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Dissolution kinetics of griseofulvin in mixed micellar solutions.

The dissolution kinetics of the poorly water soluble, lipophilic model drug substance griseofulvin were studied in solutions containing simple and mixed micelles of sodium cholate (BS) and phosphatidylcholine (PC). Variables under investigation were the concentration of BS and the ratio PC/BS. A rotating disk apparatus was used to monitor the dissolution process. With this method, (mixed) micellar diffusion coefficients could be calculated and some detailed information about the physicochemical behavior and composition of mixed PC/BS micelles could be derived.

Bile Acids and Salts↗

Treatment-seeking delay among women with acute myocardial infarction: decision trajectories and their predictors.

BACKGROUND: Women's delay in seeking treatment for acute myocardial infarction symptoms results in higher rates of mortality and morbidity for women. OBJECTIVES: To describe decision trajectories used by women when experiencing symptoms of acute myocardial infarction, and to identify predictors of the decision trajectory used by women with acute myocardial infarction. METHODS: A cross-sectional, descriptive design was used. The nonprobability sample included 52 women hospitalized for acute myocardial infarction. To elicit descriptions of decision making, focused, semistructured interviews were used in this mixed-methods study. Predictors of decision trajectories were measured with standardized instruments among the same women. Narrative analysis was used to examine the stories from the qualitative data and to identify decision trajectory types. Discriminant analysis was used to predict trajectory type membership. RESULTS: The median delay time was 4.25 hours. Most of the women used one of two trajectory types: knowing (defined as those women who knew almost immediately that they would seek help, n = 25) and managing (those women who managed an alternative hypothesis or minimized their symptoms, n = 23). Discriminant analysis correctly classified 71% (chi [4] = 11.2; n = 48; p =.02) of the cases into trajectory types on the basis of four predictor variables: social support, personal control, heart disease threat, and neuroticism. DISCUSSION: Women's behaviors during the period between onset of acute myocardial infarction symptoms and treatment seeking can be categorized into a small number of patterns termed decision trajectories. A profile of sociostructural and intrapersonal factors with potential for predicting behavior in relation to future coronary events was developed.

Adult↗

Nebulization and anti-Pseudomonas aeruginosa activity of colistin.

Colistin aerosols are frequently administered to patients with cystic fibrosis. However, questions arise concerning the effect of both jet and ultrasonic nebulizers on the properties of the drug. The aim of this study was to characterize the anti-Pseudomonas aeruginosa (PA) activity of colistin after jet (Pari LL) and ultrasonic (DP100) nebulization. A bench study was performed by capturing the aerosols, determining the drug mass, and assessing its anti-PA activity. Because the inhaled mass of colistin had to be entirely recovered for the bacteriological study, it was assessed by isotopic methods, mixing the drug with a 99mTc-labelled tracer and demonstrating that 99mTc activity accurately predicted the mass of colistin. Colistin was extracted from the filters and its antibiotic activity was determined using the method employed for the study of the bacteriostatic and bactericidal power of serum on the ATCC 27853 PA strain. The postnebulization minimum inhibitory concentrations (MIC) were 1.9 micrograms.mL-1 with DP100 and 0.5 microgram.mL-1 with Pari LL. These values were less than two dilutions different from the 1 microgram.mL-1 MIC of non-nebulized colistin. We conclude that neither jet nebulization nor ultrasonic nebulization alter the antibiotic properties of colistin and that both systems can be used to nebulize colistin.

Administration, Inhalation↗

Mechanism of cysteine oxidation by a hydroxyl radical: a theoretical study.

Cysteine oxidation by HO(.) was studied at a high level of ab initio theory in both gas phase and aqueous solution. Potential energy surface scans in the gas phase performed for the model system methanethiol+HO(.) indicate that the reactants can form two intermediate states: a sulfur-oxygen adduct and a hydrogen bound reactant complex. However these states appear to play a minor role in the reaction mechanism as long as they are fast dissociating states. Thus the main reaction channel predicted at the QCISD(T)/6-311+G(2df,2pd) level of theory is the direct hydrogen atom abstraction. The reaction mechanism is not perturbed by solvation which was found to induce only small variations in the Gibbs free energy of different reactant configurations. The larger size reactant system cysteine+HO* was treated by the integrated molecular orbital+molecular orbital (IMOMO) hybrid method mixing the QCISD(T)/6-311+G(2df,2pd) and the UMP2/6-311+G(d,p) levels of theory. The calculated potential energy, enthalpy, and Gibbs free energy barriers are slightly different from those of methanethiol. The method gave a rate constant for cysteine oxidation in aqueous solution, k=2.4 x 10(9) mol(-1) dm(3) s(-1), which is in good agreement with the experimental rate constant. Further analysis showed that the reaction is not very sensitive to hydrogen bonding and electrical polarity of the molecular environment.

