Respiratory internal kinematics of the tongue base and soft palate in obese minipigs with obstructive sleep apnea.

It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of five Yucatan and two Panepinto minipigs to verify obstructive sleep apnea (OSA), eight and four ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D deformational changes of the circumscribed regions were measured simultaneously with electromyographic activity of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in three nonobese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions, respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of deformational changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The distance changes between the dorsal surface of tongue base and soft palate during inspiration increased in normal but decreased in obese OSA minipigs.

Cubeb (Piper cubeba L.): nutritional value, phytochemical profiling and dermacosmeceutical properties.

Introduction: Cubeb, Piper cubeba L., has been used for centuries in traditional medicine and culinary practices, with a wide range of biological and pharmacological activities. Objective: Herein, we determined the phytochemical profile, mineral, fatty acids, and amino acid contents of P. cubeba berries and assessed the dermacosmeceutical properties of their water extract and essential oil (EO). These included assessing their antioxidant and antibacterial activities as well as their in vitro inhibitory activities against tyrosinase and elastase enzymes. In addition, molecular docking and molecular dynamics studies were performed on the major identified compounds of the EO. Results and discussion: A total of forty-three compounds belonging to organic acids, phenolic acids and flavonoids were found in the water extract, while 36 volatile compounds were identified in the EO with Z-isoeugenol, dihydroeugenol, ß-pinene, E-caryophyllene, and 1,8-cineole as major constituents. The berries were found to be rich in sodium and iron, have moderate zinc content along with low contents of total nitrogen, phosphorus, and potassium. Amino acid analysis revealed a considerable concentration of isoleucine and phenylalanine, whereas 11,14,17-eicosatrienoic acid and linoleic acid were identified as the major fatty acids. In the DPPH and FRAP assays, the water extract elicited considerable antioxidant activity compared to the reference compounds. Enzyme inhibitory assays revealed that the EO had a potential to inhibit tyrosinase and elastase enzymes with IC50 values of 340.56 and 86.04 µg/mL, respectively. The water extract and EO completely inhibited the bacterial growth at MIC of 50 mg/mL and 20%, respectively. At sub-MIC concentrations, the extract and the EO substantially reduced the biofilm formation by up to 26.63 and 77.77%, respectively, as well as the swimming and swarming motilities in a dose-dependent manner. Molecular docking and molecular dynamics showed that the five main components of P. cubeba EO could be the major contributors to the elastase and tyrosinase inhibitory effect. Conclusion: This study emphasizes the promising potential of P. cubeba as a valuable source of natural compounds that can be utilized for the development of innovative pharmaceuticals, dietary supplements, and dermacosmeceutical agents.

Advanced Optoelectronic Modeling and Optimization of HTL-Free FASnI3/C60 Perovskite Solar Cell Architecture for Superior Performance.

In this study, a novel perovskite solar cell (PSC) architecture is presented that utilizes an HTL-free configuration with formamide tin iodide (FASnI3) as the active layer and fullerene (C60) as the electron transport layer (ETL), which represents a pioneering approach within the field. The elimination of hole transport layers (HTLs) reduces complexity and cost in PSC heterojunction structures, resulting in a simplified and more cost-effective PSC structure. In this context, an HTL-free tin HC(NH2)2SnI3-based PSC was simulated using the solar cell capacitance simulator (SCAPS) within a one-dimensional framework. Through this approach, the device performance of this novel HTL-free FASnI3-based PSC structure was engineered and evaluated. Key performance parameters, including the open-circuit voltage (Voc), short-circuit current density (Jsc), fill factor (FF), power conversion efficiency (PCE), I-V characteristics, and quantum efficiency (QE), were systematically assessed through the modulation of physical parameters across various layers of the device. A preliminary analysis indicated that the HTL-free configuration exhibited improved I-V characteristics, with a PCE increase of 1.93% over the HTL configuration due to improved electron and hole extraction characteristics, reduced current leakage at the back contact, and reduced trap-induced interfacial recombination. An additional boost to the device's key performance parameters has been achieved through the further optimization of several physical parameters, such as active layer thickness, bulk and interface defects, ETL thickness, carrier concentration, and back-contact materials. For instance, increasing the thickness of the active layer PSC up to 1500 nm revealed enhanced PV performance parameters; however, further increases in thickness have resulted in performance saturation due to an increased rate of hole-electron recombination. Moreover, a comprehensive correlation study has been conducted to determine the optimum thickness and donor doping level for the C60-ETL layer in the range of 10-200 nm and 1012-1019 cm-3, respectively. Optimum device performance was observed at an ETL-C60 ultra-thin thickness of 10 nm and a carrier concentration of 1019 cm-3. To maintain improved PCEs, bulk and interface defects must be less than 1016 cm-3 and 1015 cm-3, respectively. Additional device performance improvement was achieved with a back-contact work function of 5 eV. The optimized HTL-free FASnI3 structure demonstrated exceptional photovoltaic performance with a PCE of 19.63%, Voc of 0.87 V, Jsc of 27.86 mA/cm2, and FF of 81%. These findings highlight the potential for highly efficient photovoltaic (PV) technology solutions based on lead-free perovskite solar cell (PSC) structures that contribute to environmental remediation and cost-effectiveness.

