Polymeric nanofiber leveraged co-delivery of anti-stromal PAK1 inhibitor and paclitaxel enhances therapeutic effects in stroma-rich 3D spheroid models.

The role of tumor stroma in solid tumors has been widely recognized in cancer progression, metastasis and chemoresistance. Cancer-associated fibroblasts (CAFs) play a crucial role in matrix remodeling and promoting cancer cell stemness and resistance via reciprocal crosstalk. Residual tumor tissue after surgical removal as well as unresectable tumors face therapeutic challenges to achieve curable outcome. In this study, we propose to develop a dual delivery approach by combining p21-activated kinase 1 (PAK1) inhibitor (FRAX597) to inhibit tumor stroma and chemotherapeutic agent paclitaxel (PTX) to kill cancer cells using electrospun nanofibers. First, the role of the PAK1 pathway was established in CAF differentiation, migration and contraction using relevant in vitro models. Second, polycaprolactone polymer-based nanofibers were fabricated using a uniaxial electrospinning technique to incorporate FRAX597 and/or PTX, which showed a uniform texture and a prolonged release of both drugs for 16 days. To test nanofibers, stroma-rich 3D heterospheroid models were set up which showed high resistance to PTX nanofibers compared to stroma-free homospheroids. Interestingly, nanofibers containing PTX and FRAX597 showed strong anti-tumor effects on heterospheroids by reducing the growth and viability by > 90 % compared to either of single drug-loaded nanofibers. These effects were reflected by reduced intra-spheroidal expression levels of collagen 1 and α-smooth muscle actin (α-SMA). Overall, this study provides a new therapeutic strategy to inhibit the tumor stroma using PAK1 inhibitor and thereby enhance the efficacy of chemotherapy using nanofibers as a local delivery system for unresectable or residual tumor. Use of 3D models to evaluate nanofibers highlights these models as advanced in vitro tools to study the effect of controlled release local drug delivery systems before animal studies.

In vitro biological evaluation and in silico insights into the antiviral activity of standardized olive leaves extract against SARS-CoV-2.

There is still a great global need for efficient treatments for the management of SARS-CoV-2 illness notwithstanding the availability and efficacy of COVID-19 vaccinations. Olive leaf is an herbal remedy with a potential antiviral activity that could improve the recovery of COVID-19 patients. In this work, the olive leaves major metabolites were screened in silico for their activity against SARS-CoV-2 by molecular docking on several viral targets such as methyl transferase, helicase, Plpro, Mpro, and RdRp. The results of in silico docking study showed that olive leaves phytoconstituents exhibited strong potential antiviral activity against SARS-CoV-2 selected targets. Verbacoside demonstrated a strong inhibition against methyl transferase, helicase, Plpro, Mpro, and RdRp (docking scores = -17.2, -20, -18.2, -19.8, and -21.7 kcal/mol.) respectively. Oleuropein inhibited 5rmm, Mpro, and RdRp (docking scores = -15, -16.6 and -18.6 kcal/mol., respectively) respectively. Apigenin-7-O-glucoside exhibited activity against methyl transferase and RdRp (docking score = -16.1 and -19.4 kcal/mol., respectively) while Luteolin-7-O-glucoside inhibited Plpro and RdRp (docking score = -15.2 and -20 kcal/mol., respectively). The in vitro antiviral assay was carried out on standardized olive leaf extract (SOLE) containing 20% oleuropein and IC50 was calculated. The results revealed that 20% SOLE demonstrated a moderate antiviral activity against SARS-CoV-2 with IC50 of 118.3 µg /mL. Accordingly, olive leaf could be a potential herbal therapy against SARS-CoV-2 but more in vivo and clinical investigations are recommended.

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.

Dual action of epigallocatechin-3-gallate in virus-induced cell Injury.

