bluuebunny/crossref_metadata_2025 huggingface dataset:
The Antibacterial Properties of Nanocomposites Based on Carbon Nanotubes and Metal Oxides Functionalized with Azithromycin and Ciprofloxacin
Authors: Stegarescu Adina , Lung Ildiko , Ciorîță Alexandra , Kacso Irina , Opriș Ocsana , Soran Maria-Loredana , Soran Albert
Published: November 2022

Different microorganisms are present in nature, some of which are assumed to be hazardous to the human body. It is crucial to control their continuing growth to improve human life. Nanomaterial surface functionalization represents a current topic in continuous evolution that supports the development of new materials with multiple applications in biology, medicine, and the environment. This study focused on the antibacterial activity of different nanocomposites based on functionalized multi-walled carbon nanotubes against four common bacterial strains. Two metal oxides (CuO and NiO) and two antibiotics (azithromycin and ciprofloxacin) were selected for the present study to obtain the following nanocomposites: MWCNT-COOH/Antibiotic, MWCNT-COOH/Fe3O4/Antibiotic, and MWCNT-COOH/Fe3O4/MO/Antibiotic. The present study included two Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Ciprofloxacin (Cip) functionalized materials (MWCNT-COOH/Fe3O4/Cip) were most efficient against all tested bacterial strains; therefore, we conclude that Cu and Ni reduce the effects of Cip. The obtained results indicate that the nanocomposites functionalized with Cip are more effective against selected bacteria strains compared to azithromycin (Azi) functionalized nanocomposites. The current work determined the antibacterial activities of different nanocomposites and gave fresh insights into their manufacture for future research regarding environmental depollution.
Nonvolatile Ternary Memristor Based on Fluorene-Benzimidazole Copolymer/Au NP Composites
Authors: Gao Meng , Du Yanting , Yu Haifeng , He Zhaohua , Wang Shuhong , Wang Cheng
Published: November 2022

A donor–acceptor type polymer of poly [2,7-(9,9-dioctyl)-fluorene-alt-7H-benzimidazo-[2,1-a]benzo[de]isoquinolin-7-one] (PF-BBO) based on benzimidazole groups was synthesized. This material was incorporated into data storage devices that exhibited good data storage characteristics. In order to improve the storage properties of the device, Au NPs were compounded in this material. We observed an increase in the ratio of switching current for the device with the PF-BBO/Au NP composite as the active layer. The device comprising 8 wt% Au NPs demonstrated optimal storage performance with a switching current ratio of 1:3.4 × 102:1.0 × 105 and a threshold voltage of −0.40 V/−0.85 V, respectively. The number of cycle times of this device was over 3000, which indicates excellent stability. Thus, the devices containing PF-BBO/Au NP composite as active materials offer a new dimension for future application prospects of high-density data storage.
Waste Citrus reticulata Assisted Preparation of Cobalt Oxide Nanoparticles for Supercapacitors
Authors: Srivastava Rishabh , Bhardwaj Shiva , Kumar Anuj , Singhal Rahul , Scanley Jules , Broadbridge Christine C. , Gupta Ram K.
Published: November 2022

The green, sustainable, and inexpensive creation of novel materials, primarily nanoparticles, with effective energy-storing properties, is key to addressing both the rising demand for energy storage and the mounting environmental concerns throughout the world. Here, an orange peel extract is used to make cobalt oxide nanoparticles from cobalt nitrate hexahydrate. The orange peel extract has Citrus reticulata, which is a key biological component that acts as a ligand and a reducing agent during the formation of nanoparticles. Additionally, the same nanoparticles were also obtained from various precursors for phase and electrochemical behavior comparisons. The prepared Co-nanoparticles were also sulfurized and phosphorized to enhance the electrochemical properties. The synthesized samples were characterized using scanning electron microscopic and X-ray diffraction techniques. The cobalt oxide nanoparticle showed a specific capacitance of 90 F/g at 1 A/g, whereas the cobalt sulfide and phosphide samples delivered an improved specific capacitance of 98 F/g and 185 F/g at 1 A/g. The phosphide-based nanoparticles offer more than 85% capacitance retention after 5000 cycles. This study offers a green strategy to prepare nanostructured materials for energy applications.
Study of Phase Transformations and Hyperfine Interactions in Fe3O4 and Fe3O4@Au Nanoparticles
Authors: Rusakov Vyacheslav S. , Kozlovskiy Artem L. , Fadeev Maxim S. , Egizbek Kamila B. , Nazarova Assel , Kadyrzhanov Kayrat K. , Shlimas Dmitriy I. , Zdorovets Maxim V.
Published: November 2022

The paper presents the results of a study of iron oxide nanoparticles obtained by chemical coprecipitation, coated (Fe3O4@Au) and not coated (Fe3O4) with gold, which were subjected to thermal annealing. To characterize the nanoparticles under study, scanning and transmission electron microscopy, X-ray diffraction, and Mössbauer spectroscopy on 57Fe nuclei were used, the combination of which made it possible to establish a sequence of phase transformations, changes in morphological and structural characteristics, as well as parameters of hyperfine interactions. During the studies, it was found that thermal annealing of nanoparticles leads to phase transformation processes in the following sequence: nonstoichiometric magnetite (Fe3−γO4) → maghemite (γ-Fe2O3) → hematite (α-Fe2O3), followed by structural ordering and coarsening of nanoparticles. It is shown that nanoparticles of nonstoichiometric magnetite with and without gold coating are in the superparamagnetic state with a slow relaxation rate. The magnetic anisotropy energy of nonstoichiometric magnetite is determined as a function of the annealing temperature. An estimate was made of the average size of the region of magnetic ordering of Fe atoms in nonstoichiometric magnetite, which is in good agreement with the data on the average sizes of nanoparticles determined by scanning electron microscopy.
Temperature-Dependent Phase Evolution in FePt-Based Nanocomposite Multiple-Phased Magnetic Alloys
Authors: Crisan Ovidiu , Crisan Alina Daniela , Randrianantoandro Nirina
Published: November 2022

