Triple network resting-state functional connectivity patterns of alcohol heavy drinking.

AIMS: Previous neuroimaging research in alcohol use disorder (AUD) has found altered functional connectivity in the brain's salience, default mode, and central executive (CEN) networks (i.e. the triple network model), though their specific associations with AUD severity and heavy drinking remains unclear. This study utilized resting-state fMRI to examine functional connectivity in these networks and measures of alcohol misuse. METHODS: Seventy-six adult heavy drinkers completed a 7-min resting-state functional MRI scan during visual fixation. Linear regression models tested if connectivity in the three target networks was associated with past 12-month AUD symptoms and number of heavy drinking days in the past 30 days. Exploratory analyses examined correlations between connectivity clusters and impulsivity and psychopathology measures. RESULTS: Functional connectivity within the CEN network (right and left lateral prefrontal cortex [LPFC] seeds co-activating with 13 and 15 clusters, respectively) was significantly associated with AUD symptoms (right LPFC: ß = .337, p-FDR = .016; left LPFC: ß = .291, p-FDR = .028) but not heavy drinking (p-FDR > .749). Post-hoc tests revealed six clusters co-activating with the CEN network were associated with AUD symptoms-right middle frontal gyrus, right inferior parietal gyrus, left middle temporal gyrus, and left and right cerebellum. Neither the default mode nor the salience network was significantly associated with alcohol variables. Connectivity in the left LPFC was correlated with monetary delay discounting (r = .25, p = .03). CONCLUSIONS: These findings support previous associations between connectivity within the CEN network and AUD severity, providing additional specificity to the relevance of the triple network model to AUD.

Empirical examination of working memory performance and its neural correlates in relation to delay discounting in two large samples.

The neurobiological basis of working memory and delay discounting are theorized to overlap, but few studies have empirically examined these relations in large samples. To address this, we investigated the association of neural activation during an fMRI N-Back working memory task with delay discounting area, as well as in- and out-of-scanner working memory measures. These analyses were conducted in two large task fMRI datasets, the Human Connectome Project and the Adolescent Brain Cognitive Development Study. Although in- and out-of-scanner working memory performance were significantly associated with N-back task brain activation regions, contrary to our hypotheses, there were no significant associations between working memory task activation and delay discounting scores. These findings call into question the extent of the neural overlap in delay discounting and working memory and highlight the need for more investigations directly interrogating overlapping and distinct brain regions across cognitive neuroscience tasks.

Handover for V2V communication in 5G using convolutional neural networks.

Vehicle communication is one of the most vital aspects of modern transportation systems because it enables real-time data transmission between vehicles and infrastructure to improve traffic flow and road safety. The next generation of mobile technology, 5G, was created to address earlier generations' growing need for high data rates and quality of service issues. 5G cellular technology aims to eliminate penetration loss by segregating outside and inside settings and allowing extremely high transmission speeds, achieved by installing hundreds of dispersed antenna arrays using a distributed antenna system (DAS). Huge multiple-input multiple-output (MIMO) systems are accomplished via DASs and huge MIMO systems, where hundreds of dispersed antenna arrays are built. Because deep learning (DL) techniques employ artificial neural networks with at least one hidden layer, they are used in this study for vehicle recognition. They can swiftly process vast quantities of labeled training data to identify features. Therefore, this paper employed the VGG19 DL model through transfer learning to address the task of vehicle detection and obstacle identification. It also proposes a novel horizontal handover prediction method based on channel characteristics. The suggested techniques are designed for heterogeneous networks or horizontal handovers using DL. In the designated surrounding regions of 5G environments, the suggested detection and handover algorithms identified vehicles with a success rate of 97 % and predicted the next station for handover.

Resilience in the face of pandemic: exploring the influence of psychological flexibility on turnover intentions and burnout among critical care nurses in COVID-19 hospitals.

