Multicomponent Approach Research Articles

Effectiveness of a Multifaceted Implementation Strategy to Increase Equitable Hospital at Home Utilization: An Interrupted Time Series Analysis.

The number of Hospital-at-Home (HaH) programs rapidly increased during the COVID-19 pandemic and after issuance of Centers for Medicare and Medicaid Services' (CMS) Acute Hospital Care at Home (AHCaH) waiver. However, there remains little evidence on effective strategies to equitably expand HaH utilization. Evaluate the effects of a multifaceted implementation strategy on HaH utilization over time. Before and after implementation evaluation using electronic health record (EHR) data and interrupted time series analysis, complemented by qualitative interviews with key stakeholders. Between December 2021 and December 2022, we identified adults hospitalized at six hospitals in North Carolina approved by CMS to participate in the AHCaH waiver program. Eligible adults met criteria for HaH transfer (HaH-eligible clinical condition, qualifying home environment). We conducted semi-structured interviews with 12 HaH patients and 10 referring clinicians. Two strategies were studied. The discrete implementation strategy (weeks 1-12) included clinician-directed educational outreach. The multifaceted implementation strategy (weeks 13-54) included ongoing clinician-directed educational outreach, local HaH assistance via nurse navigators, involvement of clinical service line executives, and individualized audit and feedback. We assessed weekly averaged HaH capacity utilization, weekly counts of unique referring providers, and patient characteristics. We analyzed themes from qualitative data to determine barriers and facilitators to HaH use. Our evaluation showed week-to-week increases in HaH capacity utilization during the multifaceted implementation strategy period, compared to discrete-period trends (slope-change odds ratio-1.02, 1.01-1.04). Counts of referring providers also increased week to week, compared to discrete-period trends (slope-change means ratio-1.05, 1.03-1.07). The increase in HaH utilization was largest among rural residents (11 to 34%). Barriers included HaH-related information gaps and referral challenges; facilitators included patient-centeredness of HaH care. A multifaceted implementation strategy was associated with increased HaH capacity utilization, provider adoption, and patient diversity. Health systems may consider similar, contextually relevant multicomponent approaches to equitably expand HaH.

Regulating the severe running-in wear of polymer composites by a dual-pin-on-disk (DPOD) multicomponent approach

Polymer composites are increasingly used as frictional components due to their self-lubricating properties. However, they tend to exhibit severe wear during the running-in stage, thus significantly impairing their service life. In the present work, a dual-pin-on-disk (DPOD) method is developed in order to reduce the running-in wear of a polytetrafluoroethylene/alumina (PTFE/Al2O3) composite when sliding against GCr15 bearing steel by introducing an assistant polymer component during the running-in stage. The results show that the running-in wear rate of the main polymer pin is reduced by up to 77.26 %. This is because the assistant pin causes excess wear debris to be released into the wear track and provides a higher shear force, thereby promoting the tribological chemical reactions and facilitating the generation of tribofilms on the worn surfaces. In addition, the processed polymer achieves a wear rate similar to that of the conventional single pin condition (∼3 × 10−7mm3/Nm) in the subsequent steady-state stage. The results of the present work are expected to increase significantly the wear life span and application prospects of the polymer composites.

Exploring the implementation of whole school emotionally based school non-attendance (EBSN) guidance in a secondary school

Aim:This research aims to explore the implementation of whole school guidance for Emotionally Based School Non-Attendance (EBSN).Method/Rationale:School attendance is an area of increasing concern and many local authorities have produced guidance to support schools and others in their practice. How such guidance is implemented is likely to have a key influence on improving outcomes however, available implementation frameworks tend to focus on time-limited, specific universal or group programmes with little guidance on the implementation of more complex multi-component whole school approaches. Action research within a mainstream secondary school in the Northwest of England was used to explore the implementation of EBSN guidance through the following research question: What do school staff perceive as key factors (facilitators and barriers) influencing implementation of EBSN guidance in their school context?Findings:Key factors identified as influencing implementation in the school context were leadership and compatibility of practice and expectations; staff knowledge, perceptions and attitudes; and resources. These themes require communication, cohesion and consistency, and they sit within the current context and its internal and external systems, including parents and the community.Limitations:Initial stages of implementation are explored but timescales did not allow for exploration of how implementation of the guidance would be sustained.Conclusions:Key reflections are explored, and findings are used to further delineate a recently developed framework relating to facilitators and barriers to implementing whole school approaches. Implications for practice and future research are outlined.