BACKGROUND: Viral infections cause damage and long-term injury to infected human tissues, demanding therapy with antiviral and wound healing medications. Consequently, safe phytochemical molecules that may control viral infections with an ability to provide wound healing to viral-induced tissue injuries, either topically or systemically, are advantageous. Herein, we hypothesized that epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, might be effective as a wound healing, antiviral, and antifibrotic therapy. RESULTS: The antiviral activities of EGCG against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Herpes simplex virus type 2 (HSV-2) as well as its wound healing activities against different monolayer tissue (continuous and primary) systems were investigated. Consider its possible wound-healing advantages as well. To determine the safe concentrations of EGCG in green monkey kidney (Vero) and Vero-E6 cell lines, MTT assay was performed and showed high CC50 values of 405.1 and 322.9 µM, respectively. The antiviral activities of EGCG against SARS-CoV-2 and HSV-2, measured as half-maximal concentration 50 (IC50) concentrations, were 36.28 and 59.88 µM, respectively. These results confirm that the EGCG has remarkable viral inhibitory activities and could successfully suppress the replication of SARS-CoV-2 and HSV-2 in vitro with acceptable selectivity indices (SI) of 11.16 and 5.39, respectively. In parallel, the EGCG exhibits significant and dose/time-dependent anti-migration effects in human breast cancer cells (MCF-7), its resistant variation (MCF-7adr), and human skin fibroblast (HSF) indicating their potential to heal injuries in different internal and topical mammalian systems. CONCLUSIONS: The EGCG has proven to be an efficient antiviral against SARS-CoV-2 and HSV-2, as well as a wound-healing phytochemical. We assume that EGCG may be a promising option for slowing the course of acute cellular damage induced by systemic (Coronavirus Disease 2019 (COVID-19)) or topical (HSV-2) viral infections.

Validation of next-generation sequencing-based chimerism testing for accurate detection and monitoring of engraftment in hematopoietic stem cell transplantation.

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a life-saving treatment for various hematological disorders. The success of allo-HSCT depends on the engraftment of donor cells and the elimination of recipient cells monitored through chimerism testing. We aimed to validate a next-generation sequencing (NGS)-based chimerism assay for engraftment monitoring and to emphasize the importance of including the most prevalent cell subsets in proficiency testing (PT) programs. We evaluated the analytical performance of NGS-based chimerism testing (AlloSeq-HCT and CareDx) with a panel of targeted 202 informative single-nucleotide polymorphisms (SNPs) (i.e., linearity and precision, analytical sensitivity and specificity, system accuracy, and reproducibility). We further compared the performance of our NGS panel with conventional short tandem repeat (STR) analysis in unfractionated whole blood and cell-subset-enriched CD3 and CD66. Our NGS-based chimerism monitoring assay has an impressive detection limit (0.3% host DNA) for minor alleles and analytical specificity (99.9%). Pearson's correlation between NGS- and STR-based chimerism monitoring showed a linear relationship with a slope of 0.8 and r = 0.973. The concordance of allo-HSCT patients using unfractionated whole blood, CD3, and CD66 was 0.95, 0.96, and 0.54, respectively. Utilization of CD3+ cell subsets for mixed chimerism detection yielded an average of 7.3 ± 7-fold higher donor percentage detection compared to their corresponding unfractionated whole blood samples. The accuracy of the NGS assay achieved a concordance of 98.6% on blinded external quality control STR samples. The reproducibility series showed near 100% concordance with respect to inter-assay, inter-tech, inter-instrument, cell flow kits, and AlloSeq-HCT software versions. Our study provided robust validation of NGS-based chimerism testing for accurate detection and monitoring of engraftment in allo-HSCT patients. By incorporating the cell subsets (CD3 and CD66), the sensitivity and accuracy of engraftment monitoring are significantly improved, making them an essential component of any PT program. Furthermore, the implementation of NGS-based chimerism testing shows potential to streamline high-volume transplant services and improve clinical outcomes by enabling early relapse detection and guiding timely interventions.