A quaternary Fe–Pt–Nb–B alloy has been fabricated by the melt spinning method with the purpose of the formation of crystallographically coherent multiple magnetic phases, emerging from the same metastable precursor, as well as to investigate the phase interactions and the influence of their coupling on magnetic performances. For this purpose, extended structural and magnetic investigations were undertaken by making use of X-ray diffraction, transmission electron microscopy, and 57Fe Mössbauer spectroscopy, as well as magnetic measurements using SQUID magnetometry. It was documented that intermediate metastable phases formed during primary crystallization, in intermediate stages of annealing, and a growth-dominated mode was encountered for the secondary crystallization stage upon annealing at 700 °C and 800 °C where fcc Fe3Pt and fct Fe2B polycrystalline were formed. The Mössbauer investigations have documented rigorously the hyperfine parameters of each of the observed phases. The fcc A1 FePt phase was shown to exhibit a peculiar ferromagnetic transition, and this transition has been proven to occur gradually between 300 K and 77 K. The magnetic measurements allowed us to identify the annealing at 700 °C as optimal for obtaining good magnetic features. Coercive field dependence shows similarities to the random anisotropy model for samples annealed at 500 °C to 700 °C which are nanocrystalline. These results show good perspectives for use in applications where different magnetic states are required at different operating temperatures.
Broadband Bi-Directional All-Dielectric Transparent Metamaterial Absorber
Authors: Cao Miao , Huang Xiaojun , Gao Lina , Li Xiaoyan , Guo Linyan , Yang Helin
Published: November 2022

Water-based absorbers have shown great development potential in the past few years. In this paper, an all-dielectric transparent bi-directional water-based broadband metamaterial absorber is designed. The simulation results indicate that absorptance of the absorber is over 90% in 5.7–41.6 GHz, and its fraction bandwidth is 151.8%. The experimental results are greatly consistent with the simulations. The designed absorber has excellent performances of polarization insensitivity, oblique incidence stability and thermal stability. When the absorptance is more than 0.8, the maximum incident angle reaches 40° in TE mode and is over 60° in TM mode. In 0–80 °C, absorptance of the absorber is hardly changed. Because of the optical transparency of the designed absorber, it can be extensively used in stealth window weapons and electromagnetic compatibility equipment.
High-Quality SiO2/O-Terminated Diamond Interface: Band-Gap, Band-Offset and Interfacial Chemistry
Authors: Cañas Jesús , Reyes Daniel F. , Zakhtser Alter , Dussarrat Christian , Teramoto Takashi , Gutiérrez Marina , Gheeraert Etienne
Published: November 2022

Silicon oxide atomic layer deposition synthesis development over the last few years has open the route to its use as a dielectric within diamond electronics. Its great band-gap makes it a promising material for the fabrication of diamond–metal–oxide field effects transistor gates. Having a sufficiently high barrier both for holes and electrons is mandatory to work in accumulation and inversion regimes without leakage currents, and no other oxide can fulfil this requisite due to the wide diamond band-gap. In this work, the heterojunction of atomic-layer-deposited silicon oxide and (100)-oriented p-type oxygen-terminated diamond is studied using scanning transmission electron microscopy in its energy loss spectroscopy mode and X-ray photoelectron spectroscopy. The amorphous phase of silicon oxide was successfully synthesized with a homogeneous band-gap of 9.4 eV. The interface between the oxide and diamond consisted mainly of single- and double-carbon-oxygen bonds with a low density of interface states and a straddling band setting with a 2.0 eV valence band-offset and 1.9 eV conduction band-offset.
Dielectric Strength of Nanofluid-Impregnated Transformer Solid Insulation
Authors: Pérez-Rosa Daniel , Montero Andrés , García Belén , Burgos Juan Carlos
Published: November 2022

The interest in developing new fluids that can be used as dielectric liquids for transformers has driven the research on dielectric nanofluids in the last years. A number of authors have reported promising results on the electrical and thermal properties of dielectric nanofluids. Less attention has been paid to the interaction of these fluids with the cellulose materials that constitute the solid insulation of the transformers. In the present study, the dielectric strength of cellulose insulation is investigated, comparing its behavior when it is impregnated with transformer mineral oil and when it is impregnated with a dielectric nanofluid. The study includes the analysis of the AC breakdown voltage and the impulse breakdown voltage of the samples. Large improvements were observed on the AC breakdown voltages of the specimens impregnated with nanofluids, while the enhancements were lower in the case of the impulse tests. The reasons for the increase in AC breakdown voltage were investigated, considering the dielectric properties of the nanofluids used to impregnate the samples of cellulose. The analysis was completed with a finite element study that revealed the effect of the nanoparticles on the electric field distribution within the test cell, and its role in the observed enhancement.
Hygroscopic Behavior of Polypropylene Nanocomposites Filled with Graphene Functionalized by Alkylated Chains
Authors: Kang Dongwoo , Kim Sung Hee , Shin Donghyeok , Oh Ji Taek , Kim Myeong-Gi , Lee Pyoung-Chan
Published: November 2022