AIM: Assess the levels of psychological flexibility, burnout, and turnover intention among critical care nurses and assess the impact of psychological flexibility on burnout, and turnover intention among critical care nurses. BACKGROUND: Burnout and turnover intentions among critical care nurses are rapidly increasing because of the challenges of COVID-19. There is a need for evidence-based interventions like psychological flexibility to be addressed in research to overcome those challenges. METHODS: A descriptive correlational research. A convenient sample of 200 critical care nurses working in COVID-19 hospitals from two governorates in Egypt. The sociodemographic and clinical data sheet, the work-related acceptance and action questionnaire, the Copenhagen burnout inventory, and the adopted version of the staff nurses' intention to leave the nursing profession questionnaire were used. RESULTS: The majority of critical care nurses reported a moderate level of psychological flexibility (75.5%, Mean = 31.23), a moderate level of burnout (65.5%, Mean = 59.61), and low to moderate levels of intention to leave (73%, Mean = 5.95). Psychological flexibility has a statistically significant negative correlation with burnout (PC = -0.304, Sig = 0.000) and the intention to leave (PC = -0.258, Sig = 0.000). In addition, psychological flexibility has a predictable effect on decreasing burnout (R2 = 0.232) and intention to leave (R2 = 0.127) among critical care nurses. CONCLUSION: critical care nurses in COVID-19 hospitals reported varied levels of burnout and an intention to leave that must be considered. The effect of psychological flexibility on burnout and intention to turnover highlighted the importance of improving it among critical care nurses by applying acceptance and commitment therapy as a management intervention.

Association between high-density mapping of atypical atrial flutter, clinical outcomes and healthcare utilization.

BACKGROUND: Success of atypical atrial flutter (AAFL) ablation has historically been limited by difficulty mapping the complex re-entrant circuits involved. While high-density (HD) mapping has become commonplace in clinical practice, there are limited data on outcomes of HD versus non-HD mapping for AAFL ablation. OBJECTIVE: To compare clinical outcomes and healthcare utilization using HD mapping versus non-HD mapping for AAFL ablation. METHODS: Retrospective analysis of all AAFL procedures between 2005 and 2022 at an academic medical center was conducted. Procedures utilizing a 16-electrode HD Grid catheter and Precision mapping system were compared to procedures using prior generation 10-20 electrode spiral catheters and the Velocity system (Abbott, IL). Cox regression models and Poisson regression models were utilized to examine procedural and healthcare utilization outcomes. Models were adjusted for left ventricular ejection fraction, CHA2DS2-VASc, and history of prior ablation. RESULTS: There were 108 patients (62% HD mapping) included in the analysis. Baseline clinical characteristics were similar between groups. Use of HD mapping was associated with a higher rate of AAFL circuit delineation (92.5% vs. 76%; p = .014) and a greater adjusted procedure success rate, defined as non-inducibility at procedure end, (aRR (95% CI) 1.26 (1.02-1.55) p = .035) than non-HD mapping. HD mapping was also associated with a lower rate of ED visits (aIRR (95% CI) 0.32 (0.14-0.71); p = .007) and hospitalizations (aIRR (95% CI) 0.32 (0.14-0.68); p = .004) for AF/AFL/HF through 1 year. While there was a lower rate of recurrent AFL through 1 year among HD mapping cases (aHR (95% CI) 0.60 (0.31-1.16) p = .13), statistical significance was not met likely due to the low sample size and higher rate of ambulatory rhythm monitoring in the HD group (61% vs. 39%, p = .025). CONCLUSION: Compared to non-HD mapping, AAFL ablation with HD mapping is associated with improvements in the ability to define the AAFL circuit, greater procedural success, and a reduction in the number of ED visits and hospitalization for AF/AFL/HF.

Multimodal modulation of hepatic ischemia/reperfusion-induced injury by phytochemical agents: A mechanistic evaluation of hepatoprotective potential and safety profiles.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a clinically fundamental phenomenon that occurs through liver resection surgery, trauma, shock, and transplantation. AIMS OF THE REVIEW: This review article affords an expanded and comprehensive overview of various natural herbal ingredients that have demonstrated hepatoprotective effects against I/R injury through preclinical studies in animal models. MATERIALS AND METHODS: For the objective of this investigation, an extensive examination was carried out utilizing diverse scientific databases involving PubMed, Google Scholar, Science Direct, Egyptian Knowledge Bank (EKB), and Research Gate. The investigation was conducted based on specific identifiable terms, such as hepatic ischemia/reperfusion injury, liver resection and transplantation, cytokines, inflammation, NF-kB, interleukins, herbs, plants, natural ingredients, phenolic extract, and aqueous extract. RESULTS: Bioactive ingredients derived from ginseng, curcumin, resveratrol, epigallocatechin gallate, quercetin, lycopene, punicalagin, crocin, celastrol, andrographolide, silymarin, and others and their effects on hepatic IRI were discussed. The specific mechanisms of action, signaling pathways, and clinical relevance for attenuation of liver enzymes, cytokine production, immune cell infiltration, oxidative damage, and cell death signaling in rodent studies are analyzed in depth. Their complex molecular actions involve modulation of pathways like TLR4, NF-κB, Nrf2, Bcl-2 family proteins, and others. CONCLUSION: The natural ingredients have promising values in the protection and treatment of various chronic aggressive clinical conditions, and that need to be evaluated on humans by clinical studies.