Exogenous application of 5-azacitidin, royal jelly and folic acid regulate plant redox state, expression level of DNA methyltransferases and alleviate adverse effects of salinity stress on Vicia faba L. plants.

DNA methylation is one of induced changes under salinity stress causing reduction in the expression of several crucial genes required for normal plant's operation. Potential use of royal jelly (RJ), folic acid (FA) and 5-azacitidine (5-AZA) on two Egyptian faba bean varieties (Sakha-3 and Giza-716) grown under saline conditions was investigated. Salinity stress affects negatively on seeds germination (G %), mitotic index, membrane stability and induced a significant increase in chromosomal abnormalities (CAs). DNA methyltransferases genes (MT1 and MT2) were highly up-regulated (∼23 and 8 folds for MT1 and MT2 in shoots of Giza-716 stressed plants). On the other hand, down regulation of other studied stress related genes: superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), heat shock protein (HSP-17.9) and proline-rich protein (GPRP) were detected in stressed plants of both studied varieties. Treating plants with RJ and FA increase G%, chlorophyll content, improves membrane properties and reduces CAs compared to non-treated stressed plants. Exogenous application of 5-AZA, RJ and FA on salinity stressed plants was associated with a significant reduction in the transcription of MT1 and MT2 which was associated with significant up regulation in the expression of Cu/Zn-SOD, CAT, GR, GPRP and HSP-17.9 encoding genes. The Lowest expression of MT1 and MT2 were induced with 5-AZA treatment in both studied varieties. Exogenous application of the FA, RJ and 5-AZA modified the methylation state of stressed plants by regulation the expression of DNA methyltransferases, subsequently, modulated the expression of studied genes and could be proposed as a promising treatment to ameliorate hazardous effects of salt stress on different plants.

Nanoparticle-Modified 3D-Printed Denture Base Resins: Influence of Denture Cleansers on the Color Stability and Surface Roughness In Vitro.

This study aimed to evaluate the influence of denture cleansers on the color, stability, and surface roughness of three-dimensional (3D)-printed denture base resins modified with zirconium dioxide nanoparticles (nano-ZrO2). A total of 440 specimens were fabricated using one heat-polymerized resin, and two 3D-printed resins (NextDent and ASIGA). According to the nano-ZrO2 content, the specimens for each resin were divided into five groups (0%, 0.5%wt, 1%wt, 3%wt, and 5%wt). Each concentration was divided into four subgroups (n = 10) based on the immersion solution (distilled water, sodium hypochlorite, Corega, and Fittydent) and immersion duration (360 and 720 days). The color changes (∆E00) and surface roughness (Ra, µm) of each specimen were measured at different time intervals (base line, 360 days, 720 days) using a spectrophotometer and a non-contact profilometer, respectively. The results were statistically analyzed using ANOVA and a post hoc Tukey's test (α = 0.05). Sodium hypochlorite showed the highest significant color change of all the denture base resins (p < 0.001). The average value of ΔE00 for sodium hypochlorite was significantly higher than the values for the other solutions (Fittydent, Corega, and water) (p < 0.001). Color stability was significantly affected by immersion time for all types of solutions except Corega (p < 0.001). All of the tested immersion solutions (distilled water, sodium hypochlorite, Corega, and Fittydent) showed a significant increase in the surface roughness of all the denture base resins (p < 0.05). Surface roughness was substantially increased by immersion time for all types of solution except Fittydent (p < 0.001). Denture cleansers can result in substantial color change and affect the surface roughness of unmodified and nanoparticle-modified denture base resins. Therefore, the selection of denture cleanser and appropriate types of material is critical for denture longevity.

Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidation.

4-Acetylpyridine 1 and malononitrile 2 were allowed to react in a 3MCRs with dimedone 3a or cyclohexa-1,3-dione 3b under reflux to afford 4-methyl-4-(pyridin-4-yl)-5,6,7,8-tetrahydro-4H-chromene derivatives 4a,b respectively. The mechanism of the reaction has been studied and the structures elucidated by analytical, spectral as well as X-ray crystallographic data. Heterocyclic compounds find widespread application in pharmaceutical and agrochemical products. Docking analyses were performed on the synthesized compounds to assess their binding modes with various amino acids of the target protein tubulin (PDB Code - 1SA0). The results indicated promising binding scores for compounds 4a and 4b, suggesting a strong affinity for the tubulin binding site. Finally, ADMET for the synthesized compounds 4a, 4b, 5, 8a and 8b were carried out. The drug likeness and pharmacokinetic properties of the prepared compounds were also evaluated. Notably, all of the novel compounds adhered to Lipinski's rule (Ro5) without any violations.

Effect of different framework materials on stresses induced in distal extension removable partial dentures: A strain gauge analysis.

PURPOSE: Evaluation of the strain transmitted to the abutments and residual ridge by polyetherketoneketone material compared to the cobalt-chromium one in distal extension removable partial dentures (RPDs) to fulfill the objective of preservation of the supporting structures. MATERIALS AND METHODS: A virtual model simulating a Kennedy class I partially edentulous mandibular arch was designed. Two models, one for each group, were printed. Five RPDs were made in each group. In group CR, the framework was milled from a cobalt-chromium alloy. While in group PK, it was milled from a polyetherketoneketone blank. Strain gauge rosettes were bonded distal to the last abutment and posteriorly in the distal end of the residual ridge. Unilateral vertical and oblique loadings were applied. Mann-Whitney U test was used for inter-group comparisons while the Friedman test was used for intra-group comparisons and corrected by Wilcoxon Signed-Rank Sum. The significance level was set at p ≤ 0.05. RESULTS: During unilateral vertical load application, a statistically significant difference was found between both groups distal to the abutment in the loaded and unloaded sides as well as the residual ridge on the unloaded side. During oblique load application, a statistically significant difference was found between both groups in all slots. CONCLUSION: Polyetherketoneketone material induces less stress on the abutments and more stress on the residual ridges compared to the cobalt-chromium ones. Therefore, it may be recommended for weak abutments supporting RPDs.

Fabrication of cellulose nanocrystals/carboxymethyl cellulose/zeolite membranes for methylene blue dye removal: understanding factors, adsorption kinetics, and thermodynamic isotherms.

This study introduces environmentally-friendly nanocellulose-based membranes for AZO dye (methylene blue, MB) removal from wastewater. These membranes, made of cellulose nanocrystals (CNCs), carboxymethyl cellulose (CMC), zeolite, and citric acid, aim to offer eco-friendly water treatment solutions. CNCs, obtained from sugarcane bagasse, act as the foundational material for the membranes. The study aims to investigate both the composition of the membranes (CMC/CNC/zeolite/citric acid) and the critical adsorption factors (initial MB concentration, contact time, temperature, and pH) that impact the removal of the dye. After systematic experimentation, the optimal membrane composition is identified as 60% CNC, 15% CMC, 20% zeolites, and 5% citric acid. This composition achieved a 79.9% dye removal efficiency and a 38.3 mg/g adsorption capacity at pH 7. The optimized membrane exhibited enhanced MB dye removal under specific conditions, including a 50 mg adsorbent mass, 50 ppm dye concentration, 50 mL solution volume, 120-min contact time, and a temperature of 25°C. Increasing pH from neutral to alkaline enhances MB dye removal efficiency from 79.9% to 94.5%, with the adsorption capacity rising from 38.3 mg/g to 76.5 mg/g. The study extended to study the MB adsorption mechanisms, revealing the chemisorption of MB dye with pseudo-second-order kinetics. Chemical thermodynamic experiments determine the Freundlich isotherm as the apt model for MB dye adsorption on the membrane surface. In conclusion, this study successfully develops nanocellulose-based membranes for efficient AZO dye removal, contributing to sustainable water treatment technologies and environmental preservation efforts.

