Ospemifene Displays Broad-Spectrum Synergistic Interactions with Itraconazole Through Potent Interference with Fungal Efflux Activities

Azole antifungals are vital therapeutic options for treating invasive mycotic infections. However, the emergence of azole-resistant isolates combined with limited therapeutic options presents a growing challenge in medical mycology. To address this issue, we utilized microdilution checkerboard assays to evaluate nine stilbene compounds for their ability to interact synergistically with azole drugs, particularly against azole-resistant fungal isolates. Ospemifene displayed the most potent azole chemosensitizing activity, and its combination with itraconazole displayed broad-spectrum synergistic interactions against Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus (ΣFICI = 0.05–0.50). Additionally, in a Caenorhabditis elegans infection model, the ospemifene-itraconazole combination significantly reduced fungal CFU burdens in infected nematodes by ~75–96%. Nile Red efflux assays and RT-qPCR analysis suggest ospemifene interferes directly with fungal efflux systems, thus permitting entry of azole drugs into fungal cells. This study identifies ospemifene as a novel antifungal adjuvant that augments the antifungal activity of itraconazole against a broad range of fungal pathogens

Repurposing Approach IdentifiesPitavastatin as a Potent AzoleChemosensitizing Agent EffectiveAgainst Azole-Resistant CandidaSpecies

The limited number of antifungals and the rising frequency of azole-resistant Candida species are growing challenges to human medicine. Drug repurposing signifies an appealing approach to enhance the activity of current antifungal drugs. Here, we evaluated the ability of Pharmakon 1600 drug library to sensitize an azole-resistant Candida albicans to the effect of fluconazole. The primary screen revealed 44 non-antifungal hits were able to act synergistically with fluconazole against the test strain. Of note, 21 compounds, showed aptness for systemic administration and limited toxic effects, were considered as potential fluconazole adjuvants and thus were termed as “repositionable hits”. A follow-up analysis revealed pitavastatin displaying the most potent fluconazole chemosensitizing activity against the test strain (ΣFICI 0.05) and thus was further evaluated against 18 isolates of C. albicans (n = 9), C. glabrata (n = 4), and C. auris (n = 5). Pitavastatin displayed broad-spectrum synergistic interactions with both fluconazole and voriconazole against ~89% of the tested strains (ΣFICI 0.05–0.5). Additionally, the pitavastatin-fluconazole combination significantly reduced the biofilm-forming abilities of the tested Candida species by up to 73%, and successfully reduced the fungal burdens in a Caenorhabditis elegans infection model by up to 96%. This study presents pitavastatin as a potent azole chemosensitizing agent that warrant further investigation

A novel pH-responsive hydrogel system based on Prunus armeniaca gum and acrylic acid: Preparation and evaluation as a potential candidate for controlled drug delivery

pH-responsive hydrogels have become effective and attractive materials for the controlled release of drugs at pre-determined destinations. In the present study, a novel hydrogel system based on Prunus armeniaca gum (PAG) and acrylic acid (AA) was prepared by a free radical mechanism using N, N-methylene bisacrylamide (MBA) as cross-linker and potassium persulfate (KPS) as initiator. A series of hydrogels varying PAG, AA, and MBA concentration was developed to determine the impact of these components. Formulated hydrogels were characterized for pH-responsive swelling, drug release, gel content, and porosity. Structural analysis was performed by FTIR, XRD, and SEM analysis. TGA study was applied to assess thermal stability. Oral acute toxicity and in vivo drug release were performed in rabbits. Hydrogels exhibited pH-dependent swelling and drug release. Swelling, drug loading and release, and porosity increased by increasing PAG and AA concentration while decreased by increasing MBA. The gel content of formulations was increased by increasing all three components. FTIR studies confirmed the development of copolymeric networks and the loading of drug. XRD studies revealed that hydrogels were amorphous, and the crystalline drug was changed into an amorphous form during loading. TGA results indicated that hydrogels were stable up to 600 °C. Acute oral toxicity results confirm that hydrogels were nontoxic up to a dose of 2 g/kg body weight in rabbits. The pharmacokinetic evaluation revealed that hydrogels prolonged the availability of the drug and the peak plasma concentration of the drug was obtained in 6 h as compared to the oral solution of the drug. Tramadol hydrochloride (THC) was used as a model drug. Hence, pH-responsive swelling and release, nontoxic nature and improved pharmacokinetics support that PAG-based hydrogels may be considered as potential controlled-release polymeric carriers

