIM1 and the (G-T-G-T-A, G-C-G-C-G, or G-T-T-C-G) haplotypes of ORAI1 were significantly associated with EPO resistance.

Novel Teixobactin Analogues Show Promising In Vitro Activity on Biofilm Formation by Staphylococcus aureus and Enterococcus faecalis.

The treatment of infections caused by biofilm-forming organisms is challenging. The newly discovered antibiotic teixobactin shows activity against a wide range of biofilm-forming bacteria. However, the laborious and low-yield chemical synthesis of teixobactin complicates its further development for clinical application. The use of more easily synthesized teixobactin analogues may offer promise in this regard. In this article, three newly developed analogues were tested for efficacy against Staphylococcus aureus and Enterococcus faecalis. Minimum inhibitory and -bactericidal concentrations were investigated. MIC values for S. aureus and E. faecalis ranged from 0.5-2 and 2-4 µg/mL, respectively. Moreover, the ability of the analogues to prevent biofilm formation and to inactivate bacterial cells in already established S. aureus biofilm on medical grade materials (PVC and PTFE) used in the production of infusion tubing and catheters were also tested. The analogues showed an ability to prevent biofilm formation and inactivate bacterial cells in established biofilms at concentrations as low as 1-2 µg/mL. Confocal laser scanning microscopy showed that the most promising analogue (TB3) inactivated S. aureus cells in a preformed biofilm and gave a reduction in biovolume. The relative ease of synthesis of the analogues and their in vitro efficacy, makes them promising candidates for pharmaceutical development.

Does dutasteride reduce the bleeding in transurethral resection of the prostate in patients on antiplatelet drugs?

Background: The aim of this study was to assess the effect of a 4-week dutasteride treatment on reducing the intraoperative and postoperative bleeding, as well as the amount and duration of irrigation required to clear the urine after transurethral resection of the prostate (TURP) ≥50 g in men receiving the antiplatelet drug (APD). Materials and methods: This double-blind randomized clinical trial included patients with a prostate size ≥50 g who were indicated for TURP and were already receiving APD. The study was conducted in the Urology Department of Cairo University over a 12-month period. Routine preoperative laboratory investigations were performed in all patients. Moreover, baseline prostate size, serum prostate-specific antigen level, and International Prostate Symptom Score were estimated. The patients were randomly divided into 2 equal groups (groups A and B). Group A, the dutasteride group, received dutasteride (0.5 mg) once daily for 4 weeks. Group B, the placebo group, received a placebo capsule once daily for 4 weeks. Both groups underwent bipolar TURP. Fifteen patients were excluded from the study; 9 patients from group A and 6 patients from group B, either due to drug intolerability or loss follow-up. Results: The mean blood loss was insignificant between the 2 groups immediately after and 24 hours after surgery (Δ hemoglobin: 1.41 ± 0.63 g/dL vs. 1.48 ± 0.54 g/dL, 2.12 ± 0.70 g/dL vs. 2.31 ± 0.78 g/dL, respectively, p = 0.631, p = 0.333; Δ hematocrit: 2.97% ± 1.51% vs. 3.16% ± 1.36%, 4.96% ± 1.87% vs. 5.73% ± 4.39%, respectively, p = 0.610, p = 0.380). However, there were significant differences in duration of indwelling urethral catheter (5.10 ± 0.55 days vs. 5.80 ± 1.79 days, p = 0.048), duration of bladder irrigation (13.60 ± 2.85 hours vs. 16.33 ± 6.62 hours, p = 0.044), and the amount of saline used for bladder irrigation (11.03 ± 2.30 L vs. 13.87 ± 6.13 L, p = 0.046) between group A and group B. respectively. Conclusions: Treatment with dutasteride for 4 weeks before TURP in men receiving APD did not significantly reduce intraoperative or postoperative bleeding after TURP but could significantly reduce the duration of indwelling catheter placement, as well as the duration and amount of saline irrigation.

The role of DNA topoisomerase 1α (AtTOP1α) in regulating arabidopsis meiotic recombination and chromosome segregation.

