FLAG-KRAS4B as a Model System for KRAS4B Proteoform and PTM Evaluation by Mass Spectrometry.

Prior analysis of intact and modified protein forms (proteoforms) of KRAS4B isolated from cell lines and tumor samples by top-down mass spectrometry revealed the presence of novel posttranslational modifications (PTMs) and potential evidence of context-specific KRAS4B modifications. However, low endogenous proteoform signal resulted in ineffective characterization, making it difficult to visualize less abundant PTMs or perform follow-up PTM validation using standard proteomic workflows. The NCI RAS Initiative has developed a model system, whereby KRAS4B bearing an N-terminal FLAG tag can be stably expressed within a panel of cancer cell lines. Herein, we present a method for combining immunoprecipitation with complementary proteomic methods to directly analyze N-terminally FLAG-tagged KRAS4B proteoforms and PTMs. We provide detailed protocols for FLAG-KRAS4B purification, proteoform analysis by targeted top-down LC-MS/MS, and validation of abundant PTMs by bottom-up LC-MS/MS with example results.

Quality Control of an Isogenic H/N/KRAS-Less Mouse Embryonic Fibroblast Cell Line Panel.

Isogenic H/N/KRAS-less mouse embryonic fibroblast (MEF) cell lines have been developed to assist in cell-based assays of RAS inhibitors. The quality control assessment of a panel of these isogenic MEFs is described here, with a focus on ensuring the proper insertion of the desired mutant RAS transgene, a determination of gene copy number, and an investigation of potential off-target mutations which could lead to phenotypes which are undesired in downstream experiments. Using this suite of quality control tools, a MEF cell line can be readily validated, and researchers can be assured of the rationale for an observed phenotype.

How can asset-based approaches reduce inequalities? Exploring processes of change in England and Spain.

Initiatives to promote health and reduce inequalities in place-based communities have increasingly adopted asset-based approaches (ABAs). However, the processes through which such initiatives might reduce inequalities are not well understood, and evidence of their impact on health is still limited. This study aimed to understand how ABAs can impact practices, relationships and the redistribution of resources to reduce health inequalities in and between less advantaged neighbourhoods. Qualitative research was conducted in two settings (England and Spain) where similar asset-based initiatives, aimed at training community members to become health promoters, were being implemented. Data were collected using theory of change workshops, 120 hours of observations and semi-structured interviews with 44 stakeholders (trained community members, voluntary and community sector organizations' workers and health professionals). A thematic analysis informed by systems thinking was carried out. Three main processes of change were identified: first, 'enabling asset-based thinking' defined as supporting people to adopt a view that values their own resources and people's skills and expertise. Second, 'developing asset-based capacities', described as developing personal skills, knowledge, self-confidence and relationships underpinned by asset-based thinking. Finally, 'changing decision-making and wider health determinants through ABAs' referred to achieving changes in neighbourhoods through mobilizing the asset-based capacities developed. These processes were associated with changes at an individual level, with potential to contribute to reducing inequalities through supporting individual empowerment and social capital. However, contextual factors were found key to enable or hinder changes in the neighbourhoods and acted as barriers to processes of collective empowerment, thus limiting ABAs' impact on health inequalities.

Extra virgin olive oil improves HDL lipid fraction but not HDL-mediated cholesterol efflux capacity: a double-blind, randomised, controlled, cross-over study (OLIVAUS).