Challenges of enzyme therapy: Why two players are better than one.

Enzyme-based therapy has garnered significant attention for its current applications in various diseases. Despite the notable advantages associated with the use of enzymes as therapeutic agents, that could have high selectivity, affinity, and specificity for the target, their application faces challenges linked to physico-chemical and pharmacological properties. These limitations can be addressed through the encapsulation of enzymes in nanoplatforms as a comprehensive solution to mitigate their degradation, loss of activity, off-target accumulation, and immunogenicity, thus enhancing bioavailability, therapeutic efficacy, and circulation time, thereby reducing the number of administrations, and ameliorating patient compliance. The exploration of novel nanomedicine-based enzyme therapeutics for the treatment of challenging diseases stands as a paramount goal in the contemporary scientific landscape, but even then it is often not enough. Combining an enzyme with another therapeutic (e.g., a small molecule, another enzyme or protein, a monoclonal antibody, or a nucleic acid) within a single nanocarrier provides innovative multidrug-integrated therapy and ensures that both the actives arrive at the target site and exert their therapeutic effect, leading to synergistic action and superior therapeutic efficacy. Moreover, this strategic approach could be extended to gene therapy, a field that nowadays has gained increasing attention, as enzymes acting at genomic level and nucleic acids may be combined for synergistic therapy. This multicomponent therapeutic approach opens opportunities for promising future developments. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Brain functional training: a perspective article.

Introduction: Physical exercise (PE) positively affects the nervous system, impacting morphology and physiology. It increases brain gray and white matter, improves cerebral blood flow, and stimulates neurogenesis, synaptogenesis, and angiogenesis, promoting brain function. Although exercise already affects cognition, some training modalities place greater demands on the cognitive aspects of physical exercise, such as perceptual-motor and visual-motor training. This type of approach aims to emphasize the cognitive adaptations that occur chronically. Specifically for older people, functional training, a multi-component approach, is a promising exercise modality that stimulates functionality using multi-joint, multi-planar exercises mirroring daily activities. However, applying a greater focus on cognitive adaptations in line with the functional training proposal for maximal benefits remains underexplored. Aim: Thus, this perspective article initially explores different exercise approaches emphasizing cognitive adaptations and proposes Brain Functional Training to improve older adult's functionality. Methods: Furthermore, we explain how brain functional training can be explored to emphasize cognitive aspects based on increasing complexity to stimulate the executive function and its subdomains. Conclusion: This proposal is one alternative to combining motor and cognitive stimuli to promote autonomy and health in older people.

Based on Network Pharmacology and Molecular Docking, the Active Components, Targets, and Mechanisms of Flemingia philippinensis in Improving Inflammation Were Excavated.

Flemingia philippinensis, a polyphenol-rich plant, holds potential for improving inflammation, but its mechanisms are not well understood. Therefore, this study employed network pharmacology and molecular docking to explore the mechanism by which Flemingia philippinensis ameliorates inflammation. In this study, 29 kinds of active ingredients were obtained via data mining. Five main active components were screened out for improving inflammation, which were flemichin D, naringenin, chrysophanol, genistein and orobol. In total, 52 core targets were identified, including AKT serine/threonine kinase 1 (AKT1), tumor necrosis factor (TNF), B-cell lymphoma-2 (BCL2), serum albumin (ALB), and estrogen receptor 1 (ESR1). Gene ontology (GO) enrichment analysis identified 2331 entries related to biological processes, 98 entries associated with cellular components, and 203 entries linked to molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis yielded 149 pathways, including those involved in EGFR tyrosine kinase inhibitor resistance, endocrine resistance, and the PI3K-Akt signaling pathway. Molecular docking results showed strong binding effects between the main active components and the core targets, with binding energies less than -5 kcal/mol. In summary, this study preliminarily elucidated the underlying mechanisms by which Flemingia philippinensis, through a multi-component, multi-target, and multi-pathway approach, ameliorates inflammation. This provides a theoretical foundation for the subsequent application of Flemingia philippinensis in inflammation amelioration.

