FA4SANS-GAN: A Novel Machine Learning Generative Adversarial Network to Further Understand Ophthalmic Changes in Spaceflight Associated Neuro-Ocular Syndrome (SANS).

Purpose: To provide an automated system for synthesizing fluorescein angiography (FA) images from color fundus photographs for averting risks associated with fluorescein dye and extend its future application to spaceflight associated neuro-ocular syndrome (SANS) detection in spaceflight where resources are limited. Design: Development and validation of a novel conditional generative adversarial network (GAN) trained on limited amount of FA and color fundus images with diabetic retinopathy and control cases. Participants: Color fundus and FA paired images for unique patients were collected from a publicly available study. Methods: FA4SANS-GAN was trained to generate FA images from color fundus photographs using 2 multiscale generators coupled with 2 patch-GAN discriminators. Eight hundred fifty color fundus and FA images were utilized for training by augmenting images from 17 unique patients. The model was evaluated on 56 fluorescein images collected from 14 unique patients. In addition, it was compared with 3 other GAN architectures trained on the same data set. Furthermore, we test the robustness of the models against acquisition noise and retaining structural information when introduced to artificially created biological markers. Main Outcome Measures: For GAN synthesis, metric Fréchet Inception Distance (FID) and Kernel Inception Distance (KID). Also, two 1-sided tests (TOST) based on Welch's t test for measuring statistical significance. Results: On test FA images, mean FID for FA4SANS-GAN was 39.8 (standard deviation, 9.9), which is better than GANgio model's mean of 43.2 (standard deviation, 13.7), Pix2PixHD's mean of 57.3 (standard deviation, 11.5) and Pix2Pix's mean of 67.5 (standard deviation, 11.7). Similarly for KID, FA4SANS-GAN achieved mean of 0.00278 (standard deviation, 0.00167) which is better than other 3 model's mean KID of 0.00303 (standard deviation, 0.00216), 0.00609 (standard deviation, 0.00238), 0.00784 (standard deviation, 0.00218). For TOST measurement, FA4SANS-GAN was proven to be statistically significant versus GANgio (P = 0.006); versus Pix2PixHD (P < 0.00001); and versus Pix2Pix (P < 0.00001). Conclusions: Our study has shown FA4SANS-GAN to be statistically significant for 2 GAN synthesis metrics. Moreover, it is robust against acquisition noise, and can retain clear biological markers compared with the other 3 GAN architectures. This deployment of this model can be crucial in the International Space Station for detecting SANS. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Telmisartan ameliorates nephropathy and restores the hippo pathway in rats with metabolic syndrome.

The main objective of this study was to determine if the telmisartan-ameliorative effects of metabolic syndrome (MetS)-evoked nephropathy are attributed to the Hippo pathway. A secondary objective was to investigate the potential of vitamin D3 to enhance telmisartan-favourable effects. A diet composed of 24% fat and 3% salt, along with drinking water containing 10% fructose, was administered for 12 weeks to induce MetS. MetS-rats were given telmisartan (5 mg/kg/day), vitamin D3 (10 µg/kg/day) or both by gavage, starting in the sixth week of experimental diet administration. Assessments performed at closure included renal function, histological examination, catalase, malondialdehyde (MDA), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphatase and tensin homolog (PTEN), and transforming growth factor-ß (TGF-ß). Matrix metalloproteinase-9 (MMP-9) immunostaining was conducted. The expression of the Hippo pathway components, as well as that of angiotensin II type 1 and type 2 (AT1 and AT2), receptors was evaluated. Telmisartan attenuated MetS-evoked nephropathy, as demonstrated by improvement of renal function and histological features, enhancement of catalase, reduction of MDA, inflammation (NF-κB, IL-6), and renal fibrosis (increased PPAR-γ and PTEN and reduced MMP-9 and TGF-ß). Telmisartan downregulated AT1-receptor, upregulated AT2-receptor and restored the Hippo pathway. Vitamin D3 replicated most of the telmisartan-elicited effects and enhanced the antifibrotic actions of telmisartan. The alleviative effects of telmisartan on MetS-evoked nephropathy may be related to the restoration of the Hippo pathway. The combination of vitamin D3 and telmisartan exerted more favourable effects on metabolic and nephropathic biomarkers compared with either one administered alone.

CYP14 family in Caenorhabditis elegans: Mitochondrial function, detoxification, and lifespan.