Olive oil (OO) polyphenols have been shown to improve HDL anti-atherogenic function, thus demonstrating beneficial effects against cardiovascular risk factors. The aim of the present study was to investigate the effect of extra virgin high polyphenol olive oil (HPOO) v. low polyphenol olive oil (LPOO) on the capacity of HDL to promote cholesterol efflux in healthy adults. In a double-blind, randomised cross-over trial, fifty participants (aged 38·5 (sd 13·9) years, 66 % females) were supplemented with a daily dose (60 ml) of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for 3 weeks. Following a 2-week washout period, participants crossed over to the alternate treatment. Serum HDL-cholesterol efflux capacity, circulating lipids (i.e. total cholesterol, TAG, HDL, LDL) and anthropometrics were measured at baseline and follow-up. No significant between-group differences were observed. Furthermore, no significant changes in HDL-cholesterol efflux were found within either the LPOO and HPOO treatment arms; mean changes were 0·54 % (95 % CI (0·29, 1·37)) and 0·10 % (95 % CI (0·74, 0·94)), respectively. Serum HDL increased significantly after LPOO and HPOO intake by 0·13 mmol/l (95 % CI (0·04, 0·22)) and 0·10 mmol/l (95 % CI (0·02, 0·19)), respectively. A small but significant increase in LDL of 0·14 mmol/l (95 % CI (0·001, 0·28)) was observed following the HPOO intervention. Our results suggest that additional research is warranted to further understand the effect of OO with different phenolic content on mechanisms of cholesterol efflux via different pathways in multi-ethnic populations with diverse diets.

Place, health and dis/advantage: A sociomaterial analysis.

The substantial literature on interactions between places/spaces and well-being/health often differentiate between physical and social aspects of geographical location. This paper sidesteps this dualism, instead considering places as sociomaterial assemblages of human and non-human materialities. It uses this posthuman and 'new materialist' perspective to explore how place-assemblages affect human capacities, in terms of both health and social dis/advantage. Based on secondary analysis of interview data on human/place interactions, it analyses the physical, sociocultural, psychological and emotional effects of place-assemblages, assessing how these produce opportunities for, and constraints upon human bodies. It than assesses how these emergent capacities affect both social dis/advantage and well-being. This analysis of how place-assemblages contribute positively or negatively to health and dis/advantage offers possibilities for further research and for social and public health policy.

An analysis of English national policy approaches to health inequalities: 'transforming children and young people's mental health provision' and its consultation process.

BACKGROUND: A national policy for England, published in 2017, entitled 'Transforming Children and Young People's Mental Health Provision' aimed to address the increasing prevalence mental health problems in children and tackle inequalities. In the context of this policy's implementation as ongoing and the effects of the Covid-19 pandemic, the need for appropriate, timely and ongoing national government commitment is vital. METHODS: A narrative review using a problem representation evaluation [1], we critiqued the policy and related consultation documents using a social determinants of health perspective. We also reviewed wider policy discourses through engaging with stakeholder responses, providing an innovative methodological contribution to scholarship on public health policy and health inequalities. RESULTS: We found absences and oversights in relation to inequalities (most notably the lack of acknowledgement that mental health can cause inequalities), access, workforce capacity, and the impacts of cuts and austerity on service provision. We suggest these inadequacies may have been avoided if stakeholder responses to the consultation process had been more meaningfully addressed. We illustrate how 'problems' are discursively created through the process of policy development, justified using specific types of evidence, and that this process is politically motivated. Local policy makers have a critical role in translating and adapting national policy for their communities but are constrained by absences and oversights in relation to health inequalities. CONCLUSIONS: This narrative review illustrates how policy discourse frames and produces 'problems', and how the evidence used is selected and justified politically. This review contributes to the existing transdisciplinary field of knowledge about how using methods from political and social science disciplines can reveal new insights when critiquing and influencing policy approaches to health inequalities.

An efficient and robust HPLC method to determine the sialylation levels of human epithelial cells.

Sialyltransferase, an enzyme responsible for attaching sialic acid to the cell surface, is reported to play a key role in cancer, making sialyltransferase a potential therapeutic target in drug development. Several methods have been developed to quantify sialic acids in biological samples however limitations exists and quantification in complex cell matrices lack investigation. Hence, this paper outlines a simple method to detect and quantify sialic acids in cancer cells for evaluating sialyltransferase activity of potential therapeutic compounds. An efficient method was developed using a reverse-phase ion-pairing HPLC-UV using triisopropanolamine as the ion-pairing agent with a C18 column. Neu5Ac was successfully eluted with the retention time 6.344 min with a flow rate of 0.4 mL/min. The proposed method was validated appropriately according to the AOAC guidelines (2013). This work demonstrates that the proposed method is not only relatively simple but also cost and time effective compared to pre-existing methods to successfully determine both free and protein-bound Neu5Ac in a complex cancer cell matrix. Furthermore, by applying the proposed method, a statistically significant decrease was observed for both HeLa and HuCCT1 cell lines with the application of deoxycholic acid-a known sialyltransferase inhibitor. Hence, the proposed method seems promisingly applicable to evaluate the effectiveness of potential sialyltransferase inhibitors.