Resistomycin Suppresses Prostate Cancer Cell Growth by Instigating Oxidative Stress, Mitochondrial Apoptosis, and Cell Cycle Arrest.

Globally, prostate cancer is among the most threatening and leading causes of death in men. This study, therefore, aimed to search for an ideal antitumor strategy with high efficacy, low drug resistance, and no or few adverse effects. Resistomycin is a natural antibiotic derived from marine actinomycetes, and it possesses various biological activities. Prostate cancer cells (PC3) were treated with resistomycin (IC12.5: 0.65 or IC25: 1.3 µg/mL) or 5-fluorouracil (5-FU; IC25: 7 µg/mL) for 24 h. MTT assay and flow cytometry were utilized to assess cell viability and apoptosis. Oxidative stress, apoptotic-related markers, and cell cycle were also assessed. The results revealed that the IC50 of resistomycin and 5-FU on PC3 cells were 2.63 µg/mL and 14.44 µg/mL, respectively. Furthermore, treated cells with the high dose of resistomycin showed an increased number of apoptotic cells compared to those treated with the lower dose. Remarkable induction of reactive oxygen species generation and lactate dehydrogenase (LDH) leakage with high malondialdehyde (MDA), carbonyl protein (CP), and 8-hydroxyguanosine (8-OHdG) contents were observed in resistomycin-treated cells. In addition, marked declines in glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in PC3 cells subjected to resistomycin therapy were observed. Resistomycin triggered observable cell apoptosis by increasing Bax, caspase-3, and cytosolic cytochrome c levels and decreasing Bcl-2 levels. In addition, notable downregulation of proliferating cell nuclear antigen (PCNA) and cyclin D1 was observed in resistomycin-treated cancerous cells. According to this evaluation, the antitumor potential of resistomycin, in a concentration-dependent manner, in prostate cancer cells was achieved by triggering oxidative stress, mitochondrial apoptosis, and cell cycle arrest in cancer cells. In conclusion, our investigation suggests that resistomycin can be considered a starting point for developing new chemotherapeutic agents for human prostate cancer.

Eucalyptus torquata L. flowers: a comprehensive study reporting their metabolites profiling and anti-gouty arthritis potential.

Gouty arthritis is one of the most common metabolic disorders affecting people. Plant based drugs can lower the risk of this health disorder. The anti-gouty potential of Eucalyptus torquata flowers methanol extract (ETME) was evaluated in vitro via measuring the inhibitory effects of five pro-inflammatory enzymes; xanthine oxidase (XO), hyaluronidase, lipoxygenase (5-LOX), cyclooxygenases COX-1, and COX-2, in addition to evaluating the inhibition of histamine release, albumin denaturation, membrane stabilization, tyrosinase, and protease inhibitory activities. Also, its antioxidant potential was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays and ferric reducing power assay (FRAP). HPLC-PDA-MS/MS was used to identify the metabolites in the tested extract. The latter exhibited substantial anti-arthritic properties in all assays with comparable potential to the corresponding reference drugs. HPLC-MS/MS analysis of this bioactive extract tentatively annotated 46 metabolites including phloroglucinols, gallic and ellagic acids derivatives, terpenes, flavonoids, fatty acids, and miscellaneous metabolites. Our study highlights the medicinal importance of E. torquata as an anti-gouty candidate and opens new avenues of gouty management.

Respiratory internal kinematics of the tongue base and soft palate in obese minipigs with obstructive sleep apnea.

It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of 5 Yucatan and 2 Panepinto minipigs to verify obstructive sleep apnea (OSA), 8 and 4 ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D dimensional changes of the circumscribed regions were measured simultaneously with electromyographic activity (EMG) of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in 3 non-obese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of dimensional changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The opposite direction of the respiratory spatial relationship between these two structures was seen in obese/OSA as compared to normal minipigs.

The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living-donor Egyptian kidney transplanted patients.