Owing to stringent international environmental and fuel efficiency requirements for lightweight automotive systems, polymer composites have attracted widespread attention. Polypropylene (PP) is a widely employed commercial polymer because of its lightweight and low cost. In this study, PP nanocomposites were fabricated to reduce the moisture absorption of PP composites in automotive headlamp housings. Alkylated chemically modified graphene (CMG-R) was synthesized to reduce the surface hydrophilicity of graphene and increase compatibility with the PP matrix. Fourier transform-infrared spectroscopy and scanning electron microscopy were performed to analyze the nanofillers. X-ray diffraction was performed to determine the interlayer spacing of the nanofiller resulting from surface treatment. Differential scanning calorimetry was used to analyze the crystallinity of the nanocomposites. The results indicated that the improved hydrophobicity of the nanofiller due to alkylation reduced the maximum moisture absorption of the PP nanocomposites by 15% compared to PP composites. The findings of this study are useful for reducing fogging in automotive headlamps.
Nanoporous Alumina Support Covered by Imidazole Moiety–Based Ionic Liquids: Optical Characterization and Application
Authors: Algarra Manuel , López Escalante Mª Cruz , Martínez de Yuso Mª Valle , Soto Juan , Cuevas Ana L. , Benavente Juana
Published: November 2022

This work analyzes chemical surface and optical characteristics of a commercial nanoporous alumina structure (NPAS) as a result of surface coverage by different imidazolium-based ionic liquids (1-butyl-3-metylimidazolium hexafluorophosphate, 3-methyl-1-octylimidazolium hexafluorophosphate, or 1-ethyl-3-methylimidazolium tetrafluoroborate). Optical characteristics of the IL/NPAS samples were determined by photoluminescence (at different excitation wavelengths (from 300 nm to 400 nm), ellipsometry spectroscopy, and light transmittance/reflectance measurements for a range of wavelengths that provide information on modifications related to both visible and near-infrared regions. Chemical surface characterization of the three IL/NPAS samples was performed by X-ray photoelectron spectroscopy (XPS), which indicates almost total support coverage by the ILs. The IL/NPAS analyzed samples exhibit different photoluminescence behavior, high transparency (<85%), and a reflection maximum at wavelength ~380 nm, with slight differences depending on the IL, while the refractive index values are rather similar to those shown by the ILs. Moreover, the illuminated I–V curves (under standard conditions) of the IL/NPAS samples were also measured for determining the efficiency energy conversion to estimate their possible application as solar cells. On the other hand, a computational quantum mechanical modeling method (DFT) was used to establish the most stable bond between the ILs and the NPAS support.
Decadal Journey of CNT-Based Analytical Biosensing Platforms in the Detection of Human Viruses
Authors: Sengupta Joydip , Hussain Chaudhery Mustansar
Published: November 2022

It has been proven that viral infections pose a serious hazard to humans and also affect social health, including morbidity and mental suffering, as illustrated by the COVID-19 pandemic. The early detection and isolation of virally infected people are, thus, required to control the spread of viruses. Due to the outstanding and unparalleled properties of nanomaterials, numerous biosensors were developed for the early detection of viral diseases via sensitive, minimally invasive, and simple procedures. To that aim, viral detection technologies based on carbon nanotubes (CNTs) are being developed as viable alternatives to existing diagnostic approaches. This article summarizes the advancements in CNT-based biosensors since the last decade in the detection of different human viruses, namely, SARS-CoV-2, dengue, influenza, human immunodeficiency virus (HIV), and hepatitis. Finally, the shortcomings and benefits of CNT-based biosensors for the detection of viruses are outlined and discussed.
Community at the Centre of Future Food Systems
Authors: Bell Colin , Love Penelope
Published: November 2022

Have you thought about what it is you love about food [...]
Subclinical Cardiovascular Disease Markers in Relation to Serum and Dietary Magnesium in Individuals from the General Population: The KORA-MRI Study
Authors: Shugaa Addin Nuha , Schlett Christopher L. , Bamberg Fabian , Thorand Barbara , Linseisen Jakob , Seissler Jochen , Peters Annette , Rospleszcz Susanne
Published: November 2022

Several studies have implied a role of magnesium in the development of cardiovascular disease (CVD). Thus, magnesium might serve as a potential risk marker for early CVD. Therefore, we investigated the association of serum magnesium and dietary magnesium intake with markers of subclinical CVD in a population-based study. We used cross-sectional data from the sub-study of the Cooperative Health Research in the Region of Augsburg (KORA-FF4). Markers of subclinical CVD, namely, left and right ventricular structure and function and carotid plaque and carotid wall thickness, were derived by magnetic resonance imaging (MRI). Multivariable-adjusted regression models were applied to assess the relationship between serum and dietary magnesium and MRI-derived subclinical CVD markers. Among 396 included participants (mean age: 56.3 ± 9.2 years; 57.8% male), 181 (45.7%) had low serum magnesium levels (<2.07 mg/dL). Among 311 subjects with complete dietary data (mean age: 56.3 ± 9.1 years; 56.3% male), 154 (49.5%) had low dietary magnesium intake (≤155.2 mg/1000 kcal/day). Serum and dietary magnesium were not correlated (p-value = 0.5). Serum magnesium was significantly associated with presence of carotid plaque (OR 1.62, p-value 0.033). Dietary magnesium was associated with higher left ventricular end-systolic and end-diastolic volume (0.04 mL/m2, 0.06 mL/m2; p-value 0.011, 0.013, respectively), and also with a decrease in left ventricular remodeling index and mean diastolic wall thickness (−0.001 g/mL/m2, −0.002 mm/m2; p-value 0.004, 0.029, respectively). In summary, there was no consistent association of serum and dietary magnesium with imaging markers of subclinical CVD.
Empire Apple (Malus domestica) Juice, Pomace, and Pulp Modulate Intestinal Functionality, Morphology, and Bacterial Populations In Vivo (Gallus gallus)
Authors: Jackson Cydney , Shukla Viral , Kolba Nikolai , Agarwal Nikita , Padilla-Zakour Olga I. , Tako Elad
Published: November 2022