CYP-14 members of the Caenorhabditis elegans (C. elegans) Cytochrome P450 (CYP) enzyme family, plays important roles in mitochondrial dysfunction, detoxification, lipid metabolism, defense and lifespan regulation. The review identifies CYP-14 members: cyp-14A1, cyp-14A2, cyp-14A3, cyp-14A4, cyp-14A5 and their homology with human CYP families. Despite limited studies on C. elegans cyp-14 members, the findings unraveled their complex crosstalk between mitochondrial stress, detoxification mechanisms, and lifespan regulation, emphasizing the complexity of these interconnected pathways as well as how their regulation depends on environmental cues changes including pH, nutrients, ROS and chemical stressors. The review underscores the translational relevance to human health, shedding light on potential human homologues and their implications in age-related, metabolic and respiratory diseases. Among other genes, cyp-14A2 and cyp-14A4 predominate the mitochondrial function, heat resistance, lipid metabolism, detoxification and lifespan pathways. In conclusion, these insights pave the way for future research, offering promising avenues for therapeutic interventions targeting CYP-14 activity to address age-related diseases and promote healthy aging.

Evaluation of Quality of Life and Satisfaction with Fixed Prostheses on Zygomatic Implants vs All-on-Four Concept: A Randomized Clinical Study.

AIM: To compare between the rehabilitation of atrophied maxilla with fixed prosthesis using two posterior zygomatic implants and two conventional anterior implants or four implants inserted according to the all-on-four concept regarding the patient quality of life and satisfaction after one year of prosthesis insertion. MATERIALS AND METHODS: Thirty-six patients with atrophic edentulous maxillae were randomized into two groups: Group I (rehabilitated with fixed prostheses supported by two zygomatic and two conventional implants in the anterior region) and group II (fixed prostheses on four implants in the anterior region following an all-on-four concept). One year after the placement of the definitive prostheses, patients completed oral health impact profile-14 and satisfaction questionnaires. RESULTS: All patients were satisfied regarding retention, stability, occlusion, comfort, cleaning, speaking, chewing, bolus quality, appearance, handling, prosthesis apart, and embarrassing, with no significant significance between two groups except satisfaction with surgical procedures and healing period. CONCLUSIONS: Using two distally tilted zygomatic implants or all-on-four concept to rehabilitate atrophied maxilla by fixed detachable prosthesis could be considered a promising functional and esthetic treatment option regarding the patient satisfaction. CLINICAL SIGNIFICANCE: Traditionally, treatment of maxillary atrophied ridges was done by bone grafting or sinus-lifting techniques; however, using all-on-four concept or zygomatic implants was a successful treatment as it has high success rates and highly satisfied by the patients. How to cite this article: Nagib MA, Ibrahim AM, Abdel-Rahman FH, et al. Evaluation of Quality of Life and Satisfaction with Fixed Prostheses on Zygomatic Implants vs All-on-Four Concept: A Randomized Clinical Study. J Contemp Dent Pract 2024;25(2):141-147.

A decade's overview of 2-aminothiophenes and their fused analogs as promising anticancer agents.

Over the past decades, cancer has been a challenging domain for medicinal chemists as it is an international health concern. In association, small molecules such as 2-aminothiophenes and their derivatives showed significant antitumor activity through variable modes of action. Therefore, this article aims to review the advances regarding these core scaffolds over the past 10 years, where 2-aminothiophenes and their fused analogs are classified and discussed according to their biological activity and mode of action, in the interest of boosting new design pathways for medicinal chemists to develop targeted antitumor candidates.

Optimizing combination therapy in prostate cancer: mechanistic insights into the synergistic effects of Paclitaxel and Sulforaphane-induced apoptosis.

