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1.
Nat Prod Res ; : 1-7, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39234930

ABSTRACT

Lichen is well-known for its various purposes. However, understanding the chemical composition and antimicrobial characteristics of Graphis cf. handelii remains insufficient. In this study, a new compound, graphinone A (1), together with three known compounds, handelone (2), 4-O-methylhiascic acid (3), and ethyl orsellinate (4) were isolated and structurally elucidated. Their chemical structures were established using comprehensive spectroscopic data (1D- and 2D-NMR and HRESIMS). Compounds 1-4 were tested for antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) and evaluated for the alpha-glucosidase inhibition.

2.
Article in English | MEDLINE | ID: mdl-39250922

ABSTRACT

BACKGROUND: Patients hospitalised for COVID-19 are at risk for multiorgan failure and death. Sodium-glucose co-transporter-2 (SGLT2) inhibitors provide cardiovascular and kidney protection in patients with cardiometabolic conditions and could provide organ protection during COVID-19. We aimed to investigate whether SGLT2 inhibitors can reduce the need for organ support in patients hospitalised for COVID-19. METHODS: This pragmatic, multicentre, open-label, randomised, controlled, platform trial was conducted across 63 sites in the USA, Spain, Brazil, Italy, and Mexico. Patients aged at least 18 years hospitalised for COVID-19 (moderate or severe illness) were randomly assigned (1:1), via an interactive voice system or web-response system, to receive locally available SGLT2 inhibitor (administered orally, once daily) plus standard-of-care or standard-of-care for 30 days. The primary outcome was organ support-free days evaluated through 21 days, assessed using intention-to-treat approach. This trial is registered on ClinicalTrials.gov, NCT04505774. FINDINGS: The first patient was randomly assigned to the SGLT2 inhibitor domain on Dec 3, 2021. On March 31, 2023, at the recommendation of the data and safety monitoring board, enrolment in the SGLT2 inhibitor domain for both moderately and severely ill hospitalised patients was stopped prematurely for futility due to a low likelihood of finding a treatment benefit. The final randomised population consisted of 575 patients (mean age 72 years [SD 13], 242 (42%) female and 154 (27%) Hispanic; 504 in the moderate illness group and 71 in the severe illness group). 573 patients had a known 21-day outcome; 215 (75%) of 285 patients in the SGLT2 inhibitor plus standard-of-care group did not require respiratory or cardiovascular organ support versus 231 (80%) of 288 patients in the standard-of-care group. The adjusted odds ratio (OR) for an SGLT2 inhibitor effect on organ support-free days was 0·74 (95% Credible Interval [CrI] 0·48-1·13; where OR higher than 1 indicated treatment benefit, yielding a posterior probability of futility P(OR <1·2) of 99% and a posterior probability of inferiority P(OR<1·0) of 91%). There were 37 deaths (13%) in the SGLT2 inhibitor plus standard-of-care group and 42 deaths (15%) in the standard-of-care group at 90 days (hazard ratio 0·91 [95% CrI 0·58-1·43], probability of hazard ratio <1 of 66%). No safety concerns were observed with SGLT2 inhibitors, including no cases of ketoacidosis. INTERPRETATION: SGLT2 inhibitors did not significantly increase days free of organ support or reduce mortality in patients hospitalised with COVID-19. SGLT2 inhibitors were well tolerated with no observed safety concerns. Overall, these findings do not support the use of SGLT2 inhibitors as standard care in patients hospitalised with COVID-19. FUNDING: National Institutes of Health.