Novel alleles in the era of next-generation sequencing-based HLA typing calls for standardization and policy.

Next-Generation Sequencing (NGS) has transformed clinical histocompatibility laboratories through its capacity to provide accurate, high-throughput, high-resolution typing of Human Leukocyte Antigen (HLA) genes, which is critical for transplant safety and success. As this technology becomes widely used for clinical genotyping, histocompatibility laboratories now have an increased capability to identify novel HLA alleles that previously would not be detected using traditional genotyping methods. Standard guidelines for the clinical verification and reporting of novelties in the era of NGS are greatly needed. Here, we describe the experience of a clinical histocompatibility laboratory's use of NGS for HLA genotyping and its management of novel alleles detected in an ethnically-diverse population of British Columbia, Canada. Over a period of 18 months, 3,450 clinical samples collected for the purpose of solid organ or hematopoietic stem cell transplantation were sequenced using NGS. Overall, 29 unique novel alleles were identified at a rate of ∼1.6 per month. The majority of novelties (52%) were detected in the alpha chains of class II (HLA-DQA1 and -DPA1). Novelties were found in all 11 HLA classical genes except for HLA-DRB3, -DRB4, and -DQB1. All novelties were single nucleotide polymorphisms, where more than half led to an amino acid change, and one resulted in a premature stop codon. Missense mutations were evaluated for changes in their amino acid properties to assess the potential effect on the novel HLA protein. All novelties identified were confirmed independently at another accredited HLA laboratory using a different NGS assay and platform to ensure validity in the reporting of novelties. The novel alleles were submitted to the Immuno Polymorphism Database-Immunogenetics/HLA (IPD-IMGT/HLA) for official allele name designation and inclusion in future database releases. A nationwide survey involving all Canadian HLA laboratories confirmed the common occurrence of novel allele detection but identified a wide variability in the assessment and reporting of novelties. In summary, a considerable proportion of novel alleles were identified in routine clinical testing. We propose a framework for the standardization of policies on the clinical management of novel alleles and inclusion in proficiency testing programs in the era of NGS-based HLA genotyping.

OPG/RANK/RANKL axis relation to cardiac iron-overload in children with transfusion-dependent thalassemia.

OPG/RANK/RANKL axis was reportedly involved in initiating various diseases, especially bone and cardiovascular diseases. This study aimed to assess the relationship between some OPG, RANK, and RANKL polymorphisms and alleles and iron-overload-induced cardiomyopathy in children with transfusion-dependent thalassemia (TDT). This study included 80 TDT children and 80 age and sex-matched controls. Real-time PCR was done for rs207318 polymorphism for the OPG gene and rs1805034, rs1245811, and rs75404003 polymorphisms for the RANK gene, and rs9594782 and rs2277438 polymorphisms for the RANKL gene. Cardiac T2* MRI and ejection fraction (EF) were done to assess the myocardial iron status and cardiac function. In this study, there were no significant differences in frequencies of the studied polymorphisms between cases and controls (p > 0.05 in all). In TDT children, OPG rs2073618 (G > C) had a significant relation to myocardial iron overload (p = 0.02). Its C allele had significantly more frequent normal EF than its G allele (p = 0.04). RANK rs75404403 (C > DEL) had a significant relation to cardiac dysfunction (p = 0.02). Moreover, the C allele of that gene had significantly more frequent affected EF than its DEL allele (p = 0.02). The A allele of RANKL rs2277438 (G > A) had significantly less frequent severe cardiac iron overload than the G allele (p = 0.04). In conclusion, the OPG/ RANK/RANKL genes may act as genetic markers for iron-induced cardiomyopathy in TDT children. Some of the studied genes' polymorphisms and alleles were significantly related to myocardial iron overload and cardiac dysfunction in TDT children.

Does sequential examination under anaesthesia provide a reliable method to determine a management plan for unstable lateral compression pelvic ring injuries? a prospective study.

