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Abstract Background Deprescribing has been defined as the planned process of reducing or stopping medications that may no longer be beneficial or are causing harm, with the goal of reducing medication burden while improving patient quality of life. At present, little is known about the specific challenges of decision-making to support deprescribing for patients who are accessing palliative care. By exploring the perspectives of healthcare professionals, this qualitative study aimed to address this gap, and explore the challenges of, and potential solutions to, making decisions about deprescribing in a palliative care context. Methods Semi-structured interviews were conducted with healthcare professionals in-person or via video call, between August 2022 – January 2023. Perspectives on approaches to deprescribing in palliative care; when and how they might deprescribe; and the role of carers and family members within this process were discussed. Interviews were audio-recorded and transcribed verbatim. Reflexive thematic analysis enabled the development of themes. QSR NVivo (Version 12) facilitated data management. Ethical approval was obtained from the NHS Health Research Authority (ref 305394). Results Twenty healthcare professionals were interviewed, including: medical consultants, nurses, specialist pharmacists, and general practitioners (GPs). Participants described the importance of deprescribing decision-making, and that it should be a considered, proactive, and planned process. Three themes were developed from the data, which centred on: (1) professional attitudes, competency and responsibility towards deprescribing; (2) changing the culture of deprescribing; and (3) involving the patient and family/caregivers in deprescribing decision-making. Conclusions This study sought to explore the perspectives of healthcare professionals with responsibility for making deprescribing decisions with people accessing palliative care services. A range of healthcare professionals identified the importance of supporting decision-making in deprescribing, so it becomes a proactive process within a patient’s care journey, rather than a reactive consequence. Future work should explore how healthcare professionals, patients and their family can be supported in the shared decision-making processes of deprescribing. Trial registration Ethical approval was obtained from the NHS Health Research Authority (ref 305394).

ABSTRACT Introduction Despite increased awareness of the detrimental relationship between homelessness and health, people experiencing homelessness remain an underserved population in health and social care research. Due to barriers affecting the accessibility of medicine and healthcare services, as well as reported competing priorities such as food and shelter, evidence has demonstrated that people experiencing homelessness are less likely to undergo routine examinations, receive diagnoses and adhere to prescribed medical treatments. To enhance service design and access for those experiencing homelessness, it is critical to better recognise, understand and address the barriers these individuals face. This meta‐ethnography aims to identify barriers, enablers and interventions to begin addressing this inequality gap. Methods A systematic literature search was undertaken in October and re‐ran in December 2023 across four databases: MEDLINE, Embase, CINAHL and Scopus. Qualitative studies were included if they addressed barriers, enablers and interventions aimed at tackling medicines and health service inequalities among populations experiencing homelessness. Study quality was assessed using the Joanna Briggs Institute critical appraisal checklist. Data were synthesised using a meta‐ethnographic approach, as outlined by Noblit and Hare. The review was registered on PROSPERO (CRD42024511502) and performed according to PRISMA guidelines. Results This meta‐ethnographic systematic review synthesised data from eight studies across multiple countries. Three overarching third‐order constructs (termed ‘themes’) were developed through reciprocal translation and centred around: recognising and acknowledging the discrimination, stigma and barriers experienced when using current services; exploring safe and practical use of medicines and the promotion of general health education and appreciating strategies to tackle inequalities, namely community outreach programmes designed for homeless communities. Conclusion This work highlighted the barriers, enablers and interventions that sought to address the inequalities affecting people experiencing homelessness in accessing medication and healthcare services. Future research should utilise lived‐experience narratives and co‐design to further explore ways to tackle wider healthcare accessibility inequalities for this minoritised population. Trial Registration Not applicable, as this is a systematic review. Patient or Public Contribution Public contributors (minority research champions and one public health research champion, H.K.G. and T.G.) informed and shaped this project during study design and conceptualisation. They helped to ensure that the study was conducted, and the findings were reported with sensitivity.