Approximately $20 billion of apple sales are generated annually in the United States. With an estimated 5 million tons produced yearly in the U.S. within the last decade, apple consumption is considered ubiquitous. Apples are comprised of bioactive constituents such as phytochemicals and prebiotics that may potentiate intestinal health and the gut microbiome. This study aimed to evaluate the effects of Empire apple juice, pomace, and pulp soluble extracts on intestinal functionality, morphology, and the microbiome in vivo (Gallus gallus). There were five treatment groups: non-injected (NI); 18 MΩ H2O (H2O); 6% apple juice (AJ); 6% apple pomace (APo); 6% apple pulp (APu). The eggs were treated by intra-amniotic administration of the samples on day 17 of incubation. After hatching, the blood, tissue, and cecum samples were collected for further analyses—including duodenal histomorphology, hepatic and duodenal mRNA expression, and cecal bacterial populations. Crypt depth was significantly (p < 0.5) shortest in AJ when compared to APo and APu. APo and APu soluble extracts significantly improved villi surface area compared to NI and H2O control groups. The highest count of Paneth cells per crypt was observed in APo as compared to all groups. In addition, the expression of brush border membrane micronutrient metabolism and functional proteins varied between treatments. Lastly, Lactobacillus cecal microbial populations increased significantly in the AJ group, while AJ, APu, and APu increased the abundance of Clostridium (p < 0.5). Ultimately, these results indicate the potential of Empire apple pomace to improve host intestinal health and the gut microbiome.
Insufficient Physical Activity Is a Global Marker of Severity in Alcohol Use Disorder: Results from a Cross-Sectional Study in 382 Treatment-Seeking Patients
Authors: Ternay Julia de , Larrieu Agathe , Sauvestre Laura , Montègue Solène , Guénin Monique , Icard Christophe , Rolland Benjamin
Published: November 2022

Improving physical activity (PA) in patients with alcohol use disorder (AUD) has recently emerged as an important component of the global treatment strategy to improve drinking outcomes and quality of life. However, this new approach should focus on AUD patients with insufficient baseline PA and requires this subgroup to be better characterized. In a population of 382 treatment-seeking AUD patients, PA was assessed using the International Physical Activity Questionnaire, and participants were divided into two groups: insufficient PA group and sufficient PA group. The severity of the AUD was assessed using the DSM-5 criteria, the Alcohol Use Disorder Identification Test, and the Severity of Alcohol Dependence Questionnaire. In logistic regression models, individuals with insufficient PA were more likely than other AUD individuals to present a higher Body Mass Index (p < 0.001), a higher number of AUD DSM-5 criteria (p < 0.05), more frequent opioid use (p < 0.05), higher scores at the Fagerström Test for Nicotine Dependence (p < 0.001), State-Trait Anxiety Inventory (p < 0.001), impulsivity scale (p < 0.05), Pittsburgh Sleep Quality Inventory (p < 0.05), and lower WHO Quality of Life (p < 0.001) scores. In AUD, an insufficient baseline PA is associated with several markers of severity, and physical exercise interventions should be part of a multimodal treatment program integrating the global impairments of patients.
Complications of the Low Phenylalanine Diet for Patients with Phenylketonuria and the Benefits of Increased Natural Protein
Authors: McWhorter Nicole , Ndugga-Kabuye Mesaki K. , Puurunen Marja , Ernst Sharon L.
Published: November 2022

Phenylketonuria (PKU) is an inherited disorder in which phenylalanine (Phe) is not correctly metabolized leading to an abnormally high plasma Phe concentration that causes profound neurologic damage if left untreated. The mainstay of treatment for PKU has centered around limiting natural protein in the diet while supplementing with medical foods in order to prevent neurologic injury while promoting growth. This review discusses several deleterious effects of the low Phe diet along with benefits that have been reported for patients with increased natural protein intake while maintaining plasma Phe levels within treatment guidelines.
Supervised Exercise in Water: Is It a Viable Alternative in Overweight/Obese People with or without Type 2 Diabetes? A Pilot Study
Authors: Pippi Roberto , Vandoni Matteo , Tortorella Matteo , Bini Vittorio , Fanelli Carmine Giuseppe
Published: November 2022

The study of the effects of a water-based exercise program in overweight/obese people with or without type 2 diabetes is a topic of relatively recent interest. This type of exercise presents some advantages in reducing the risk of injury or trauma, and it can be a valuable therapeutic card to play for sedentary or physically inactive patients who have chronic metabolic diseases. This work aims to make a contribution showing the effects of a water-based exercise intervention, supervised by graduates in sports sciences, in a group of overweight/obese people with or without type 2 diabetes. In total, 93 adults (age 60.59 ± 10.44 years), including 72 women (age 60.19 ± 10.97 years) and 21 men (age 61.95 ± 8.48 years), were recruited to follow a water-based exercise program (2 sessions/week, for 12 weeks) at the C.U.R.I.A.Mo. Healthy Lifestyle Institute of Perugia University. Results showed an improvement in body mass index (−0.90 ± 1.56, p = 0.001), waist circumference (−4.32 ± 6.03, p < 0.001), and systolic (−7.78 ± 13.37, p = 0.001) and diastolic (−6.30 ± 10.91, p = 0.001) blood pressure. The supervised water-based intervention was useful in managing patients with metabolic diseases who often present with other health impairments, such as musculoskeletal problems or cardiovascular or rheumatic disease that could contraindicate gym-based exercise.
Prognostic Factors for Delayed Healing of Complex Wounds in Adults: A Scoping Review Protocol
Authors: Marques Raquel , Lopes Marcos , Ramos Paulo , Neves Amado João , Alves Paulo
Published: November 2022