PURPOSE: To assess the reliability of sequential examination under anaesthesia (EUA) to determine pelvic instability and to evaluate radiological and functional outcomes in unstable lateral compression (LC) injuries. METHODS: A prospective case series study was conducted from 2020 to 2022 at a university hospital on 43 cases with LC injuries that met the inclusion criteria. Sequential EUA was carried out in three steps. Posterior-only fixation or anterior-posterior fixation was done according to the algorithm. Each patient was followed up for at least 12 months, both radiologically and functionally. RESULTS: Forty cases proved unstable and were fixed. None showed secondary displacement in the anterior-posterior fixation group. However, five cases (19.2%) of the posterior-only fixation group showed secondary displacement with a mean of 5.9 mm. Four cases of them had tetra-ramic injuries. There is a high tendency for secondary displacement at 14.5 mm or more preoperative displacement of the rami. Patients with secondary displacement showed comparable functional outcome scores to patients without secondary displacement. Posterior-only fixation showed shorter operative time, lesser radiological exposure, blood loss and iatrogenic nerve injury than anterior-posterior fixation. CONCLUSION: EUA is a reliable method to determine pelvic instability and management plan for LC fractures with unilateral anterior ring injury. Anterior-posterior fixation is needed if there is a tetra-ramic fracture or initial anterior ring displacement of 14.5 mm or more, irrespective of EUA.

Exploring the Potential of Zirconium-89 in Diagnostic Radiopharmaceutical Applications: An Analytical Investigation.

This study highlights the use of 89Zr-oxalate in diagnostic applications with the help of WinAct and IDAC2.1 software. It presents the biodistribution of the drug in various organs and tissues, including bone, blood, muscle, liver, lung, spleen, kidneys, inflammations, and tumors, and analyzes the maximum amount of nuclear transformation per Bq intake for each organ. The retention time of the maximum nuclear transformation and the absorbed doses of the drug in various organs and tissues are also examined. Data from clinical and laboratory studies on radiopharmaceuticals are used to estimate the coefficients of transition. The accumulation and excretion of the radiopharmaceutical in the organs is assumed to follow an exponential law. The coefficients of transition from the organs to the blood and vice versa are estimated using a combination of statistical programs and digitized data from the literature. WinAct and IDAC 2.1 software are used to calculate the distribution of the radiopharmaceutical in the human body and to estimate the absorbed doses in organs and tissues. The results of this study can provide valuable information for the biokinetic modeling of wide-spectrum diagnostic radiopharmaceuticals. The results show that 89Zr-oxalate has a high affinity for bones and a relatively low impact on healthy organs, making it helpful in targeting bone metastases. This study provides valuable information for further research on the development of this drug for potential clinical applications.

Endobronchial mucormycosis diagnosed by fiberoptic bronchoscopy.

Introduction: Endobronchial mucormycosis is very rare with only few cases reported in the literature. Here, we report a rare presentation of pulmonary mucormycosis in a diabetic patient who presented with left lung collapse. Bronchoscopy revealed an endobronchial growth, mimicking a tumor, causing complete occlusion of the left main bronchus. Histopathology confirmed the diagnosis of invasive mucormycosis. Case presentation: Male patient 35 years old with accidental discovered Diabetes Mellitus, complained of hoarseness of voice and dry irritating cough that didn't respond to antitussives and nonspecific treatment. CT chest was done and revealed left total lung collapse. Fiberoptic bronchoscopy was done and revealed total occlusion of the left main bronchus with whitish fungating glistening tissue from which biopsies were obtained. Histopathological examination was consistent with mucormycosis. A trial of medical treatment failed after which the patient was referred for surgical resection. Conclusion: Successful treatment of mucormycosis requires early diagnosis; prompt administration of antifungal therapy, and surgical intervention when applicable. Aggressive surgical intervention to remove necrotic tissue is generally accepted as the therapeutic mainstay for endobronchial obstructing mucormycosis.