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Significant photocatalytic decomposition of malachite green dye in aqueous solutions utilizing facilely synthesized barium titanate nanoparticles

Abstract The release of malachite green dye into water sources has detrimental effects on the liver, kidneys, and respiratory system. Additionally, this dye can impede photosynthesis and disrupt the growth and development of plants. As a result, in this study, barium titanate nanoparticles (BaTiO3) were facilely synthesized using the Pechini sol–gel method at 600 °C (abbreviated as EA600) and 800 °C (abbreviated as EA800) for the efficient removal of malachite green dye from aqueous media. The Pechini sol–gel method plays a crucial role in the production of barium titanate nanoparticles due to its simplicity and ability to precisely control the crystallite size. The synthesized barium titanate nanoparticles were characterized by several instruments, such as X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), Fourier transform infrared spectroscopy, and a diffuse reflectance spectrophotometer. The XRD analysis confirmed that the mean crystallite size of the EA600 and EA800 samples is 14.83 and 22.27 nm, respectively. Furthermore, the HR-TEM images confirmed that the EA600 and EA800 samples exhibit irregular and polyhedral structures, with mean diameters of 45.19 and 72.83 nm, respectively. Additionally, the synthesized barium titanate nanoparticles were utilized as catalysts for the effective photocatalytic decomposition of malachite green dye in aqueous media. About 99.27 and 93.94% of 100 mL of 25 mg/L malachite green dye solution were decomposed using 0.05 g of the EA600 and EA800 nanoparticles within 80 min, respectively. The effectiveness of synthesized BaTiO3 nanoparticles as catalysts stems from their unique characteristics, including small crystallite sizes, a low rate of hole/electron recombination owing to ferroelectric properties, high chemical stability, and the ability to be regenerated and reused multiple times without any loss in efficiency

Facile Synthesis and Characterizations of Mixed Metal Oxide Nanoparticles for the Efficient Photocatalytic Degradation of Rhodamine B and Congo Red Dyes

Photocatalytic degradation has been suggested to be a cheap and efficient way to dispose of organic pollutants, such as dyes. Therefore, our research team strives to produce nanophotocatalysts in a simple and inexpensive way. In this work, the Pechini sol–gel technique was employed for the facile synthesis of Mn0.5Zn0.5Fe2O4/Fe2O3 and Fe0.5Mn0.5Co2O4/Fe2O3 as mixed metal oxide nanoparticles for the efficient photocatalytic degradation of Rhodamine B and Congo Red dyes. XRD, FT-IR, a N2 adsorption/desorption analyzer, EDS, FE-SEM, and an UV–Vis diffuse reflectance spectrophotometer were used to characterize the produced samples. The XRD patterns revealed that the average crystallite size of the Fe0.5Mn0.5Co2O4/Fe2O3 and Mn0.5Zn0.5Fe2O4/Fe2O3 samples is 90.25 and 80.62 nm, respectively. The FE-SEM images revealed that the Fe0.5Mn0.5Co2O4/Fe2O3 sample consists of cubic and irregular shapes with an average diameter of 1.71 µm. Additionally, the Mn0.5Zn0.5Fe2O4/Fe2O3 sample consists of spherical shapes with an average diameter of 0.26 µm. The energy gaps of the Fe0.5Mn0.5Co2O4/Fe2O3 and Mn0.5Zn0.5Fe2O4/Fe2O3 samples are 3.50 and 4.3 eV and 3.52 and 4.20 eV, respectively. In the presence of hydrogen peroxide, the complete degradation of 100 mL of 20 mg/L of Rhodamine B and Congo Red dyes occurred at pH = 8 and 3, respectively, within 50 min, using 0.1 g of the synthesized samples

Efficient Disposal of Basic Fuchsin Dye from Aqueous Media Using ZrO₂/MgMn₂O₄/Mg(Mg_0.333Mn_1.333)O₄ as a Novel and Facilely Synthesized Nanocomposite