(1) Background: The high prevalence of persons with wounds and its consequences for a person’s quality of life makes the issue a relevant focus of attention for healthcare professionals. Through prognostic factors for healing, the individual risk of complications can be predicted, is possible to predict imminent delays and guide decision-making, thus helping healthcare professionals. (2) Methods: A scoping review performed according to JBI methodology and guided by the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR) checklist will aim to identify the studies that meet predefined eligibility criteria. Five databases and gray literature will be the sources used to research adults with pressure ulcers, venous leg ulcers, arterial ulcers, or diabetic foot ulcers and report the prognostic factors for delayed healing in any care setting. (3) Results: This review will consider all quantitative and mixed studies in the last five years. The selection of articles will be carried out by two reviewers independently, using EndNoteWeb and Rayyan. Prognostic factors will be presented by design study, sampling, setting, outcome, wound type, and statistical methods. (4) Conclusions: Mapping prognostic factors for delayed healing could also be a starting point for a systematic review and meta-analyses to quantify the value of each factor.
Phaeohyphomycosis due to Exophiala in Aquarium-Housed Lumpfish (Cyclopterus lumpus): Clinical Diagnosis and Description
Authors: McDermott Colin T. , Innis Charles J. , Nyaoke Akinyi C. , Tuxbury Kathryn A. , Cavin Julie M. , Weber E. Scott , Edmunds Deana , Lair Stéphane , Spangenberg Jill V. , Hancock-Ronemus Amy L. , Hadfield Catherine A. , Clayton Leigh A. , Waltzek Thomas B. , Cañete-Gibas Connie F. , Wiederhold Nathan P. , Frasca Salvatore
Published: November 2022

Phaeohyphomycosis caused by Exophiala species represents an important disease of concern for farmed and aquarium-housed fish. The objective of this study was to summarize the clinical findings and diagnosis of Exophiala infections in aquarium-housed Cyclopterus lumpus. Clinical records and postmortem pathology reports were reviewed for 15 individuals from 5 public aquaria in the United States and Canada from 2007 to 2015. Fish most commonly presented with cutaneous ulcers and progressive clinical decline despite topical or systemic antifungal therapy. Antemortem fungal culture of cutaneous lesions resulted in colonial growth for 7/12 samples from 8 individuals. Amplification of the internal transcribed spacer region (ITS) of nuclear rDNA identified Exophiala angulospora or Exophiala aquamarina in four samples from three individuals. Postmortem histopathologic findings were consistent with phaeohyphomycosis, with lesions most commonly found in the integument (11/15), gill (9/15), or kidney (9/15) and evidence of fungal angioinvasion and dissemination. DNA extraction and subsequent ITS sequencing from formalin-fixed paraffin-embedded tissues of seven individuals identified E. angulospora, E. aquamarina, or Cyphellophora sp. in four individuals. Lesion description, distribution, and Exophiala spp. identifications were similar to those reported in farmed C. lumpus. Antemortem clinical and diagnostic findings of phaeohyphomycosis attributable to several species of Exophiala provide insight on the progression of Exophiala infections in lumpfish that may contribute to management of the species in public aquaria and under culture conditions.
The Characterization of Cardiac Explants Reveals Unique Fibrosis Patterns and a Predominance of CD8+ T Cell Subpopulations in Patients with Chronic Chagas Cardiomyopathy
Authors: Díaz Martha Lucía , Delgado Fredy A. , Martínez Ruth A , Jaimes Mayra Alejandra , Echeverría Luis Eduardo , Gómez-Ochoa Sergio Alejandro , Mantilla-Hernández Julio César , González Clara Isabel
Published: November 2022

Aim: The present study aimed to characterize the histopathological findings and the phenotype of inflammatory cells in the myocardial tissue of patients with end-stage heart failure (ESHF) secondary to CCC in comparison with ESHF secondary to non-Chagas cardiomyopathies (NCC). Methods: A total of 32 explanted hearts were collected from transplanted patients between 2014 and 2017. Of these, 21 were classified as CCC and 11 as other NCC. A macroscopic analysis followed by a microscopic analysis were performed. Finally, the phenotypes of the inflammatory infiltrates were characterized using flow cytometry. Results: Microscopic analysis revealed more extensive fibrotic involvement in patients with CCC, with more frequent foci of fibrosis, collagen deposits, and degeneration of myocardial fibers, in addition to identifying foci of inflammatory infiltrate of greater magnitude. Finally, cell phenotyping identified more memory T cells, mainly CD8+CD45RO+ T cells, and fewer transitioning T cells (CD45RA+/CD45RO+) in patients with CCC compared with the NCC group. Conclusions: CCC represents a unique form of myocardial involvement characterized by abundant inflammatory infiltrates, severe interstitial fibrosis, extensive collagen deposits, and marked cardiomyocyte degeneration. The structural myocardial changes observed in late-stage Chagas cardiomyopathy appear to be closely related to the presence of cardiac fibrosis and the colocalization of collagen fibers and inflammatory cells, a finding that serves as a basis for the generation of new hypotheses aimed at better understanding the role of inflammation and fibrogenesis in the progression of CCC. Finally, the predominance of memory T cells in CCC compared with NCC hearts highlights the critical role of the parasite-specific lymphocytic response in the course of the infection.
Dose-Dependent Von Willebrand Factor Inhibition by Aptamer BB-031 Correlates with Thrombolysis in a Microfluidic Model of Arterial Occlusion
Authors: Shea Susan M. , Thomas Kimberly A. , Rassam Rassam M. G. , Mihalko Emily P. , Daniel Christina , Sullenger Bruce A. , Spinella Philip C. , Nimjee Shahid M.
Published: November 2022