3.
Clin Infect Dis ; 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39271151

ABSTRACT

BACKGROUND: Extrapulmonary complications (EPCs) are common in patients hospitalized for COVID-19, but data on their clinical consequences and association with viral replication and systemic viral dissemination is lacking. METHODS: Patients hospitalized for COVID-19 and enrolled in the TICO (Therapeutics for Inpatients with COVID-19) platform trial at 114 international sites between August 2020 and November 2021 were included in a prospective cohort study. We categorized EPCs into 39 event types within 9 categories and estimated their frequency through day 28 and their association with clinical outcomes through day 90. We analyzed the association between baseline viral burden (plasma nucleocapsid antigen [N-Ag] and upper airway viral load [VL]) and EPCs, adjusting for other baseline factors. RESULTS: 2,625 trial participants were included in the study. The median age was 57 years (IQR 46-68), 57.7% were male, and 537 (20.5%) had at least one EPC. EPCs were associated with higher day-90 all-cause mortality (HR 9.6, 95% CI 7.3, 12.7) after adjustment for other risk factors. The risk of EPCs increased with increasing baseline plasma N-Ag (HR 1.21 per log10 ng/L increase, 95% CI 1.09, 1.34), and upper airway VL (HR 1.12 per log10 copies/mL increase, 95% CI 1.04, 1.19), after adjusting for comorbidities, disease severity, inflammatory markers, and other baseline factors. Trial treatment allocation had no effect on EPC risk. CONCLUSIONS: Systemic viral dissemination as evidenced by high plasma N-Ag and high respiratory viral burden are associated with development of EPCs in COVID-19, which in turn are associated with higher 90-day mortality.

4.
Acta Psychol (Amst) ; 249: 104463, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39180834

ABSTRACT

The study investigates the impact of tourist behavior change on travel agencies in developing countries, with a focus on strategies for enhancing the tourist experience. The research aims to identify the main factors influencing tourist purchasing behavior and understand their relationship with the customer experience. Data were collected from 368 experienced tourists in Ho Chi Minh City and Hanoi, Vietnam, using a combination of convenience and random sampling. Partial Least Squares Structural Equation modeling (PLS-SEM) is employed to analyze the research model. The findings confirm that product quality, product price, brand image, and marketing strategy significantly influence tourist purchasing behavior. Importantly, the results highlight the indirect effect of these factors on purchasing behavior, mediated through customer experience. It suggests that enhancing the customer experience is a crucial aspect of influencing tourist purchasing decisions. Based on these findings, industry managers and travel agents in developing countries should prioritize enhancing customer experience and building a strong brand through personalized services, digital integration, and active social media engagement. Implementing dynamic pricing strategies and targeted marketing campaigns that address safety concerns and highlight local experiences are crucial for competitiveness and attracting travelers post-crisis. Future research should explore the long-term effects of these strategies on travel agency performance and adapt the model to specific regional contexts. By adopting these multifaceted approaches, travel agencies in developing countries can enhance their competitiveness and better navigate the changing tourist behavior in the post-crisis era.


Subject(s)
Consumer Behavior , Developing Countries , Tourism , Humans , Adult , Male , Vietnam , Female , Marketing , Travel , Middle Aged , Young Adult
5.
Biofabrication ; 16(4)2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39121873

ABSTRACT

Current biofabrication strategies are limited in their ability to replicate native shape-to-function relationships, that are dependent on adequate biomimicry of macroscale shape as well as size and microscale spatial heterogeneity, within cell-laden hydrogels. In this study, a novel diffusion-based microfluidics platform is presented that meets these needs in a two-step process. In the first step, a hydrogel-precursor solution is dispersed into a continuous oil phase within the microfluidics tubing. By adjusting the dispersed and oil phase flow rates, the physical architecture of hydrogel-precursor phases can be adjusted to generate spherical and plug-like structures, as well as continuous meter-long hydrogel-precursor phases (up to 1.75 m). The second step involves the controlled introduction a small molecule-containing aqueous phase through a T-shaped tube connector to enable controlled small molecule diffusion across the interface of the aqueous phase and hydrogel-precursor. Application of this system is demonstrated by diffusing co-initiator sodium persulfate (SPS) into hydrogel-precursor solutions, where the controlled SPS diffusion into the hydrogel-precursor and subsequent photo-polymerization allows for the formation of unique radial stiffness patterns across the shape- and size-controlled hydrogels, as well as allowing the formation of hollow hydrogels with controllable internal architectures. Mesenchymal stromal cells are successfully encapsulated within hollow hydrogels and hydrogels containing radial stiffness gradient and found to respond to the heterogeneity in stiffness through the yes-associated protein mechano-regulator. Finally, breast cancer cells are found to phenotypically switch in response to stiffness gradients, causing a shift in their ability to aggregate, which may have implications for metastasis. The diffusion-based microfluidics thus finds application mimicking native shape-to-function relationship in the context of tissue engineering and provides a platform to further study the roles of micro- and macroscale architectural features that exist within native tissues.