Lead-Free Ternary Glass for Radiation Protection: Composition and Performance Evaluation for Solar Cell Coverage.

Solar cells in superstrate arrangement need a protective cover glass as one of its main components. The effectiveness of these cells is determined by the cover glass's low weight, radiation resistance, optical clarity, and structural integrity. Damage to the cell covers brought on by exposure to UV irradiation and energetic radiation is thought to be the root cause of the ongoing issue of a reduction in the amount of electricity that can be generated by solar panels installed on spacecraft. Lead-free glasses made of xBi2O3-(40 - x)CaO-60P2O5 (x = 5, 10, 15, 20, 25, and 30 mol%) were created using the usual approach of melting at a high temperature. The amorphous nature of the glass samples was confirmed using X-ray diffraction. At energies of 81, 238, 356, 662, 911, 1173, 1332, and 2614 keV, the impact of various chemical compositions on gamma shielding in a phospho-bismuth glass structure was measured. The evaluation of gamma shielding revealed that the results of the mass attenuation coefficient of glasses increase as the Bi2O3 content increases but decrease as the photon energy increases. As a result of the study conducted on the radiation-deflecting properties of ternary glass, a lead-free low-melting phosphate glass that exhibited outstanding overall performance was developed, and the optimal composition of a glass sample was identified. The 60P2O5-30Bi2O3-10CaO glass combination is a viable option for use in radiation shielding that does not include lead.

New potential anti-SARS-CoV-2 and anti-cancer therapies of chitosan derivatives and its nanoparticles: Preparation and characterization.

Chitosan (CS) is a biopolymer and has reactive amine/hydroxyl groups facilitated its modifications. The purpose of this study is improvement of (CS) physicochemical properties and its capabilities as antiviral and antitumor through modification with 1-(2-oxoindolin-3-ylidene)thiosemicarbazide (3A) or 1-(5-fluoro-2-oxoindolin-3-ylidene)thiosemicarbazide (3B) via crosslinking of poly(ethylene glycol)diglycidylether (PEGDGE) using microwave-assisted as green technique gives (CS-I) and (CS-II) derivatives. However, (CS) derivatives nanoparticles (CS-I NPs) and (CS-II NPs) are synthesized via ionic gelation technique using sodium tripolyphosphate (TPP). Structures of new (CS) derivatives are characterized using different tools. The anticancer, antiviral efficiencies and molecular docking of (CS) and its derivatives are assayed. (CS) derivatives and its nanoparticles show enhancement in cell inhibition toward (HepG-2 and MCF-7) cancer cells in comparison with (CS). (CS-II NPs) reveals the lowest IC50 values are 92.70 ± 2.64 µg/mL and 12.64 µ g/mL against (HepG-2) cell and SARS-CoV-2 (COVID-19) respectively and the best binding affinity toward corona virus protease receptor (PDB ID 6LU7) -5.71 kcal / mol. Furthermore, (CS-I NPs) shows the lowest cell viability% 14.31 ± 1.48 % and the best binding affinity -9.98 kcal/moL against (MCF-7) cell and receptor (PDB ID 1Z11) respectively. Results of this study demonstrated that (CS) derivatives and its nanoparticles could be potentially employed for biomedical applications.

Essential Oil of Cestrum diurnum L.: GC/MS Analysis, in Vitro and in Silico Anti-HCoV-229E Effects and Inhibitory Activity against LPS-Induced Inflammation.