Improved Rigidin-Inspired Antiproliferative Agents with Modifications on the 7-Deazahypoxanthine C7/C8 Ring Systems.

To improve their aqueous solubility characteristics, water-solubilizing groups were added to some antiproliferative, rigidin-inspired 7-deazahypoxanthine frameworks after molecular modeling seemed to indicate that structural modifications on the C7 and/or C8 phenyl groups would be beneficial. To this end, two sets of 7-deazahypoxanthines were synthesized by way of a multicomponent reaction approach. It was subsequently determined that their antiproliferative activity against HeLa cells was retained for those derivatives with a glycol ether at the 4'-position of the C8 aryl ring system, while also significantly improving their solubility behavior. The best of these compounds were the equipotent 6-[4-(2-ethoxyethoxy)benzoyl]-2-(pent-4-yn-1-yl)-5-phenyl-1,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 33 and 6-[4-(2-ethoxyethoxy)benzoyl]-5-(3-fluorophenyl)-2-(pent-4-yn-1-yl)-1,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 59. Similarly to the parent 1, the new derivatives were also potent inhibitors of tubulin assembly. In treated HeLa cells, live cell confocal microscopy demonstrated their impact on microtubulin dynamics and spindle morphology, which is the upstream trigger of mitotic delay and cell death.

Efeitos de intervenções de base escolar na pressão arterial de crianças com obesidade: metanálise

Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), a systematic review with metanalysis was conducted to identify and summarize the effects of school-based physical activity interventions that sought to control and / or reduce blood pressure (systolic and diastolic) in children and / or adolescents with overweight and / or obesity. In September 2022, potential studies were searched in five electronic databases (Pubmed, Scielo, Scopus, Sportdiscus, and Web of Science) and in reference lists. Randomized controlled trials conducted in schools with interventions involving physical activity and assessment of systolic and diastolic blood pressure in children and adolescents aged 6 to 19 years with overweight and / or obesity were considered for synthesis. The risk of bias was assessed using an adapted version of the Effective Public Health Practice Project tool (EPHPP). Metanalysis was developed from the random model. Four studies were included. For systolic blood pressure, a summary effect of -0.10 (95% CI: -0.39; 0.19; I2 = 0%) was observed. For diastolic pressure, the metanalysis indicated -0.33 (95% CI: -0.62; -0.04; I2 = 11%). Considering the promising effects on diastolic blood pressure, we suggest the development of more school-based interventions based on physical activity practice for overweight and / or obese populations, which may also add environmental elements, longer duration, multicomponent approaches, and parent / guardian involvement to their strategies.

Gut-directed hypnosis and hypnotherapy for irritable bowel syndrome: a mini-review.

Irritable bowel syndrome (IBS) is a frequent health condition which can be associated with functional disability and reduced health-related quality of life. IBS is classified as a disorder of the brain-gut axis. IBS is a very heterogenous condition with regards to the underlying pathophysiological mechanisms, the clinical picture and the amount of functional impairment. Within a biopsychosocial model of IBS psychosocial factors can play a role in the in the predisposition, triggering and development of chronicity. Somatic or psychosocial or a mixture of both factors might predominate in an individual patient. Gut-directed hypnosis is a special type of medical hypnosis combining standardised gut-directed suggestions (hypnosis) with suggestions tailored to the psychological characteristics of the patient (hypnotherapy). Of brain-gut behavioral therapies, cognitive bahvioral-based interventions and gut-directed hypnosis have the largest evidence for both short-term and long-term efficacy in controlled trials for IBS and are recommended by current European and North American gastroenterology guidelines as second line treatment options. Standardised gut-directed hypnosis is available by audiotapes and can be part of a multicomponent self-management approach by digital health applications. It can be used - based on the patient's preferences-as first line therapy for mild forms of IBS. Severe forms of IBS require face-to-face interdisciplinary management. Standardised gut-directed hypnosis and hypnotherapy tailored to the individual patient can be part of this approach.