Abstract Introduction Cultural competence is an important attribute underpinning interactions between healthcare professionals, such as pharmacists, and patients from ethnic minority communities. Health‐ and medicines‐related inequalities affecting people from underrepresented ethnic groups, such as poorer access to healthcare services and poorer overall treatment outcomes in comparison to their White counterparts, have been widely discussed in the literature. Community pharmacies are the first port of call for healthcare services accessed by diverse patient populations; yet, limited research exists which explores the perceptions of culturally competent care within the profession, or the delivery of cultural competence training to community pharmacy staff. This research seeks to gather perspectives of community pharmacy teams relating to cultural competence and identify possible approaches for the adoption of cultural competence training. Methods Semistructured interviews were conducted in‐person, over the telephone or via video call, between October and December 2022. Perspectives on cultural competence and training were discussed. Interviews were audio‐recorded and transcribed verbatim. The reflexive thematic analysis enabled the development of themes. QSR NVivo (Version 12) facilitated data management. Ethical approval was obtained from the Newcastle University Ethics Committee (reference: 25680/2022). Results Fourteen participants working in community pharmacies were interviewed, including eight qualified pharmacists, one foundation trainee pharmacist, three pharmacy technicians/dispensers and two counter assistants. Three themes were developed from the data which centred on (1) defining and appreciating cultural competency within pharmacy services; (2) identifying pharmacies as ‘cultural hubs’ for members of the diverse, local community and (3) delivering cultural competence training for the pharmacy profession. Conclusion The results of this study offer new insights and suggestions on the delivery of cultural competence training to community pharmacy staff, students and trainees entering the profession. Collaborative co‐design approaches between patients and pharmacy staff could enable improved design, implementation and delivery of culturally competent pharmacy services. Patient or Public Contribution The Patient and Public Involvement and Engagement group at Newcastle University had input in the study design and conceptualisation. Two patient champions inputted to ensure that the study was conducted, and the findings were reported, with cultural sensitivity.

Abstract Introduction Undertaking physical activity, pre‐ and post‐operatively, can benefit recovery time and improve post‐surgical outcomes. One cohort of patients that have reported these benefits are those undergoing surgery for breast cancer. Yet, what remains unclear is the level to which physical activity interventions are implemented into standard surgical care for patients with breast cancer. Aims This systematic review aimed to examine existing qualitative evidence focusing on pre‐ and post‐operative physical activity interventions to better understand the benefits and shortcomings of physical activity within the surgical journey. Methods A systematic literature search was undertaken in November 2022, across five databases: MEDLINE, PsycINFO, Embase, CINAHL, and Scopus. Qualitative studies involving people with breast cancer who had undertaken a physical activity intervention, either pre‐ and/or post‐operatively, were included for analysis. The review was registered on PROSPERO: CRD42022372466 and performed according to PRISMA guidelines. The Critical Appraisal Skills Programme qualitative study checklist was used to assess study quality. Results Fourteen studies were included, comprising the perspectives of 418 people receiving surgery for breast cancer. One study implemented preoperative physical activity interventions; the remaining studies focused on post‐operative interventions. A narrative systematic review was undertaken due to heterogeneity in reported results. Four themes were developed by thematic analysis, centring on: (1) factors promoting engagement with physical activity interventions; (2) factors preventing engagement with physical activity interventions; (3) the impact of pre‐ and post‐operative interventions on physical and psychological health; and (4) participant recommendations for pre‐ and post‐operative interventions. Conclusion Pre‐ and post‐operative physical activity interventions were well‐accepted. Patients recognised factors which promoted or prevented engagement with interventions, as well as pre‐ and post‐operative physical and psychological benefits that arose as a result. Evidence based co‐design studies may further inform successful implementation of prescribed physical activity into standard care for surgical breast cancer patients.