BACKGROUND: Combination therapies in cancer treatment have demonstrated synergistic or additive outcomes while also reducing the development of drug resistance compared to monotherapy. This study explores the potential of combining the chemotherapeutic agent Paclitaxel (PTX) with Sulforaphane (SFN), a natural compound primarily found in cruciferous vegetables, to enhance treatment efficacy in prostate cancer. METHODS: Two prostate cancer cell lines, PC-3 and LNCaP, were treated with varying concentrations of PTX, SFN, and their combination. Cell viability was assessed using the thiazolyl blue tetrazolium bromide (MTT) assay to determine the EC50 values. Western blot analysis was conducted to evaluate the expression of Bax, Bcl2, and Caspase-3 activation proteins in response to individual and combined treatments of PTX and SFN. Fluorescent microscopy was employed to observe morphological changes indicative of apoptotic stress in cell nuclei. Flow cytometry analysis was utilized to assess alterations in cell cycle phases, such as redistribution and arrest. Statistical analyses, including Student's t-tests and one-way analysis of variance with Tukey's correction, were performed to determine significant differences between mono- and combination treatments. RESULTS: The impact of PTX, SFN, and their combination on cell viability reduction was evaluated in a dose-dependent manner. The combined treatment enhanced PTX's effects and decreased the EC50 values of both drugs compared to individual treatments. PTX and SFN treatments differentially regulated the expression of Bax and Bcl2 proteins in PC-3 and LNCaP cell lines, favoring apoptosis over cell survival. Our data indicated that combination therapy significantly increased Bax protein expression and the Bax/Bcl2 ratio compared to PTX or SFN alone. Flow cytometry analysis revealed alterations in cell cycle phases, including S-phase arrest and an increased population of apoptotic cells. Notably, the combination treatments did not have a discernible impact on necrotic cells. Signs of apoptotic cell death were confirmed through Caspase-3 cleavage, and morphological changes in cell nuclei were assessed via western blot and fluorescent microscopy. CONCLUSION: This combination therapy of PTX and SFN has the potential to improve prostate cancer treatment by minimizing side effects while maintaining efficacy. Mechanistic investigations revealed that SFN enhances PTX efficacy by promoting apoptosis, activating caspase-3, inducing nuclear morphology changes, modulating the cell cycle, and altering Bax and Bcl2 protein expression. These findings offer valuable insights into the synergistic effects of PTX and SFN, supporting the optimization of combination therapy and providing efficient therapeutic strategies in preclinical research.

Development of 1,5-diarylpyrazoles as EGFR/JNK-2 dual inhibitors: design, synthesis, moleecular docking, and bioactivity evaluation.

The eradication of multifactorial diseases, such as cancer, requires the design of drug candidates that attack multiple targets that contribute to the progression and proliferation of such diseases. Here, 1,5-diarylpyrazole derivatives bearing vanillin or sulfanilamide are developed as potential dual inhibitors of epidermal growth factor receptor (EGFR)/c-Jun N-terminal kinase 2 (JNK-2) for possible anticancer activity. These derivatives inhibited the growths of DLD-1, HeLa, K-562, SUIT-2 and HepG2 cancer cell lines, with minimum concentration required to inhibit half of the cellular growth (IC50) values of 2.7-63 µM. The tests confirmed that 5b and 5d were potent JNK-2 inhibitors, with IC50 of 2.0 and 0.9 µM, respectively, whereas 6 h selectively inhibited EGFR protein kinase (EGFR-PK) (IC50 = 1.7 µM). Notably, 6c inhibited both kinases, with IC50 values of 2.7 and 3.0 µM against EGFR-PK and JNK-2, respectively, offering a reference for designing mutual inhibitors of EGFR/JNK-2. The docking studies revealed the ability of the pyrazole ring to bind to the hinge region of the ATP binding site, thereby supporting the experimental inhibitory results. Furthermore, the developed compounds could induce apoptosis and induce cell cycle arrest at different cell phases.

Flavipin from fungi as a potential inhibitor of rheumatoid arthritis signaling molecules.

Flavipin, a fungal lower molecular weight biomolecule (MW 196.16 g/mol), has not been yet extensively studied for beneficial preclinical and clinical applications. In recent years, various preclinical mouse models including adjuvant-induced arthritis (AIA) were employed to understand mechanisms associated with Rheumatoid arthritis (RA) and to develop new therapeutic drugs. In the current study, we studied the inhibitory effect of Flavipin on major signaling molecules involved in the inflammatory response during RA using both in-silico virtual interaction and in vivo mouse model of AIA. Our in-silico results clarified that Flavipin interacts with the tumor necrosis factor alpha (TNF-α) through conventional hydrogen binding (H-H) at one of TNF-α critical amino acids tyrosine residues, Tyr119, with binding energy (b.e.) -5.9. In addition, Flavipin binds to ATP-binging sites of the Jesus kinases, JAK1, JAK2 and JAK3, through H-H (b. e. between -5.8 and -6.1) and then it may inhibit JAKs, regulators of RA signaling molecules. Moreover, our molecular dynamics stimulation for the docked TNF-α/Flavipin complex confirmed the specificity and the stability of the interaction. In vitro, Flavipin is not toxic to normal cells at doses below 50 µM (its IC50 in normal fibroblast cell line was above 100 µM). However, in vivo, the arthritis score and hind paw oedema parameters were modulated in Flavipin treated mice. Consistent with the in-silico results the levels of the TNF-α, the nuclear transcription factor kappaB (NF-κB) and the signal transduction and activator of transcription (STAT3, downstream of JAKs) were modulated at joint tissues of the hind-paw of Flavipin/AIA treated mice. Our data suggest Flavipin as a potential therapeutic agent for arthritis can inhibit RA major signaling molecules.