A systematic scoping review characterising studies investigating workplace nutritional interventions in male employees

Non-communicable diseases (NCDs) are the predominant cause of death in the UK(1) and place an economic burden on societies(2). An unhealthy diet is one of the four main behavioural risk factors for NCDs(3) and thus, interventions targeting dietary behaviour are of particular interest in the prevention of NCDs. The workplace may be a valuable setting for these interventions as employees represent a large proportion of the population in the UK(4). In the male population, NCDs and several risk factors typically manifest at a younger age(5) and, additionally, males participate less in health-promoting activities(6).The aim of this scoping review was to identify and characterise the evidence base to determine if a future full systematic review on nutrition interventions in the workplace to improve health and well- being in males is feasible.The review was conducted adhering to the PRISMA guideline for Scoping Reviews(7). Three electronic databases (Ovid, PubMed, and The Cochrane Library) were systematically searched for relevant publications responding to the research question from inception. No restrictions were made in the search and all study types were eligible. Articles that were not available in English were excluded from the review. Eligible studies were reviewed using a pre-defined data extraction form and references hand-searched for relevant publications. Data synthesis was focused on describing application-oriented aspects and outcome analyses were reduced to anthropometric outcomes.Of the 1,224 publications from the initial database search, 46 were included in the review, with an additional 15 studies identified from hand-searching, resulting in 61 included reports on 57 interventions. Four main approaches to nutrition interventions at the workplace were identified; educational, environmental, individual counselling, and meal provision/replacement. Most interventions used multicomponent approaches. One of the 61 included reports followed a qualitative design. Anthropometric outcomes were reported in the majority (83.6%) of studies, followed by bioclinical outcomes (45.9%), other outcomes were food (34.4%) and nutrient intake (22.9%), smoking habits (14.8%) and, one study reported on Quality of Life. Of the studies reporting anthropometric outcomes 69% reported to be effective in improving body weight, 47.8% BMI and 54.5% waist circumference. No determinants of successful interventions such as type, duration, workplace participation were identified.This review suggests that nutrition interventions at the workplace are effective in improving several anthropometric outcomes. A future full systematic review is feasible but should consider narrowing the research question to account for limitations in the current evidence base as differences in reporting of design, population, intervention, and outcomes severely limited data analyses. Furthermore, to enable high-quality research, the development of a reporting tool, such as the TIDieR checklist (8) is recommended.

Pure Hydrogen and Methane Permeation in Carbon-Based Nanoporous Membranes: Adsorption Isotherms and Permeation Experiments.

This paper presents the results of adsorption and permeation experiments of hydrogen and methane at elevated temperatures on a carbon-based nanoporous membrane material provided by Fraunhofer IKTS. The adsorption of pure components was measured between 90 °C and 120°C and pressures up to 45 bar. The Langmuir adsorption isotherm shows the best fit for all data points. Compared to available adsorption isotherms of H2 and CH4 on carbon, the adsorption on the investigated nanoporous carbon structures is significantly lower. Single-component permeation experiments were conducted on membranes at temperatures up to 220 °C. After combining the experimental results with a Maxwell-Stefan surface diffusion model, Maxwell-Stefan surface diffusion coefficients Dis were calculated. The calculated values are in line with an empirical model and thus can be used in future multi-component modeling approaches in order to better analyze and design a membrane system. The published adsorption data fill a gap in the available adsorption data for CH4 and H2.