Meiosis is a critical process in sexual reproduction, and errors during this cell division can significantly impact fertility. Successful meiosis relies on the coordinated action of numerous genes involved in DNA replication, strand breaks, and subsequent rejoining. DNA topoisomerase enzymes play a vital role by regulating DNA topology, alleviating tension during replication and transcription. To elucidate the specific function of DNA topoisomerase 1α ( A t T O P 1 α ) in male reproductive development of Arabidopsis thaliana, we investigated meiotic cell division in Arabidopsis flower buds. Combining cytological and biochemical techniques, we aimed to reveal the novel contribution of A t T O P 1 α to meiosis. Our results demonstrate that the absence of A t T O P 1 α leads to aberrant chromatin behavior during meiotic division. Specifically, the top1α1 mutant displayed altered heterochromatin distribution and clustered centromere signals at early meiotic stages. Additionally, this mutant exhibited disruptions in the distribution of 45s rDNA signals and a reduced frequency of chiasma formation during metaphase I, a crucial stage for genetic exchange. Furthermore, the atm-2×top1α1 double mutant displayed even more severe meiotic defects, including incomplete synapsis, DNA fragmentation, and the presence of polyads. These observations collectively suggest that A t T O P 1 α plays a critical role in ensuring accurate meiotic progression, promoting homologous chromosome crossover formation, and potentially functioning in a shared DNA repair pathway with ATAXIA TELANGIECTASIA MUTATED (ATM) in Arabidopsis microspore mother cells.

Pirfenidone targeted mechanisms for alleviating methotrexate-induced testiculopathy in Wistar rats.

Testicular injury and affected spermatogenesis are major complications of methotrexate (MTX) use. Oxidative stress is one contributing process leading to inflammation and apoptosis induction. Pirfenidone (PFD) is a well-known anti-fibrotic drug prescribed for interstitial lung fibrosis, in addition to anti-inflammatory, antioxidative, and antiapoptotic capabilities. The study aimed to explore the potential protection afforded by PFD in a rat model of MTX-induced testiculopathy. The experimental design included four groups, each containing seven adult Wistar rats: control, PFD (500 mg/kg/day, orally)-, MTX (0.5 mg/kg, intraperitoneal, twice weekly)-, and PFD/MTX-treated groups. Treatment continued for 4 weeks. Blood and testicular samples were harvested for biochemical, histological, immunohistochemical, and polymerase chain reaction (PCR) analyses. Also, the testicular damage and spermatogenic activity were graded by the testicular injury and Johnsen scoring system, respectively. PFD positively affected the serum testosterone (TST) level, reduced the testicular inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß)], reduced the testicular oxidative burden, increased superoxide dismutase (SOD), and protected the testicular histological structure. In addition, antifibrotic effects, anti-caspase-3, and PCNA enhancement activity were recorded. PFD exhibited a protective potential and mitigated the MTX-induced testiculopathy via suppression of testicular oxidative stress, inflammation, fibrosis, and apoptosis and retaining the testicular proliferative efficacy as confirmed by histological, immunohistochemical, and biochemical methods.

A two-variant model of SARS-COV-2 transmission: estimating the characteristics of a newly emerging strain.

BACKGROUND: The Covid-19 pandemic has been characterized by the emergence of novel SARS-CoV-2 variants, each with distinct properties influencing transmission dynamics, immune escape, and virulence, which, in turn, influence their impact on local populations. Swift analysis of the properties of newly emerged variants is essential in the initial days and weeks to enhance readiness and facilitate the scaling of clinical and public health system responses. METHODS: This paper introduces a two-variant metapopulation compartmental model of disease transmission to simulate the dynamics of disease transmission during a period of transition to a newly dominant strain. Leveraging novel S-gene dropout analysis data and genomic sequencing data, combined with confirmed Covid-19 case data, we estimate the epidemiological characteristics of the Omicron variant, which replaced the Delta variant in late 2021 in Philadelphia, PA. We utilized a grid-search method to identify plausible combinations of model parameters, followed by an ensemble adjustment Kalman filter for parameter inference. RESULTS: The model successfully estimated key epidemiological parameters; we estimated the ascertainment rate of 0.22 (95% credible interval 0.15-0.29) and transmission rate of 5.0 (95% CI 2.4-6.6) for the Omicron variant. CONCLUSIONS: The study demonstrates the potential for this model-inference framework to provide real-time insights during the emergence of novel variants, aiding in timely public health responses.