Computer Simulation↗

Aldehyde and monocyclic aromatic hydrocarbon mixing ratios at an urban site in Las Vegas, Nevada.

Oxidation of benzene, toluene, ethylbenzene, and xylenes (BTEX) in air, of significance due to, for example, the potential for O3 formation, is believed to be initiated by OH attack on the ring (addition) or on the alkyl side chain (H abstraction). A series of ring-breaking reactions follows, with major products predicted to be alpha-dicarbonyls, simple aldehydes, and organic acids. To test this prediction, ambient air mixing ratios of aldehydes (formaldehyde, acetaldehyde, benzaldehyde, glyoxal, and pyruvaldehyde), along with some supporting BTEX data, were measured at an urban site in Las Vegas, NV. Samples were collected on sorbents and determined by chromatographic methods; mixing ratios were compared to ambient levels of CO, O3, and NOx. A meteorological analysis (temperature, wind speed, and wind direction) was also included. Statistically significant relationships were noted among the BTEX hydrocarbons (HCs) and among the photochemically derived species (e.g., O3, NO2, and some of the aldehydes), although there was seasonal variation. The observations are consistent with a common primary source (i.e., vehicular exhaust or fuel evaporation) for the BTEX compounds and a common secondary source (e.g., OH attack) for glyoxal and pyruvaldehyde.

Air Pollutants↗

Implementation of a Face-To-Face Vs Virtual Peer-Integrated Collaborative Care Intervention for Mental Health Treatment of Physical Trauma Survivors: A Qualitative Study of Lessons from the COVID-19 Pandemic.

OBJECTIVE: We assessed the impact of the COVID-19 pandemic on the implementation of a peer-integrated enhancement of integrated clinical care intervention to address the mental health needs of 450 patients undergoing treatment for a physical injury. METHODS: Qualitative data were collected by 7 clinician investigators of a randomized controlled trial acting as participant observers in a trauma care setting of a major U.S. metropolitan hospital and analyzed in collaboration with an external mixed methods specialist. RESULTS: The pandemic created or exacerbated several implementation barriers, including increased risk of infection, homelessness, hospitalizations and comorbid conditions such as fentanyl overdoses that increased demand on emergency department and Trauma Center services, imposition of safety measures to reduce risk of infection in clinical settings, transition from face-to-face to virtual interactions with study patients, shortages of specialty mental health providers, suspension of recruitment of patients into the study, scheduling calls with patients, and an increased workload for the study clinical interventionists. Peer specialists perceived the transition to virtual interactions with patients reduced their effectiveness; however, this was not reflected in assessments of patient satisfaction with services received and may have inadvertently increased adoption by Trauma Center staff. Reduction in reach of the intervention to target population was temporary. CONCLUSIONS: The COVID-19 pandemic exacerbated existing barriers and created new barriers to successfully implementing evidence-based practices in trauma care settings, resulting in an attenuation of their effectiveness. However, the shift from face-to-face to virtual services delivery may have actually led to improved implementation outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03569878. Registered June 15, 2018.

Humans↗

Clinical relevance of recipient leukocyte infusion as antitumor therapy following nonmyeloablative allogeneic hematopoietic cell transplantation.

