Ca2+ dynamics in interstitial cells: foundational mechanisms for the motor patterns in the gastrointestinal tract.

The gastrointestinal (GI) tract displays multiple motor patterns that move nutrients and wastes through the body. Smooth muscle cells (SMCs) provide the forces necessary for GI motility, but interstitial cells, electrically coupled to SMCs, tune SMC excitability, transduce inputs from enteric motor neurons, and generate pacemaker activity that underlies major motor patterns, such as peristalsis and segmentation. The interstitial cells regulating SMCs are interstitial cells of Cajal (ICC) and PDGF receptor (PDGFR)α+ cells. Together these cells form the SIP syncytium. ICC and PDGFRα+ cells express signature Ca2+-dependent conductances: ICC express Ca2+-activated Cl- channels, encoded by Ano1, that generate inward current, and PDGFRα+ cells express Ca2+-activated K+ channels, encoded by Kcnn3, that generate outward current. The open probabilities of interstitial cell conductances are controlled by Ca2+ release from the endoplasmic reticulum. The resulting Ca2+ transients occur spontaneously in a stochastic manner. Ca2+ transients in ICC induce spontaneous transient inward currents and spontaneous transient depolarizations (STDs). Neurotransmission increases or decreases Ca2+ transients, and the resulting depolarizing or hyperpolarizing responses conduct to other cells in the SIP syncytium. In pacemaker ICC, STDs activate voltage-dependent Ca2+ influx, which initiates a cluster of Ca2+ transients and sustains activation of ANO1 channels and depolarization during slow waves. Regulation of GI motility has traditionally been described as neurogenic and myogenic. Recent advances in understanding Ca2+ handling mechanisms in interstitial cells and how these mechanisms influence motor patterns of the GI tract suggest that the term "myogenic" should be replaced by the term "SIPgenic," as this review discusses.

Interstitial cells of the sip syncytium regulate basal membrane potential in murine gastric corpus.

Smooth muscle cells (SMCs), Interstitial cells of Cajal (ICC) and Platelet-derived growth factor receptor α positive (PDGFRα+) cells form an integrated, electrical syncytium within the gastrointestinal (GI) muscular tissues known as the SIP syncytium. Immunohistochemical analysis of gastric corpus muscles showed that c-KIT+/ANO1+ ICC-IM and PDGFRα+ cells were closely apposed to one another in the same anatomical niches. We used intracellular microelectrode recording from corpus muscle bundles to characterize the roles of intramuscular ICC and PDGFRα+ cells in conditioning membrane potentials of gastric muscles. In muscle bundles, that have a relatively higher input impedance than larger muscle strips or sheets, we recorded an ongoing discharge of stochastic fluctuations in membrane potential, previously called unitary potentials or spontaneous transient depolarizations (STDs) and spontaneous transient hyperpolarizations (STHs). We reasoned that STDs should be blocked by antagonists of ANO1, the signature conductance of ICC. Activation of ANO1 has been shown to generate spontaneous transient inward currents (STICs), which are the basis for STDs. Ani9 reduced membrane noise and caused hyperpolarization, but this agent did not block the fluctuations in membrane potential quantitatively. Apamin, an antagonist of small conductance Ca2+-activated K+ channels (SK3), the signature conductance in PDGFRα+ cells, further reduced membrane noise and caused depolarization. Reversing the order of channel antagonists reversed the sequence of depolarization and hyperpolarization. These experiments show that the ongoing discharge of STDs and STHs by ICC and PDGFRα+ cells, respectively, exerts conditioning effects on membrane potentials in the SIP syncytium that would effectively regulate the excitability of SMCs.

Mapping a sustainable approach: biosynthesis of lactobacilli-silver nanocomposites using whey-based medium for antimicrobial and bioactivity applications.