Safety and feasibility of intravenous sotalol loading for the prevention of ventricular arrhythmias.

BACKGROUND: The use of intravenous (IV) sotalol loading following recent U.S. Food and Drug Administration (FDA) approval of a 1-day loading protocol has reduced the obligatory 3-day hospital stay for sotalol initiation when given orally. Several studies have recently demonstrated the safety and feasibility of IV loading for patients with atrial arrhythmias. However, there is a paucity of data on the feasibility and safety of IV sotalol loading for patients with ventricular arrhythmias. This study aims to assess the safety, feasibility, and length of stay (LOS) outcomes of IV sotalol loading for the prevention of ventricular arrhythmias. METHODS: A retrospective analysis was performed of all patients undergoing IV sotalol loading and oral sotalol initiation for ventricular arrhythmias, or IV sotalol loading for atrial arrhythmias between August 2021 and December 2023 at Northwestern University. Baseline characteristics, success of sotalol initiation/loading, changes in heart rate (HR) and QT/QTc, safety, and LOS were compared between patients undergoing sotalol loading/initiation for ventricular arrhythmias (IV vs. PO) and between patients undergoing IV sotalol loading for ventricular arrhythmias vs. for atrial arrhythmias. RESULTS: A total of 28 patients underwent sotalol loading/initiation for ventricular arrhythmias (N = 15 IV and N = 13 PO) and 41 patients underwent IV sotalol loading for atrial arrhythmias. Baseline characteristics of congestive heart failure history and left ventricular ejection fraction were worse in the ventricular arrhythmias group. There was no significant difference in the successful completion of IV sotalol loading for ventricular arrhythmias compared to oral sotalol initiation for ventricular arrhythmias or IV sotalol loading for atrial arrhythmias (86.7% vs. 92.3% vs. 90.2%, p = 0.88). There was a significant increase in ΔQTc following IV sotalol infusion for ventricular arrhythmias compared to following PO sotalol initiation for ventricular arrhythmias (46.4 ± 29.2 ms vs. 8.9 ± 32.6 ms, p = 0.004) and following IV sotalol infusion for atrial arrhythmias (46.4 ± 29.2 ms vs. 24.0 ± 25.1 ms, p = 0.018). ΔHR following IV sotalol infusion for ventricular arrhythmias was similar to ΔHR following PO sotalol initiation for ventricular arrhythmias and ΔHR following IV sotalol infusion for atrial arrhythmias (- 7.5 ± 8.7 bpm vs. - 8.5 ± 13.9 bpm vs. - 8.3 ± 13.2 bpm, p = 0.87). There were no significant differences in discontinuation for QTc prolongation (6.7% vs. 1.7% vs. 2.4%, p = 0.64) and bradycardia (13.3% vs. 7.7% vs. 9.8%, p = 0.88) between IV sotalol loading for ventricular arrhythmias, PO sotalol initiation for ventricular arrhythmias, and IV sotalol loading for atrial arrhythmias. There were no instances of hypotension, life-threatening ventricular arrhythmias, heart failure, or death. Length of stay was significantly shorter for IV sotalol loading compared to PO sotalol initiation for ventricular arrhythmias (1.1 ± 0.36 days vs. 4.2 ± 1.0 days, p < 0.0001). CONCLUSION: IV sotalol loading appears feasible and safe for use in ventricular arrhythmias and results in a decreased length of stay. Despite increased comorbidities and greater increase in QTc interval following IV sotalol infusion in the ventricular arrhythmias group, there were no significant differences in successful completion of loading or adverse outcomes when compared to PO sotalol initiation for ventricular arrhythmias and IV loading for atrial arrhythmias.