Stress experienced by dental students performing clinical training in different dental disciplines: a cross-sectional study.

OBJECTIVES: To assess the stress level, the impact of stress factors, and discrepancies between fourth- and fifth-year undergraduate clinical students at the University of Jordan. METHODS: A cross-sectional study was conducted in the academic year 2022/2023. The study group included fourth- and fifth-year dental students at the University of Jordan (n = 382) who were asked to voluntarily fill in an online dental environment stress (DES) questionnaire. Analysis was conducted using Mann-Whitney U test, independent t-test, χ2 test, and Spearman ρ rank correlations. Statistical significance was inferred when P < .05. RESULTS: Fourth-year students reported higher levels of nervousness before treating patients for the first time. Fifth-year students faced more difficulty, higher stress, and/or fear regarding the amount of assigned work, provided treatment, completed requirements, failing the course, time to finish assignments, patient comprehensive care, and financial expenses of the course. Comparison between groups revealed that the fifth-year students scored higher levels of stress on the total DES score and all partial DES scores. Furthermore, the total DES questionnaire scores were significantly correlated with grade point average (GPA) among the total study sample and the prosthodontics clinical course marks among the fourth-year students' group. CONCLUSIONS: The stress level among students in clinical courses was influenced by their academic performance, gender, year level, and the type and time needed for the provided treatment. Completing course requirements was among the most commonly faced stressors. Future research endeavors might be considered to study each clinical factor, its impact on students' stress level, and how to manage and positively improve these factors.

Image dataset of healthy and infected fig leaves with Ficus leaf worm.

This work presents an extensive dataset comprising images meticulously obtained from diverse geographic locations within Iraq, depicting both healthy and infected fig leaves affected by Ficus leafworm. This particular pest poses a significant threat to economic interests, as its infestations often lead to the defoliation of trees, resulting in reduced fruit production. The dataset comprises two distinct classes: infected and healthy, with the acquisition of images executed with precision during the fruiting season, employing state-of-the-art high-resolution equipment, as detailed in the specifications table. In total, the dataset encompasses a substantial 2,321 images, with 1,350 representing infected leaves and 971 depicting healthy ones. The images were acquired through a random sampling approach, ensuring a harmonious blend of balance and diversity across data emanating from distinct fig trees. The proposed dataset carries substantial potential for impact and utility, featuring essential attributes such as the binary classification of infected and healthy leaves. The presented dataset holds the potential to be a valuable resource for the pest control industry within the domains of agriculture and food production.

Prognostic accuracy of qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients presenting with suspected infection to the emergency department (PASSEM) Multicenter prospective external validation cohort study protocol.

BACKGROUND: Early identification of a patient with infection who may develop sepsis is of utmost importance. Unfortunately, this remains elusive because no single clinical measure or test can reflect complex pathophysiological changes in patients with sepsis. However, multiple clinical and laboratory parameters indicate impending sepsis and organ dysfunction. Screening tools using these parameters can help identify the condition, such as SIRS, quick SOFA (qSOFA), National Early Warning Score (NEWS), or Modified Early Warning Score (MEWS). We aim to externally validate qSOFA, SIRS, and NEWS/NEWS2/MEWS for in-hospital mortality among adult patients with suspected infection who presenting to the emergency department. METHODS AND ANALYSIS: PASSEM study is an international prospective external validation cohort study. For 9 months, each participating center will recruit consecutive adult patients who visited the emergency departments with suspected infection and are planned for hospitalization. We will collect patients' demographics, vital signs measured in the triage, initial white blood cell count, and variables required to calculate Charlson Comorbidities Index; and follow patients for 90 days since their inclusion in the study. The primary outcome will be 30-days in-hospital mortality. The secondary outcome will be intensive care unit (ICU) admission, prolonged stay in the ICU (i.e., ≥72 hours), and 30- as well as 90-days all-cause mortality. The study started in December 2021 and planned to enroll 2851 patients to reach 200 in-hospital death. The sample size is adaptive and will be adjusted based on prespecified consecutive interim analyses. DISCUSSION: PASSEM study will be the first international multicenter prospective cohort study that designated to externally validate qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients with suspected infection presenting to the ED in the Middle East region. STUDY REGISTRATION: The study is registered at ClinicalTrials.gov (NCT05172479).