Knowledge, attitude, and practices of pharmacy students in 7 Middle Eastern countries concerning antibiotic resistance: A cross-sectional study.

Addressing antimicrobial resistance (AMR) stands as a major global health challenge threatening humanity. Resolving this issue can be initiated through emphasizing the significance of AMR education among students in health colleges during their undergraduate studies. Hence, the aim of this study is to assess the pharmacy students' knowledge, attitudes, and practices regarding antibiotic resistance in 7 Middle Eastern countries. A cross-sectional study was conducted among undergraduate pharmacy students at universities in Egypt, Jordan, Saudi Arabia, Lebanon, the United Arab Emirates, Qatar, and Kuwait between March 2021 and January 2022. The first section of the questionnaire gathered demographic information. The knowledge section comprised 7 questions. Subsequently, the questionnaire explored participants' attitudes (6 items) and practices (2 items) concerning antibiotic resistance. Mann-Whitney and Kruskal-Wallis tests were used to compare the median knowledge score between different demographic groups. Logistic regression was used to estimate odds ratios, with 95% confidence intervals (CIs) for being more knowledgeable about antibiotic resistance. A 2-sided P < .05 was considered statistically significant. A total of 4265 pharmacy students were involved in this study (Egypt (2249), Jordan (n = 704), Saudi Arabia (n = 531), Lebanon (n = 401), United Araba Emirates (n = 130), Qatar (n = 129), and Kuwait (n = 121)). The median knowledge score for the participating pharmacy students was 5.00 (IQR = 4.00-6.00) out of 7, equals to 71.4% with 4th, and 5th year students and bachelor of pharmacy program students have higher odds of being more knowledgeable about antibiotics resistance compared to other students (P < .05). The majority of the students agreed that antibiotic resistance is increasing, they should be more concerned regarding antibiotic consumption and that government should create more awareness of antibiotic resistance, and that they should have enough knowledge to prevent antibiotic resistance. Around 3 quarters of the students (73.0%) confirmed that they take antibiotic only after getting prescription from their physician and almost half (51.7%) reported that they take antibiotic to manage their fever. The study concluded good educational programs in Middle East pharmacy schools with the need for targeted educational interventions promoting responsible antibiotic stewardship practices among future pharmacists.

A randomized, double-blind phase 2b trial to evaluate efficacy of ChAd63-KH for treatment of post kala-azar dermal leishmaniasis.

In a recent phase 2a clinical trial, the candidate leishmaniasis vaccine ChAd63-KH was shown to be safe and immunogenic in Sudanese patients with post kala-azar dermal leishmaniasis (PKDL). However, its value as a stand-alone therapeutic was unknown. To assess the therapeutic efficacy of ChAd63-KH, we conducted a randomized, double-blind, placebo-controlled phase 2b trial (ClinicalTrials.gov: NCT03969134). Primary outcomes were safety and efficacy (≥90% improvement in clinical disease). Secondary outcomes were change in severity grade and vaccine-induced immune response. 86 participants with uncomplicated PKDL of ≥6 month duration were randomized to receive ChAd63-KH (7.5 × 1010 viral particles, once by the intramuscular route) or placebo. 75 participants (87%) completed the trial as per protocol. No severe or serious adverse events were observed. At day 90 post-vaccination, 6/40 (15%) and 4/35 (11%) participants in the vaccine and placebo groups, respectively, showed ≥90% clinical improvement (risk ratio [RR] 1.31 [95% confidence interval (CI), 0.40-4.28], p = 0.742). There were also no significant differences in PKDL severity grade between study arms. Whole-blood transcriptomic analysis identified transcriptional modules associated with interferon responses and monocyte and dendritic cell activation. Thus, a single vaccination with ChAd63-KH showed no therapeutic efficacy in this subset of Sudanese patients with PKDL.

Potential human health risk assessment associated with Hg, Cd, Pb, and As in sardines and shrimp from four Egyptian coastal governorates.