Use of K-Y Jelly on Throat Packs for Postoperative Sore Throat after Nasal Surgery: A Randomized Controlled Trial.

Introduction Postoperative sore throat (POST) is a fairly common side effect of general anesthesia. The K-Y jelly is a well-known lubricant used in many medical procedures. Objective In this randomized study, we evaluated the use of throat packs soaked with K-Y jelly for POST outcomes in patients submitted to nasal surgery. Methods The present double-blinded, randomized, controlled study included 140 ASA I-II patients undergoing nasal surgery under general anesthesia. Patients received either or K-Y jelly or water-soaked X-ray detectable throat packs fully inserted into the mouth to occlude the oropharynx. Results Comparison between the studied groups regarding the severity of POST assessed by visual analog scale revealed significantly lower POST levels in the K-Y jelly group on recovery from anesthesia, and at 2, 4, and 6 hours postoperatively. Conclusions The use of K-Y jelly-soaked throat packs was associated with less severe POST after nasal surgery.

Accuracy of Apple Watch to Measure Cardiovascular Indices in Patients with Chronic Diseases: A Cross Sectional Study.

Background: The validity of the Apple Watch to measure the heart rate (HR) and oxygen saturation (Spo2) for patients with chronic diseases such as diabetes mellitus (DM), dyslipidemia, and hypertension is still unclear. Therefore, this study aims to investigate the accuracy of the Apple Watch in measuring the Spo2 and HR in patients with chronic diseases. Methods: Forty-one patients with chronic diseases, including 20 with hypertension, 10 with diabetes, and 11 with dyslipidemia, completed a cross-sectional study. All participants used the Apple Watch against the Polar chest strap and the pulse oximeter at rest and during moderate intensity exercise sessions to measure HR and the SpO2 at rest for 5 minutes, during exercise for 16 minutes, and followed by 3 minutes of rest. The HR was measured during all previous periods, but evaluation of the Spo2 included 5 measures, done only before and after exercise, with a minute interval between each measure. Results: Overall, a strong correlation exists between measuring the SpO2 using the Apple Watch against the pulse oximeter (Contec) at rest (r = 0.92, p < 0.001) and after exercise (r = 0.86, p < 0.001) in all patients. The HR had a very strong correlation between the Apple Watch and the Polar chest strap (r = 0.99, p < 0.001) in all patients. There was no significant difference (p = 0.76) between the twenty-seven white and fourteen brown-skinned patients. Conclusion: The Apple Watch is valid to measure the HR and SpO2 in patients with chronic diseases. Clinical Trial Registration No: NCT05271864.

Sodium alginate films incorporated with Lepidium sativum (Garden cress) extract as a novel method to enhancement the oxidative stability of edible oil.

This study addresses the growing interest in bio-based active food packaging by infusing Lepidium sativum (Garden cress) seeds extract (GRCE) into sodium alginate (SALG) films at varying concentrations (1, 3, and 5 %). The GRCE extract revealed six phenolic compounds, with gallic and chlorogenic acids being prominent, showcasing substantial total phenolic content (TPC) of 139.36 µg GAE/mg and total flavonoid content (TFC) of 26.46 µg RE/mg. The integration into SALG films significantly increased TPC, reaching 30.73 mg GAE/g in the film with 5 % GRCE. This enhancement extended to DPPH and ABTS activities, with notable rises to 66.47 and 70.12 %, respectively. Physical properties, including tensile strength, thickness, solubility, and moisture content, were positively affected. A reduction in water vapor permeability (WVP) was reported in the film enriched with 5 % GRCE (1.389 × 10-10 g H2O/m s p.a.). FT-IR analysis revealed bands indicating GRCE's physical interaction with the SALG matrix, with thermal stability of the films decreasing upon GRCE integration. SALG/GRCE5 effectively lowered the peroxide value (PV) of sunflower oil after four weeks at 50 °C compared to the control, with direct film-oil contact enhancing this reduction. Similar trends were observed in the K232 and K270 values.

Development and optimization of vildagliptin solid lipid nanoparticles loaded ocuserts for controlled ocular delivery: A promising approach towards treating diabetic retinopathy.

