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This study aimed to compare the pre- and post-operative temporomandibular joint (TMJ) condylar position in dentofacial deformity (DFD) patients who had orthognathic surgeries using cone beam computed tomography (CBCT). A retrospective study evaluating the pre- and post-operative CBCT for 79 DFD patients (equivalent to 158 TMJs) (mean age = 26.62 ± 9.5 years) with a bilateral sagittal split osteotomy with or without Le Fort I surgeries (n = 29 Class II DFD, n = 50 Class III DFD) was performed. This included the compartmental measurement of TMJ spaces, in addition to the measurement of intercondylar distances and angles. Condylar position centricity was assessed using the Pullinger and Hollender formula. Clinical data were analysed for DFD class, the type of surgery and post-operative CBCT timing. Pre- and post-operative measurements were compared statistically using a paired t-test, Wilcoxon signed-rank test, and Stuart-Maxwell test. TMJ condyles tended to relocate post-operatively in a posterosuperior position with internal rotation in Class II DFD and a superior position with internal rotation in Class III DFD. However, the overall changes were within <0.5 mm translation and <4° rotation and the number of concentrically positioned condyles (according to the Pullinger and Hollender formula) did not change significantly. Orthognathic surgery is associated with minor post-operative translational and rotational condylar positional changes in Class II and III DFDs.
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The rapid advancement of computational infrastructure has led to unprecedented growth in machine learning, deep learning, and computer vision, fundamentally transforming the analysis of retinal images. By utilizing a wide array of visual cues extracted from retinal fundus images, sophisticated artificial intelligence models have been developed to diagnose various retinal disorders. This paper concentrates on the detection of Age-Related Macular Degeneration (AMD), a significant retinal condition, by offering an exhaustive examination of recent machine learning and deep learning methodologies. Additionally, it discusses potential obstacles and constraints associated with implementing this technology in the field of ophthalmology. Through a systematic review, this research aims to assess the efficacy of machine learning and deep learning techniques in discerning AMD from different modalities as they have shown promise in the field of AMD and retinal disorders diagnosis. Organized around prevalent datasets and imaging techniques, the paper initially outlines assessment criteria, image preprocessing methodologies, and learning frameworks before conducting a thorough investigation of diverse approaches for AMD detection. Drawing insights from the analysis of more than 30 selected studies, the conclusion underscores current research trajectories, major challenges, and future prospects in AMD diagnosis, providing a valuable resource for both scholars and practitioners in the domain.
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A Virtual Power Plant (VPP) is a centralized energy system that manages, and coordinates distributed energy resources, integrating them into a unified entity. While the physical assets may be dispersed across various locations, the VPP integrates them into a virtual unified entity capable of responding to grid demands and market signals. This paper presents a tri-level hierarchical coordinated operational framework of VPP. Firstly, an Improved Pelican Optimization Algorithm (IPOA) is introduced to optimally schedule Distributed Energy Resources (DERs) within the VPP, resulting in a significant reduction in generation costs. Comparative analysis against conventional algorithms such as Genetic Algorithm (GA) and Particle Swarm Optimization (PSO) demonstrates IPOA's superior performance, achieving an average reduction of 8.5% in generation costs across various case studies. The second stage focuses on securing the optimized generation data from rising cyber threats, employing the capabilities of machine learning, preferably, a convolutional autoencoder to learn the normal patterns of the optimized data to detect deviations from the optimized generation data to prevent suboptimal decisions. The model exhibits exceptional performance in detecting manipulated data, with a False Positive Rate (FPR) of 1.92% and a Detection Accuracy (DA) of 98.06%, outperforming traditional detection techniques. Lastly, the paper delves into the dynamic nature of the day ahead market that the VPP participates in. In responding to the grid by selling its optimized generated power via the day-ahead market, the VPP employs the Prophet model, another machine learning technique to forecast the spot market price for the day-ahead to mitigate the adverse effects of price volatility. By utilizing Prophet forecasts, the VPP achieves an average revenue increase of 15.3% compared to scenarios without price prediction, emphasizing the critical role of predictive analytics in optimizing economic gains. This tri-level coordinated approach adopted addresses key challenges in the energy sector, facilitating progress towards achieving universal access to clean and affordable energy.