Von Willebrand Factor (VWF) plays a critical role in thrombus formation, stabilization, and propagation. Previous studies have demonstrated that targeted inhibition of VWF induces thrombolysis when administered in vivo in animal models of ischemic stroke. The study objective was to quantify dose-dependent inhibition of VWF-platelet function and its relationship with thrombolysis using BB-031, an aptamer that binds VWF and inhibits its function. VWF:Ac, VWF:RCo, T-TAS, and ristocetin-induced impedance aggregometry were used to assess BB-031-mediated inhibition of VWF. Reductions in original thrombus surface area and new deposition during administration of treatment were measured in a microfluidic model of arterial thrombolysis. Rotational thromboelastometry was used to assess changes in hemostasis. BB-031 induced maximal inhibition at the highest dose (3384 nM) in VWF:Ac, and demonstrated dose-dependent responses in all other assays. BB-031, but not vehicle, induced recanalization in the microfluidic model. Maximal lytic efficacy in the microfluidic model was seen at 1692 nM and not 3384 nM BB-031 when assessed by surface area. Minor changes in ROTEM parameters were seen at 3384 nM BB-031. Targeted VWF inhibition by BB-031 results in clinically measurable impairment of VWF function, and specifically VWF-GPIb function as measured by VWF:Ac. BB-031 also induced thrombolysis as measured in a microfluidic model of occlusion and reperfusion. Moderate correlation between inhibition and lysis was observed. Additional studies are required to further examine off-target effects of BB-031 at high doses, however, these are expected to be above the range of clinical targeted dosing.
Indoline-5-Sulfonamides: A Role of the Core in Inhibition of Cancer-Related Carbonic Anhydrases, Antiproliferative Activity and Circumventing of Multidrug Resistance
Authors: Krymov Stepan K. , Scherbakov Alexander M. , Dezhenkova Lyubov G. , Salnikova Diana I. , Solov’eva Svetlana E. , Sorokin Danila V. , Vullo Daniela , De Luca Viviana , Capasso Clemente , Supuran Claudiu T. , Shchekotikhin Andrey E.
Published: November 2022

The overexpression and activity of carbonic anhydrase (CA, EC 4.2.1.1) isoforms CA IX and CA XII promote the accumulation of exceeding protons and acidosis in the extracellular tumor environment. Sulfonamides are effective inhibitors of most families of CAs. In this study, using scaffold-hopping, indoline-5-sulfonamide analogs 4a–u of the CA IX-selective inhibitor 3 were designed and synthesized to evaluate their biological properties. 1-Acylated indoline-5-sulfonamides demonstrated inhibitory activity against tumor-associated CA IX and XII with KI values up to 132.8 nM and 41.3 nM. Compound 4f, as one of the most potent inhibitors of CA IX and XII, exhibits hypoxic selectivity, suppressing the growth of MCF7 cells at 12.9 µM, and causes partial inhibition of hypoxia-induced CA IX expression in A431 skin cancer cells. 4e and 4f reverse chemoresistance to doxorubicin of K562/4 with overexpression of P-gp.
Analysis of Time-Dependent Pharmacokinetics Using In Vitro–In Vivo Extrapolation and Physiologically Based Pharmacokinetic Modeling
Authors: Kim Min-Chang , Lee Young-Joo
Published: November 2022

SCR430, a sorafenib derivative, is an investigational drug exhibiting anti-tumor action. This study aimed to have a mechanistic understanding of SCR430’s time-dependent pharmacokinetics (TDPK) through an ex vivo study combined with an in vitro–in vivo extrapolation (IVIVE) and physiologically based pharmacokinetic (PBPK) modeling. A non-compartmental pharmacokinetic analysis was performed after intravenous SCR430 administration in female Sprague-Dawley rats for a control group (no treatment), a vehicle group (vehicle only, 14 days, PO), and a repeated-dosing group (SCR430, 30 mg/kg/day, 14 days, PO). In addition, hepatic uptake and metabolism modulation were investigated using isolated hepatocytes from each group of rats. The minimal PBPK model based on IVIVE was constructed to explain SCR430’s TDPK. Repeated SCR430 administration decreased the systemic exposure by 4.4-fold, which was explained by increased hepatic clearance (4.7-fold). The ex vivo study using isolated hepatocytes from each group suggested that the increased hepatic uptake (9.4-fold), not the metabolic activity, contributes to the increased hepatic clearance. The minimal PBPK modeling based on an ex vivo study could explain the decreased plasma levels after the repeated doses. The current study demonstrates the TDPK after repeated dosing by hepatic uptake induction, not hepatic metabolism, as well as the effectiveness of an ex vivo approach combined with IVIVE and PBPK modeling to investigate the TDPK.
In Silico Drug Repurposing Framework Predicts Repaglinide, Agomelatine and Protokylol as TRPV1 Modulators with Analgesic Activity
Authors: Andrei Corina , Mihai Dragos Paul , Zanfirescu Anca , Nitulescu George Mihai , Negres Simona
Published: November 2022