BACKGROUND: Tacrolimus (TAC) is the mainstay of immunosuppressive regimen for kidney transplantations. Its clinical use is complex due to high inter-individual variations which can be partially attributed to genetic variations at the metabolizing enzymes CYP3A4 and CYP3A5. Two single nucleotide polymorphisms (SNPs), CYP3A4*22 and CYP3A5*3, have been reported as important causes of differences in pharmacokinetics that can affect efficacy and/or toxicity of TAC. OBJECTIVE: Investigating the effect of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration in Egyptian renal recipients. METHODS: Overall, 72 Egyptian kidney transplant recipients were genotyped for CYP3A4*22 G>A and CYP3A5*3 T>C. According to the functional defect associated with CYP3A variants, patients were clustered into: poor (PM) and non-poor metabolizers (Non-PM). The impact on dose adjusted through TAC concentrations (C0) and daily doses at different time points after transplantation was evaluated. RESULTS: Cyp3A4*1/*22 and PM groups require significantly lower dose of TAC (mg/kg) at different time points with significantly higher concentration/dose (C0/D) ratio at day 10 in comparison to Cyp3A4*1/*1 and Non-PM groups respectively. However, CyP3A5*3 heterozygous individuals did not show any significant difference in comparison to CyP3A5*1/*3 individuals. By comparing between PM and Non-PM, the PM group had a significantly lower rate of recipients not reaching target C0 at day 14. CONCLUSION: This is the first study on Egyptian population to investigate the impact of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration. This study and future multicenter studies can contribute to the individualization of TAC dosing in Egyptian patients.

Evaluation of the biocompatibility, antibacterial and anticancer effects of a novel nano-structured Fe-Mn-based biodegradable alloys in-vitro study.

Scientific backgrounds: Development of nanostructured biodegradable alloys has generated a great deal of interest in the recent years as they offer promising bioactive materials for reconstruction of bony defects following traumatic fractures or surgical excision of tumors. Objectives: The aim of the current study was to investigate the biocompatibility of Iron-Manganese -based alloys (Fe-Mn) with addition of copper (Cu), Tungsten (W) and cobalt (Co) to obtain 3 different alloys namely, Fe-Mn-Cu, Fe-Mn-W, and Fe-Mn-Co on normal oral epithelial cell line,and their possible anticancer effect on MG-63: osteosarcoma cell line. Materials and methods: The sulforhodamine B (SRB) assay was used to assess cell viability percentage of both cell lines after exposure to discs of the proposed experimental alloys. Moreover, the antibacterial effect of such alloys against Escherichia coli (E. coli) was tested using disc diffusion susceptibility (Kirby-Bauer method) and colony suspension method. Results: The cell viability percentage of oral epithelial cell line showed a significant increase in all the experimental groups in comparison to the control group. The highest percentage was observed in Fe-Mn-Co group, followed by Fe-Mn-W then Fe-Mn-Cu, at 24 and 72-h intervals, respectively. While the cell viability percentage of osteosarcoma cell line showed significant increase in all the experimental groups at 24-h intervals, it showed a significant drop in all the study groups at 72-h intervals. The lowest percentage was observed in Fe-Mn-Cu group, followed by Fe-Mn-W then Fe-Mn-Co. Moreover, all the examined study groups didn't show any inhibition zones against E. coli reference culture. Conclusions: The novel nanostructured biodegradable Fe-Mn-Cu, Fe-Mn-W, and Fe-Mn-Co metal alloys exhibit good biocompatibility on oral epithelial cell lines with the enhancement of cell proliferation in a time-dependent manner that favors bone regeneration. On the other hand, all the alloys manifested possible anticancer activity against MG-63: osteosarcoma cell line. Furthermore, our study sheds the light on the importance of Co, W and Cu as promising alloying elements. However, the antibacterial activity of the examined alloys is still questionable. Clinical relevance: The novel nanostructured biodegradable Fe-Mn-Cu, Fe-Mn-W, and Fe-Mn-Co metal alloys offer promising bioactive materials for reconstruction of bony defects following traumatic fractures or surgical excision of tumors, In addition, they could be excellent alternatives for undegradable or non-resorbable alloys that are commonly used. Moreover, they could be used as beneficial 3D printing materials to obtain patient-specific medical implants that favor bone regeneration in addition to manufacturing of plates and screws suitable for fracture fixation.