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OBJECTIVE: To assess the diagnostic efficacy of integrating B-mode and color Doppler capabilities of ultrasound (US) to establish a robust standalone diagnostic tool for the diagnosis of ureteric stones as an alternative to non-contrast-enhanced computed tomography (NCCT). METHODS: A total of 140 consecutive patients diagnosed with ureteric stones using NCCT were enrolled. On the same day, US in both B-mode and Color Doppler was performed by an experienced radiologist who was blinded to the NCCT scan results. The diagnostic rate of US for stone detection was recorded. Additionally, baseline patient and stone characteristics were analyzed for their association with the accuracy of stone detection using US. RESULTS: US exhibited a high sensitivity of 91.43%, detecting 128 out of 140 stone foci. Notably, ureteric stones in the proximal and uretero-vesical junction (UVJ) segments were readily identifiable compared to those in the pelvic region (p = 0.0003). Additionally, hydronephrosis enhanced the US's ability to detect stones (p < 0.0001). Conversely, abdominal gases and obesity adversely affected US capabilities (p < 0.0001 and p = 0.009, respectively). Stone side, size, and density showed no statistically significant impact (p > 0.05). CONCLUSIONS: US with its color Doppler capabilities could serve as a reliable and safe alternative imaging modality in the diagnostic work up of patients with ureterolithiasis. Factors including stone location, Hydronephrosis, weight and abdominal gases significantly influenced its accuracy.
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Tomografía Computarizada por Rayos X , Ultrasonografía Doppler en Color , Cálculos Ureterales , Humanos , Cálculos Ureterales/diagnóstico por imagen , Ultrasonografía Doppler en Color/métodos , Masculino , Femenino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Anciano , Adulto , Exposición a la Radiación/análisis , Sensibilidad y Especificidad , Anciano de 80 o más Años , Estudios Prospectivos , Adulto JovenRESUMEN
A study was carried out to compare the infection rates of Leishmania donovani in Phlebotomus orientalis sandflies at different microhabitats of a VL endemic village in Gedarif state, Sudan. DNA extracts of 1078 P. orientalis sand fly females sampled by CDC light traps from indoor, outdoor, peri-domestic, and sylvatic sites, in three transmission seasons, March-June 2016-18, in Helat-Belo village, were subjected to independent PCR amplifications targeting Leishmania kDNA and the cpb gene followed by ITS1 region sequencing. Leishmania kDNA was detected in 1.4% of the 1078 P. orientalis females captured in the area. Two of these specimens showed a characteristic 741 bp band of L. donovani after cpb gene amplification. The DNA sequence of the ITS1 region of the parasites matched the ITS1 L. donovani genotype F. There were no signficant differences between rates of infection of L. donovani in P. orientalis captured at different sites. Blood meals found in infected flies origninated from human (5 specimens), cattle (4 specimens) and donkey (2 specimens). The finding of fresh cow and donkey blood in the infected flies suggests the possible role of these animals in the zoopotentiation and/or zooprophylaxis against VL. The study provides important information for VL transmission models and control programs in East Africa.
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Workplace violence experienced by healthcare providers (HCPs) in Sudan has gone viral, driving many HCPs outside the country. Globally, HCPs have accepted workplace violence as a phenomenon integral to their clinical work, causing an underreporting of incidents. This study reviews the causes and explores solutions for the phenomenon. Search strategies were conducted using internet sources including PubMed, Embase, Google Scholar, and Cochrane. References to Sudan were limited to HCPs in public healthcare facilities. A descriptive analysis was conducted on the global status of workplace violence toward HCPs. Future interventions were examined and discussed considering Sudan's circumstances. Results showed the "pandemic" nature of the phenomenon. Workplace violence contributes to the deterioration of the quality and efficiency of the healthcare system with consequences for effective healthcare delivery. It is concluded that a multiapproach intervention needs to be integrated to circumvent the standing multifactorial situation. Statutory actions are needed towards the widespread violence and impunity. Workplace organizational procedures are needed to address the patient's needs that overwhelm scarce resources. Robust educational efforts are recommended by HCP training bodies, the media, and other stakeholders to improve the doctor/patient relationship.