Pain is one of the most common symptoms experienced by patients. The use of current analgesics is limited by low efficacy and important side effects. Transient receptor potential vanilloid-1 (TRPV1) is a non-selective cation channel, activated by capsaicin, heat, low pH or pro-inflammatory agents. Since TRPV1 is a potential target for the development of novel analgesics due to its distribution and function, we aimed to develop an in silico drug repositioning framework to predict potential TRPV1 ligands among approved drugs as candidates for treating various types of pain. Structures of known TRPV1 agonists and antagonists were retrieved from ChEMBL databases and three datasets were established: agonists, antagonists and inactive molecules (pIC50 or pEC50 < 5 M). Structures of candidates for repurposing were retrieved from the DrugBank database. The curated active/inactive datasets were used to build and validate ligand-based predictive models using Bemis–Murcko structural scaffolds, plain ring systems, flexophore similarities and molecular descriptors. Further, molecular docking studies were performed on both active and inactive conformations of the TRPV1 channel to predict the binding affinities of repurposing candidates. Variables obtained from calculated scaffold-based activity scores, molecular descriptors criteria and molecular docking were used to build a multi-class neural network as an integrated machine learning algorithm to predict TRPV1 antagonists and agonists. The proposed predictive model had a higher accuracy for classifying TRPV1 agonists than antagonists, the ROC AUC values being 0.980 for predicting agonists, 0.972 for antagonists and 0.952 for inactive molecules. After screening the approved drugs with the validated algorithm, repaglinide (antidiabetic) and agomelatine (antidepressant) emerged as potential TRPV1 antagonists, and protokylol (bronchodilator) as an agonist. Further studies are required to confirm the predicted activity on TRPV1 and to assess the candidates’ efficacy in alleviating pain.
Development and Characterization of Cyclodextrin-Based Nanogels as a New Ibuprofen Cutaneous Delivery System
Authors: Cirri Marzia , Nerli Giulia , Mennini Natascia , Maestrelli Francesca , Mura Paola
Published: November 2022

Nanogels combine the properties of hydrogels and nanocarrier systems, resulting in very effective drug delivery systems, including for cutaneous applications. Cyclodextrins (CDs) have been utilised to enhance the nanogels’ loading ability towards poorly soluble drugs and promote/sustain drug release. However, formation of CD-based nanogels requires the use of specially modified CDs, or of crosslinking agents. The aim of this work was to develop a CD-based nanogel to improve the cutaneous delivery of ibuprofen by using the soluble β-cyclodextrin/epichlorohydrin polymer (EPIβCD) without adding any potentially toxic crosslinker. The use of EPIβCD enabled increasing ibuprofen loading due to its complexing/solubilizing power towards the poorly soluble drug and prolonging drug release over time due to the nanogel formation. DLS analysis proved that EPIβCD allowed the formation of nanostructures ranging from 60 up to 400 nm, depending on the gelling agent type and the gel preparation method. EPIβCD replacement with monomeric HPβCD did not lead in any case to nanogel formation. Permeation experiments using skin-simulating artificial membranes proved that the EPIβCD-based nanogel enhanced ibuprofen solubility and release, increasing its permeation rate up to 3.5 times, compared to a reference formulation without CD and to some commercial gel formulations, and also assured a sustained release. Moreover, EPIβCD replacement with HPβCD led to a marked increase in drug solubility and initial release rate, but did not provide a prolonged release due to the lack of a nano-matrix structure controlling drug diffusion.
Oral Delivery of Niclosamide as an Amorphous Solid Dispersion That Generates Amorphous Nanoparticles during Dissolution
Authors: Jara Miguel O. , Warnken Zachary N. , Sahakijpijarn Sawittree , Thakkar Rishi , Kulkarni Vineet R. , Christensen Dale J. , Koleng John J. , Williams Robert O.
Published: November 2022

Niclosamide is an FDA-approved anthelmintic that is being studied in clinical trials as a chemotherapeutic and broad-spectrum antiviral. Additionally, several other applications are currently in the preclinical stage. Unfortunately, niclosamide is a poorly water soluble molecule, with reduced oral bioavailability, which hinders its use for new indications. Moreover, niclosamide is a poor glass former; in other words, the molecule has a high tendency to recrystallize, and it is virtually impossible to generate a stable amorphous solid employing the neat molecule. Previously, our group reported the development of an amorphous solid dispersion (ASD) of niclosamide (niclosamide ASD) that generates nanoparticles during its dissolution, not only increasing niclosamide’s apparent solubility from 6.6 ± 0.4 to 481.7 ± 22.2 µg/mL in fasted state simulated intestinal fluid (FaSSIF) but also its oral bioavailability 2.6-fold in Sprague–Dawley rats after being administered as a suspension. Nevertheless, niclosamide ASD undergoes recrystallization in acidic media, and an enteric oral dosage form is needed for its translation into the clinic. In this work, we further characterized the nanoparticles that generated during the dissolution of the niclosamide ASD. Cryogenic transmission electron microscopy (Cryo-TEM) and wide-angle X-ray scattering (WAXS) revealed that the nanoparticles were amorphous and had a particle size of ~150 nm. The oral dosage forms of niclosamide ASD were formulated using commercial enteric capsules (Capsuline® and EudracapTM) and as enteric-coated tablets. The enteric dosage forms were tested using pH-shift dissolution and acid-uptake tests, using the USP type II dissolution apparatus and the disintegration apparatus, respectively. The capsules exhibited a higher percentage of weight gain, and visual rupture of the Capsuline capsules was observed. Eudracap capsules protected the formulation from the acidic media, but polymer gelling and the formation of a nondispersible plug were noted during dissolution testing. In contrast, enteric-coated tablets protected the formulation from acid ingress and maintained the performance of niclosamide ASD granules during dissolution in FaSSIF media. These enteric-coated tablets were administered to beagle dogs at a niclosamide dose of 75 mg/kg, resulting in plasma concentrations of niclosamide higher than those reported in the literature using solubilized niclosamide at a higher dose (i.e., 100 mg/kg). In summary, an enteric oral dosage form of niclosamide ASD was formulated without hindering the generation of nanoparticles while maintaining the increase in the niclosamide’s apparent solubility. The enteric-coated tablets successfully increased the niclosamide plasma levels in dogs when compared to a niclosamide solution prepared using organic solvents.
Y-Site Compatibility Studies of Ketoprofen with Parenteral Nutrition Admixtures for Central and Peripheral Administration
Authors: Dettlaff Katarzyna , Gostyńska Aleksandra , Ziółkowska Natalia , Stawny Maciej
Published: November 2022