Dermato-cosmeceutical properties of Pseudobombax ellipticum (Kunth) Dugand: Chemical profiling, in vitro and in silico studies.

Plant extracts and their individual components have been used to manage skin aging for several decades. Recently, the discovery of new natural bioactive agents, that not only enhance the skin health but also offer protection against various deleterious factors, such as free radicals, ultraviolet radiation, and microbial infections, has been a potential target by many researchers. The aim of the current work was to investigate the phytochemical profile of an ethanol bark extract from Pseudobombax ellipticum, and to evaluate its antioxidant, antiaging and antibacterial activities in vitro. Molecular docking and molecular dynamics studies were adopted to estimate and confirm the binding affinity of several compounds and explain their binding pattern at the binding sites of four target enzymes associated with skin aging, namely collagenase, elastase, tyrosinase, and hyaluronidase. HPLC-MS/MS analysis led to the tentative identification of 35 compounds comprising phenolic acids, and their glycosides, procyanidins and flavonoid glycosides. The extract demonstrated a promising in vitro antioxidant activity in the DPPH and FRAP assays (IC50 56.45 and 15.34 µg/mL, respectively), and was able to inhibit the aforementioned key enzymes with comparable results to the reference drugs. In addition, the extract (6.25 mg/mL) inhibited the biofilm production of Pseudomonas aeruginosa and diminished the swimming and swarming motilities. The docked compounds revealed appreciable binding energy with the tested enzymes and were stable throughout the molecular dynamic simulations. In view of this data, P. ellipticum bark can be regarded as a good candidate for prospective application in derma-cosmeceutical preparations.

Three-Dimensional Echocardiography As A Predictor Of Positive Response To Cardiac Resynchronisation Therapy.

Objectives: To assess patients with three-dimensional echocardiography before cardiac resynchronisation therapy device implantation to predict the responders, and to determine the response 3 months post-intervention. Method: The descriptive study was conducted at Kafrelsheikh University Hospital, Egypt, from January 2020 to March 2022, and comprised patients of either gender who underwent cardiac resynchronisation therapy device implantation. The patients were assessed clinically and with three-dimensional echocardiography using 16-segment systolic dyssynchrony index asthe main parameter compared at baseline and 3 months after implantation. The patients were classified as non-responders, clinical responders, and clinical and echocardiographic responders. Data was analysed using SPSS 23. RESULTS: Of the 40 patients, 23(57.5%) were males and 17(42.5%) were females. The overall mean age was 57.43±10.47 years, mean body weight was 81.30±11.33kg, mean height was 171.15±10.56cm), and mean body surface area was 1.93±0.17m2. Of the total, 14(35%) patients were hypertensive, 10(25%) diabetic, 15(37.5%) ischaemic and 2(5%) patients had atrial fibrillation. There were 8(20%) non-responders, 8(20%) clinical responders, and 24(60%) clinical and echocardiographic responders to therapy. Mean systolic dyssynchrony index at baseline was a positive highly significant predictor of post-therapy response (p<0.01). A positive highly significant correlation was also found between post-therapy response and end-systolic volume, three-dimensional ejection fraction, New York Heart Association class and QRS width (p<0.01). CONCLUSIONS: Three-dimensional 16-segmentsystolic dyssynchrony index wasfound to be a significantly effective tool to predict response to cardiac resynchronisation therapy device implantation.

Role Of Speckle Tracking Echocardiography In Prediction Of Responders To Cardiac Resynchronization Therapy.