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The increase in eye disorders among older individuals has raised concerns, necessitating early detection through regular eye examinations. Age-related macular degeneration (AMD), a prevalent condition in individuals over 45, is a leading cause of vision impairment in the elderly. This paper presents a comprehensive computer-aided diagnosis (CAD) framework to categorize fundus images into geographic atrophy (GA), intermediate AMD, normal, and wet AMD categories. This is crucial for early detection and precise diagnosis of age-related macular degeneration (AMD), enabling timely intervention and personalized treatment strategies. We have developed a novel system that extracts both local and global appearance markers from fundus images. These markers are obtained from the entire retina and iso-regions aligned with the optical disc. Applying weighted majority voting on the best classifiers improves performance, resulting in an accuracy of 96.85%, sensitivity of 93.72%, specificity of 97.89%, precision of 93.86%, F1 of 93.72%, ROC of 95.85%, balanced accuracy of 95.81%, and weighted sum of 95.38%. This system not only achieves high accuracy but also provides a detailed assessment of the severity of each retinal region. This approach ensures that the final diagnosis aligns with the physician's understanding of AMD, aiding them in ongoing treatment and follow-up for AMD patients.
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Atrofia Geográfica , Degeneración Macular Húmeda , Humanos , Anciano , Fondo de Ojo , Retina , Degeneración Macular Húmeda/diagnóstico , Atrofia Geográfica/diagnóstico por imagen , Aprendizaje AutomáticoRESUMEN
Helicobacter pylori (H. pylori) infection has a variety of clinical outcomes, and host genetic factors play an important role in this process. Cytokines are important factors in mediating and controlling the inflammatory process during H. pylori infection. Interleukin-8 (IL-8) plays a critical role in the epithelial cell response to H. pylori infection and the development of H. pylori-related gastric disorders. The IL-8 gene has an A/T base pair polymorphism in the promoter region (-251), which has been linked to an increase in interleukin production by gastric epithelial cells. In this context, the goal of our study was to determine the polymorphism in the IL-8 gene and its relation to H. pylori infection and H. pylori-associated gastric diseases. Gastric biopsy specimens were collected from 44 patients with H. pylori infection and 29 patients without H. pylori infection. The rapid urease test and detection of the glmM gene were used to diagnose H. pylori infection. Polymerase chain reaction-restriction fragment length polymorphism was used to identify the polymorphism in the Il-8 gene (at position-251). The presence of the A/A and T/A genotypes of the IL-8 gene was found to be significantly associated with susceptibility to H. pylori infection (p = 0.012 and p = 0.004, respectively). Also, the IL-8 A allele was significantly associated with H. pylori infection in our study (p = 0.002). We did not find a significant association between IL-8 gene polymorphism and a higher risk of gastritis and peptic ulcer disease. In conclusion, IL-8 gene polymorphism at -251 position was significantly associated with H. pylori infection.