Objective: Poor therapeutic adherence and the contributing factors have been extensively researched in several chronic diseases, including COPD. However, the influence of ethnicity on adherence to nonsurgical treatment interventions for COPD (e.g. smoking cessation and pulmonary rehabilitation) is not well understood. This scoping review was performed to better understand variations in adherence among people from minority ethnic communities diagnosed with COPD. Method: This scoping review was designed based on the refined frameworks of Arksey and O'Malley, developed by JBI (Joanna Briggs Institute). Systematic searches were performed across three databases: CINHAL (EBSCO), MEDLINE (Ovid) and Embase (Ovid). Results: Out of 3654 identified records, 37 studies were deemed eligible for inclusion; these were conducted in various countries and involved populations of diverse ethnic groups diagnosed with COPD. The included studies considered provision and/or adherence to medication (n=8, 21.6%), smoking cessation (n=11, 29.7%), influenza vaccinations (n=7, 18.9%), pulmonary rehabilitation (n=11, 29.7%) and oxygen therapy (n=2, 5.4%). Outcomes varied widely between studies within a single intervention (e.g. initiation, adherence and completion of pulmonary rehabilitation programme). However, most of the included studies suggested the presence of inequalities linked to ethnicity across interventions. Conclusion: This review indicated the presence of poor adherence to nonsurgical interventions among people from minority ethnic backgrounds living with COPD. However, due to the heterogeneity in population groups considered and compared within the individual studies, it is challenging to identify and understand the key inequalities influencing adherence to nonsurgical interventions. Further research is needed to better explore this.

Abstract Introduction Medicines‐centred consultations are vital to support medicine effectiveness and optimize health outcomes for patients. However, inequalities negatively impact ethnic minority populations when accessing medicines advice. It is important to identify opportunities to improve access for these communities however, knowledge of how best to achieve this is lacking; this study will generate recommendations to improve access to medicines advice from community pharmacies for people from ethnic minority communities. Methods A series of codesign workshops, with four groups of patient‐stakeholders, were conducted between September–November 2021; they took place in‐person or via video call (adhering to COVID‐19 restrictions). Existing evidence‐based perceptions affecting access to medicines advice were critiqued and recommendations were generated, by use of reflexive thematic analysis, to improve access for ethnic minority patients. The workshops were audio‐recorded and transcribed verbatim. QSR NVivo (Version 12) facilitated data analysis. Results Twelve participants were recruited using purposive sampling; including eight UK citizens, two asylum seekers and two participants in receipt of residency visas. In total, four different ethnic minority groups were represented. Each participant took part in a first and second workshop to share and cocreate recommendations to improve access to medicines advice in community pharmacies. Three recommendations were developed and centred on: (i) delivering and providing culturally competent medicines advice; (ii) building awareness of accessing medicines advice from community pharmacies; and (iii) enabling better discussions with patients from ethnic minority communities. Conclusions These recommendations have the potential to support community pharmacy services to overcome ethnic inequalities affecting medicines advice; service commissioners should consider these findings to best meet the needs of ethnic minority patients. Cultural competence training for community pharmacy staff could support the creation of pharmacies as inclusive healthcare settings. Collaborative working with ethnic minority communities could enable specific tailoring of medicines‐centred services to best meet their needs. Patient or Public Contribution The National Institute for Health Research (NIHR) and Newcastle University Patient and Public Involvement and Engagement group had extensive input in the study design and conceptualization. Seven patient champions were appointed to the steering group to ensure that the research was conducted, and findings were reported, with cultural competence. Trial Registration Not applicable.

Abstract Introduction Regular reviews of medications, including prescription reviews and adherence reviews, are vital to support pharmacological effectiveness and optimize health outcomes for patients. Despite being more likely to report a long‐term illness that requires medication when compared to their white counterparts, individuals from ethnic minority communities are less likely to engage with regular medication reviews, with inequalities negatively affecting their access. It is important to understand what barriers may exist that impact the access of those from ethnic minority communities and to identify measures that may act to facilitate improved service accessibility for these groups. Methods Semi‐structured interviews were conducted between June and August 2021 using the following formats as permitted by governmental COVID‐19 restrictions: in person, over the telephone or via video call. Perspectives on service accessibility and any associated barriers and facilitators were discussed. Interviews were audio‐recorded and transcribed verbatim. Reflexive thematic analysis enabled the development of themes. QSR NVivo (Version 12) facilitated data management. Ethical approval was obtained from the Health Research Authority (ref: 21/HRA/1426). Results In total 20 participants from ethnic minority communities were interviewed; these participants included 16 UK citizens, 2 refugees and 2 asylum seekers, and represented a total of 5 different ethnic groups. Three themes were developed from the data regarding the perceived barriers and facilitators affecting access to medication reviews and identified approaches to improve the accessibility of such services for ethnic minority patients. These centred on (1) building knowledge and understanding about medication reviews; (2) delivering medication review services; and (3) appreciating the lived experience of patients. Conclusion The results of this study have important implications for addressing inequalities that affect ethnic minority communities. Involving patients and practitioners to work collaboratively in coproduction approaches could enable better design, implementation and delivery of accessible medication review services that are culturally competent. Patient or Public Contribution The National Institute for Health Research Applied Research Collaboration and Patient and Public Involvement and Engagement group at Newcastle University supported the study design and conceptualization. Seven patient champions inputted to ensure that the research was conducted, and the findings were reported, with cultural sensitivity.