Objectives: To assess heart failure patients by speckle tracking echocardiography before cardiac resynchronisation therapy implantation to predict the outcome. Method: The descriptive follow-up study was conducted at Kafrelsheikh and Mansoura University Hospitals, Egypt, from January 2020 to May 2022, and comprised heart failure patients of either gender who had ejection fraction ≤35%, QRS width ≥130msec and symptomatic even on optimal medical therapy. They were subjected to full clinical evaluation, electrocardiogram, basic and speckle tracking echocardiography with calculation of maximal septal to lateral delay at baseline and 3 months after cardiac resynchronisation therapy implantation. The patients were classified according to response into group I having non-responders, group II having patients who improved clinically only, and group III having responders both in clinical and echocardiographic terms. Data was analysed using SPSS 23. RESULTS: Of the 38 patients with mean age 55.24±11.23 years, 16(42%) were females and 22(57.9%) were males. There were 7(18.4%) patients in group I, 7(18.4%) in group II and 24(63.2%) in group III. There was a positive significant correlation between response to cardiac resynchronisation therapy CRT and increase in maximalseptal to lateral delay at baseline (p<0.01). There was an inverse significant correlation between response to cardiac resynchronisation therapy and decrease in maximal septal to lateral delay 3 months after the implantation (p=0.036). CONCLUSIONS: Maximal septal to lateral delay was found to be a good tool to predict the response to cardiac resynchronisation therapy before implantation.

Thymus satureioides Coss. combats oral ulcer via inhibition of inflammation, proteolysis, and apoptosis.

Oral ulcer is a frequent condition that commonly affects the tongue and in which 75% of the patients experience pain, and 25% report taste changes. The available therapies are not sufficiently effective for rapid and complete healing of tongue ulcers. We previously annotated the metabolites of Thymus satureioides (TS) aerial parts and reported their antioxidant, dermacosmeceutical and hepatoprotective properties. In this study, we performed in silico analysis, by applying network pharmacology and molecular docking, followed by experimental validation of the effect of local application of T. satureioides (TS) gel at two different concentrations on the healing of acetic-acid-induced tongue ulcer in rats. Salvianolic acid A, phloretic acid caffeate, rosmarinic acid, apigenin, and luteolin were the top bioactive ingredients of TS extract. Network pharmacology showed that the most relevant targets of these active constituents were TLR4, COX-2, MMP-9, TNF-α, and Caspase-3. Molecular docking showed that rosmarinic acid and salvianolic acid had a relatively strong binding affinity, compared to the other compounds, toward all the target proteins. Experimental validation in tongue ulcer model in rats and immunohistochemistry experiments showed that application of a gel containing TS extract (5 and 10%) was effective in healing the tongue ulcer via downregulation of COX-2, TNF-α, MMP-9, and Caspase-3. This study suggests that T. satureioides extract could act as a topical treatment for tongue ulcers by combating inflammation, apoptosis, and proteolysis. The possible treatment potential of some constituents including rosmarinic acid and salvianolic acid in oral ulcerations awaits further investigations to confirm their potency.

Sensitivity and specificity of chest ultrasound in the diagnosis of pulmonary embolism in the emergency department: A case-control study.

Objectives: The present study was designed to evaluate the role of chest ultrasound in the diagnosis of acute pulmonary embolism (PE) and determine its accuracy using multi-detector CT-pulmonary angiography (MD-CTPA) as a gold standard technique for PE diagnosis. Patients and methods: A prospective case-control study was performed with 75 patients who presented to the emergency department of Minia Cardiothoracic University Hospital with clinical suspicion of PE. All patients were evaluated clinically and by laboratory tests to assess the risk of PE. Thoracic ultrasound (TUS) was then performed for all patients for signs suggestive of PE. Finally, MD-CTPA was performed to confirm or exclude the presence of PE. Results: Patients were subdivided into two groups according to the result of MD-CTPA; group I (patients with PE) and group II (control group without PE). In our study, PE was present in the lower lobe in 75% of cases, then in the middle in 13% and in the upper lobe in 3.8% of cases. The majority of lesions in TUS were wedge-shaped lesions. No vascular flow was detected in 83% of PE-confirmed patients. The current study revealed that TUS has 81.25% sensitivity, 95% specificity, 98.3% positive predictive value, 77.2% negative predictive value and 87% accuracy in the diagnosis of PE. Univariate regression analysis revealed that the presence of wedge-shaped pleural-based lesions in grayscale US and the absence of flow signals by colour Doppler sonography (CDS) increase the possibility of PE. Wedge-shaped pleural-based lesions increase the possibility of PE by 1.48 times (P=0.0001), and the absence of flow signals by CDS increases the possibility of PE by 92.89 times (P=0.00001). Multivariate regression analysis revealed that adding absent flow signals by CDS to wedge-shaped pleural-based lesions by grayscale US increases the possibility of a PE diagnosis by 50.28 times (P=0.001). Conclusion: Chest ultrasound is a simple, safe, noninvasive, inexpensive, bedside diagnostic radiological technique that can be used in the emergency department for suspected PE or as an alternative to MD-CTPA when CTPA is contraindicated. Wedge-shaped lesions and the absence of flow signals by CDS increase the diagnostic value of ultrasound for PE.