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Infecciones por Helicobacter , Interleucina-8 , Humanos , Genotipo , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/genética , Helicobacter pylori , Interleucina-8/genética , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
PURPOSE: To compare the therapeutic response and clinical outcome of CT-guided percutaneous microwave (MWA) and radiofrequency ablation (RFA) for the treatment of small- and medium-sized HCC. MATERIALS AND METHODS: In this prospective trial, 50 patients with HCC were randomly assigned to MWA or RFA treatment. MRI was performed 24âh before and after ablation and subsequently in 3-month intervals. Ablation volumes, ablation durations, adverse events (AE), technique efficacy, technical success, local tumor progression (LTP), disease-free survival (DFS), intrahepatic distant recurrence (IDR), and overall survival (OS) rates were evaluated. RESULTS: The mean ablation volume was 66.5âcm³ for MWA and 29.2 âcm³ for RFA (pâ<â0.01). The mean ablation durations for MWA and RFA were 11.2â±â4.0âmin and 16.3â±â4.7âmin, respectively (pâ<â0.01). Six mild AEs were documented (pâ>â0.05). All treatments had a technical success rate and a technique efficacy rate of 100â% (50/50, pâ=â1.00). LTP within 2 years occurred in 1/25 (4â%) in the MWA group and in 4/25 (16â%) in the RFA group (pâ=â0.06). IDR within 2 years was 8/25 (32â%) for MWA and 14/25 (56â%) for RFA (pâ<â0.05). The median DFS was 24.5 months and 13.4 months for MWA and RFA, respectively (pâ=â0.02). The 1-, 2-, 3-year OS rates were 100â%, 80â%, 72â% in the MWA group and 72â%, 64â%, 60â% in the RFA group, respectively (pâ≥â0.14). CONCLUSION: The clinical outcome after MWA or RFA for HCC treatment was very similar with no significant differences in LTP or OS.âHowever, MWA shows a trend toward better DFS with fewer IDRs than RFA. KEY POINTS: · MWA allows for larger ablation volumes and a shorter treatment duration compared to RFA in patients with HCC.. · MWA shows a trend toward better disease-free survival and fewer intrahepatic distant recurrences compared to RFA.. · The three-year survival rates show no significant difference between the two methods..
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Recently, there has been a growing interest in polymer insulating materials that incorporate nanoscale inorganic additives, as they have shown significantly improved dielectric, thermal, and mechanical properties, making them highly suitable for application in high-voltage insulating materials for electrical machines. This study aims to improve the dielectric and thermal properties of a commercial polyester varnish by incorporating different concentrations of titanium dioxide nanoparticles (TiO2) with proper surface functionalization. Permafil 9637 dipping varnish is the varnish used for this investigation, and vinyl silane is the coupling agent used in the surface functionalization of TiO2 nanoparticles. First, nanoparticles are characterized through Fourier transform infrared spectroscopy to validate the success of their surface functionalization. Then, varnish nanocomposites are characterized through field emission scanning electron microscopy to validate the dispersion and morphology of nanoparticles within the varnish matrix. Following characterization, varnish nanocomposites are evaluated for thermal and dielectric properties. Regarding thermal properties, the thermal conductivity of the prepared nanocomposites is assessed. Regarding dielectric properties, both permittivity and dielectric losses are evaluated over a wide frequency range, starting from 20 Hz up to 2 MHz. Moreover, the AC breakdown voltage is measured for varnish nanocomposites, and the obtained data are incorporated into a finite element method to obtain the dielectric breakdown strength. Finally, the physical mechanisms behind the obtained results are discussed, considering the role of nanoparticle loading and surface functionalization.
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Psoriasis is a chronic inflammatory condition associated with genetic and immunological susceptibility. The objective of the study was to evaluate pruritus and sleep quality in correlation (r) to psoriasis severity and to detect their impact on quality of life. Two hundred (200) patients with psoriasis were included. Psoriasis severity was determined using the psoriasis area severity index (PASI), the quality of life (QoL) was assessed by the psoriasis disability index (PDI) questionnaire, and the sleep quality was evaluated by the Pittsburgh sleep quality index (PSQI). Finally, the severity of itching was evaluated using a 12-item pruritus severity scale (PSS). Poor sleep quality was found in 16.0% of patients in this study. Poor sleep was detected among 50.0% of cases with severe psoriasis. PASI scores correlated significantly with sleep quality, duration and sleep disturbances (p < 0.001). The global PSQI and PASI were also significantly correlated (p = 0.004). In conclusion patients complaining of psoriasis exacerbated by pruritus and sleep problems demonstrated lower quality of life in all domains. Sleep disturbances and depressive symptoms impairing quality of life should be taken into consideration when screening patients suffering from psoriasis.