Background Regular daily nebulised antibiotics are widely used in managing bronchiectasis. This patient population typically has severe bronchiectasis requiring multiple other medications. Given that little is known about patients’ views and preferences for such therapies, this was the focus of our study. Methods To explore patient lived-experience using nebulised antibiotics, focus groups and semi-structured interviews were conducted with patients and carers; these were audio-recorded and transcribed to enable thematic analysis. QSR NVivo software facilitated data management. The themes developed from the qualitative data analysis were then used to co-design a questionnaire to capture attitudes and preferences towards nebulised therapy. Questionnaires were completed by patients and statistical analysis was performed. Ethical approval was obtained (13/WS/0036). Results The study's focus groups comprised 13 patients and carers, and 101 patients completed the questionnaire. Patients described nebulised therapy as an imposition on their daily routine, in turn affecting reported rates of adherence. Results demonstrated that 10% of all patients using nebulised antibiotics found these hard/very hard to administer. Further, 53% of participants strongly agreed/agreed that they would prefer an antibiotic delivered by an inhaler over a nebuliser, if it were as effective at preventing exacerbations. Notably, only 10% of participants wished to remain on nebulised therapy. Conclusions Inhaled antibiotics delivered via dry powder devices were deemed quicker and easier to use by patients. Providing they were at least as effective as current nebulised treatments, patients deemed inhaled antibiotics to be a preferable treatment option.

Abstract Introduction Healthcare inequalities and ethnicity are closely related. Evidence has demonstrated that patients from ethnic minority groups are more likely to report a long‐term illness than their white counterparts; yet, in some cases, minority groups have reported poorer adherence to prescribed medicines and may be less likely to access medicine services. Knowledge of the barriers and facilitators that impact ethnic minority access to medicine services is required to ensure that services are fit for purpose to meet and support the needs of all. Methods Semistructured interviews with healthcare professionals were conducted between October and December 2020, using telephone and video call‐based software. Perspectives on barriers and facilitators were discussed. Interviews were audio‐recorded and transcribed verbatim. Reflexive thematic analysis enabled the development of themes. QSR NVivo (Version 12) facilitated data management. Ethical approval was obtained from the Newcastle University Faculty of Medical Sciences Ethics Committee. Results Eighteen healthcare professionals were interviewed across primary, secondary and tertiary care settings; their roles spanned medicine, pharmacy and dentistry. Three themes were developed from the data regarding the perceived barriers and facilitators affecting access to medicine services for ethnic minority patients. These centred around patient expectations of health services; appreciating cultural stigma and acceptance of certain health conditions; and individually addressing communication and language needs. Conclusion This study provides much‐needed evidence relating to the barriers and facilitators impacting minority ethnic communities when seeking medicine support. The results of this study have important implications for the delivery of person‐centred care. Involving patients and practitioners in coproduction approaches could enable the design and delivery of culturally sensitive and accessible medicine services. Patient or Public Contribution The Patient and Public Involvement and Engagement (PPIE) group at Newcastle University had extensive input in the design and concept of this study before the research was undertaken. Throughout the work, a patient champion (Harpreet Guraya) had input in the project by ensuring that the study was conducted, and the findings were reported, with cultural sensitivity.