Potential application of hydroxypropyl methylcellulose/shellac embedded with graphene oxide/TiO2-Nps as natural packaging film.

Graphene oxide (GO), TiO2-NPs, HPMC, and shellac are environmentally green polymers and nanocomposites. This work aimed to create biodegradable composite films made of HPMC/shellac, HPMC/shellac-GO, and HPMC/shellac-GO/TiO2-NPs by film casting. TiO2-HPMC/shellac-GO matrix's dispersibility and mixing ability were characterized and observed using FTIR and XRD. XRD analysis shows that the crystallinity decreased within the composites due to breaking H-bonding. Compared to HPMC/shellac, TGA/DTG demonstrated the composite films' superior thermal stability. TiO2 (0.08-0.16 %) was cast into a composite film comprising HPMC, shellac, and GO. The homogeneity of TiO2 distribution in the composite film was shown using a SEM, which was also used to display the morphology of nanocomposite films. Nanocomposite films' thickness, air permeability, tensile strength, Young's modulus, and burst strength were examined. The results demonstrated that natural films prepared by a combination of shellac/GO with HPMC enhanced the fabricating of films' properties, the tensile strength increased by 231 % (from 16 to 53 MPa) in HPMC and HPSG2 (HPMC 1.9 g/shellac 0.25 g/GO 0.125 g in 100 mL) respectively, whereas the contact angle did not change. And after addition of TiO2-NPs, there were high enhancements in HPMC films' properties, such tensile strength increased by 212 % (from 16 to 50 MPa), burst strength increased by 20.96 % (3.1 to 3.75 Kg/cm2), and the contact angle by 60.86 % (48 to 74°) in HPMC and HPSGT2 respectively. Compared to HPMC films, films exhibited the highest levels of antibacterial activity against E. coli, B. mycoides, and C. albicans. So, the composite films from HPMC/shellac/GO/TiO2-NPs are promising potential packaging materials.

Living Longer or Better-Patient's Choice in Cardiac Surgery Is Gender-Dependent-A Multicenter Study.

In view of the increasing age of cardiac surgery patients, questions arise about the expected postoperative quality of life and the hoped-for prolonged life expectancy. Little is known so far about how these, respectively, are weighted by the patients concerned. This study aims to obtain information on the patients' preferences. Between 2015 and 2017, data were analyzed from 1349 consecutive patients undergoing cardiac surgery at seven heart centers in Germany. Baseline data regarding the patient's situation as well as a questionnaire regarding quality of life versus lifespan were taken preoperatively. Patients were divided by age into four groups: below 60, 60-70, 70-80, and above 80 years. As a result, when asked to decide between quality of life and length of life, about 60% of the male patients opted for quality of life, independent of their age. On the other hand, female patients' preference for quality of life increased significantly with age, from 51% in the group below sixty to 76% in the group above eighty years. This finding suggests that female patients adapt their preferences with age, whereas male patients do not. This should impact further the treatment decisions of elderly patients in cardiac surgery within a shared decision-making process.

Interstitial cells of Cajal - pacemakers of the gastrointestinal tract.

Gastrointestinal (GI) organs display spontaneous, non-neurogenic electrical, and mechanical rhythmicity that underlies fundamental motility patterns, such as peristalsis and segmentation. Electrical rhythmicity (aka slow waves) results from pacemaker activity generated by interstitial cells of Cajal (ICC). ICC express a unique set of ionic conductances and Ca2+ handling mechanisms that generate and actively propagate slow waves. GI smooth muscle cells lack these conductances. Slow waves propagate actively within ICC networks and conduct electrotonically to smooth muscle cells via gap junctions. Slow waves depolarize smooth muscle cells and activate voltage-dependent Ca2+ channels (predominantly CaV1.2), causing Ca2+ influx and excitation-contraction coupling. The main conductances responsible for pacemaker activity in ICC are ANO1, a Ca2+ -activated Cl- conductance, and CaV3.2. The pacemaker cycle, as currently understood, begins with spontaneous, localized Ca2+ release events in ICC that activate spontaneous transient inward currents due to activation of ANO1 channels. Depolarization activates CaV 3.2 channels, causing the upstroke depolarization phase of slow waves. The upstroke is transient and followed by a long-duration plateau phase that can last for several seconds. The plateau phase results from Ca2+ -induced Ca2+ release and a temporal cluster of localized Ca2+ transients in ICC that sustains activation of ANO1 channels and clamps membrane potential near the equilibrium potential for Cl- ions. The plateau phase ends, and repolarization occurs, when Ca2+ stores are depleted, Ca2+ release ceases and ANO1 channels deactivate. This review summarizes key mechanisms responsible for electrical rhythmicity in gastrointestinal organs.