Subject(s)
Hydrogels , Microfluidics , Tissue Engineering , Hydrogels/chemistry , Humans , Microfluidics/methods , Microfluidics/instrumentation , Mesenchymal Stem Cells/cytology
6.
Polymers (Basel) ; 16(12)2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38932033

ABSTRACT

Amid the growing demand for sustainable pavement solutions and the need to incorporate recycled materials into construction practices, this study explored the viability of using crushed thermal power plant bottom ash as a filler in polymer-modified asphalt concrete mixtures. Conventional lime filler was replaced with bottom ash at varying levels (0%, 25%, 50%, and 75%), and the resulting mixtures were evaluated using several performance tests. The optimal replacement level was determined to be 25%, based on the results of the indirect tensile strength (ITS) test. Comparisons between the control mixture and the 25% bottom ash-modified mixture were conducted using the dynamic modulus test, Cantabro test, Hamburg wheel tracking (HWT) test, and tensile strength ratio (TSR) test. The findings indicate that the 25% bottom ash-modified mixture demonstrated improved performance across multiple parameters. The HWT test showed enhanced rut durability, with a recorded depth of 7.56 mm compared to 8.9 mm for the control mixture. The Cantabro test results revealed lower weight loss percentages for the modified mixture, indicating better abrasion resistance. The dynamic modulus test indicated higher resilience and stiffness in both high- and low-frequency stages. The TSR test highlighted improved moisture resistance, with higher TSR values after 10 wet-drying cycles. These improvements are attributed to the fine particle size and beneficial chemical composition of bottom ash, which enhance the asphalt mixture's density, binder-aggregate adhesion, and overall durability. The results suggest that incorporating 25% crushed bottom ash as a filler in polymer-modified asphalt concrete mixtures is a viable and sustainable approach to improving pavement performance and longevity.

7.
Cells ; 13(10)2024 May 19.
Article in English | MEDLINE | ID: mdl-38786098

ABSTRACT

Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however, how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A. We found that PI 3-kinase activation promoted cell-cycle progression, especially when growth signals were limiting, as well as cell migration, both in a collective monolayer and as single cells. Furthermore, we showed that KMT2D inactivation had relatively little influence on these processes, except for single-cell migration, which KMT2D inactivation promoted in synergy with PI 3-kinase activation. The combination of these two genetic alterations induced expression of the ARPC5L gene that encodes a subunit of the Arp2/3 complex. ARPC5L depletion fully abolished the enhanced migration persistence exhibited by double-mutant cells. Our reconstitution approach in MCF10A has thus revealed both the cell function and the single-cell migration, and the underlying Arp2/3-dependent mechanism, which are synergistically regulated when KMT2D inactivation is combined with the activation of the PI 3-kinase.


Subject(s)
Actin-Related Protein 2-3 Complex , Cell Movement , Epithelial Cells , Histone-Lysine N-Methyltransferase , Phosphatidylinositol 3-Kinases , Humans , Cell Movement/genetics , Epithelial Cells/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Histone-Lysine N-Methyltransferase/metabolism , Histone-Lysine N-Methyltransferase/genetics , Actin-Related Protein 2-3 Complex/metabolism , Actin-Related Protein 2-3 Complex/genetics , Female , Mammary Glands, Human/metabolism , Mammary Glands, Human/cytology , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Neoplasm Proteins/metabolism , Neoplasm Proteins/genetics , Mutation/genetics , Cell Line
8.
J Phys Chem B ; 128(22): 5281-5292, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38785765

ABSTRACT

Molecular dynamics simulation is a powerful tool for characterizing the solution structural ensembles of cyclic peptides. However, the ability of simulation to recapitulate experimental results and make accurate predictions largely depends on the force fields used. In our work here, we evaluate the performance of seven state-of-the-art force fields in recapitulating the experimental NMR results in water of 12 benchmark cyclic peptides, consisting of 6 cyclic pentapeptides, 4 cyclic hexapeptides, and 2 cyclic heptapeptides. The results show that RSFF2+TIP3P, RSFF2C+TIP3P, and Amber14SB+TIP3P exhibit similar and the best performance, all recapitulating the NMR-derived structure information on 10 cyclic peptides. Amber19SB+OPC successfully recapitulates the NMR-derived structure information on 8 cyclic peptides. In contrast, OPLS-AA/M+TIP4P, Amber03+TIP3P, and Amber14SBonlysc+GB-neck2 could only recapitulate the NMR-derived structure information on 5 cyclic peptides, the majority of which are not well-structured.