Abstract Background There is increasing interest in the role of community pharmacy in the early diagnosis and prevention of cancer. This study set out to examine how often community pharmacists (CPs) encourage patients to spot or respond to potential signs and symptoms of cancer, and how often they help people to make an informed decision about taking part in bowel cancer screening. Methods Data from 400 UK CPs, who completed the 2018 Cancer Research UK Healthcare Professional Tracker survey, were analysed. The primary outcomes were: ‘how often CPs encourage patients to spot or respond to potential signs and symptoms of cancer’ and ‘how often CPs encourage eligible people to make an informed decision to participate in bowel cancer screening’. Associations between behaviours and demographic and psychological variables (Capability, Opportunity and Motivation) were assessed using multivariate logistic regression. Results Most (n = 331, 82.8%) CPs reported occasionally, frequently or always encouraging patients to spot or respond to potential signs and symptoms of cancer, while only half (n = 203, 50.8%) reported occasionally, frequently or always helping people make an informed decision to participate in bowel cancer screening. Female sex (aOR: 3.20, 95%CI: 1.51, 6.81; p

IntroductionA high prevalence of diabetes and diabetes-related complications in people from minority ethnic communities in high income countries is of significant concern. Several studies have indicated low adherence rates to antidiabetic medication in ethnic minority groups. Poor adherence to antidiabetic medication leads to a higher risk of complications and potential mortality. This review aims to qualitatively explore the barriers to and facilitators of adherence to antidiabetic medication among ethnic minority groups in high-income countries.MethodsA comprehensive search of MEDLINE, Embase, CINAHL, PsycINFO, and Global Health databases for qualitative studies exploring the barriers to or facilitators of adherence to antidiabetic medication in minority ethnic groups was conducted from database inception to March 2023 (PROSPERO CRD42022320681). A quality assessment of the included studies was conducted using the Critical Appraisal Skills Programme (CASP) tool. Key concepts and themes from relevant studies were synthesised using a meta-ethnographic approach. The Grading of Recommendations Assessment, Development and Evaluation Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) approach was used to assess the Confidence in the review findings.ResultOf 13,994 citations screened, 21 studies that included primary qualitative studies were selected, each of which involved people from minority ethnic communities from eight high income countries. This qualitative evidence synthesis has identified three overarching themes around the barriers to and facilitators of adherence to antidiabetic medication among ethnic minority groups.: 1) cultural underpinnings, 2) communication and building relationships, and 3) managing diabetes during visiting home countries. Based on the GRADE-CERQual assessment, we had mainly moderate- and high-confidence findings.ConclusionMultiple barriers and facilitators of adherence to antidiabetic medication among people from minority ethnic communities in high-income countries have been identified. A medication adherence intervention focusing on identified barriers to adherence to antidiabetic medication in these communities may help in improving diabetes outcomes in these groups.

Objectives Adherence to prescribed medication is an essential component of diabetes management to obtain optimal outcomes. Understanding the relationship between medication adherence and ethnicity is key to optimising treatment for all people with different chronic illnesses, including those with diabetes. The aim of this review is to examine whether the adherence to antidiabetic medications differed by ethnicity among people with diabetes. Methods A systematic review was conducted of studies reporting adherence to antidiabetic medication amongst people from different ethnic groups. MEDLINE, Embase, CINAHL, and PsycINFO were searched from their inception to June 2022 for quantitative studies with a specific focus on studies assessing adherence to antidiabetic medications (PROSPERO: CRD42021278392). The Joanna Briggs Institute critical appraisal checklist and a second checklist designed for studies using retrospective databases were used to assess study quality. A narrative synthesis approach was used to summarize the results based on the medication adherence measures. Results Of 17,410 citations screened, 41 studies that included observational retrospective database research and cross-sectional studies were selected, each of which involved diverse ethnic groups from different settings. This review identified a difference in the adherence to antidiabetic medications by ethnicity in 38 studies, despite adjustment for several confounding variables that may otherwise explain these differences. Conclusion This review revealed that adherence to antidiabetic medication differed by ethnicity. Further research is needed to explore the ethnicity-related factors that may provide an explanation for these disparities.