Heavy metal contamination in seafood is a developing concern due to the potential negative consequences on human health. Egypt's coastal regions are important for seafood production and consumption, making it critical to assess the safety of these aquatic resources. The current study examined toxic metal levels (Hg, Pb, Cd, and AS) in 96 samples of sardine and shrimp from four Egyptian coastal governorates (Alexandria, Kafr El-Sheikh, Damietta, and Port Said) from 2019 to 2021. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) was used to investigate the four hazardous metals. The recovery percentages of the determined metals ranged between 97 % and 99 %. Limits of detection (LOD) and limit of quantification (LOQ) for the determined metals ranged from 0.001 to 0.0077 mg/l and from 0.0035 to 0.026 mg/l, respectively. Mercury (Hg) was not found in any of the samples tested. The concentrations of Pb and Cd in the sardines and shrimp samples were higher in the winter seasons than in the summer seasons. Meanwhile, the difference in seasons had no effect on the concentration of As in the sardines and shrimp samples. The highest concentrations of the other three metals in the sardine and shrimp samples were used to calculate the Estimated Daily Intake (EDI), Target Hazard Quotient (THQ), and Hazard Index (HI). The obtained THQ as well as the HI of Pb, Cd, and As were all less than 1.0 (with the exception of sardine samples from Kafr El-Sheikh Governorate, which recorded 1.262), indicating that there is no significant health risk to the consumer from consuming such sardines and shrimp from these governorates. The effect of different seasons on the concentrations of the metals under study does not have a specific behavior, but varies according to the governorate, the type of sample, and the type of contaminated metal. Due to the high level of contamination with heavy metals in sardine samples collected from Kafr El-Sheikh governorate (TTHQ = 1.26), an environmental study is required to determine the causes of contamination and control them.

Comparative Analysis of Dosimetry: IMRT versus 3DCRT in Left-Sided Breast Cancer Patients with Considering Some Organs in Out - of - Field Borders.

Purpose: The local management approach for node-positive breast cancer has undergone substantial evolution. Consequently, there exists a pressing need to enhance our treatment strategies by placing greater emphasis on planning and dosimetric factors, given the availability of more conformal techniques and delineation criteria, achieving optimal goals of radiotherapy treatment. The primary aim of this article is to discuss how the extent of regional nodal coverage influences the choice between IMRT and 3D radiation therapy for patients. Patients and Methods: A total of 15 patients diagnosed with left breast cancer with disease involved lymph nodes were included in this study. Delivering the recommended dose required the use of a linear accelerator (LINAC) with photon beams energy of 6 mega voltage (6MV). Each patient had full breast radiation using two planning procedures: intensity-modulated radiotherapy (IMRT) and three-dimensional radiotherapy (3D conformal). Following the guidelines set forth by the Radiation Therapy Oncology Group (RTOG), the planned treatment coverage was carefully designed to fall between 95% and 107% of the recommended dose. Additionally, Dose Volume Histograms (DVHs) were generated the dose distribution within these anatomical contours. Results and Conclusion: The DVH parameters were subjected to a comparative analysis, focusing on the doses absorbed by both Organs at Risk (OARs) and the Planning Target Volume (PTV). The findings suggest that low doses in IMRT plan might raise the risk of adverse oncological outcomes or potentially result in an increased incidence of subsequent malignancies. Consequently, the adoption of inverse IMRT remains limited, and the decision to opt for this therapy should be reserved for situations where it is genuinely necessary to uphold a satisfactory quality of life. Additionally, this approach helps in reducing the likelihood of developing thyroid problems and mitigates the risk of injuries to the supraclavicular area and the proximal head of the humerus bone.

Management strategies and outcomes of thromboembolism prevention in atrial fibrillation co-existing with immune thrombocytopenia: A review of evidence.