OBJECTIVE: Graft-versus-leukemia effects of donor lymphocytes have been considered to be central to the therapeutic benefit of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for malignant diseases. Surprisingly, some patients who reject donor grafts following nonmyeloablative HCT have sustained remissions of advanced, chemorefractory hematologic malignancies. In murine mixed chimeras prepared with nonmyeloablative conditioning, we previously showed that recipient leukocyte infusions (RLIs) induce loss of donor chimerism and mediate antitumor responses against host-type tumors. We assessed the clinical relevance of our mouse model. METHODS: Mixed chimeric mice were generated by a nonmyeloablative protocol and some of them received host-derived tumor cells and/or RLIs or donor lymphocyte infusion (DLI). We examined chimerism, graft-versus-host disease (GVHD), and tumor survival. RESULTS: RLI is still effective when the leukocytes are obtained from tumor-bearing mice. Established mixed chimerism is required prior to the induced rejection to achieve maximum antitumor effects. The antitumor effects of RLI are not dependent on a specific donor strain or conditioning protocol. In contrast to DLI, RLI leads to donor cell rejection without the risk of GVHD. CONCLUSION: Together, these data reinforce the clinical potential of RLI therapy as a new HCT strategy that does not carry the risk of GVHD.

Animals↗

The Role of Artificial Intelligence for Intimate Partner Violence Prevention: A Systematic Review.

INTRODUCTION: Intimate partner violence (IPV), encompassing physical, sexual, emotional and economic abuse, remains a pervasive global health concern. Traditional prevention efforts face obstacles such as underreporting, delayed detection and limited personalised support. Emerging artificial intelligence (AI) approaches offer new opportunities to enhance IPV prevention. AIM: This systematic review maps and synthesises evidence on AI-driven tools in IPV prevention based on studies published between 2004 and 2024. METHODS: Following PRISMA 2020 guidelines and PROSPERO registration, we searched PubMed, Embase, CINAHL, PsycINFO, IEEE Xplore and Web of Science. Eligible studies explicitly evaluated AI technologies targeting IPV prediction, screening, intervention or support delivery. Study quality was appraised using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Of 1304 records initially identified, 41 studies met eligibility criteria. AI applications ranged from machine learning (ML) for risk prediction and natural language processing (NLP) for IPV detection in clinical and social media data, to image analysis for forensic evaluation and chatbot-based support. Predictive modelling demonstrated strong discriminative performance, while NLP-based screening detected IPV with notable sensitivity. Chatbots showed feasibility and user acceptability, but evidence of their direct impact on reducing IPV incidence was limited, with one randomised controlled trial showing a modest reduction. Key challenges identified included algorithmic bias, data privacy risks and barriers to integration across health and social care systems. DISCUSSION: AI-informed interventions show promise for improving IPV detection, risk assessment, and scalable support, but questions remain about long-term effectiveness, ethical fairness, transparency and equitable implementation. Future interdisciplinary research should address these concerns to responsibly deploy AI in IPV prevention. RELEVANCE TO CLINICAL PRACTICE: The findings highlight the importance of trauma-informed, culturally responsive care and provider training in AI applications. Nurse-led innovation and policy advocacy will be crucial for safe, equitable integration of AI in IPV prevention.

Artificial Intelligence↗

PNA encoding (PNA=peptide nucleic acid): from solution-based libraries to organized microarrays.

Microarray-based technologies have attracted attention in chemical biology by virtue of their miniaturized format, which is well suited to probe ligand-protein interactions or investigate enzymatic activity in complex biological mixtures. A number of research groups have reported the preparation of surfaces on microarrays with specific functional groups to chemoselectively attach small molecules from libraries. We have developed an alternative method whereby libraries are encoded with peptide nucleic acid (PNA), such that libraries which exist as mixtures in solution self-assemble into an organized microarray through hybridization to produce readily available DNA arrays. This allows libraries synthesized by split and mix methods to be decoded in a single step. An asset of this method compared to direct spotting is that libraries can be used in solution for bioassays prior to self-assembly into the microarray format.

Combinatorial Chemistry Techniques↗

Qualitative evidence of service user experiences and perspectives on long-acting injectable buprenorphine for opioid treatment - a scoping review.