Extra virgin olive oil high in polyphenols improves antioxidant status in adults: a double-blind, randomized, controlled, cross-over study (OLIVAUS).

PURPOSE: Olive oil polyphenols have been associated with cardiovascular health benefits. This study examined the antioxidant and anti-inflammatory effect of extra-virgin high polyphenol olive oil (HPOO) vs. low polyphenol olive oil (LPOO) in healthy Australian adults. METHODS: In a double-blind cross-over trial, 50 participants (aged 38.5 ± 13.9 years, 66% females) were randomized to consume 60 mL/day of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for three weeks. Following a 2-week wash-out period, participants crossed-over to the alternate treatment. Plasma oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC), high-sensitivity C-reactive protein (hs-CRP) and anthropometrics were measured at baseline and follow-up. RESULTS: Fourty-three participants completed the study. Although there were no significant differences between treatments in the total sample, plasma ox-LDL decreased by 6.5 mU/mL (95%CI - 12.4 to - 0.5) and TAC increased by 0.03 mM (95% CI 0.006-0.05) only in the HPOO arm. Stratified analyses were also performed by cardiovascular disease risk status defined by abdominal obesity (WC > 94 cm in males, > 80 cm in females) or inflammation (hs-CRP > 1 mg/L). In the subgroup with abdominal obesity, ox-LDL decreased by 13.5 mU/mL (95% CI - 23.5 to - 3.6) and TAC increased by 0.04 mM (95% CI 0.006-0.07) only after HPOO consumption. In the subgroup with inflammation, hs-CRP decreased by 1.9 mg/L (95% CI - 3.7 to -0.1) only in the HPOO arm. CONCLUSIONS: Although there were no significant differences between treatments, the changes observed after HPOO consumption demonstrate the antioxidant and anti-inflammatory effect of this oil, which is more pronounced in adults with high cardiometabolic risk (Clinical Trial Registration: ACTRN12618000706279).

A critique of the English national policy from a social determinants of health perspective using a realist and problem representation approach: the 'Childhood Obesity: a plan for action' (2016, 2018, 2019).

BACKGROUND: The UK government released Chapter 1 of the 'Childhood Obesity: a plan for action' (2016), followed by Chapter 2 (2018) and preliminary Chapter 3 was published for consultation in 2019 (hereon collectively 'The Policy'). The stated policy aims were to reduce the prevalence of childhood obesity in England, addressing disparities in health by reducing the gap (approximately two-fold) in childhood obesity between those from the most and least deprived areas. METHODS: Combining a realist approach with an analysis of policy discourses, we analysed the policies using a social determinants of health (SDH) perspective (focusing on socio-economic inequalities). This novel approach reveals how the framing of policy 'problems' leads to particular approaches and interventions. RESULTS: While recognising a social gradient in relation to obesity measures, we critique obesity problem narratives. The Policy included some upstream, structural approaches (e.g. restrictions in food advertising and the soft-drinks industry levy). However, the focus on downstream individual-level behavioural approaches to reduce calorie intake and increase physical activity does not account for the SDH and the complexity and contestedness of 'obesity' and pays insufficient attention to how proposals will help to reduce inequalities. Our findings illustrate that individualising of responsibility to respond to what wider evidence shows is structural inequalities, can perpetuate damaging narratives and lead to ineffective interventions, providing caution to academics, practitioners and policy makers (local and national), of the power of problem representation. Our findings also show that the problem framing in The Policy risks reducing important public health aims to encourage healthy diets and increase opportunities for physical activity (and the physical and mental health benefits of both) for children to weight management with a focus on particular children. CONCLUSIONS: We propose an alternative conceptualisation of the policy 'problem', that obesity rates are illustrative of inequality, arguing there needs to be policy focus on the structural and factors that maintain health inequalities, including poverty and food insecurity. We hope that our findings can be used to challenge and strengthen future policy development, leading to more effective action against health inequalities and intervention-generated inequalities in health.