This review aimed to assess bleeding risks and explore management options in atrial fibrillation (AF) patients with immune thrombocytopenia (ITP), aiming to formulate an optimal therapeutic approach for improved patient prognosis. Employing MeSH terms, a comprehensive search strategy identified articles on bleeding risks and management guidelines in AF combined with ITP. Original research papers were included, while animal studies, reviews, and non-English articles were excluded. From four databases, 1891 articles were initially retrieved, resulting in 10 relevant full-text articles. Eight studies investigated the effectiveness of anticoagulants in managing concurrent AF and ITP, demonstrating reduced bleeding risk and promising outcomes. Two papers explored surgical interventions, particularly left atrial appendage closure, suggesting its safety for AF management in patients with primary hemostatic disorders, including thrombocytopenia. While the pathophysiological mechanisms of AF and ITP remain unclear, anticoagulation regimens exhibited promising reductions in bleeding risks. Larger studies are warranted to enhance understanding and investigate optimal treatments for AF and ITP.

Microglia depletion and repopulation do not alter the effects of cranial irradiation on hippocampal neurogenesis.

Cranial radiotherapy can cause lifelong cognitive complications in childhood brain tumor survivors, and reduced hippocampal neurogenesis is hypothesized to contribute to this. Following irradiation (IR), microglia clear dead neural progenitors and give rise to a neuroinflammatory microenvironment, which promotes a switch in surviving progenitors from neuronal to glial differentiation. Recently, depletion and repopulation of microglia were shown to promote neurogenesis and ameliorate cognitive deficits in various brain injury models. In this study, we utilized the Cx3cr1CreERt2-YFP/+Rosa26DTA/+ transgenic mouse model to deplete microglia in the juvenile mouse brain before subjecting them to whole-brain IR and investigated the short- and long-term effects on hippocampal neurogenesis. Within the initial 24 h after IR, the absence of microglia led to an accumulation of dead cells in the subgranular zone, and 50-fold higher levels of the chemokine C-C motif ligand 2 (CCL2) in sham brains and 7-fold higher levels after IR. The absence of microglia, and the subsequent repopulation within 10 days, did neither affect the loss of proliferating or doublecortin-positive cells, nor the reduced growth of the granule cell layer. Our results argue against a role for a pro-inflammatory microenvironment in the dysregulation of hippocampal neurogenesis and suggest that the observed reduction of neurogenesis was solely due to IR.

Impaired energy metabolism and altered brain histoarchitecture characterized by inhibition of glycolysis and mitochondrial electron transport-linked enzymes in rats exposed to diisononyl phthalate.

The brain is an energy demanding organ, constituting about 20 % of the body's resting metabolic rate. An efficient energy metabolism is critical to neuronal functions. Glucose serves as the primary essential energy source for the adult brain and plays a critical role in supporting neural growth and development. Endocrine disrupting chemicals (EDCs) such as phthalates has been shown to have a negative impact on neurological functions. The impact of diisononyl phthalate (DiNP) on neural energy transduction using cellular energy metabolizing enzymes as indicators was examined. Over the course of 14 days, eighteen (18) albino rats divided into three groups (1,2 and 3) of six albino rats were given Tween-80/saline, 20 and 200 mg/kg body weight respectively. In the brain, we assessed histological changes as well as activities of selected enzymes of energy metabolism such as the glycolytic pathway, citric acid cycle and mitochondrial electron transport-linked complexes. Activities of the glycolytic and TCA cycle enzymes assayed were significantly decreased except citrate synthase activity with no statistically significant change following the administration of DiNP. Also, respiratory chain complexes (Complex I-IV) activities were significantly reduced when compared to control. DiNP exposure altered the histological integrity of various brain sections. These include degenerated Purkinje neurons, distortion of the granular layer and Purkinje cell layer. Data from this study indicated impaired brain energy metabolism via down-regulation of enzymes of cellular respiration of the glycolytic and oxidative phosphorylation pathways and altered brain histoarchitecture orchestrated by DiNP exposure.

Molybdenum tungsten hydrogen oxide doped with phosphorus for enhanced oxygen/hydrogen evolution reactions.