Diabetes mellitus (DM) is the most prevalent cause of diabetic retinopathy (DRP). DRP has been recognized for a long time as a microvascular disease. Many drugs were used to treat DRP, including vildagliptin (VLD). In addition to its hypoglycemic effect, VLD minimizes ocular inflammation and improves retinal blood flow for individuals with type 2 diabetes mellitus. Nevertheless, VLD can cause upper respiratory tract infections, diarrhea, nausea, hypoglycemia, and poor tolerability when taken orally regularly due to its high water solubility and permeability. Effective ocular administration of VLD is achieved using solid lipid nanoparticles (SLNPs), which improve corneal absorption, prolonged retention, and extended drug release. Ocuserts (OCUs) are sterile, long-acting ocular dosage forms that diminish the need for frequent dosing while improving residence time and stability. Therefore, this study intends to develop VLD solid lipid nanoparticle OCUs (VLD-SLNPs-OCUs) to circumvent the issues commonly associated with VLD. SLNPs were prepared using the double-emulsion/melt dispersion technique. The optimal formula has been implemented in OCUs. Optimization and development of VLD-SLNPs-OCUs were performed using a Box-Behnken Design (BBD). VLD-SLNPs-OCUs loading efficiency was 95.28 ± 2.87%, and differential scanning calorimetry data (DSC) showed the full transformation of VLD to an amorphous state and the excellent distribution in the prepared OCUs matrices. The in vivo release of VLD from the optimized OCUs after 24 h was 35.12 ± 2.47%, consistent with in vitro drug release data of 36.89 ± 3.11. The optimized OCUs are safe to use in the eye, as shown by the ocular irritation test. VLD-SLNPs-OCUs provide extended VLD release, an advantageous alternative to conventional oral dose forms, resulting in fewer systemic adverse effects and less variation in plasma drug levels. VLD-SLNPs-OCUs might benefit retinal microvascular blood flow beyond blood glucose control and may be considered a promising approach to treating diabetic retinopathy.

Physicochemical modifications in microwave-irradiated chitosan: biopharmaceutical and medical applications.

Biopharmaceutical and biomedical applications of chitosan has evolved exponentially in the past decade, owing to its unique physicochemical properties. However, further applications can be garnered from modified chitosan, specifically, depolymerized chitosan, with potentially useful applications in drug delivery or biomedicine. The use of microwave irradiation in depolymerization of chitosan appears to be more consequential than other methods, and results in modification of key physicochemical properties of chitosan, including molecular weight, viscosity and degree of deacetylation. In-depth review of such microwave-depolymerized chitosan and subsequent potential biopharmaceutical or biomedical applications has not been presented before. Herein, we present a detailed review of key physicochemical changes in chitosan following various depolymerization approaches, with focus on microwave irradiation and how these changes impact relevant biopharmaceutical or biomedical applications.

Use of K-Y Jelly on Throat Packs for Postoperative Sore Throat after Nasal Surgery: A Randomized Controlled Trial

Abstract Introduction Postoperative sore throat (POST) is a fairly common side effect of general anesthesia. The K-Y jelly is a well-known lubricant used in many medical procedures. Objective In this randomized study, we evaluated the use of throat packs soaked with K-Y jelly for POST outcomes in patients submitted to nasal surgery. Methods The present double-blinded, randomized, controlled study included 140 ASA I-II patients undergoing nasal surgery under general anesthesia. Patients received either or K-Y jelly or water-soaked X-ray detectable throat packs fully inserted into the mouth to occlude the oropharynx. Results Comparison between the studied groups regarding the severity of POST assessed by visual analog scale revealed significantly lower POST levels in the K-Y jelly group on recovery from anesthesia, and at 2, 4, and 6 hours postoperatively. Conclusions The use of K-Y jelly-soaked throat packs was associated with less severe POST after nasal surgery.

Effect of an educational program on pediatric nurses' knowledge, practice, and self-confidence about level of consciousness scales.