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Psoriasis , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Sueño-Vigilia , Humanos , Calidad de Vida , Calidad del Sueño , Índice de Severidad de la Enfermedad , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Prurito/complicaciones , Psoriasis/complicaciones , Psoriasis/diagnóstico , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/diagnósticoRESUMEN
The enhancement of the thermal properties of insulating oils has positively reflected on the performance of the electrical equipment that contains these oils. Nanomaterial science plays an influential role in enhancing the different properties of liquids, especially insulating oils. Although a minimum oil circuit breaker (MOCB) is one of the oldest circuit breakers in the electrical network, improving the insulating oil properties develops its performance to overcome some of its troubles. In this paper, 66 kV MOCB is modeled by COMSOL Multiphysics software. The internal temperature and the internally generated heat energy inside the MOCB during the making process of its contacts are simulated at different positions of the movable contact. This simulation is introduced for different modified insulating oils (mineral oil and synthetic ester oil) with different types of nanoparticles at different concentrations (0.0, 0.0025, 0.005, and 0.01 wt%). From the obtained results, it is noticed that the thermal stress on the MOCB can be reduced by the use of high thermal conductivity insulating oils. Nano/insulating oils decrease internal temperature and generate heat energy inside the MOCB by about 17.5%. The corresponding physical mechanisms are clarified considering the thermophoresis effect.
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Mineral oil (MO) is the most popular insulating liquid that is used as an insulating and cooling medium in electrical power transformers. Indeed, for green energy and environmental protection requirements, many researchers introduced other oil types to study the various characteristics of alternative insulating oils using advanced diagnostic tools. In this regard, natural ester oil (NEO) can be considered an attractive substitute for MO. Although NEO has a high viscosity and high dielectric loss, it presents fire safety and environmental advantages over mineral oil. Therefore, the retrofilling of aged MO with fresh NEO is highly recommended for power transformers from an environmental viewpoint. In this study, two accelerated aging processes were applied to MO for 6 and 12 days to simulate MO in service for 6 and 12 years. Moreover, these aged oils were mixed with 80% and 90% fresh NEO. The dielectric strength, relative permittivity, and dissipation factor were sensed using a LCR meter and oil tester devices for all prepared samples to support the condition assessment performance of the oil mixtures. In addition, the electric field distribution was analyzed for a power transformer using the oil mixtures. Furthermore, the dynamic viscosity was measured for all insulating oil samples at different temperatures. From the obtained results, the sample obtained by mixing 90% natural ester oil with 10% mineral oil aged for 6 days is considered superior and achieves an improvement in dielectric strength and relative permittivity by approximately 43% and 48%, respectively, compared to fresh mineral oil. However, the dissipation factor was increased by approximately 20% but was at an acceptable limit. On the other hand, for the same oil sample, due to the higher molecular weight of the NEO, the viscosities of all mixtures were at a higher level than the mineral oil.
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BACKGROUND: Cancer is a well-known risk factor for venous thromboembolism (VTE). A combined strategy of D-dimer testing and clinical pre-test probability is usually used to exclude VTE. However, its effectiveness is diminished in cancer patients due to reduced specificity, ultimately leading to a decreased clinical utility. This review article seeks to provide a comprehensive summary of how to interpret D-dimer testing in cancer patients. METHODS: In accordance with PRISMA standards, literature pertaining to the diagnostic and prognostic significance of D-dimer testing in cancer patients was carefully chosen from reputable sources such as PubMed and the Cochrane databases. RESULTS: D-dimers have not only a diagnostic value in ruling out VTE but can also serve as an aid for rule-in if their values exceed 10-times the upper limit of normal. This threshold allows a diagnosis of VTE in cancer patients with a positive predictive value of more than 80%. Moreover, elevated D-dimers carry important prognostic information and are associated with VTE reoccurrence. A gradual increase in risk for all-cause death suggests that VTE is also an indicator of biologically more aggressive cancer types and advanced cancer stages. Considering the lack of standardization for D-dimer assays, it is essential for clinicians to carefully consider the variations in assay performance and the specific test characteristics of their institution. CONCLUSIONS: Standardizing D-dimer assays and developing modified pretest probability models specifically for cancer patients, along with adjusted cut-off values for D-dimer testing, could significantly enhance the accuracy and effectiveness of VTE diagnosis in this population.