Ketoprofen (KTF) is often used in hospital wards, especially in its intravenous form. According to the literature review, the compatibility of ketoprofen with parenteral nutrition (PN) admixtures has not yet been investigated. For this reason, we aimed to provide data contributing to physical compatibility to ensure the safe co-administration of these medications. In this study, we examined the compatibility of KTF with eight selected commercial PN admixtures intended for central (Lipoflex Special, Omegaflex Special, Kabiven, SmofKabiven) and peripheral (Lipoflex peri, Omegaflex peri, Kabiven Peripheral, Olimel Peri N4E) administration. The KTF solution for infusion was combined in three different volume ratios with studied PN admixtures reflecting the conditions in clinical practice. The evaluation of undesirable physical destabilization of oil-in-water system or precipitate formation involved the visual inspection and the determination of mean droplet diameter, zeta potential, pH, and turbidity changes. The results of compatibility of KTF with eight commercial PN admixtures showed that three of them: Kabiven, SmofKabiven, and Kabiven Peripheral, are incompatible with KTF and should not be concomitantly administered.
Successful Development and Implementation of a Large Virtual Interprofessional Education Activity Applying the Social Determinants of Health
Authors: Kodweis Karl R. , Hall Elizabeth A. , Renfro Chelsea P. , Thomas-Gosain Neena , Lennon-Dearing Robin , Walker Jonathon K. , Kiles Tyler M.
Published: November 2022

Interprofessional education (IPE) activities provide students insight into healthcare teams, shared decision-making, and social determinants of health (SDOH). Virtual IPE activities with large student populations or across multicampus have not been evaluated. The study aimed to explore the interprofessional competency growth in students, across several disciplines, following participation in a large-scale, virtual IPE activity. Students from pharmacy, medicine, social work, and physician assistant programs across Tennessee participated in an IPE patient case and SDOH in fall 2020 and fall 2021. Pre- and postsurveys included Likert ranking of 16 statements based on the 2011 Interprofessional Education Collaborative (IPEC) framework. A total of 607 students completed surveys (overall response rate, 76%). Wilcoxon signed-rank tests were performed on the pre-/postsurvey data, in aggregate and by discipline. Significant increases in all IPEC competency statements were seen, both in aggregate (100% of statements with p < 0.001) and in pharmacy (100% of statements with p < 0.001) and medicine subgroups (94% of statements with p < 0.001). Implementing large virtual IPE activities involving a complex patient case and SDOH significantly increased student IPEC competency outcomes for participating students, whether in aggregate or on a discipline-specific basis.
Pharmacy Workplace Wellbeing and Resilience: Themes Identified from a Hermeneutic Phenomenological Analysis with Future Recommendations
Authors: Schommer Jon , Gaither Caroline , Alvarez Nancy , Lee SuHak , Shaughnessy April , Arya Vibhuti , Planas Lourdes , Fadare Olajide , Witry Matthew
Published: November 2022

This study applied a hermeneutic phenomenological approach to better understand pharmacy workplace wellbeing and resilience using respondents’ written comments along with a blend of the researchers’ understanding of the phenomenon and the published literature. Our goal was to apply this understanding to recommendations for the pharmacy workforce and corresponding future research. Data were obtained from the 2021 APhA/NASPA National State-Based Pharmacy Workplace Survey, launched in the United States in April 2021. Promotion of the online survey to pharmacy personnel was accomplished through social media, email, and online periodicals. Responses continued to be received through the end of 2021. A data file containing 6973 responses was downloaded on 7 January 2022 for analysis. Usable responses were from those who wrote an in-depth comment detailing stories and experiences related to pharmacy workplace and resilience. There were 614 respondents who wrote such comments. The findings revealed that business models driven by mechanized assembly line processes, business metrics that supersede patient outcomes, and reduction of pharmacy personnel’s professional judgement have contributed to the decline in the experience of providing patient care in today’s health systems. The portrait of respondents’ lived experiences regarding pharmacy workplace wellbeing and resilience was beyond the individual level and revealed the need for systems change. We propose several areas for expanded inquiry in this domain: (1) shared trauma, (2) professional responsibility and autonomy, (3) learned subjection, (4) moral injury and moral distress, (5) sociocultural effects, and (6) health systems change.