This study explores a sustainable approach for synthesizing silver nanocomposites (AgNCs) with enhanced antimicrobial and bioactivity using safe Lactobacillus strains and a whey-based medium (WBM). WBM effectively supported the growth of Lactobacillus delbrueckii and Lactobacillus acidophilus, triggering a stress response that led to AgNCs formation. The synthesized AgNCs were characterized using advanced spectroscopic and imaging techniques such as UV‒visible, Fourier transform infrared (FT-IR) spectroscopy, transmission electron (TEM), and scanning electron microscopy with energy dispersive X-ray analysis (SEM-Edx). Lb acidophilus-synthesized AgNCs in WBM (had DLS size average 817.2-974.3 ± PDI = 0.441 nm with an average of metal core size 13.32 ± 3.55 nm) exhibited significant antimicrobial activity against a broad spectrum of pathogens, including bacteria such as Escherichia coli (16.47 ± 2.19 nm), Bacillus cereus (15.31 ± 0.43 nm), Clostridium perfringens (25.95 ± 0.03 mm), Enterococcus faecalis (32.34 ± 0.07 mm), Listeria monocytogenes (23.33 ± 0.05 mm), methicillin-resistant Staphylococcus aureus (MRSA) (13.20 ± 1.76 mm), and filamentous fungi such as Aspergillus brasiliensis (33.46 ± 0.01 mm). In addition, Lb acidophilus-synthesized AgNCs in WBM exhibit remarkable free radical scavenging abilities, suggesting their potential as bioavailable antioxidants. These findings highlight the dual functionality of these biogenic AgNCs, making them promising candidates for applications in both medicine and nutrition.

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.

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.

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.

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.

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.

Effect of Ridge Splitting of Mandibular Knife Edge Ridges with Two-implant Retained Overdenture with Locator Attachments on Peri-implant Bone Level and Posterior Ridge Resorption: A One-year Preliminary Study.

AIM: This study was conducted to evaluate peri-implant bone height changes and posterior ridge resorption by using two-implant retained polyetheretherketone (PEEK) overdentures with locator attachments following expansion of mandibular knife edge ridges by ridge splitting. MATERIALS AND METHODS: Eighteen patients were selected for ridge splitting followed by expansion, implant placement, and bone graft application. Six months later, the fabrication of PEEK overdentures retained by locator attachments was accomplished. Friedman test, Wilcoxon signed-rank test, and Spearman correlation were used to evaluate the changes over time. RESULTS: Peri-implant bone height loss increased significantly with the advance of time between 6 and 12 months following denture insertion. Posterior area index changes were significant over time when measured at the time of denture insertion and twelve months following denture insertion. CONCLUSION: The effect of using PEEK as overdenture base material retained with two locator attachments allowed sharing the load between the peri-implant bone anteriorly and residual ridge posteriorly in cases with ridge splitting technique. CLINICAL SIGNIFICANCE: Using PEEK as an overdenture base material is a successful means of bone preservation. How to cite this article: Helmy MA, El-Shaheed NH, El Waseef FA, et al. Effect of Ridge Splitting of Mandibular Knife Edge Ridges with Two-implant Retained Overdenture with Locator Attachments on Peri-implant Bone Level and Posterior Ridge Resorption: A One-year Preliminary Study. J Contemp Dent Pract 2023;24(11):834-839.

Impact of LaZnFe2O4 supported NiWO4@D400-MMT@CMS/MMA nanocomposites as a catalytic system in remediation of dyes from wastewater.

Herein, a novel nanocomposite based on lanthanum zinc ferrite and nickel tungstate was created by incorporation between (MMT-jeffamine-400) nanoparticles (NPs), chloromethyl styrene as a binder and polymethyl methacrylate monomer using solution polymerization. The as-designed nanocomposites were employed to confiscate xylenol orange "X.O" as an acidic dye and rhodamine B "RhB" as "an amphoteric dye" from colored wastewater. The impact of several parameters such as solution pH, initial dye concentration, the effect of time, and the effect of temperature was explored. The consequences indicated that the pure organoclay had negligible adsorption while that composed of organoclay with PMMA@CMS-polymer incorporated with LaZnFe2O4@NiWO4 particles detached more than 90% for xylenol orange (XO) and 93% for "rhodamine B" molecules. Electrostatic interactions are the predominant factor in the adsorption of cationic and amphoteric adsorbates, as proven by zeta-potential measurement. Additionally, the adsorbent may be regenerate and utilized up to five times with good adsorption capabilities by adding sodium hydroxide. As a result, the removal can be effectively accomplished using the nanocomposite as an adsorbent. The actual and theoretical adsorption capacity values for both dyes at all doses were closely matched, which supported the adsorption kinetics data that fit the pseudo-first order rate model well. The adsorption data's correlation values (0.995 for XO and 0.98 for RhB) indicated that both dyes' Langmuir adsorption would perform well. Furthermore, the adsorption of XO and RhB dyes on the adsorbent is confirmed to be a viable reaction by the negative values of ΔGo. The enhanced adsorbent material for the removal of amphoteric and anionic dyes from waste water is the synthesized LaZnFe2O4 supported NiWO4@D400-MMT@CMS/MMA nanocomposites, which exhibits a reusability affinity of up to five cycles.