Cestrum diurnum L. (Solanaceae) is a fragrant ornamental tree cultivated in different parts around the world. In this study, the essential oil (EO) of the aerial parts was extracted by hydrodistillation (HD), steam distillation (SD) and microwave-assisted hydro-distillation (MAHD). GC/MS analysis of the three EOs revealed that phytol represents the major component in SD-EO and MAHD-EO (40.84 and 40.04 %, respectively); while in HD-EO it only represented 15.36 %. The SD-EO showed a strong antiviral activity against HCoV-229E with IC50 of 10.93 µg/mL, whereas, MAHD-EO and HD-EO showed a moderate activity with IC50 values of 119.9 and 148.2 µg/mL, respectively. The molecular docking of EO major components: phytol, octadecyl acetate and tricosane showed a strong binding to coronavirus 3-CL (pro). Moreover, the three EOs (50 µg/mL) decreased the levels of NO, IL-6 and TNF-α and suppressed IL-6 and TNF-α gene expression in LPS-induced inflammation model in RAW264.7 macrophage cell lines.

GC-MS Determination of Undeclared Phthalate Esters in Commercial Fragrances: Occurrence, Profiles and Assessment of Carcinogenic and Non-Carcinogenic Risk Associated with Their Consumption among Adult Consumers.

Phthalates are chemicals that are extensively used in the manufacturing of cosmetic products. The occurrence of phthalate esters in personal care products may pose adverse effects on consumers' health. In this work, a simple, fast and reliable GC-MS method was developed and validated for concurrent determination of phthalate esters in fragrances. Simple procedures were employed for sample preparation and clean up. The recoveries achieved were in the range of 94.9% to 105.6% with RSD ≤ 4.06. The detection limits were in the range of 0.0010 to 0.0021 µg/mL. The GC-MS method was utilized to investigate the occurrence of phthalate esters in different brands of perfumes sold in the Saudi Arabian market. Diethyl phthalate was detected in all analyzed samples, with a maximum concentration of 5766 µg/mL, and di (2-ethylhexyl) phthalate was detected in the majority of the analyzed samples (95%), with a mean concentration of 55.9 µg/mL and a highest concentration of 377.7 µg/mL. Additionally, the exposure to phthalate esters due to the consumption of perfumes was investigated among the adult Saudi population for the first time. It was found that the systemic exposure dose, measured at mean concentrations, ranged from 4.59 × 10-4 to 4.29 × 10-2 (mg/kg/day) and from 5.00 × 10-4 to 4.68 × 10-2 (mg/kg/day) for male and female users, respectively. Moreover, the non-carcinogenic risk of the investigated phthalate esters and the carcinogenic risk of DEHP were also evaluated. The non-carcinogenic risk values of the detected phthalate esters were greater than 100, which indicates that exposure to these phthalate esters is unlikely to produce non-carcinogenic health effects to consumers. However, at maximum DEHP concentrations, the carcinogenic risk values were 5.49 × 10-5 for male users and 5.98 × 10-5 for female users, which indicates the possibility of DEHP to pose a carcinogenic health effect if present at high levels. Regular monitoring of undeclared chemicals such as phthalate esters in personal care products marketed in Saudi Arabia is extremely important to ensure consumers' safety. To the best of the authors' knowledge, this is the first study to assess the health risk associated with consumption of perfumes in Saudi Arabia.

Pleural manometry during thoracocentesis in patients with malignant pleural effusion: A randomized controlled trial.

Background: Large-volume therapeutic thoracocentesis may be associated with pulmonary congestion or a more serious complication; re-expansion pulmonary edema (RPE). We investigated whether monitoring pleural pressure with manometry during thoracocentesis would prevent these pulmonary symptoms/RPE and allow larger volume drainage. Methods: We did a randomized controlled trial involving 110 patients with large malignant pleural effusions. Patients were randomly allocated to obtain thoracocentesis with or without pleural manometry. We measured the incidence of pulmonary congestion symptoms, total fluid aspirated, and pleural pressures in both groups. This trial is listed on ClinicalTrials.gov as NCT04420663. Results: The mean amount of total thoracocentesis fluid withdrawn from the control group was 945.4±78.9 (mL) and 1690.9±681.0 (mL) from the intervention group (P<0.001). Clinical symptoms of pulmonary congestion appeared in (n=20) (36.3%) of patients in the intervention group while no symptoms appeared in controls (P<0.001). The difference between opening and closing pressures between the non-symptomatic cluster and the symptomatic cluster was (32.8±15.6 versus 42.2±13) respectively (P=0.02). Total fluid withdrawn from the non-symptomatic cluster was 1828.5±505 mL in comparison to 1,450±875 mL in the symptomatic cluster (P=0.04). Conclusion: Pleural manometry can be used to increase the volume of fluid removed on each occasion in patients with malignant pleural effusion. In our study, pleural manometry was associated with a larger number of pulmonary congestion symptoms/RPE. We believe that manometry may be a useful tool to not exceed a 17 cm H2O gradient in pleural pressure which should be avoided to prevent pulmonary congestion symptoms or RPE. Pulmonary congestion symptoms/RPE are not related to the amount of volume withdrawn but to the gradient of pleural pressure drop. Our conclusion does support the adoption of pleural manometry whenever large-volume thoracocentesis is intended.