The Effect of the Advocacy Social-Emotional Learning Program on Emotional Competence

School leaders are integrating social and emotional skills content into their academic curriculum to create a supportive learning environment and improve the implicit curriculum. The Generation Schools Network (GSN) Advocacy Program is a comprehensive, multi-component schoolwide initiative designed to promote students' social-emotional competence, college and career readiness, and academic success. Overall, the GSN Advocacy Program represents a holistic approach that promotes the interconnectedness of social-emotional development and academic success, aiming to prepare students for the challenges and opportunities they will encounter. The study aimed to test for baseline equivalence between the comparison and intervention groups regarding school climate, leadership, school connectedness, emotional distress, self-awareness, self-management, social awareness, relationship skills, and responsible decision-making. This quasi-experimental process compared secondary students in the intervention group (125) participating in the yearlong GSN Advocacy Program with students in the comparison group (115). After controlling for pre-assessment variables of social-emotional competence, the analysis of covariance (ANCOVA) revealed significant improvements among students in the intervention group for total social-emotional competence and constructs of school climate and school connectedness. The program's multi-component approach, including structural support through professional development for implementers and specific social-emotional learning lessons, helped students develop social-emotional skills. Accordingly, students also demonstrated increased interaction with others, an improved sense of school connectedness, and an enhanced ability to handle emotional distress, which is crucial for academic stressors. This study suggests that the multi-component approach, including student-centered social-emotional competency instruction and environmental focus, engendered the intervention group's acquisition of social-emotional skills. Accordingly, by adopting a multi-component approach that addresses these various aspects of social-emotional programming, school leaders can create a holistic support system that nurtures students' social-emotional competence, resilience, and overall well-being. This comprehensive approach enhances students' academic success and equips them with the skills and attitudes necessary for success beyond the classroom.

Green Synthesis of 2-isonicotinoyl-4,6-dihydroimidazo[4,5-c] Pyrazol-5 (2H)-one Derivatives via One-pot Multicomponent Approach as a Potent Antifungal Agent

Green Synthesis of 2-isonicotinoyl-4,6-dihydroimidazo[4,5-c] Pyrazol-5 (2H)-one Derivatives via One-pot Multicomponent Approach as a Potent Antifungal Agent

The Effects of a Nonpharmacological Intervention Practice for Older Adults with Mild Cognitive Impairment and Their Family Caregivers in China

ABSTRACT Mild cognitive impairment (MCI) marks a critical phase in the progression to dementia. In our study, social workers utilized the Multicomponent Nonpharmacological Intervention Approach (MCNIA) to aid MCI participants (N = 52) and their caregivers, dividing into intervention and control groups. The intervention group underwent an additional regimen of non-pharmacological therapies besides pharmacological treatment. Our findings highlighted that: 1) MCNIA significantly enhanced cognitive and daily living abilities in the intervention group; 2) Caregivers experienced reduced burdens and improved social support; 3) Correlation analyses involving biomarkers indicated that MCNIA was particularly effective in alleviating depression in those with slightly more severe cognitive impairment.

Factors influencing adoption of sexual and reproductive health intervention for adolescents in Ebonyi, Nigeria.

School and Community-embedded reproductive health interventions have been implemented in developing countries, with evidence that they led to improved sexual and reproductive health among adolescents. However, this type of intervention is rarely evaluated for its potential adoption and use. This study evaluated the constraints and enablers of the adoption of a school and community-embedded intervention that used community engagement, capacity building, partnerships and collaborations to deliver sexual and reproductive health services to adolescents. The intervention was implemented between 2019 and 2021 in six local government areas in Ebonyi State. The results on adoption presented here were collected four months into the mid-phase of the project, targeting adolescents, parents, adult family members, healthcare providers, local authorities, and community members. Sixteen in-depth interviews were conducted with policymakers, 14 with health service providers and 18 Focus Group Discussions (FGDs) with parents, community leaders and adolescents who were part of the implementation process. The coding reliability approach, a type of thematic data analysis was used, that involves early theme development and the identification of evidence for the themes. The adoption of school and community-embedded reproductive health intervention was strong among stakeholders at the early stages of the implementation process. Multi-stakeholder involvement and its multi-component approach made the intervention appealing, thereby enabling its adoption. However, at the later stage, the adoption was constrained by beliefs and norms about sexual and reproductive health (SRH) and the non-incentivisation of stakeholders who acted as advocates at the community level. The sustainability of the intervention may be threatened by the non-incentivisation of stakeholders and the irregular supply of materials and tools to facilitate SRH advocacy at the community level. The inclusive community-embedded reproductive health intervention was adopted by stakeholders because of the enablers which include timely stakeholder engagement. However, for it to be sustainable, implementers must address the non-incentivising of community-level advocates which serve as constraints.