The development of efficient electrocatalysts for hydrogen and oxygen evolution reactions (HER and OER) is pivotal for advancing cleaner and sustainable fuel production technologies. The conventional electrocatalysts have limited stability and higher overpotentials, and there is demand to explore advanced materials and synthesis methods. In this context, a novel bifunctional electrocatalyst has been devised through the phosphidation of tungsten molybdenum oxide (P-Mo0.69W0.31H0.98O3) at relatively low temperatures. This innovative approach aims to enhance the efficiency of HER and OER while minimizing the overpotential values and maintaining higher stability. Specifically, the individual performance of Mo0.69W0.31H0.98O3 has been significantly boosted by doping it with phosphorus at a low temperature of 300 °C. This doping process results in a unique morphology for the catalyst, leading to a notable improvement in OER/HER performances. P-Mo0.69W0.31H0.98O3 exhibits a potential of 320 mV at 10 mA cm-2 in a KOH electrolyte, demonstrating both high activity and long-term stability. Additionally, P-Mo0.69W0.31H0.98O3 exhibits commendable HER performance, requiring only 380 mV at 100 mA cm-2. This combination of efficient OER and HER performance positions P-Mo0.69W0.31H0.98O3 as representing a significant advancement in the field of electrocatalysis, additionally addressing the fundamental gap by providing stable and hybrid catalyst for various electrochemical devices. Given its cost-effectiveness and exceptional activity, P-Mo0.69W0.31H0.98O3 holds significant potential for advancing the field of electrocatalysis and contributing to the development of cleaner and sustainable fuel production methods.

Longitudinal Multiparametric Quantitative MRI Evaluation of Acute and Chronic Multiple Sclerosis Paramagnetic Rim Lesions.

BACKGROUND: Multiple sclerosis (MS) paramagnetic rim lesions (PRLs) are markers of chronic active biology and exhibit complex iron and myelin changes that may complicate quantification when using conventional MRI approaches. PURPOSE: To conduct a multiparametric MRI analysis of PRLs. STUDY TYPE: Retrospective/longitudinal. SUBJECTS: Ninety-five progressive MS subjects with at least one persistent PRL who were enrolled in the CONSONANCE trial. FIELD STRENGTH/SEQUENCE: 3-T/Susceptibility-weighted, T1-weighted, T2-weighted, and fluid-attenuated inversion recovery. ASSESSMENT: Acute/chronic PRLs and non-PRLs were measured at screening, 24, 48, and 96 weeks using quantitative magnetic susceptibility (QS), R2*, and standardized T1w/T2w ratio (sT1w/T2w). PRL analyses were performed for whole lesion, core, and rim. The correlations between PRL core and rim sT1w/T2w, QS, and R2* were assessed. STATISTICAL TESTS: Linear mixed models. A P-value <0.05 was considered significant. RESULTS: There was a significant decrease in sT1w/T2w (-0.24 ± -5.3 × 10-3) and R2* (-3.6 ± 2.2 Hz) but a significant increase in QS (+21 ± 1.3 ppb) using whole-lesion analysis of chronic PRLs compared to non-PRLs at screening. Tissue damage accumulated at the 96-week time point was more evident in acute/chronic PRLs compared to acute/chronic non-PRLs (ΔsT1w/T2w = -0.21/-0.24 ± 0.033/0.0053; ΔR2* = -4.4/-3.6 ± 1.4/2.2 Hz). New, acute PRL sT1w/T2w significantly increased in lesion core (+4.3 × 10-3 ± 1.2 × 10-4) and rim (+5.6 × 10-3 ± 1.2 × 10-4) 24 weeks post lesion inception, suggestive of partial recovery. Chronic PRLs, contrastingly, showed significant decreases in sT1w/T2w over the initial 24 weeks for both core (-2.1 × 10-4 ± 2.0 × 10-5) and rim (-2.4 × 10-4 ± 2.0 × 10-5), indicative of irreversible tissue damage. Significant positive correlations between PRL core and rim sT1w/T2w (R2 = 0.53), R2* (R2 = 0.69) and QS (R2 = 0.52) were observed. DATA CONCLUSION: Multiparametric assessment of PRLs has the potential to be a valuable tool for assessing complex iron and myelin changes in chronic active PRLs of progressive MS patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Smaller thoracic canal diameters are associated with thoracic radiculopathy and abdominal pain after spinal cord stimulator paddle lead placement.