COVID-19-associated neurological sequelae: A case series on cerebral microbleeds and encephalopathy.

BACKGROUND: Critical illness-associated cerebral microbleeds and leukoencephalopathy connected to coronavirus disease 2019 (COVID-19) infection are emerging areas of concern in current medical literature. METHODS: We reviewed cases of patients with COVID-19-associated neurological manifestations to study the prevalence and outcome of such conditions. Case Series Findings: Our review yielded seven distinct patients. Six exhibited cerebral microbleeds, primarily localized in the juxtacortical white matter and the corpus callosum. In contrast, one individual presented with leukoencephalopathy. Tragically, of these patients, five succumbed to their ailments. One was discharged with mild cognitive impairments, while another underwent a tracheostomy and was subsequently moved to a long-term care establishment. CONCLUSION: Our findings underscore the significance of neuro-radiological observations in those grappling with severe manifestations of COVID-19, drawing attention to the possible neurological repercussions of the virus.

Evaluation and comparison of retention and patient satisfaction with milled polyetheretherketone versus metal maxillary obturators.

STATEMENT OF PROBLEM: Metal and polyetheretherketone (PEEK) have been used to rehabilitate maxillary defects with obturators, each having advantages and disadvantages. However, patient satisfaction with the obturator retention of each material is unclear. PURPOSE: The purpose of this crossover clinical study was to compare retention and patient satisfaction between a milled cobalt chromium and a milled PEEK framework, each with a hollow bulb extension in polymethyl methacrylate (PMMA). MATERIAL AND METHODS: Twenty patients who had received unilateral total maxillectomy and were treated in the prosthodontic department's maxillofacial clinic were enrolled in this crossover study. Each participant wore 2 different types of obturators for 6 months after insertion. Type CoCr received a milled cobalt chromium framework with a hollow bulb extension in PMMA first, and type Pk received a milled modified PEEK (BioHPP) framework with a hollow bulb extension in PMMA first. Patient satisfaction and retention force were measured immediately, at 3 months, and at 6 months after obturator insertions. The Fischer exact, chi-squared, and Monte Carlo tests were used to compare qualitative data. One-way ANOVA with the post hoc Tukey test was used for pair-wise comparison, and repeated measures ANOVA was used to compare before and after treatment at 3 and 6 months. RESULTS: No significant difference was found between types in obturator insertion (P>.999), appearance of the upper lip (P>.999), mouth feeling (P=.301), pronunciation of words (P=.217), and talking in public (P=.589). A significant difference between types was found in speech after 6 months of obturator insertion (P=.016), swallowing liquids and food (P=.04), masticating foods (P=.007), appearance of clasps on anterior teeth (P=.002), satisfaction with appearance (P=.005), or avoidance of family events (P=.014) after 6 months of insertion. Types of obturators showed a statistically significant decrease in retention force with time (P<.001). CONCLUSIONS: Although the retention force was less with PEEK than with Co-Cr clasps engaging the same undercuts, this retention force was adequate for retaining removable partial dentures. Co-Cr clasps can be considered better than PEEK clasps because they engage the same undercuts regarding loss of retention with time. Quality of life in patients after maxillary resection could be improved by using maxillary obturators. Type Pk was better than type CoCr in terms of esthetics, but the retention of the PEEK obturator after 6 months decreased because of wear, leading to difficulty swallowing food or liquids, mastication, and speech.

Dental Students' Perception and Self-Perceived Confidence Level in Key Dental Procedures for General Practice and the Impact of Competency Implementation on Their Confidence Level, Part I (Prosthodontics and Conservative Dentistry).