Suggested Guidelines for the Treatment of Mycosis Fungoides in Countries with Limited Resources.

The treatment options for mycosis fungoides (MF) have been expanding but unfortunately many of the currently used treatment modalities are unavailable in Egypt and other African/Arab countries. In addition, there is a lack of consensus on the treatment of hypopigmented MF (HMF), which is a frequently encountered variant in our population. We aimed to develop regional treatment guidelines based on the international guidelines but modified to encompass the restricted treatment availability and our institutional experience. Special attention was also given to studies conducted on patients with skin phototype (III-IV). Treatment algorithm was formulated at Ain-Shams cutaneous lymphoma clinic through the collaboration of dermatologists, haematologists, and oncologists. Level of evidence is specified for each treatment option. For HMF, phototherapy is recommended as a first line treatment, while low-dose methotrexate is considered a second line. For early classical MF, we recommend Psoralen-ultraviolet A (PUVA), which is a well-tolerated treatment option in dark phenotype. Addition of either retinoic acid receptor (RAR) agonist and/or methotrexate is recommended as a second line. Total skin electron beam (TSEB) is considered a third-line option. For advanced stage, PUVA plus RAR agonist and/or methotrexate is recommended as first line, TSEB or monochemotherapy is considered a second line option. Polychemotherapy is regarded as a final option. All patients with complete response (CR) enter a maintenance and follow-up schedule. We suggest a practical algorithm for the treatment of MF for patients with dark phenotype living in countries with limited resources.

Metabolic profiling and biological potential of the marine sponge associated Nocardiopsis sp. UR67 along with docking studies.

This work was performed to dig into the phytochemical composition and bioactivities of Nocardiopsis sp. UR67 associated with the marine sponge Callyspongia sp. It was fermented in suspension and immobilised in calcium alginate bead cultures. The ethyl acetate extracts, afforded from the broth in each case named EG-49 and J-48g, respectively, revealed 16 chemical principles mostly belonging to polyketides, macrolides, and peptides. EG-49 and J-48g displayed anti-Candida albicans activity with IC50 values of 8.1 and 8.3 µg/mL, and a substantial cytotoxic effect against lung adenocarcinoma H1650 at IC50 12.6 and 13.7 µg/mL, respectively. However, only EG-49 exhibited a noteworthy anti-trypanosomal activity at 7.5 µg/mL. Molecular docking of the characterised compounds against Trypanosoma brucei trypanothione reductase demonstrated the highest binding models of griseochelin-methyl ester (9) and filipin-II (11), which drew considerable significance of the metabolites derived from Nocardiopsis sp. UR67 developing potential T. brucei trypanothione reductase inhibitors.

Predictors of Pathological Gastroesophageal Reflux among Emirati Patients with Reflux Symptoms Who Undergo Wireless pH Monitoring.