Neuro-amelioration of Ficus lyrata (fiddle-leaf fig) extract conjugated with selenium nanoparticles against aluminium toxicity in rat brain: relevance to neurotransmitters, oxidative, inflammatory, and apoptotic events.

Aluminium is a non-essential metal, and its accumulation in the brain is linked with potent neurotoxic action and the development of many neurological diseases. This investigation, therefore, intended to examine the antagonistic efficacy of Ficus lyrata (fiddle-leaf fig) extract (FLE) conjugated with selenium nanoparticles (FLE-SeNPs) against aluminium chloride (AlCl3)-induced hippocampal injury in rats. Rats were allocated to five groups: control, FLE, AlCl3 (100 mg/kg), AlCl3 + FLE (100 mg/kg), and AlCl3 + FLE-SeNPs (0.5 mg/kg). All agents were administered orally every day for 42 days. The result revealed that pre-treated rats with FLE-SeNPs showed markedly lower acetylcholinesterase and Na+/K+-ATPase activities in the hippocampus than those in AlCl3 group. Additionally, FLE-SeNPs counteracted the oxidant stress-mediated by AlCl3 by increasing superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents in rat hippocampus. Besides, the formulated nanoparticles decreased the hippocampal malondialdehyde, carbonyl protein, and nitric oxide levels of AlCl3-exposed animals. Furthermore, FLE-SeNPs attenuated neural tissue inflammation, as demonstrated by decreased interleukin-1 beta, interleukin-6, nuclear factor kappa B, and glial fibrillary acidic protein. Remarkable anti-apoptotic action was exerted by FLE-SeNPs by increasing B cell lymphoma 2 and decreasing caspase-3 and Bcl-2-associated-X protein in AlCl3-exposed rats. The abovementioned results correlated well with the hippocampal histopathological findings. Given these results, SeNPs synthesized with FLE imparted a remarkable neuroprotective action against AlCl3-induced neurotoxicity by reversing oxidative damage, neuronal inflammation, and apoptosis in exposed rats.

Apple (Malus domestica Borkh) leaves attenuate indomethacin-induced gastric ulcer in rats.

Malus domestica Borkh, the apple tree, exhibited numerous pharmacological properties including antioxidant, neuroprotective, anti-inflammatory, anticancer and antimicrobial activities. The present work aimed to annotate the secondary metabolites from a butanol fraction of apple leaves (BLE), evaluate the gastro-protective and healing effects of this fraction against indomethacin-induced gastric ulcers in rats and to identify its mechanism of action. BLE (100, and 200 mg/kg) was orally administered in rats as an acute treatment against indomethacin-induced gastric ulcer in comparison with famotidine as reference anti-ulcer drug. The stomachs of rats were collected to determine the ulcer index, the preventive ratio, measure the activity of glutathione peroxidase (GPx), and estimate the expression of cyclooxygenase-2 (COX-2), and heat shock protein 70 (HSP70). Furthermore, we evaluated both inflammatory and oxidative stress markers in the gastric tissues. We also performed histopathological study of gastric mucosa using H&E stain and periodic Schiff base stain to evaluate both gastric injury scores and gastric mucus content respectively. Pretreatment with BLE markedly lowered the severity of gastric injury induced by indomethacin, decreased oxidative stress, inflammatory cytokines, and COX-2 expression in the examined gastric tissues. The gastric healing effect of BLE was associated with increased mucoglycoproteins, and HSP70 expression. Additionally, gastric healing effect of high dose of BLE was superior to that of famotidine in decreasing gastric injury scores, COX-2, inflammatory cytokines, lipid peroxidation and in increasing gastric mucin content, HSP70, and reduced glutathione. These findings indicate that BLE is effective in accelerating ulcer healing by boosting HSP70 expression, and decreasing COX-2 expression, oxidative stress, and gastric inflammation which might be related to the presence of 21 phytoconstituents.