Exploring the local policy context for reducing health inequalities in children and young people: an in depth qualitative case study of one local authority in the North of England, UK.

BACKGROUND: Improving children and young people's (CYP) health and addressing health inequalities are international priorities. Reducing inequalities is particularly pertinent in light of the Covid-19 outbreak which has exacerbated already widening inequalities in health. This study aimed to explore understandings of inequality, the anticipated pathways for reducing inequalities among CYP and key factors affecting the development and implementation of policy to reduce inequalities among CYP at a local level. METHODS: We carried out a qualitative case study of one local government region in the North of England (UK), comprising semi structured interviews (n = 16) with service providers with a responsibility for child health, non-participant observations of key meetings (n = 6 with 43 participants) where decisions around child health are made, and a local policy documentation review (n = 11). We employed a novel theoretical framework, drawing together different approaches to understanding policy, to guide our design and analysis. RESULTS: Participants in our study understood inequalities in CYP health almost exclusively as socioeconomically patterned inequalities in health practices and outcomes. Strategies which participants perceived to reduce inequalities included: preventive support and early intervention, an early years/whole family focus, targeted working in local areas of high deprivation, organisational integration and whole system/place-based approaches. Despite demonstrating a commitment to a social determinants of health approach, efforts to reduce inequalities were described as thwarted by the prevalence of poverty and budget cuts which hindered the ability of local organisations to work together. Participants critiqued national policy which aimed to reduce inequalities in CYP health for failing to recognise local economic disparities and the interrelated nature of the determinants of health. CONCLUSIONS: Despite increased calls for a 'whole systems' approach to reducing inequalities in health, significant barriers to implementation remain. National governments need to work towards more joined up policy making, which takes into consideration regional disparities, allows for flexibility in interpretation and addresses the different and interrelated social determinants of health. Our findings have particular significance in light of Covid-19 and indicate the need for systems level policy responses and a health in all policies approach.

Non-human matter, health disparities and a thousand tiny dis/advantages.

The materialist thread within health sociology has observed a clear gradient linking inequalities in health with measures of social class and poverty. More recently, Bourdieu's approach to social class complemented the 'economic capital' of Marxist analysis with 'symbolic' capitals such as 'social' and 'cultural'. However, efforts to assess how symbolic capital interacts with health disparities reveal complex or contradictory effects. In this paper, we re-materialise the study of health and social position via a new materialist focus on the interactions between humans and non-human matter (NHM). We analyse empirical data to disclose the range of human/NHM interactions in daily life, and how these affect people's health status. These interactions establish physical, psychological and social opportunities and constraints on what human bodies can do, contributing to relative advantages and disadvantages. We argue for a revised materialist understanding of sociomaterial position as constituted by a 'thousand tiny dis/advantages', and suggest that health and wellbeing are inextricably linked to dis/advantage.

A systems map of the determinants of child health inequalities in England at the local level.

Children and young people in the UK have worse health outcomes than in many similar western countries and child health inequalities are persistent and increasing. Systems thinking has emerged as a promising approach to addressing complex public health issues. We report on a systems approach to mapping the determinants of child health inequalities at the local level in England for young people aged 0-25, and describe the resulting map. Qualitative group concept mapping workshops were held in two contrasting English local authorities with a range of stakeholders: professionals (N = 35); children and young people (N = 33) and carers (N = 5). Initial area maps were developed, and augmented using data from qualitative interviews with professionals (N = 16). The resulting local maps were reviewed and validated by expert stakeholders in each area (N = 9; N = 35). Commonalities between two area-specific system maps (and removal of locality-specific factors) were used to develop a map that could be applied in any English local area. Two rounds of online survey (N = 21; N = 8) experts in public health, local governance and systems science refined the final system map displaying the determinants of child health inequalities. The process created a map of over 150 factors influencing inequalities in health outcomes for children aged 0-25 years at the local area level. The system map has six domains; physical environment, governance, economic, social, service, and personal. To our knowledge this is the first study taking a systems approach to addressing inequalities across all aspects of child health. The study shows how group concept mapping can support systems thinking at the local level. The resulting system map illustrates the complexity of factors influencing child health inequalities, and it may be a useful tool in demonstrating to stakeholders the importance of policies that tackle the systemic drivers of child health inequalities beyond those traditionally associated with public health.