BACKGROUND: Nurses of pediatric acute critical care units routinely assess the Level of Consciousness (LOC). The precise, exact, and restriction-free evaluation tool aids pediatric nurses in LOC assessment and clinical decision-making. This study aimed to examine the effect of an educational program on pediatric nurses' knowledge, practice, and self-confidence about level of consciousness scales. METHODS: This pretest-post, single-group, quasi-experimental, double-site study included 49 pediatric nurses. The Glasgow Coma Scale (GCS)/Pediatric Glasgow Coma Scale (PGCS) and Pediatric Full Outline of UnResponsiveness Score Scale (PFSS) knowledge questionnaire and pediatric nurse practice checklist were developed and adopted. Self-reflection confidence statements were rated 1-5 (not confident-confident). RESULTS: The results of the study indicate that there were significant increases in knowledge, practice, and self-confidence after the intervention. The paired samples tests revealed that knowledge scores significantly increased from the pretest to the posttest for both GCS/PGCS (pretest mean:7.91, posttest mean:9.95) and PFSS (pretest mean:2.1, posttest mean:6.79). Practice scores also showed significant improvement for both GCS/PGCS (pretest mean: 4.12, post-test mean: 6.22) and PFSS (pretest mean: 2.46, post-test mean: 5.79). Furthermore, self-confidence significantly improved for GCS/PGCS (pretest mean:16.08, posttest mean:18.79) and PFSS (pretest mean:10.32, posttest mean:17.81). The statistical analyses supported the significance of these improvements (p < 0.001 for all except self-confidence in GCS/PGCS with p < 0.005). CONCLUSION: The educational program improved pediatric nurses' GCS/PGCS and PFSS knowledge, practice, and self-confidence. IMPLICATIONS TO PRACTICE: Effective teaching of pediatric nurses is required to address gaps in care practices and improve the use of the Consciousness Level Assessment Scales.

Characterization and Bio-Evaluation of the Synergistic Effect of Simvastatin and Folic Acid as Wound Dressings on the Healing Process.

Wound healing is a significant healthcare problem that decreases the patient's quality of life. Hence, several agents and approaches have been widely used to help accelerate wound healing. The challenge is to search for a topical delivery system that could supply long-acting effects, accurate doses, and rapid healing activity. Topical forms of simvastatin (SMV) are beneficial in wound care. This study aimed to develop a novel topical chitosan-based platform of SMV with folic acid (FA) for wound healing. Moreover, the synergistic effect of combinations was determined in an excisional wound model in rats. The prepared SMV-FA-loaded films (SMV-FAPFs) were examined for their physicochemical characterizations and morphology. Box-Behnken Design and response surface methodology were used to evaluate the tensile strength and release characteristics of the prepared SMV-FAPFs. Additionally, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction pattern (XRD), and animal studies were also investigated. The developed SMV-FAPFs showed a contraction of up to 80% decrease in the wound size after ten days. The results of the quantitative real-time polymerase chain reaction (RT-PCR) analysis demonstrated a significant upregulation of dermal collagen type I (CoTI) expression and downregulation of the inflammatory JAK3 expression in wounds treated with SMV-FAPFs when compared to control samples and individual drug treatments. In summary, it can be concluded that the utilization of SMV-FAPFs holds great potential for facilitating efficient and expeditious wound healing, hence presenting a feasible substitute for conventional topical administration methods.

Synthesis, Physicochemical Characterization using a Facile Validated HPLC Quantitation Analysis Method of 4-Chloro-phenylcarbamoyl-methyl Ciprofloxacin and Its Biological Investigations.

A novel derivative of ciprofloxacin (Cpx) was synthesized and characterized using various analytical techniques, including FT-IR spectroscopy, UV-Vis spectroscopy, TEM and SEM analysis, 1H NMR, 13C NMR, and HPLC analysis. The newly prepared Cpx derivative (Cpx-Drv) exhibited significantly enhanced antibacterial properties compared to Cpx itself. In particular, Cpx-Drv demonstrated a 51% increase in antibacterial activity against S. aureus and a 30% improvement against B. subtilis. It displayed potent inhibitory effects on topoisomerases II (DNA gyrase and topoisomerase IV) as potential molecular targets, with IC50 values of 6.754 and 1.913 µg/mL, respectively, in contrast to Cpx, which had IC50 values of 2.125 and 0.821 µg/mL, respectively. Docking studies further supported these findings, showing that Cpx-Drv exhibited stronger binding interactions with the gyrase enzyme (PDB ID: 2XCT) compared to the parent Cpx, with binding affinities of -10.3349 and -7.7506 kcal/mole, respectively.

Anti-Tumor Activity of Orally Administered Gefitinib-Loaded Nanosized Cubosomes against Colon Cancer.