BACKGROUND: There is substantial literature on opioid treatment program (OTP) formulations and how they relate to the pharmacotherapy service user experience. As a newer formulation, less is known about service user experiences of long-acting injectable buprenorphine (LAIB). The aim of this scoping review is to map the qualitative evidence and gaps in the literature on service user experiences and perspectives of LAIB. METHODS: Our search strategy included Medline, Embase, PsycINFO, CINAHL, Scopus and Web Science, and citation chaining, from January 2016 to June 2025. Studies were included if reporting qualitative descriptions of LAIB service user experiences of treatment for opioid dependence, inclusive of qualitative, mixed methods (description of qualitative data only), case reports and English language. Articles were screened by two reviewers. A living experience first author led the analysis using inductive coding and thematic analysis, to produce a descriptive summary of synthesised findings alongside key study characteristics and quality appraisal, adhering to the Systematic reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) checklist. RESULTS: After screening 838 titles/abstracts and reviewing 150 full texts, 40 studies met the eligibility criteria. All were conducted in high income countries, principally the US (n=12); Australia (n=10); and England and Wales (n=9). We identified five themes: Navigating LAIB treatment; Embodied and relational effects of LAIB; Impact and role of the service provider; Narratives of harm reduction and recovery; Stigma and criminalisation. LAIB was commonly experienced as increasing convenience, stability and freedom from daily supervised dosing, enabling improved work, travel, privacy and social participation. Reduced clinic/dosing contact often lessened enacted stigma and treatment burden. However, experiences were heterogenous. Some participants described injection-site discomfort, uncertainty about dose adequacy, reduced flexibility once injected, and ambivalence about LAIB effects. There was inconsistency in LAIB service user reports on service connection, isolation and psychosocial support. Treatment experiences were strongly shaped by provider practices. CONCLUSIONS: Findings underscore the need for integrated, flexible, harm-reduction oriented and person-centred LAIB treatment models that prioritise choice, autonomy and therapeutic relationships to maximise benefit for service users. However, evidence of LAIB service user experiences is concentrated in high-income countries, and the absence of perspectives from low- and middle-income country settings represents a substantial gap in the evidence base.

LAIB↗

High vacuum as a method of reducing porosity of polymethylmethacrylate.

In total hip arthroplasty, fracture and subsequent premature loosening are directly related to the strength of the cement mantle serving as an interface between bone and prosthesis. The cement has been shown to be weakened by its porosity, which enhances the formation of microfractures that contribute to crack propagation. By means of a vacuum mixing method for preparing the cement, nearly all the porosity can be removed and cement strength enhanced by about 17%.

Biomechanical Phenomena↗

Outcomes and effectiveness of decision aids for families affected by hereditary cancer syndromes: A scoping review.

PURPOSE: In the past 15 years, numerous decision aids (DAs) have been developed to assist families affected by hereditary cancer syndromes in decision-making for managing inheritance and cancer risk. We identified the range and characteristics of DAs, focusing on their development stage according to guideline recommendations, their outcomes, and effectiveness. METHODS: A comprehensive search was conducted in MEDLINE, EMBASE, Cochrane, CINAHL, and PsycINFO, along with manual searches. Eligible articles reported DAs for supporting families affected by hereditary cancer syndromes, published in English from inception to July 2024. Quality was assessed using the Mixed-Methods Appraisal Tool. RESULTS: From 15,066 records, 32 studies with a moderate risk of bias, reporting 23 unique DAs, were identified. Most DAs targeted women (69.6%) with hereditary breast and ovarian cancer syndrome (73.9%) in North America and Europe (81.3%), primarily supporting decisions on cancer risk-reduction strategies (56.5%) and genetic testing/counseling (47.8%). Only 4 DAs were consistent with guideline-recommended development process, including prototype development, alpha- and beta-testing. Development and alpha-testing outcomes included user experience, understandability, and psychological impact. Beta-testing evaluated decision-making capacity, quality of the decision-making process, psychological impact, and impact on decisions. DAs consistently improved decision-making capacity and quality of the decision-making process but showed variable effects on psychological outcomes and actual decision in risk management. CONCLUSION: DAs are underdeveloped for genetic, racial, or gender minorities, according to guideline-recommended development process. Future research should develop DAs for broader populations and clarify their effectiveness, particularly regarding psychological outcomes.

Humans↗

Computer Aided Analysis of Split and Mix Combinatorial Libraries.