In this work, amorphous and crystalline novel products based on Zr, Mg, and Mn were facilely fabricated through the Pechini sol–gel procedure using inexpensive chemicals and an uncomplicated apparatus. Also, these products showed high efficiency as novel adsorbents in getting rid of basic fuchsin dye from aqueous solutions. The adsorbent, which was fabricated before calcination, was abbreviated as KE. In addition, the adsorbents, which were created at 500 and 700 °C, were designated as KE500 and KE700, respectively. The created adsorbents were characterized using high-level transmission electron microscopy (HR-TEM), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), N2 adsorption/desorption analyzer, and field emission scanning electron microscope (FE-SEM). The XRD showed that the KE adsorbent is amorphous, whereas the KE500 and KE700 adsorbents are mixtures of ZrO2, MgMn2O4, and Mg(Mg0.333Mn1.333)O4 nanostructures. The HR-TEM exhibited that the KE adsorbent consists of very fine irregular shapes, whereas the KE500 adsorbent contains quasi-spherical particles with a mean diameter of 45.16 nm. Furthermore, the HR-TEM exhibited that the KE700 adsorbent consists of polyhedral shapes with a mean diameter of 76.28 nm. Furthermore, the BET surface area of the KE, KE500, and KE700 adsorbents is 67.85, 20.15, and 13.60 m2/g, respectively. Additionally, the elimination of basic fuchsin dye by the KE, KE500, and KE700 adsorbents is exothermic, physical in nature, and follows the pseudo-first-order as well as Langmuir equations. Further, the maximum uptake capabilities of the KE, KE500, and KE700 adsorbents toward basic fuchsin dye are 239.81, 174.83, and 93.19 mg/g, respectively

Facile synthesis of a novel nanocomposite for determination of mercury and copper ions in food and water samples

This paper describes the modification of sodium aluminum silicate hydrate by 3-bromo-5-chlorosalicylaldehyde to form a new composite. Furthermore, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), Transmission electron microscopy (TEM), CHN elemental analysis, Nitrogen gas sorption analyzer, and Scanning electron microscopy (SEM) tools were used for characterizing the synthesized composite. The XRD pattern of the synthesized composite shows a halo at 2Θ = 25°, confirming the destruction of the crystalline structure of the nanomaterial owing to the association with an organic substance. The synthesized composite was utilized for the removal and preconcentration of mercury and copper ions from water and food samples. The maximum adsorption capacity of the synthesized composite towards mercury and copper ions is 107.53 and 130.89 mg/g, respectively. In addition, the relative standard deviation was less than 3 %, showing excellent reproducibility. The dynamic analytical ranges are 0.8–380 μg/L and 1.00–550 μg/L for copper and mercury ions, respectively. The preconcentration factor is 10

Efficient Disposal of Rhodamine 6G and Acid Orange 10 Dyes from Aqueous Media Using ZrO₂/CdMn₂O₄/CdO as Novel and Facilely Synthesized Nanocomposites

It is essential to remove rhodamine 6G and acid orange 10 dyes from contaminated water because they can induce cancer and irritate the lungs, skin, mucous, membranes, and eyes. Hence, in the current work, the Pechini sol–gel method was used for the facile synthesis of ZrO2/CdMn2O4/CdO as novel nanocomposites at 600 and 800 °C. The synthesized nanocomposites were used as novel adsorbents for the efficient removal of rhodamine 6G and acid orange 10 dyes from aqueous media. The nanocomposites, which were synthesized at 600 and 800 °C, were abbreviated as EK600 and EK800, respectively. The synthesized nanocomposites were characterized by EDS, XRD, N2 adsorption/desorption analyzer, and FE-SEM. The patterns of XRD showed that the average crystal size of the EK600 and EK800 nanocomposites is 68.25 and 85.32 nm, respectively. Additionally, the images of FE-SEM showed that the surface of the EK600 nanocomposite consists of spherical, polyhedral, and rod shapes with an average grain size of 99.36 nm. Additionally, the surface of the EK800 nanocomposite consists of polyhedral and spherical shapes with an average grain size of 143.23 nm. In addition, the BET surface area of the EK600 and EK800 nanocomposites is 46.33 and 38.49 m2/g, respectively. The optimal conditions to achieve the highest removal of rhodamine 6G and acid orange 10 dyes are pH = 8, contact time = 24 min, and temperature = 298 kelvin. The greatest removal capacity of the EK600 and EK800 adsorbents towards rhodamine 6G dye is 311.53 and 250.63 mg/g, respectively. Additionally, the greatest removal capacity of the EK600 and EK800 adsorbents towards acid orange 10 dye is 335.57 and 270.27 mg/g, respectively. The removal of rhodamine 6G and acid orange 10 dyes using the EK600 and EK800 adsorbents is spontaneous, exothermic, follows the Langmuir adsorption isotherm, and fits well with the pseudo-first-order kinetic model