Background: Evaluating the level of dental students' competence is crucial for validating their preparedness for graduation. Confidence has a significant role in achieving competence. There are limited studies that assess the level of self-perceived confidence among final-year dental students regarding their ability to conduct key dental procedures. This study aims to assess the self-perceived confidence level of final-year dental students in performing essential dental procedures across various dental disciplines and to assess the effect of implementing competencies in the curriculum on the self-perceived confidence level of students by comparing two cohorts of final-year students in two different years 2016 (Traditional Cohort) and 2019 (Competencies Cohort). Materials and Methods: An questionnaire was answered by two cohorts of final-year dental students: one group in 2016 before the implementation of the competency-based assessment system (group 1, n = 153), and the other in 2019 after the implementation of this system (group 2, n = 199), the same questionnaire was used for both cohorts. The results from the two groups were compared regarding the degree of self-perceived confidence in conducting key dental procedures. The data were analysed using SPSS statistics and Levene's Test for Equality of Variances and t-test for Equality of Means calculated. Results: Group 1 showed a significantly higher means of self-perceived confidence levels than group 2 in the ability to conduct seven out of the 20 prosthodontics procedures studied: providing patients with Cobalt-Chromium (Co-Cr) removable partial dentures (RPD) (3.77 vs. 3.56), providing the patient with Acrylic RPD (3.70 vs. 3.23), treatment planning for partially edentulous patients (3.83 vs. 3.34), giving OHIs for denture patients (4.17 vs. 3.95), dealing with CD postinsertion complaints (3.97 vs. 3.76), giving postinsertion instructions for removable prostheses cases (4.12 vs. 3.82), and providing patients with immediate dentures (2.67 vs. 2.32). The same applies to 6 out of 16 conservative dentistry procedures: placing anterior composite (4.41 vs. 4.12), placing posterior composite (4.43 vs. 3.88), placing posterior amalgam (4.29 vs. 4.02), placing matrix band for Class II restorations (4.24 vs. 3.71), placing a prefabricated post (3.34 vs. 2.88), and placing fiber post (3.45 vs. 3.34). On the other hand, group 2 shows higher means of self-perceived confidence than group 1 in only two conservative dentistry procedures: onlay restorations (2.18 vs. 2.76) and inlay restorations (2.22 vs. 2.75). No significant differences in means of self-perceived confidence were found between the two groups in the remaining 21 procedures studied. Conclusions: This study has shown that final-year dental students have high self-perceived confidence levels in doing simple dental procedures yet less confidence in more complex ones. Although, students' self-perceived confidence decreases after the introduction of a competency-based assessment system. Competency implementation and execution criteria may differ between schools which may have an impact on final outcomes. Hence, there is a need for regular evaluation of competencies being assessed to maintain a curriculum that is up to date.

The deleterious effects of cadmium on oxidative stress markers, drug-metabolizing, and antioxidant enzyme activities: Role of Silymarin and Garlic as Antioxidants.

Exposure to cadmium has been related to liver and kidney diseases such as polycystic and nephrotic syndrome. It is still unclear how cadmium contributes to these diseases. It is believed that the induction of oxidative stress resulting from the inhibition of antioxidant enzyme activities and changes in drug-metabolizing enzymes in the liver could explain the role of cadmium in the development of different diseases in the kidney and probably other organs. Changes in oxidative stress markers, antioxidant enzymes, and drug-metabolizing enzyme activities were assessed in the liver of male rats exposed to cadmium chloride. Additionally, the protective effects of silymarin and garlic extract against cadmium toxicosis were evaluated. Rats were randomly divided into eight groups as follows, groups 1, 2, 3, 4, and 5, received orally saline, CdCl2 (1 mg/kg), garlic extract [800 mg/kg], silymarin (25 mg/kg) and silymarin plus garlic extract respectively for 28 consecutive days. Rats in groups 6, 7, and 8 were pretreated with the same doses of garlic, silymarin, and garlic plus silymarin, respectively for two hours before cadmium administration. The Western immunoblotting technique was used to investigate the protein expression of cytochrome P450 isozymes. Spectrophotometric methods were used to assess the activity of both antioxidant- and drug-metabolizing enzymes. Free radical levels [measured as thiobarbituric acid reactive substances (TBARS)], catalase, superoxide dismutase, and glutathione peroxidase activities increased whereas the levels of glutathione and the activities of glutathione S-transferase, glutathione reductase, and glutamyl transferase, cytochrome P450, aryl hydrocarbon dehydrogenase (AHH), dimethylnitrosamine-N-demethylase I (DMN-dI), 7-ethoxycoumarine-O-deethylase (ECOD), cytochrome b5 and NADPH-Cytochrome-c-reductase enzyme activities decreased after cadmium treatment. Furthermore, Western immunoblotting data revealed that glutathione peroxidase protein expression increased following cadmium exposure, but cytochrome P450 2E1 and 3A4 expressions were downregulated. However, pretreatment of rats with silymarin or garlic extract or both before cadmium administration was found to restore the protein expression of cytochrome P450 2E1 and 3A4, the level of free radicals, antioxidant enzymes, drug-metabolizing enzyme activities to their normal levels. Similarly, histological studies revealed that silymarin and/or garlic extract reduced the liver damage caused by cadmium. Silymarin and/or garlic extract reduced the adverse effects of cadmium on the activity of both drug-metabolizing and antioxidant enzymes activity. These antioxidants could be provided to those who work in cadmium-based sectors to help them cope with the adverse effects of cadmium on their kidneys. In addition, Inhibiting drug-metabolizing enzyme activity should be considered when administering therapeutic medications to persons exposed to cadmium because most therapeutic drugs and many endogenous substances are largely metabolized by these enzymes.