Subject(s)
Molecular Dynamics Simulation , Peptides, Cyclic , Peptides, Cyclic/chemistry , Solutions , Protein Conformation , Nuclear Magnetic Resonance, Biomolecular , Magnetic Resonance Spectroscopy
10.
Hum Genomics ; 18(1): 38, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627868

ABSTRACT

BACKGROUND: Congenital ichthyosis (CI) is a collective group of rare hereditary skin disorders. Patients present with epidermal scaling, fissuring, chronic inflammation, and increased susceptibility to infections. Recently, there is increased interest in the skin microbiome; therefore, we hypothesized that CI patients likely exhibit an abnormal profile of epidermal microbes because of their various underlying skin barrier defects. Among recruited individuals of Southeast Asian ethnicity, we performed skin meta-genomics (i.e., whole-exome sequencing to capture the entire multi-kingdom profile, including fungi, protists, archaea, bacteria, and viruses), comparing 36 CI patients (representing seven subtypes) with that of 15 CI age-and gender-matched controls who had no family history of CI. RESULTS: This case-control study revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis showed distinct microbial populations, decreases in commensal microbiota, and higher colonization by pathogenic species associated with CI; these were correlated with increased production of inflammatory cytokines and Th17- and JAK/STAT-signaling pathways in peripheral blood mononuclear cells. In the wounds of CI patients, we identified specific changes in microbiota and alterations in inflammatory pathways, which are likely responsible for impaired wound healing. CONCLUSIONS: Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI and should provide critical information for improving therapeutic management of CI patients.


Subject(s)
Ichthyosis , Microbiota , Humans , Case-Control Studies , Leukocytes, Mononuclear , Southeast Asian People , Inflammation/genetics , Microbiota/genetics , Ichthyosis/genetics
11.
ACS Nano ; 18(12): 8571-8599, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38483840

ABSTRACT

T cell-based adoptive cell therapy (ACT) has emerged as a promising treatment for various diseases, particularly cancers. Unlike other immunotherapy modalities, ACT involves directly transferring engineered T cells into patients to eradicate diseased cells; hence, it necessitates methods for effectively activating and expanding T cells in vitro. Artificial antigen-presenting cells (aAPCs) have been widely developed based on biomaterials, particularly micro- and nanoparticles, and functionalized with T cell stimulatory antibodies to closely mimic the natural T cell-APC interactions. Due to their vast clinical utility, aAPCs have been employed as an off-the-shelf technology for T cell activation in FDA-approved ACTs, and the development of aAPCs is constantly advancing with the emergence of aAPCs with more sophisticated designs and additional functionalities. Here, we review the recent advancements in particle-based aAPCs for T cell activation in ACTs. Following a brief introduction, we first describe the manufacturing processes of ACT products. Next, the design and synthetic strategies for micro- and nanoparticle-based aAPCs are discussed separately to emphasize their features, advantages, and limitations. Then, the impact of design parameters of aAPCs, such as size, shape, ligand density/mobility, and stiffness, on their functionality and biomedical performance is explored to provide deeper insights into the design concepts and principles for more efficient and safer aAPCs. The review concludes by discussing current challenges and proposing future perspectives for the development of more advanced aAPCs.


Subject(s)
Antigen-Presenting Cells , Lymphocyte Activation , Humans , Immunotherapy/methods , T-Lymphocytes , Cell- and Tissue-Based Therapy , Immunotherapy, Adoptive
12.
Polymers (Basel) ; 16(5)2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38475283