Combinatorial chemistry using split and pool synthesis involves making and testing mixtures of compounds in pools which are subsets of the larger compound collection. These subsets are created during the synthesis of the collection through a resin splitting and mixing method. Tests are conducted on each of the final pools of mixtures and the individual compounds within a mixture of interest are then identified through some deconvolution scheme, originally involving selective re-synthesis. It is possible that different schemes for splitting and mixing will have different consequences on the overall effort necessary to deconvolute interesting mixtures. The evaluation of different protocols of splitting and mixing involves consideration of more possibilities than can be exhaustively or optimally determined manually in a realistic time frame for most compound collections. We present herein a computational scheme to aid in this analysis. The approach exhaustively examines possible splitting and mixing strategies for the interrelated values of total library size, number of combinatorial steps, number of reaction vessels, and number of compounds per final pool. Weighting factors may be introduced into the various steps. The resulting complete list of splitting and mixing options is scored based on a variable weighting strategy for the total effort of synthesis and deconvolution. The results indicate the splitting/mixing strategy used has an impact on overall efficiency and should be considered in the design of compound libraries.

Journal Article↗

A comparative systematic review of pharmacist education systems and pharmacy service quality in ASEAN-5: Indonesia, Malaysia, Thailand, the Philippines, and Singapore.

BACKGROUND: The global transition toward patient-centered pharmaceutical care has exposed structural disparities in ASEAN pharmacy workforce training and deployment. This review examines four research questions: how pharmacy education systems and accreditation standards differ across Indonesia, Malaysia, Thailand, the Philippines, and Singapore (collectively, the ASEAN-5); the extent to which pre-registration education influences clinical service scope and professional confidence; how education reform and regulatory change have shaped pharmacist clinical roles; and what barriers and enablers exist for regional qualification harmonization. METHODS: A systematic literature review following PRISMA 2020 was conducted. Searches of PubMed/MEDLINE and Scopus, supplemented by grey literature, were completed in May 2026. Of 78 unique records screened, 46 studies published between 2005 and 2026 met inclusion criteria. Quality appraisal used an adapted Mixed Methods Appraisal Tool; synthesis employed narrative thematic analysis. RESULTS: The five countries represent four structurally distinct pharmacy education architectures: Thailand's standardized six-year Doctor of Pharmacy with dual specialization tracks; four-year Bachelor of Pharmacy programmes in Malaysia and the Philippines with institutional variation; Indonesia's clinically underdeveloped system despite rapid expansion; and Singapore's four-year Bachelor of Pharmacy followed by a nationally mandated one-year pre-registration pathway. Evidence links deeper clinical training to broader practice scope, higher confidence, and improved patient outcomes. Reform produced uneven results: Thailand's PharmD transition improved clinical recognition but exposed deployment paradoxes; Singapore achieved the strongest training-to-practice alignment; Indonesia's health insurance reforms were not absorbed by an underprepared workforce; the Philippines lacks a national competency framework. No binding mutual recognition arrangement was identified; divergent qualification structures, incompatible accreditation systems, and an asymmetric evidence base remain the primary barriers. DISCUSSION: These findings indicate that clinical service scope is bounded less by national policy ambition than by the depth and clinical orientation of the pre-registration education that precedes it, and that credentialing reforms which outpace a health system's capacity to absorb new clinical roles, or the reverse, do not by themselves translate into expanded practice. CONCLUSIONS: Pharmacy education across the ASEAN-5 remains nationally distinct and clinically uneven. Clinical service scope is directly bounded by pre-registration education quality. No country has fully closed the education-practice gap. Regional harmonization requires national-level educational reform as a prerequisite.

Humans↗

Physical properties of solid dispersion of a nonsteroidal anti-inflammatory drug (M-5011) with Eudragit E.

Some acidic nonsteroidal anti-inflammatory drugs (NSAIDs) are poorly soluble in the stomach. In this study, M-5011, d-2-[4-(3-methyl-2-thienyl) phenyl] propionic acid, was used as a model substance. To increase the dissolution rate of M-5011, a solid dispersion of M-5011 was prepared by the powder mixing method using Eudragit E-100 (aminoacryl methacrylate copolymer) as a carrier. Evaluation by X-ray diffraction and differential scanning calorimetry (DSC) revealed that M-5011 easily formed a solid dispersion with E-100. The dissolution behavior of a physical mixture prepared immediately after mixing and the mixture stored for 14 days at 40 degrees C were examined. It was observed that the former, containing a great deal of E-100, showed a fairly good dissolution behavior, and the latter had a better dissolution rate. The mechanism of the interaction of M-5011 and E-100 was investigated by infrared (IR) spectroscopy and nuclear magnetic resonance (NMR). The interaction was simulated by NMR using a monomer of Eudragit E-100.