Subperiosteal implants constructed with digital technology: A systematic review.

STATEMENT OF PROBLEM: Atrophied jaw is a condition where there is insufficient bone quantity and quality. Several treatment plans are available for treating atrophied jaws, including subperiosteal implants. PURPOSE: To evaluate the spectrum of subperiosteal implants for severely atrophied jaws using digital technology. MATERIALS AND METHODS: An electronic and manual search was conducted in the PubMed, Scopus, and Google Scholar databases. Publications of cohort studies, case series, and case reports written in English without data restrictions that reported on subperiosteal implant management of patients with severely atrophied jaws in a completely and partially edentulous population. RESULTS: A total of 26 articles, comprising 302 cases, were analyzed. In patients with severely atrophied jaws. The success rate was 87.7%, the surviving rate was 95.3%. The most common complications were biological, such as dehiscence and framework exposure. The rates of biologic complications were 11.5%, and the rates of prosthetic problems were 5.9%. CONCLUSIONS: Subperiosteal implants designed and constructed using digital technology are a promising treatment in the short term. Attention should be directed to decrease the biological complication. Correct designing, implanting, fixing, and patient selection and maintenance are critical for the success of the treatment. Longer prospective studies with larger population are needed to view the effect on hard and soft tissue.

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.

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.

Intraprostatic Injection of Tranexamic Acid Decrease Blood Loss During Monopolar Transurethral Resection of the Prostate: A Randomized Controlled Clinical Trial.

OBJECTIVE: To assess the role of intraprostatic injection of tranexamic acid (TXA) in reducing blood loss during transurethral resection of the prostate (TURP). METHODS: We conducted a randomized, controlled, double-blind trial involving 60 patients with benign prostatic hyperplasia aged 50-85years, undergoing monopolar TURP. Patients' prostatic weights ranged from 50 to 80 g. They were divided equally into two groups: group I received an intraprostatic injection of 1 g of TXA (Cyklokapron) dissolved in 50 mL of 0.9 % saline at multiple sites, while group II (control) received a 60 mL saline injection. Comprehensive clinical assessments and standard laboratory tests, including screenings for TXA hypersensitivity, were performed for all patients. RESULTS: Group I exhibited significantly lower intraoperative blood loss and hemoglobin concentration in irrigation fluid immediately postsurgery and at the 6-hour postoperative mark compared to group II (P < .05). Coagulation parameters-activated partial thromboplastin time, prothrombin time, fibrinogen level, and thrombin clotting time-showed no significant differences between the groups preoperatively or at 6 and 24 hours postoperatively. No thromboembolic events or other complications were reported in either group. CONCLUSION: The intraprostatic injection of TXA during monopolar TURP is safe, with minimal adverse effects, and effectively reduces blood loss. REGISTRATION: The study was registered on ClinicalTrials.gov No (ID: NCT05913466).

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.

Efficacy of Salvia officinalis Shrub as a Sustainable Feed Additive for Reducing Ruminal Methane Production and Enhancing Fermentation in Ruminants.

The objective of this study was to evaluate the effects of the inclusion of dried Salvia officinalis (SO) shrub leaves on nutrient degradability, ruminal in vitro fermentation, gas production (GP), methane (CH4), and carbon dioxide (CO2) productions. Dried and ground SO shrub leaves were included at 0% (control), 0.5%, 1%, 1.5%, and 2% DM of a diet consisting of (per kg DM) 500 g concentrate feed mixture, 400 g berseem hay, and 100 g rice straw. The diet was incubated for 48 h. The asymptotic GP and the rate of GP changed linearly and quadratically (p < 0.01), with the highest GP observed at 1% inclusion of SO and then decreasing thereafter with greater inclusion (i.e., 1.5% and 2%), while CH4 production and its rate decreased linearly (p < 0.01) with all levels of SO inclusion. A linear increase in CO2 production and its rate was also found with an increasing level of SO inclusion in the diet (p < 0.05). Furthermore, the degradability of DM, NDF, and the concentration of total short-chain fatty acids and acetate changed linearly and quadratically, with the greatest being found at 1% SO inclusion and then steadily declining after (p < 0.01) with the 1.5% and 2% inclusion levels. Meanwhile, the propionate, NH3-N, and microbial crude protein levels showed similar trends, with the plateau found at 1% inclusion of SO, where there was no change in butyrate concentration. Moreover, the pH, metabolizable energy, and partitioning factor (PF24) also changed linearly and quadratically (p < 0.05), where the pH and PF24 were considerably reduced and ME increased with a 1% inclusion of SO (p < 0.05). In summary, SO at 1% inclusion in the diet showed the potential to improve gas production kinetics, nutrient degradability, and the ruminal fermentation profile, with a more significant reduction in ruminal CH4 production suggesting that SO at 1% could be included in the ruminant diet to reduce their carbon footprint and increase the production performance.