ABSTRACT

This manuscript presents a comprehensive study on the sustainable optimization of asphalt mixtures tailored for regions prone to flooding. The research addresses the challenges associated with water damage to asphalt pavements by incorporating innovative additives. The study centers on incorporating recycled Low-Density Polyethylene (LDPE) and a tailored Carnauba-Soybean Oil Additive, advancing asphalt mixtures with a Control mix, LDPE (5%) + Control, and LDPE (5%) + 3% Oil + Control. A critical aspect of the research involves subjecting these mixtures to 30 wetting and drying cycles, simulating the conditions prevalent in tropical flood-prone areas. The incorporation of innovative additives in asphalt mixtures has demonstrated significant improvements across various performance parameters. Tensile Strength Ratio (TSR) tests revealed enhanced tensile strength, with the LDPE (5%) + 3% Oil-modified mixture exhibiting an impressive TSR of 85.7%. Dynamic Modulus tests highlighted improved rutting resistance, showcasing a remarkable increase to 214 MPa in the LDPE (5%) with a 3% Oil-modified mixture. The Semi-Circular Bending (SCB) test demonstrated increased fracture resistance and energy absorption, particularly in the LDPE (5%) with 3% Oil-modified mixture. Hamburg Wheel-Tracking (HWT) tests indicated enhanced moisture resistance and superior rutting resistance at 20,000 cycles for the same mixture. Cantabro tests underscored improved aggregate shatter resistance, with the LDPE (5%) + 3% Oil-modified mixture exhibiting the lowest weight loss rate at 9.820%. Field tests provided real-world insights, with the LDPE (5%) + 3% Oil mixture displaying superior stability, a 61% reduction in deflection, and a 256% improvement in surface modulus over the control mixture. This research lays the groundwork for advancing the development of sustainable, high-performance road pavement materials, marking a significant stride towards resilient infrastructure in flood-prone areas.

13.
JID Innov ; 4(2): 100261, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38445231

ABSTRACT

IL-23 is central to psoriasis pathogenesis. Biologics targeting IL-23 are important therapies against psoriasis. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab bind the IL-23 p19 subunit, whereas ustekinumab binds p40; however, the structural composition of the IL-23-binding epitopes and how these molecular properties relate to clinical efficacy are not known. Utilizing epitope data derived from hydrogen-deuterium exchange or crystallographic experiments, we mapped inhibitor epitope locations, hydrophobicity, and surface charge onto the IL-23 surface. Molecular properties of each inhibitor epitope, including solvent-accessible surface area, were correlated to binding affinity, kinetic values, and clinical efficacy scores for plaque psoriasis through linear regression analysis. Each IL-23 inhibitor binds an epitope with a unique size, composition, and location except for a 10-residue overlap region outside of the IL-23 receptor epitope. We observed strong correlations between epitope surface area and KD and koff but not kon. Epitope surface area, KD, and koff were further associated with short-term (10-16 weeks) and long-term (44-60 weeks) clinical efficacy according to PASI-90 responses, with risankizumab demonstrating highest efficacy among IL-23 biologics. In contrast, kon, epitope hydrophobicity, polarity, and charge content did not correlate with efficacy. These data exemplify how molecular principles of medications within a therapeutic class can explain their differential clinical responses.

14.
Heliyon ; 10(4): e25763, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38404884

ABSTRACT

Purpose: Cultured lichen mycobionts are valuable sources of new natural compounds. Mycobiont of Graphis handelii growing in Vietnam was isolated, cultivated and chemically investigated. The crude extract of this cultured mycobiont showed potent alpha-glucosidase inhibition with an IC50 value of 50 µg/mL. Methods: Multiple chromatographic methods were applied to the extract to isolate compounds. The combination of Nuclear Magnetic Resonance analysis and high-resolution mass spectroscopy determined their chemical structures. Electrophilic bromination/chlorination was applied to obtain new derivatives using NaBr/H2O2 and NaCl/H2O2 reagents. Compounds were evaluated for enzyme inhibitory activities, including alpha-glucosidase inhibition, HIV-1 reverse transcriptase inhibition, SARS-CoV-2 main protease (Mpro) inhibition, anti-inflammatory activity, and cytotoxicity against several cancer cell lines. A molecular docking study for anti-SARS-CoV-2 was conducted to understand the inhibitory mechanism. Results: A new diphenyl ether, handelone (1) and a known compound xylarinic acid A (2) were isolated and elucidated. Four synthetic products 6'-bromohandelone (1a), 2'-bromohandelone (1b), 2',6'-dibromohandelone (1c), and 2',6'-dichlorohandelone (1d) were prepared. Compound 1 showed good activity against Mpro with an IC50 value of 5.2 µM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays. Conclusion: A new compound, handelone (1) was isolated from the cultured mycobiont of Graphis handelii. From these compounds, four new derivatives were prepared. Compound 1 showed good activity against Mpro with an IC50 value of 5.2 µM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays.