Cardiovascular risk factor mediation of the effects of education and Genetic Risk Score on cardiovascular disease: a prospective observational cohort study of the Framingham Heart Study.

OBJECTIVES: Level of education and genetic risk are key predictors of cardiovascular disease (CVD). While several studies have explored the causal mechanisms of education effects, it remains uncertain to what extent genetic risk is mediated by established CVD risk factors. This study sought to investigate this and explored the mediation of education and genetic effects on CVD by established cardiovascular risk factors in the Framingham Heart Study (FHS). DESIGN: Prospective observational cohort study. PARTICIPANTS: 7017 participants from the FHS. SETTING: Community-based cohort of adults in Framingham, Massachusetts, USA. PRIMARY OUTCOME MEASURE: Incident CVD. The total effects of education and genetic predisposition using a 63-variant genetic risk score (GRS) on CVD, as well as those mediated by established CVD risk factors, were assessed via mediation analysis based on the counterfactual framework using Cox proportional hazards regression models. RESULTS: Over a median follow-up time of 12.0 years, 1091 participants experienced a CVD event. Education and GRS displayed significant associations with CVD after adjustment for age and sex and the established risk factors smoking, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), body mass index, systolic blood pressure (SBP) and diabetes. For education effects, smoking, HDL-C and SBP were estimated to mediate 18.8% (95% CI 9.5% to 43%), 11.5% (95% CI 5.7% to 29.0%) and 4.5% (95% CI 1.6% to 13.3%) of the total effect of graduate degree, respectively, with the collective of all risk factors combined mediating 38.5% (95% 24.1% to 64.9%). A much smaller proportion of the effects of GRS were mediated by established risk factors combined (17.6%, 95% CI 2.4% to 35.7%), with HDL-C and TC mediating 11.5% (95% CI 6.2% to 21.5%) and 3.1% (95% CI 0.2% to 8.3%), respectively. CONCLUSIONS: Unlike education inequalities, established risk factors mediated only a fraction of GRS effects on CVD. Further research is required to elucidate the underlying causal mechanisms of genetic contributions to CVD.

Power, control, communities and health inequalities III: participatory spaces-an English case.

This article-third in a series of three-uses theoretical frameworks described in Part 1, and empirical markers reported in Part 2, to present evidence on how power dynamics shifted during the early years of a major English community empowerment initiative. We demonstrate how the capabilities disadvantaged communities require to exercise collective control over decisions/actions impacting on their lives and health (conceptualized as emancipatory power) and the exercise of power over these communities (conceptualized as limiting power) were shaped by the characteristics of participatory spaces created by and/or associated with this initiative. Two main types of participatory spaces were identified: governance and sense-making. Though all forms of emancipatory power emerged in all spaces, some were more evident in particular spaces. In governance spaces, the development and enactment of 'power to' emerged as residents made formal decisions on action, allocated resources and managed accountability. Capabilities for alliance building-power with-were more likely to emerge in these spaces, as was residents' resistance to the exercise of institutional power over them. In contrast, in sense-making spaces residents met informally and 'made sense' of local issues and their ability to influence these. These processes led to the development of power within capabilities and power to resist stigmatizing forms of productive power. The findings highlight the importance of designing community initiatives that: nurture diverse participatory spaces; attend to connectivity between spaces; and identify and act on existing power dynamics undermining capabilities for collective control in disadvantaged communities.

Randomized controlled trial comparing Parent Led Therapist Supervised Articulation Therapy (PLAT) with routine intervention for children with speech disorders associated with cleft palate.