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.

New Diaryl-1,2,4-triazolo[3,4-a]pyrimidine Hybrids as Selective COX-2/sEH Dual Inhibitors with Potent Analgesic/Anti-inflammatory and Cardioprotective Properties.

COX-2-selective drugs were withdrawn from the market just a few years after their development due to cardiovascular side effects. As a result, developing a selective COX-2 inhibitor as an anti-inflammatory agent with cardioprotective characteristics has become a prominent objective in medicinal chemistry. New 15 diaryl-1,2,4-triazolo[3,4-a]pyrimidine hybrids 8a-o were synthesized and investigated in vitro as dual COX-2/sEH inhibitors. Compounds 8b, 8m, and 8o have the highest potency and selectivity as COX-2 inhibitors (IC50 = 15.20, 11.60, and 10.50 µM, respectively; selectivity index (COX-1/COX-2) = 13, 20, and 25, respectively), compared to celecoxib (COX-2; IC50 = 42 µM; SI = 8). The 5-LOX inhibitory activity of compounds 8b, 8m, and 8o was further examined in vitro. Compounds 8m and 8o, the most effective COX-2 selective inhibitors, demonstrated stronger 5-LOX inhibitory action than the reference quercetin, with IC50 values of 2.90 and 3.05 µM, respectively. Additionally, compounds 8b, 8m, and 8o were the most potent dual COX-2/sEH inhibitors, with IC50 values against sEH of 3.20, 2.95, and 2.20 nM, respectively, and were equivalent to AUDA (IC50 = 1.2 nM). In vivo investigations also demonstrated that these compounds were the most efficacious as analgesic/anti-inflammatory derivatives with a high cardioprotective profile against cardiac biomarkers and inflammatory cytokines. The docking data analysis inquiry helped better understand the binding mechanisms of the most active hybrids within the COX-2 active site and supported their COX-2 selectivity. Compounds 8b, 8m, and 8o exhibited a similar orientation to rofecoxib and celecoxib, with a larger proclivity to enter the selectivity side pocket than the reference compounds.

Interstitial cell of Cajal-like cells (ICC-LC) exhibit dynamic spontaneous activity but are not functionally innervated in mouse urethra.

Urethral smooth muscle cells (USMC) contract to occlude the internal urethral sphincter during bladder filling. Interstitial cells also exist in urethral smooth muscles and are hypothesized to influence USMC behaviours and neural responses. These cells are similar to Kit+ interstitial cells of Cajal (ICC), which are gastrointestinal pacemakers and neuroeffectors. Isolated urethral ICC-like cells (ICC-LC) exhibit spontaneous intracellular Ca2+ signalling behaviours that suggest these cells may serve as pacemakers or neuromodulators similar to ICC in the gut, although observation and direct stimulation of ICC-LC within intact urethral tissues is lacking. We used mice with cell-specific expression of the Ca2+ indicator, GCaMP6f, driven off the endogenous promoter for Kit (Kit-GCaMP6f mice) to identify ICC-LC in situ within urethra muscles and to characterize spontaneous and nerve-evoked Ca2+ signalling. ICC-LC generated Ca2+ waves spontaneously that propagated on average 40.1 ± 0.7 µm, with varying amplitudes, durations, and spatial spread. These events originated from multiple firing sites in cells and the activity between sites was not coordinated. ICC-LC in urethra formed clusters but not interconnected networks. No evidence for entrainment of Ca2+ signalling between ICC-LC was obtained. Ca2+ events in ICC-LC were unaffected by nifedipine but were abolished by cyclopiazonic acid and decreased by an antagonist of Orai Ca2+ channels (GSK-7975A). Phenylephrine increased Ca2+ event frequency but a nitric oxide donor (DEA-NONOate) had no effect. Electrical field stimulation (EFS, 10 Hz) of intrinsic nerves, which evoked contractions of urethral rings and increased Ca2+ event firing in USMC, failed to evoke responses in ICC-LC. Our data suggest that urethral ICC-LC are spontaneously active but are not regulated by autonomic neurons.