INTRODUCTION: It is not uncommon for patients to experience postoperative neurologic deficit, thoracic radiculopathy, abdominal pain, or lower extremity paresthesia after the implantation of thoracic spinal cord stimulator (SCS) paddle leads. Smaller thoracic canal diameters have previously been associated with postoperative neurologic deficits. OBJECTIVE: This imaging study examined whether postoperative SCS neurologic complaints other than neurologic deficit may be correlated with thoracic spinal canal diameter. METHODS: Patients who underwent thoracic laminotomy for SCS paddle lead placement between January 2018 and March 2023 were identified. Preoperative thoracic canal diameter was measured on MRI or CT imaging in the sagittal plane from T5/6 to T11/12. The canal diameters of patients with and without new postoperative neurologic complaints were compared. RESULTS: Two hundred forty-six patients underwent thoracic laminotomy for SCS paddle lead placement. Thoracic radiculopathy, abdominal pain, and lower extremity paresthesia occurred in 3.7% (9/246), 2.8% (7/246), and 2.0% (5/246) patients, respectively. The mean canal diameter for patients without neurologic complaint, thoracic radiculopathy, abdominal pain, and lower extremity paresthesia was 13.1 mm, 12.0 mm (p < 0.0001), 12.1 mm (p < 0.01), and 12.8 mm (p = 0.365), respectively. CONCLUSION: A smaller thoracic canal diameter is associated with postoperative thoracic radiculopathy and abdominal pain. We believe that surgical planning to create adequate space for SCS leads is critical in preventing postoperative neurologic complaints of deficit, thoracic radiculopathy, and abdominal pain.

Hibiscus schizopetalus boosts wound healing via restoring redox balance and hindering inflammatory responses in rats: Insights on metabolome profiling and molecular docking.

Hibiscus species (Malvaceae) possess a plethora of appealing pharmacological activities with an extended history of customary use in diverse medical conditions. The present study aimed at comparing the metabolomic analyses of three Hibiscus species native to Egypt, namely H. tiliaceus, H. schizopetalus extract (HSE), and H. rosa-sinensis, alongside identifying a promising natural wound healing candidate. Chemical profiling of the leaf extracts was achieved via UPLC-ESI/MS/MS-guided analysis that resulted in the tentative identification of a total of 48 secondary metabolites pertaining to phenolic acids, flavonoids, anthocyanins, fatty acids, and fatty amides. Remarkably, in vitro studies revealed that HSE exhibited the topmost wound healing activity. Subsequently, HSE was formulated into hydro- and nanogel (1% w/v) formulations for further assessing its efficacy in the wound excision model. HSE-nanogel demonstrated a significant in vivo wound contraction activity alongside improving histopathological abnormalities. Mechanistically, HSE-nanogel upregulated the wound antioxidant status through increasing the levels of reduced glutathione (GSH) and catalase activity. Moreover, HSE-nanogel suppressed the wound inflammatory responses by diminishing the expressions of NF-ĸB, TNF-α, and IL-6. Molecular docking studies were performed on HSE's major constituents using CDOCKER, which further supported the in vivo findings. Collectively, HSE nanogel exhibits notable aptitude as a wound-healing agent, warranting further clinical appraisal.

Optimal techno-economic assessment of isolated microgrid integrated with fast charging stations using radial basis deep learning.

The global transportation electrification commerce sector is now booming. Stakeholders are paying an increased attention to the integration of electric vehicles and electric buses into  the transportation networks. As a result, there is an urgent need to invest in public charging infrastructure, particularly for fast charging facilities. Consequently, and to complete the portfolio of the green environment, these fast-charging stations (FCSs) are designed using 100% of renewable energy sources (RESs). Thus, this paper proposes an optimization model for the techno-economic assessment of FCSs comprising photovoltaic and wind turbines with various energy storage devices (ESDs). In this regard, the FCS performance is evaluated using flywheels and super capacitors due to their high-power density and charging/discharging cycles and rates. Then, optimal sizing of these distributed generators is attained considering diverse technical and economical key performance indicators. Afterwards, the problem gets more sophisticated by investigating the effect of RES's uncertainties on the selection criterion of the FCS's components, design and capacity. Eventually, as an effort dedicated to an online energy management approach, a deep learning methodology based on radial basis network (RBN) is implemented, validated, and carried out. In stark contrast to conventional optimization approaches, RBN demonstrates its superiority by obtaining the optimum solutions in a relatively short amount of time.