Network Pharmacology, Molecular Docking, and Experimental Validation on Guiluoshi Anzang Decoction Against Premature Ovarian Insufficiency.

Premature Ovarian Insufficiency (POI) is a disease suffered by women under the age of 40 when ovarian function has declined, seriously affecting both the physical and mental health of women. Guiluoshi Anzang decoction (GLSAZD) has been used for a long time and has a unique therapeutic effect on improving ovarian function. This study aims to investigate the mechanism of GLSAZD in treating POI through network pharmacology, molecular docking, and experimental verification. In this study, the active ingredients of Guiluoshi Anzang Decoction and the targets of POI were obtained from TCMSP, BATMANN-TCM, Uniprot, GeneCards, and other databases, and network pharmacology analysis was performed. Molecular docking was conducted to validate the affinity of the main active ingredient of GLSAZD to key POI targets. A POI SD rat model was established, and HE staining, ELISA, Real-time PCR, and Western blot experiments were performed to verify the predicted core targets and the therapeutic effects. 10 core targets and the top 5 ingredients were screened out. Molecular docking showed core targets AKT1, CASP3, TNF, TP53, and IL6 had stable binding with the core 5 ingredients quercetin, kaempferol, beta-sitosterol, luteolin, and Stigmasterol. GO and KEGG enrichment analysis demonstrated the mechanism involved in the positive regulation of gene expression, PI3K-AKT signaling pathway, and apoptosis signaling pathways. Animal experiments indicated GLSAZD could up-regulate the protein expression of p-PI3K and p-AKT1 and the mRNA expression of STAT3 and VEGF, down-regulate TP53 and Cleaved Caspase-3 protein expression in rat`s ovarian tissues and serum TNF-α and IL-6 protein levels, activate PI3K-AKT signaling pathway and inhibit the apoptosis signaling pathway. GLSAZD treats POI through multi-component, multi-target, and multi-pathway approaches. This study provided evidence for its clinical application in treating POI and shed light on the study of traditional medicine of the Guangxi Zhuang Autonomous Region in China.

Development of a minimum clinical dataset for preoperative comprehensive geriatric assessment using a modified Delphi technique.

To construct a standardised, consensus-guided minimum clinical dataset (MCDS) for preoperative comprehensive geriatric assessment and optimisation (CGA) in Australia and Aotearoa New Zealand. We conducted a review of the international perioperative literature to identify CGA domains and tools for potential inclusion in the MCDS. We invited members of the Australian and New Zealand Society for Geriatric Medicine to participate in a Delphi study to obtain consensus on MCDS tools. Participants were asked to rate proposed tools using Likert scales (when >2 tools) or make a binary choice between two proposed tools. Consensus was considered to be achieved when there was at least 75% concordance between the two rounds amongst the participants, and at least one variable attaining over 50% of participants' votes. Domains that did not achieve consensus in Round 1 were carried over to Round 2. There were 73 participants in Round 1 of the Delphi study and 47 participants in Round 2. Consensus was achieved on tool/s recommended for every MCDS domain: Clinical Frailty Scale (frailty); sMMSE, RUDAS, MoCA (cognition); 4AT (delirium); timed-up-and-go (physical function); GDS-15 (mood); Barthel Index (functional status); and MUST (malnutrition). We recommend clinicians delivering preoperative CGA consider the use of the MCDS we have constructed when assessing older people contemplating surgery, as part of a multicomponent and multidisciplinary approach to optimising perioperative outcomes.