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Productos de Degradación de Fibrina-Fibrinógeno , Neoplasias , Humanos , Neoplasias/sangre , Neoplasias/complicaciones , Neoplasias/diagnóstico , Valor Predictivo de las Pruebas , Factores de Riesgo , Tromboembolia Venosa/sangre , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/prevención & control , Bioensayo/normas , Sensibilidad y EspecificidadRESUMEN
Background: Nail psoriasis is a challenging chronic condition affecting patients functionally and psychologically. Nail involvement is observed in 15-80% of psoriatic patients with occasional presence of isolated nail psoriasis. Objectives: To evaluate dermoscopic features of nail psoriasis and correlate them clinically. Methods: The study included fifty subjects with nail psoriasis. Psoriasis skin and nail severity was evaluated using psoriasis area severity index (PASI) and nail psoriasis severity index (NAPSI). Dermoscopy of the nails (onychoscopy) was performed, and features were recorded and analyzed. Results: The most common clinical and dermoscopic findings were pitting (86%) and onycholysis (82%). Among all dermoscopic features of nail psoriasis, only longitudinal striations and subungual hyperkeratosis were significantly higher in patients with moderate to severe psoriasis than in patients with mild psoriasis (P=0.028; P=0.042, respectively). PASI scores correlated positively but none significantly with NAPSI scores (r = 0.132, P=0.360), and similarly, no significant correlation was observed between the duration of psoriasis and the dermoscopic NAPSI (r = 0.022, P=0.879). Conclusion: Dermoscopy can serve as a useful tool for early diagnosis of psoriatic nail changes not always visible to the naked eye and is a non-invasive easy-to-use confirmatory tool for nail changes in psoriatic disease or in isolated nail involvement.
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To exploit the advantageous properties of approved drugs to hasten anticancer drug discovery, we designed and synthesized a series of fluoroquinolone (FQ) analogs via functionalization of the acid hydrazides of moxifloxacin, ofloxacin, and ciprofloxacin. Under the NCI-60 Human Tumor Cell Line Screening Assay, (IIIf) was the most potent among moxifloxacin derivatives, whereas (VIb) was the only ofloxacin derivative with significant effects and ciprofloxacin derivatives were devoid of activity. (IIIf) and (VIb) were further selected for five-dose evaluation, where they showed potent growth inhibition with a mean GI50 of 1.78 and 1.45 µM, respectively. (VIb) elicited a more potent effect reaching sub-micromolar level on many cell lines, including MDA-MB-468 and MCF-7 breast cancer cell lines (GI50 = 0.41 and 0.42 µM, respectively), NSCLC cell line HOP-92 (GI50 = 0.50 µM) and CNS cell lines SNB-19 and U-251 (GI50 = 0.51 and 0.61 µM, respectively). (IIIf) and (VIb) arrested MCF-7 cells at G1/S and G1, respectively, and induced apoptosis mainly through the intrinsic pathway as shown by the increased ratio of Bax/Bcl-2 and caspase-9 with a lesser activation of the extrinsic pathway through caspase-8. Both compounds inhibited topoisomerase (Topo) with preferential activity on type II over type I and (VIb) was marginally more potent than (IIIf). Docking study suggests that (IIIf) and (VIb) bind differently to Topo II compared to etoposide. (IIIf) and (VIb) possess high potential for oral absorption, low CNS permeability and low binding to plasma proteins as suggested by in silico ADME calculations. Collectively, (IIIf) and (VIb) represent excellent lead molecules for the development of cytotoxic agents from quinolone scaffolds.