15.
Angew Chem Int Ed Engl ; 63(5): e202317522, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38085688

ABSTRACT

The prevalence of drug-resistant bacterial pathogens foreshadows a healthcare crisis. Calcium-dependent antibiotics (CDAs) are promising candidates to combat infectious diseases as many of them show modes of action (MOA) orthogonal to widespread resistance mechanisms. The calcium dependence is nonetheless one of the hurdles toward realizing their full potential. Using laspartomycin C (LspC) as a model, we explored the possibility of reducing, or even eliminating, its calcium dependence. We report herein a synthetic LspC analogue (B1) whose activity no longer depends on calcium and is instead induced by phenylboronic acid (PBA). In LspC, Asp1 and Asp7 coordinate to calcium to anchor it in the active conformation; these residues are replaced by serine in B1 and condense with PBA to form a boronic ester with the same anchoring effect. Using thin-layer chromatography, MS, NMR, and complementation assays, we demonstrate that B1 inhibits bacterial growth via the same MOA as LspC, i.e., sequestering the cell wall biosynthetic intermediate undecaprenyl phosphate. B1 is as potent and effective as LspC against several Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Our success in converting a CDA to a boron-dependent antibiotic opens a new avenue in the design and functional control of drug molecules.


Subject(s)
Anti-Bacterial Agents , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/chemistry , Calcium , Boron , Bacteria , Microbial Sensitivity Tests
16.
Harm Reduct J ; 20(1): 177, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38057789

ABSTRACT

BACKGROUND: Harm reduction strategies can decrease morbidity and mortality associated with substance use. Various barriers limit conversation around substance use between clinicians and patients. Graphic medicine techniques can inform and encourage patient-centered conversations about substance use. We describe the co-development of a harm reduction-focused graphic medicine comic that depicts the infectious risks associated with injection drug use and patient-centered approaches to providing education about potential risk mitigation strategies. METHODS: We formed a co-design group of veterans with lived experience with substance use, physicians, health services researchers, and community-based harm reduction leaders. Over the course of ten sessions, the co-design team developed a storyline and key messages, reviewed draft content and worked with a graphic designer to develop a comic incorporating the veterans' input. During each session, co-design leads presented drafts of the comic and invited feedback from the group. The comic was edited and adapted via this iterative process. RESULTS: The comic depicts a fictionalized clinical vignette in which a patient develops an injection-related abscess and presents to their primary care provider. The dialogue highlights key healthcare principles, including patient autonomy and agency, and highlights strategies for safer use, rather than emphasizing abstinence. Feedback from co-design group participants highlights lessons learned during the development process. DISCUSSION: Graphic medicine is ideally suited for a patient-centered curriculum about harm reduction. This project is one of several interventions that will be integrated into VA facilities nationally to support incorporation of harm reduction principles into the care of persons who inject drugs.


Subject(s)
Drug Users , Substance Abuse, Intravenous , Substance-Related Disorders , Veterans , Humans , Harm Reduction , Substance Abuse, Intravenous/complications , Substance-Related Disorders/therapy , Substance-Related Disorders/complications
17.
Polymers (Basel) ; 15(22)2023 Nov 19.
Article in English | MEDLINE | ID: mdl-38006186

ABSTRACT

This research investigates the quantitative impact of incorporating epoxy resin and crumb rubber powder (CRP) into cement asphalt mortar (CAM) for railway track stabilization. The study reveals significant improvements in various key parameters compared to conventional CAM. The modified CAM exhibits a 12.7% reduction in flow time, indicative of enhanced flowability, and a substantial 62.4% decrease in the mixing stability gap, demonstrating superior mixing stability. Additionally, the modified CAM displays remarkable early-age compressive strength, with increases of up to 15.3% compared to traditional CAM formulations. Importantly, the modified CAM showcases robust resistance to challenging environmental conditions, with only a 6.7% strength reduction after exposure to sulfuric acid, highlighting its acid resistance, and exceptional freeze-thaw resistance, with a mere 1.5% strength reduction after undergoing six cycles. In a mock-up test simulating real-world conditions, the modified CAM effectively prevents ballast layer settlement, underscoring its potential to enhance the durability of railway track infrastructure. These quantitative findings not only endorse the practical feasibility of epoxy resin and CRP-enhanced CAM but also suggest its potential to contribute significantly to railway track longevity, reduce maintenance expenditures, and ensure operational reliability.