Development and Assessment of 1,5-Diarylpyrazole/Oxime Hybrids Targeting EGFR and JNK-2 as Antiproliferative Agents: A Comprehensive Study through Synthesis, Molecular Docking, and Evaluation.

New 1,5-diarylpyrazole oxime hybrid derivatives (scaffolds A and B) were designed, synthesized, and then their purity was verified using a variety of spectroscopic methods. A panel of five cancer cell lines known to express EGFR and JNK-2, including human colorectal adenocarcinoma cell line DLD-1, human cervical cancer cell line Hela, human leukemia cell line K562, human pancreatic cell line SUIT-2, and human hepatocellular carcinoma cell line HepG2, were used to biologically evaluate for their in vitro cytotoxicity for all the synthesized compounds 7a-j, 8a-j, 9a-c, and 10a-c. The oxime containing compounds 8a-j and 10a-c were more active as antiproliferative agents than their non-oxime congeners 7a-j and 9a-c. Compounds 8d, 8g, 8i, and 10c inhibited EGFR with IC50 values ranging from 8 to 21 µM when compared with sorafenib. Compound 8i inhibited JNK-2 as effectively as sorafenib, with an IC50 of 1.0 µM. Furthermore, compound 8g showed cell cycle arrest at the G2/M phase in the cell cycle analysis of the Hela cell line, whereas compound 8i showed combined S phase and G2 phase arrest. According to docking studies, oxime hybrid compounds 8d, 8g, 8i, and 10c exhibited binding free energies ranging from -12.98 to 32.30 kcal/mol at the EGFR binding site whereas compounds 8d and 8i had binding free energies ranging from -9.16 to -12.00 kcal/mol at the JNK-2 binding site.

Exploring Salinity Tolerance Mechanisms in Diverse Wheat Genotypes Using Physiological, Anatomical, Agronomic and Gene Expression Analyses.

Salinity is a widespread abiotic stress that devastatingly impacts wheat growth and restricts its productivity worldwide. The present study is aimed at elucidating biochemical, physiological, anatomical, gene expression analysis, and agronomic responses of three diverse wheat genotypes to different salinity levels. A salinity treatment of 5000 and 7000 ppm gradually reduced photosynthetic pigments, anatomical root and leaf measurements and agronomic traits of all evaluated wheat genotypes (Ismailia line, Misr 1, and Misr 3). In addition, increasing salinity levels substantially decreased all anatomical root and leaf measurements except sclerenchyma tissue upper and lower vascular bundle thickness compared with unstressed plants. However, proline content in stressed plants was stimulated by increasing salinity levels in all evaluated wheat genotypes. Moreover, Na+ ions content and antioxidant enzyme activities in stressed leaves increased the high level of salinity in all genotypes. The evaluated wheat genotypes demonstrated substantial variations in all studied characters. The Ismailia line exhibited the uppermost performance in photosynthetic pigments under both salinity levels. Additionally, the Ismailia line was superior in the activity of superoxide dismutase (SOD), catalase activity (CAT), peroxidase (POX), and polyphenol oxidase (PPO) enzymes followed by Misr 1. Moreover, the Ismailia line recorded the maximum anatomical root and leaf measurements under salinity stress, which enhanced its tolerance to salinity stress. The Ismailia line and Misr 3 presented high up-regulation of H+ATPase, NHX2 HAK, and HKT genes in the root and leaf under both salinity levels. The positive physiological, anatomical, and molecular responses of the Ismailia line under salinity stress were reflected on agronomic performance and exhibited superior values of all evaluated agronomic traits.