BackgroundA patient’s capability, motivation, and opportunity to change their lifestyle are determinants of successful outcomes following bariatric surgery. Lifestyle changes before and after surgery, including improved dietary intake and physical activity levels, have been associated with greater postsurgical weight loss and improved long-term health. Integrating patient-centered digital technologies within the bariatric surgical pathway could form part of an innovative strategy to promote and sustain healthier behaviors, and provide holistic patient support, to improve surgical success. Previous research focused on implementing digital technologies and measuring effectiveness in surgical cohorts. However, there is limited work concerning the desires, suggestions, and reflections of patients undergoing bariatric surgery. This qualitative investigation explores patients’ perspectives on technology features that would support behavior changes during the pre- and postoperative periods, to potentially maintain long-term healthy lifestyles following surgery. ObjectiveThis study aims to understand how digital technologies can be used to support patient care during the perioperative journey to improve weight loss outcomes and surgical success, focusing on what patients want from digital technologies, how they want to use them, and when they would be of most benefit during their surgical journey. MethodsPatients attending bariatric surgery clinics in one hospital in the North of England were invited to participate. Semistructured interviews were conducted with purposively sampled pre- and postoperative patients to discuss lifestyle changes and the use of digital technologies to complement their care. The interviews were audio recorded and transcribed verbatim. Reflexive thematic analysis enabled the development of themes from the data. Ethical approval was obtained from the National Health Service Health Research Authority. ResultsA total of 20 patients were interviewed (preoperative phase: 40% (8/20); postoperative phase: 60% (12/20). A total of 4 overarching themes were developed and related to the optimization of technology functionality. These centered on providing tailored content and support; facilitating self-monitoring and goal setting; delivering information in an accessible, trusted, and usable manner; and meeting patient information-seeking and engagement needs during the surgical pathway. Functionalities that delivered personalized feedback and postoperative follow-up were considered beneficial. Individualized goal setting functionality could support a generation of digitally engaged patients with bariatric conditions as working toward achievable targets was deemed an effective strategy for motivating behavior change. The creation of digital package of care checklists between patients and clinicians was a novel finding from this study. ConclusionsPerceptions of patients undergoing bariatric surgery validated the integration of digital technologies within the surgical pathway, offering enhanced connectedness and support. Recommendations are made relating to the design, content, and functionality of digital interventions to best address the needs of this cohort. These findings have the potential to influence the co-design and integration of person-centered, perioperative technologies.

Abstract Evidence strongly supports improved outcomes following surgery when patients are more physically active, have better dietary intake, or are generally fitter prior to surgery. Having an operation is a major life event for patients, and many are not educated around what they can do as individuals to aid a speedier and more successful recovery following their operation. What if there was a time point before surgery where clinicians could inspire patients to adjust their lifestyles for the better, in order to see fewer complications after surgery? This is where the concept of teachable moments comes into play. This commentary explores the concept of teachable moments and their value in surgical patient care and discusses the potentially under-utilized opportunities on hand to the surgical multidisciplinary team to remotely support patients using digital health technologies.

The popularity of genealogical research is linked to the growth of online genealogy services such as Ancestry.com, which, as of 2020, has over three million paid subscribers. Another 18 million people have taken genetic ancestry tests through the company’s subsidiary, AncestryDNA. This article interrogates how Ancestry presents information on race and ethnicity to users, asking if it is possible for researchers to build a critical racial identity using Ancestry’s services. Applying an understanding of whiteness that comes from critical race studies, the article examines the way race, and whiteness in particular, is presented in the business’s marketing, web features, and products such as AncestryDNA. These examinations reveal a company selling customers family history narratives that comport with the mythology of American egalitarianism, while at the same time essentializing race and ethnicity. The implications of these findings are significant for information professionals because Ancestry relies on partnerships with libraries and archives to supply material for the website’s research database. These partnerships compel archivists and librarians to scrutinize Ancestry’s information ethics. The article calls for further discussion and research into how information professionals can be agents for change in how race and ethnicity are treated in online genealogy spaces.

We study the association between fiscal policy and subjective wellbeing using fiscal data on 34 countries across 129 country-years, combined with over 170,000 people’s subjective wellbeing scores. While past research has found that ‘distortionary taxes’ (e.g. income taxes) are associated with slow growth relative to ‘non-distortionary’ taxes (GST/VAT), we find that distortionary taxes are associated with higher levels of subjective wellbeing than non-distortionary taxes. This relationship holds when we control for macro-economic variables and country fixed effects. If this relationship is causal, it would offer an explanation as to why governments pursue these policies that harm economic growth. We find that richer people’s subjective wellbeing is less harmed by indirect taxes than people with lower incomes, while “unproductive expenditure” is associated with higher wellbeing for the middle class relative to others, possibly reflecting middle class capture. We see little evidence for differential effects of fiscal policy on people living in different sized settlements. Devolving a portion of expenditure to subnational government is associated with higher subjective wellbeing but devolving tax collection to subnational government is associated with monotonically lower subjective wellbeing.