Background: Diagnosis of gastroesophageal reflux disease (GERD) relies on recognizing symptoms of reflux and mucosal changes during esophagogastroduodenoscopy. The desired response to acid suppression therapy is reliable resolution of GERD symptoms; however, these are not always reliable, hence the need for pH testing in unclear cases. Our objective was to identify potential predictors of a high DeMeester score among patients with potential GERD symptoms to identify patients most likely to have pathological GERD. Methods: We conducted a retrospective case-control study on patients who underwent wireless pH monitoring from January 2020 to April 2022. Cases were patients with a high DeMeester score (more than 14.7), indicating pathological reflux, and controls were those without. We collected clinical and demographic data, including age, sex, body mass index (BMI), smoking status, non-steroidal anti-inflammatory drugs (NSAIDs) use, and presence of atypical symptoms. Results: 86 patients were enrolled in the study. 46 patients with high DeMeester scores were considered cases, and 40 patients with DeMeester scores less than 14.7 were considered controls. Esophagitis (grade A) was found in 41.1% of the cases and in 22.5% of the control group. In our study, age of more than 50 years compared with age of 20-29 years and being overweight appeared to be predictors of true pathological reflux among patients with reflux symptoms who underwent wireless pH monitoring. Conclusion: Age above 50 years compared with age between 20-29 years and being overweight appeared to be predictors of true pathological reflux among patients with reflux symptoms who underwent wireless oesophageal pH monitoring. The presence of oesophagitis was approximately four times more likely to be associated with true pathological reflux.

Evaluation of the outcome of a proposed more physiological bypass surgery technique in morbid obesity: Long term 3 years follows up.

Background: Obesity is a chronic condition that affects millions globally; consequently, bariatric surgery is the key to this serious issue. Bariatric procedures are rapidly expanding in number and methods to address the recognized problems. So, it would make a sense for surgeons and patients if there is a more physiological bypass surgery technique in Morbid obesity. This study aims to evaluate the outcome proposed technique. Patients and methods: The present study is a retrospective analysis on 256 participants subjected to the proposed bypass procedure from December 1999 to January 2017, the participants were followed up for an interval of 3years. Results: The findings of the present study revealed a significant Excess Weight Loss (EWL). In addition, patients experienced decreased calcium, iron, vitamin B12, Hemoglobin, zinc, and Prothrombin Concentration. However, three to six months after surgery, they experienced a significant improvement until they reached normal levels without any supplement by the end of 12,18 months, with a three-year follow-up. Conclusion: This proposed Bypass Operation aims to adequate digestions as well as selective absorption without inducing any vital deficit. Most of study's population showed no elements inadequacies, although few percentages emerged during the interval of maximal weight reduction, and it were transient and minimal. No minerals or vitamins were needed.

Assessment of Tissue Adequacy by EBUS in Conjunction with PET Scan and Operator's Experience.

Mediastinal lymph node assessment is a crucial step in non-small cell lung cancer staging. Positron emission tomography (PET) has been the gold standard for the assessment of mediastinal lymphadenopathy, though it has limited specificity. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is quick, accurate, and a less invasive method for obtaining a diagnostic sample in contrast to mediastinoscopy. We performed a retrospective chart analysis of 171 patients to assess the adequacy of tissue obtained by EBUS for diagnosis and molecular profiling as well as the assessment of staging and lymph node (LN) stations diagnostic yield, in correlation to PET scan and the operator's level of experience. A significantly increased tissue adequacy was observed based on the operators' experience, with the highest adequacy noted in trained Interventional Pulmonologist (IP) (100%), followed by >5 years of experience (93.33%), and 88.89% adequacy with <5 years of experience (p = 0.0019). PET-CT scan 18F-fluorodeoxyglucose (FDG) uptake in levels 1, 2, and 3 LN had a tissue adequacy of 76.67%, 54.64%, and 35.56%, respectively (p = 0.0009). EBUS bronchoscopy method could be used to achieve an accurate diagnosis, with IP-trained operators yielding the best results. There is no correlation with PET scan positivity, indicating that both PET and EBUS are complementary methods needed for staging.