Can on-line gait training improve clinical practice? Study protocol for feasibility randomised controlled trial of an on-line educational intervention to improve clinician’s gait-related decision-making in ambulant children and young people with cerebral palsy

BackgroundInstrumented gait analysis (IGA) is an assessment and research tool with proven impacts on clinical decision-making for the management of ambulant children and young people with cerebral palsy (CYPwCP) but is underused and variably understood by relevant clinicians. Clinicians’ difficulties in gaining expertise and confidence in using IGA are multifactorial and related to access for clinical decision-making, limited training opportunities and inability to translate this training into clinical practice.MethodsThe primary aim of this study is to test the feasibility of an educational intervention to advance clinicians’ application of gait analysis in CYPwCP, to inform a definitive trial. The secondary aim is to measure the effect that appropriate IGA training has on physiotherapists’ knowledge, skills, confidence and behaviours. This will be a two-arm feasibility randomised controlled trial with an experimental and control group. The 6-week on-line intervention uses a multicomponent approach grounded in behavioural change techniques. A repeated measures design will be adopted, whereby participants will complete outcome measures at baseline, immediately after the intervention and at 4 months. The primary outcome measures (trial feasibility-related outcomes) are recruitment and engagement. The secondary outcome measures (trial research-related outcomes) are knowledge, skills, confidence and practice change. Outcome measures will be collected via online questionnaires and during observed skill assessments. Analysis of data will use descriptive statistics, two-way mixed ANOVA model and qualitative content analysis.DiscussionThis study will determine feasibility of the definitive randomised control trial of educational intervention delivered to advance clinicians’ application of gait analysis in CYPwCP. This study offers the shift in emphasis from regarding IGA as a tool to a focus on clinicians’ requirements for access, training and a well-defined role to optimise utilisation of IGA. The impact of this should be better engagement with IGA and clinical practice change. This study will contribute to a body of educational research into clinical education of healthcare professionals and IGA training offering insight into high levels of evaluation evidence including clinical behaviour change.Trial registrationProtocol has been registered with the Open Science Framework (osf.io/nweq6) in June 2023.

Role of Foreign Phases, Synergistic Effects, and Morphology in the HER Performance of Trimetallic Pentlandites with Non-Equimolar Co:Fe:Ni Ratio

Since pentlandites are among the most promising catalysts for hydrogen evolution reactions (HER), in this study, we investigated the influence of different cobalt, iron, and nickel substitutions in the cationic sublattice and the form of the material (powder, ingot, sintered pellet) on catalytic performance. This complements previous results regarding a multi-component approach in these chalcogenides. It was shown that in the case of sulfur-rich pentlandites with a non-equimolar ratio of Co, Fe, and Ni, the impact of intrinsic material properties is smaller than the surface-related effects. Among powder forms, catalysts based on a combination of Fe and Co perform the best. However, in volumetric forms, extremely high contents of individual metals are favorable, albeit they are associated with active precipitations of foreign phases. The presence of these phases positively affects the recorded currents but slows down the reaction kinetics. These findings shed light on the nuanced interplay between material composition, form, and HER properties, offering insights for tailored catalyst design.

Concurrent inhibition of IR, ITGB1, and CD36 perturbated the interconnected network of energy metabolism and epithelial-to-mesenchymal transition in breast cancer cells.

Altered energy metabolism is an emerging hallmark of cancer and plays a pivotal in cell survival, proliferation, and biosynthesis. In a rapidly proliferating cancer, energy metabolism acts in synergism with epithelial-to-mesenchymal transition (EMT), enabling cancer stemness, dissemination, and metastasis. In this study, an interconnected functional network governing energy metabolism and EMT signaling pathways was targeted through the concurrent inhibition of IR, ITGB1, and CD36 activity. A novel multicomponent MD simulation approach was employed to portray the simultaneous inhibition of IR, ITGB1, and CD36 by a 2:1 combination of Pimozide and Ponatinib. Further, in-vitro studies revealed the synergistic anticancer efficacy of drugs against monolayer as well as tumor spheroids of breast cancer cell lines (MCF-7 and MDA-MB-231). In addition, the combination therapy exerted approximately 40% of the apoptotic population and more than 1.5- to 3-fold reduction in the expression of ITGB1, IR, p-IR, IRS-1, and p-AKT in MCF-7 and MDA-MB-231 cell lines. Moreover, the reduction in fatty acid uptake, lipid droplet accumulation, cancer stemness, and migration properties were also observed. Thus, targeting IR, ITGB1, and CD36 in the interconnected network with the combination of Pimozide and Ponatinib represents a promising therapeutic approach for breast cancer.