Hanatoxin 1 (HaTx1) is a polypeptide toxin isolated from spider venoms. HaTx1 inhibits the voltage-gated potassium channel kv2.1 potently with nanomolar affinities. Its receptor site has been shown to contain the S3b-S4a paddle of the voltage sensor (VS). Here, the binding of HaTx1 to the VSs of human Kv2.1 in the open and resting states are examined using a molecular docking method and molecular dynamics. Molecular docking calculations predict two distinct binding modes for the VS in the resting state. In the two binding modes, the toxin binds the S3b-S4a from S2 and S3 helices, or from S1 and S4 helices. Both modes are found to be stable when embedded in a lipid bilayer. Only the mode in which the toxin binds the S3b-S4a paddle from S2 and S3 helices is consistent with mutagenesis experiments, and considered to be correct. The toxin is then docked to the VS in the open state, and the toxin-VS interactions are found to be less favorable. Computational mutagenesis calculations performed on F278R and E281K mutant VSs show that the mutations may reduce toxin binding affinity by weakening the non-bonded interactions between the toxin and the VS. Overall, our calculations reproduce a wide range of experimental data, and suggest that HaTx1 binds to the S3b-S4a paddle of Kv2.1 from S2 and S3 helices.

Several subtypes of voltage-gated Na+ (NaV) channels are important targets for pain management. μ-Conotoxins isolated from venoms of cone snails are potent and specific blockers of different NaV channel isoforms. The inhibitory effect of μ-conotoxins on NaV channels has been examined extensively, but the mechanism of toxin specificity has not been understood in detail. Here the known structure of μ-conotoxin PIIIA and a model of the skeletal muscle channel NaV1.4 are used to elucidate elements that contribute to the structural basis of μ-conotoxin binding and specificity. The model of NaV1.4 is constructed based on the crystal structure of the bacterial NaV channel, NaVAb. Six different binding modes, in which the side chain of each of the basic residues carried by the toxin protrudes into the selectivity filter of NaV1.4, are examined in atomic detail using molecular dynamics simulations with explicit solvent. The dissociation constants (Kd) computed for two selected binding modes in which Lys9 or Arg14 from the toxin protrudes into the filter of the channel are within 2 fold; both values in close proximity to those determined from dose response data for the block of NaV currents. To explore the mechanism of PIIIA specificity, a double mutant of NaV1.4 mimicking NaV channels resistant to μ-conotoxins and tetrodotoxin is constructed and the binding of PIIIA to this mutant channel examined. The double mutation causes the affinity of PIIIA to reduce by two orders of magnitude.

Functional adult literacy interventions have been regarded for many decades by policy makers as an effective way of imparting health knowledge. Supported by research on the statistical relationships between women's literacy rates and health indicators, this dominant policy discourse is based on assumptions that non-literate women lack understanding and confidence, and that formal programmes and institutions constitute the main sites of learning. Proposing a broader conceptualisation of literacy as a social practice and of health as connected with social justice, this article draws on policy analysis and the authors' earlier research in Nepal to re-examine the relationship between gender, literacy and health. By comparing health and literacy approaches used within the education and health sectors and taking account of new and indigenous informal learning practices, the article points to ways of investigating the complex interaction of factors that influence inequalities in gender and health at community level.

Nurture groups (NGs) are recognised as an effective early practice for the development of children with social, emotional and behavioural difficulties (SEBD). Early educators outline enhanced social and emotional development, academic attainment and secure attachments with peers and adults. Nevertheless, there is limited data reporting on the efficacy of this approach for children with autism spectrum disorder (ASD). This small-scale phenomenological study reports Scottish primary teachers' experiences of NGs in promoting wellbeing in autistic pupils. Data were gathered through an online questionnaire. Results were mixed in that they suggest some significant progress in academic attainment, with slight improvements in emotional and social functioning. After the inclusion of pupils in NGs, continued positive impact appeared to persist with both difficulties in emotional expression and in forming secure attachments with peers and adults. This indicates that for good NG practice for autistic pupils there is a need for structural modifications and curriculum adaptations to create an 'autism-friendly' environment.