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Antineoplásicos , Fluoroquinolonas , Humanos , Estructura Molecular , Relación Estructura-Actividad , Fluoroquinolonas/farmacología , Moxifloxacino/farmacología , Proliferación Celular , Puntos de Control del Ciclo Celular , Antineoplásicos/química , Línea Celular Tumoral , Ciprofloxacina/farmacología , Apoptosis , Ofloxacino/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Ciclo CelularRESUMEN
Virtual simulation-based learning has opened a vista for surmounting ethical issues with the use of animals in compliance with one of the '3Rs' in ethical principles for animal use, which is 'replacement.' It's effective in terms of time, place, and cost. For instance, the time for drug application in cancer models would be less with virtual simulations, and the cost of maintenance and update of the software is less than that of breeding and feeding experimental animals. This paper examines the effects of utilizing a virtual computer tool simulating real pharmacology laboratory equipment in the second semester of a large-scale basic medical course. We looked at the theories of education and instructional designs and used them to develop a virtual computer lab that could help our students meet the intended learning outcomes. We analyzed, developed, implemented, and finally evaluated the students' reactions (at the Kirkpatrick level) using a self-administered questionnaire with responses on a three-point Likert scale. Feedback was obtained from 60 out of 82 (73.2 %) level 4 medical undergraduate students of both sexes, 39/60 (65%) were from the male section of the college. Sixty percent of the students admitted that the software is simple. Sixty percent agreed that it was good. Fifty-seven percent denied previous exposure to the simulation lab. Fifty-two percent reported that the practical lab's content was good, 53.3% rated the achievement of the practical objectives as good, 48.3% rated the practical enforcement of theoretical knowledge as good, 61.7% estimated getting realistic results, 48.3% agreed that the simulation lab encourages formulating a live experiment to test the hypothesis, and 51.7 % decided that the time framework was long. Thirty-eight percent appreciated the learning experience, and 45% felt that it should be repeated elsewhere. Students from the female section opted to record different determinations. The experience of using the virtual computer lab as part of the teaching program in pharmacology confirms the educational value of simulation. By adding a flexible reliable teaching method, we believe it served as a valuable tool for assisting teaching and learning in our context. Moreover, it is perceived as favorable by a good number of our students.
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Sigma 2 receptor (σ2R) is overexpressed in select cancers and is regarded as a biomarker for tumor proliferation. σ2R ligands are emerging as promising theranostics for cancer and neurodegenerative diseases. Herein, we describe the design and synthesis of a series of novel quinolyl pyrazinamides as selective and potent σ2R ligands that show sub-micromolar potency in pancreatic cancer cell lines. Compounds 14 (JR1-157) and 17 (JR2-298) bind σ2R with Ki of 47 and 10 nM, respectively. Importantly, compound 14 has an oral bioavailability of 60% and shows significant in vivo efficacy without obvious toxicity in a syngeneic model of pancreatic cancer. The cytotoxicity of the quinolyl pyrazinamides significantly enhanced in the presence of copper and diminished in the presence of the copper-chelator tetrathiomolybdate. In conclusion, compound 14 is water-soluble, metabolically stable, orally active, and increases the expression of the autophagy marker LC3B and warrants further development for the treatment of pancreatic cancer.
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Neoplasias Pancreáticas , Receptores sigma , Humanos , Ligandos , Pirazinamida , Cobre , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Receptores sigma/metabolismo , Neoplasias PancreáticasRESUMEN
Upcoming experimental and epidemiological data have identified the endogenous non-proteinogenic amino acid L-homoarginine (L-hArg) not only as a novel biomarker for cardiovascular disease but also as being directly involved in the pathogenesis of cardiac dysfunction. The association of low L-hArg levels with adverse cardiovascular events and mortality has proposed the idea of nutritional supplementation to rescue pathways inversely associated with cardiovascular health. Subsequent clinical and experimental studies contributed significantly to our knowledge of potential effects on the cardiorenal axis, acting either as a biomarker or a cardiovascular active agent. In this review article, we provide a comprehensive summary of the L-hArg metabolism, pathophysiological aspects, and current developments in the field of experimental and clinical evidence in favor of protective cardiovascular effects. Establishing a reliable biomarker to identify patients at high risk to die of cardiovascular disease represents one of the main goals for tackling this disease and providing individual therapeutic guidance.