Acrylates↗

Peripheral regulation of graft-versus-host alloreactivity in mixed chimeric miniature swine.

BACKGROUND: Despite the presence of circulating donor-derived T cells during the induction of mixed chimerism across MHC barriers in miniature swine, severe graft-versus-host disease was avoided in the majority of animals. In this study, we investigated the possible roles of recipient and donor lymphoid populations in the regulation of donor-anti-recipient alloreactivity. METHODS: Mixed chimerism across a full MHC-mismatch barrier was established in miniature swine using a high-dose allogeneic peripheral blood stem cell protocol. Peripheral blood mononuclear cells from mixed chimeric swine were co-cultured with naïve donor-matched responders and naïve recipient-matched stimulators in mixed lymphocyte reactions. RESULTS: Peripheral blood mononuclear cells from mixed chimeras inhibited donor-anti-recipient proliferation. This suppression was radioresistant to 25 Gy. Suppression of donor-anti-recipient alloreactivity was not observed in mixed lymphocyte co-cultures when donor-derived cells were added in the absence of recipient-derived cells. CONCLUSIONS: These results suggest an association between the presence of an active and relatively radioresistant cell population, demonstrable in vitro, and the regulation of graft-versus-host disease across MHC barriers in mixed chimeric miniature swine.

Animals↗

Tobacco use in popular movies during the past decade.

OBJECTIVE: The top 50 commercially successful films released per year from 1991 to 2000 were content coded to assess trends in tobacco use over time and attributes of films predictive of higher smoking rates. DESIGN: This observational study used media content analysis methods to generate data about tobacco use depictions in films studied (n = 497). Films are the basic unit of analysis. Once films were coded and preliminary analysis completed, outcome data were transformed to approximate multivariate normality before being analysed with general linear models and longitudinal mixed method regression methods. MAIN OUTCOME MEASURES: Tobacco use per minute of film was the main outcome measure used. Predictor variables include attributes of films and actors. Tobacco use was defined as any cigarette, cigar, and chewing tobacco use as well as the display of smoke and cigarette paraphernalia such as ashtrays, brand names, or logos within frames of films reviewed. RESULTS: Smoking rates in the top films fluctuated yearly over the decade with an overall modest downward trend (p < 0.005), with the exception of R rated films where rates went up. CONCLUSIONS: The decrease in smoking rates found in films in the past decade is modest given extensive efforts to educate the entertainment industry on this issue over the past decade. Monitoring, education, advocacy, and policy change to bring tobacco depiction rates down further should continue.

Age Factors↗

An ethno-medical perspective on research participation: a qualitative pilot study.

BACKGROUND: Recruitment of racial/ethnic minorities for clinical research continues to be problematic, yet critical to ensuring that research data will be applicable to diverse populations. There is a paucity of information about culturally appropriate methods for recruiting and retaining racial/ethnic minorities in research. OBJECTIVE: To cross-culturally assess perceptions of research participation by African American and immigrant Latinos living in the inner-city community of Watts, Los Angeles, California, using qualitative methods. DESIGN: Focus groups using ethnically matched moderators were convened with African American and immigrant Latino participants. Discussion was facilitated using a script that focused on perceived "feelings" and "perceptions" about research. Discussions were audiotaped, transcribed, and analyzed using manual and computerized statistically based software (mixed) methods. RESULTS: African Americans and immigrant Latinos shared several barriers and motivators to research. However, they also reported barriers and motivators to research that were distinct to each group. Latinos were more interested in healthcare and health information, and African Americans were more concerned with issues of trust and quality of care. Most participants said they would participate in research if they were better informed, or if they or a family member had an illness. Improving communication was reported as being important for motivating participation in clinical research. Overall, socioecologically and socioeconomically based domains were shared, whereas historically and/or socioculturally based domains were distinct. CONCLUSIONS: Using an ethno-medical science model, we demonstrated that it is possible to identify shared barriers and motivators to research participation between 2 distinct cultural groups. This approach can be useful in developing targeted community-based strategies to increase minority participation in clinical trials.

Adult↗