Gefitinib (GFT) is a tyrosine kinase inhibitor drug used as a first-line treatment for patients with advanced or metastatic non-small cell lung, colon, and breast cancer. GFT exhibits low solubility and hence low oral bioavailability, which restricts its clinical application. One of the most important trends in overcoming such problems is the use of a vesicular system. Cubosomes are considered one of the most important vesicular systems used to improve solubility and oral bioavailability. In this study, GFT cubosomal nanoparticles (GFT-CNPs) were prepared by the emulsification method. The selected formulation variables were analyzed and optimized by full factorial design and response surface methodology. Drug entrapment efficiency (EE%), transmission electron microscopy, particle size, polydispersity index, in vitro release and its kinetics, and the effect of storage studies were estimated. The chosen GFT-CNPs were subjected to further investigations as gene expression levels of tissue inhibitors of metalloproteinases-1 (TIMP-1) and matrix metalloproteinases-7 (MMP-7), colon biomarkers, and histopathological examination of colon tissues. The prepared GFT-CNPs were semi-cubic in shape, with high EE%, smaller vesicle size, and higher zeta potential values. The in vivo data showed a significant decrease in the serum level of embryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and gene expression level of TIMP-1 and MMP-7. Histopathological examination showed enhancement in cancer tissue and highly decreased focal infiltration in the lamina propria after treatment with GFT-CNPs.

Prognostic role of pulmonary hemodynamics before transcatheter aortic valve replacement among patients with severe aortic stenosis.

BACKGROUND: Pulmonary hypertension (PH) frequently co-exists in patients with severe aortic stenosis (AS). In this study, we sought to identify the implications of invasive pulmonary hemodynamics on major adverse cardiac events (MACE), biventricular function and NYHA functional class after transcatheter aortic valve replacement (TAVR). METHODS: Invasive hemodynamics via right heart catheterization (RHC) were performed pre-TAVR. Patients were stratified per mean PA pressure (mPAP), diastolic pulmonary gradient (DPG) and pulmonary vascular resistance (PVR), and followed at 1-month and 1-year intervals up to 6 years. MACE outcomes included cardiovascular death and heart failure hospitalizations post-TAVR. RESULTS: Among 215 patients, Kaplan-Meir estimates demonstrated an increased 1-year risk of MACE from 8% among those without pre-TAVR PH to 27% among patients with pre-existing PH. Specifically, the MACE risk was 32% among PH patients with PVR ≥ 3WU (p = .04) and 53% among PH patients with DPG ≥ 7 mm Hg (p < .01). On univariate Cox regression, RV stroke work index (RVSWI) (HR,1.02; p = .02), and pulmonary hemodynamic index (PHI) (HR,1.27; p = .047) were identified as additional predictors of MACE post-TAVR. On multivariable Cox regression analysis, SvO2 (HR, 0.95; p = .01) and PVR (HR, 1.2; p = .04) were demonstrated as predictive of MACE post-TAVR. A significant improvement in LVEF (2-Factor ANOVA, p < .01) and RV fractional area change (RVFAC%) (p < .01) was noted as assessed at baseline, 1-month and 1-year follow up post-TAVR. There was a significant interaction between pre-TAVR PH status and time post procedure with respect to NYHA functional class (p = .03), that is, the manner and degree of change in NYHA class over time depended on pre-TAVR PH status. CONCLUSIONS: Defining invasive pulmonary hemodynamics, such as mPAP, PVR, and DPG among patients with severe AS undergoing TAVR has significant prognostic implications. Routine risk stratification by utilizing invasive hemodynamics can better identify patients who will have functional improvement and improved outcomes post-TAVR.

Transcervical pharyngeal pouch stapling.

BACKGROUND: Pharyngeal pouches are generally treated with surgery, via either an endoscopic or an external approach. Large pouches extending to the mediastinum carry an increased risk of post-operative mediastinitis in the event of a leak following external approach surgery, and may not always be amenable to endoscopic stapling. METHODS: Transcervical stapling is a newly described technique that uses the endoluminal stapling approach but in which the diverticuloscope is inserted into the pharynx via a neck incision. CONCLUSIONS: This technique has been used successfully on three patients with large pharyngeal pouches, where endoscopic stapling was not possible due to access limitations.