18.
Polymers (Basel) ; 15(21)2023 Oct 29.
Article in English | MEDLINE | ID: mdl-37959936

ABSTRACT

Rising traffic volume, heavy loads, and construction activities have raised concerns about expansion joint device damage. This study focuses on developing an innovative expansion joint using polymer-modified rubber asphalt as the filling material to enhance its service life. Styrene-butadiene-styrene (SBS) emerged as a suitable modifier for rubber-modified asphalt, significantly improving elasticity and adhesion. Through the strategic combination of 3- and 2-block linear SBS, the elasticity and adhesion properties were significantly improved, resulting in the formulation of a well-suited polymer-modified rubber asphalt binder. The developed asphalt binder exhibits impressive elastic recovery (61.1% to 66.1%), surpassing commercial products, with enhanced constructability and workability (15% to 21% viscosity reduction). The carefully engineered mastic asphalt mixture showcases self-leveling characteristics at a moderate 210 °C, addressing historical constructability challenges. Settlement is 40% less than traditional hot mix asphalt for surface layers, with improved moisture and stripping resistance, enhancing existing asphalt plug joint durability and workability. Collectively, this novel mixture, comprising polymer-modified rubber and mastic asphalt, showcases the potential to enhance the durability of existing asphalt plug joints while ensuring superior constructability and workability.

19.
Nat Prod Res ; : 1-7, 2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37635675

ABSTRACT

Mikania micrantha Kunth is widely known as potential herbal medicine, although it is an invasive alien species in Southeast Asia. In this study, the essential oils from leaves and stems of M. micrantha were extracted by hydrodistillation method, and the chemical profiles of essential oils were then analysed by gas chromatography (GC) and gas chromatography coupled with mass spectrometry (GC/MS). It was found that there were similarities and differences in chemical compositions and their percentage between the essential oils obtained from these two parts. The dominant components of leaves essential oil are ß-Cubebene, Germacrene D, and α-Zingiberene, accounting for 11.34%, 10.96%, and 10.76%, respectively. Additionally, the major components of stems essential oils are D-Limonene (16.99%), ß-Pinene (7.91%), and α-Zingiberene (7.26%). The research sheds fresh light on the chemical makeup of M. micrantha essential oils, emphasising their potential for the future.

20.
Polymers (Basel) ; 15(15)2023 Aug 03.
Article in English | MEDLINE | ID: mdl-37571187

ABSTRACT

This research addresses the urgent need for sustainable and durable asphalt mixtures by quantitatively investigating the effects of incorporating waste plastic aggregate (WPA) and magnesium-based additives. This study explores WPA content levels of 3%, 5%, and 7% wt of aggregate in combination with a fixed 3% wt epoxy resin content to the asphalt binder, supplemented with the 1.5% wt magnesium-based additive. The novelty of this research lies in its comprehensive analysis of various performance parameters, including deformation strength, indirect tensile strength (ITS), rut depth, and dynamic stability, to assess the impact of WPA, epoxy resin, and the magnesium-based additive on asphalt mixture properties. The results demonstrate significant improvements in key performance aspects with increasing WPA content. The WPA mixtures exhibit enhanced deformation strength, with values of 4.01, 3.7, and 3.32 MPa for 3, 5, and 7% wt WPA content, respectively, compared to the control mixture. Furthermore, the inclusion of WPA and epoxy resin, along with the magnesium-based additive, contributes to improved adhesion, cohesion, and resistance to stripping damage. Notably, the 7% wt WPA mixture showcases exceptional performance, characterized by a final rut depth of 2.66 mm and a dynamic stability of 7519 passes per millimeter, highlighting its superior rutting resistance and load-bearing capacity. This study also reveals the influence of WPA content on ITS and stiffness properties, with the 5% wt WPA mixture achieving an optimal balance between strength and stiffness. Overall, this research highlights the potential of incorporating WPA, epoxy resin, and magnesium-based additives in asphalt mixtures to enhance their performance and durability. By utilizing plastic waste materials and optimizing their combination with epoxy reinforcement, along with the innovative use of magnesium-based additive, the findings contribute to the development of sustainable infrastructure materials and pave the way for further advancements in the field.

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