BACKGROUND: A total of 68% of pre-school children with cleft palate have speech problems requiring speech therapy. There is a lack of access to regular targeted therapy. Parent training leads to positive outcomes in early communication skills in cleft palate and non-cleft speech disorders. Connected health has been used to address inadequate access to therapy, providing intervention to those who would not otherwise receive therapy. AIMS: To evaluate the speech, activity and participation outcomes of Parent Led, Therapist Supervised, Articulation Therapy (PLAT) compared with routine speech therapy intervention in parent-child dyads. METHODS & PROCEDURES: A total of 44 children, aged 2.9-7.5 years, were included in a two-centre, two-phase randomized controlled trial. Informed consent and assent were obtained. Participants and speech and language therapists (SLTs) were unblinded to the groups. Parents, in the parent-trained group (n = 23), attended 2 days' training, received a detailed speech therapy programme, and undertook intervention over 12 weeks supported by the cleft specialist SLT using FaceTime and one face-to-face session. In the control arm (n = 21), parent-child dyads received six therapy sessions over 12 weeks with a research SLT, comparable with usual care. Speech recordings were undertaken pre- and post-intervention. Percent consonant correct (PCC) was analysed by external SLTs blinded to the time and group. Activity and participation were measured using the Intelligibility in Context Scale (ICS) and Focus on Outcomes for Children Under Six (FOCUS) questionnaire. OUTCOMES & RESULTS: There was no evidence of an interaction between Time and Group or an overall statistical difference between groups for PCC scores. There was a statistically significant difference over time for both groups (words: p < 0.002; confidence interval (CI) = 9.38-16.27; d = 0.57; sentences: p < 0.002; CI = 16.04-25.97; d = 0.23). Effect sizes were medium for words and small for sentences. For intelligibility and participation, there was no evidence of an interaction between Time and Group or an overall statistical difference between groups. A statistically significant difference over time was found for intelligibility (F = 29.97, d.f. = 1, 42, p < 0.001, 95 % CI = 1.45-3.15 d = 0.46) and for participation (F = 14.19, d.f. = 1, 41, p < 0.001 95% CI = 7.63-25.03; d = 0.36) with FOCUS results indicating clinically meaningful (parent-led group) and significant (control group) change in participation. CONCLUSIONS & IMPLICATIONS: PLAT can be as effective as routine care in changing speech, activity and participation outcomes for children with cleft palate, when supported by a specialist cleft SLT using connected health. What this paper adds What is already known on this subject Over 50% of children with cleft palate require speech therapy. However, there is a lack of timely, accessible speech therapy services in the UK and Ireland. Previous studies have shown that parents can deliver therapy effectively, and that connected health can support the delivery of speech therapy. This study aims to provide evidence that parent-led therapy with the supervision of a specialist cleft therapist using FaceTime is effective. What this paper adds to existing knowledge This randomized controlled trial indicates that parents can be trained to deliver therapy for children with cleft palate speech disorders, under the supervision of an SLT. This approach results in improved speech, activity and participation outcomes similar to routine care. What are the potential or actual clinical implications of this work? This study indicates that both parent-led articulation therapy and routine care showed meaningful gains in speech, activity and participation, and that parent-led articulation therapy when supported by a cleft SLT using connected health could be an additional service delivery model for children with cleft palate speech disorders.

Galectin-3 deficiency in pregnancy increases the risk of fetal growth restriction (FGR) via placental insufficiency.

Fetal growth restriction (FGR) is the most common pregnancy complication in developed countries. Pregnancies affected by FGR, frequently concur with complications and high risk of neonatal morbidity and mortality. To date, no approved treatment is available for pregnant women affected with FGR. The objective of this study was to investigate the contribution of galectin-3 (gal-3), a ß-galactoside binding protein involved in pregnancy, placental function and fetal growth. We demonstrated that lack of gal-3 during mouse pregnancy leads to placental dysfunction and drives FGR in the absence of a maternal preeclampsia syndrome. Analysis of gal-3 deficient dams revealed placental inflammation and malperfusion, as well as uterine natural killer cell infiltration with aberrant activation. Our results also show that FGR is associated with a failure to increase maternal circulating gal-3 levels during the second and third trimester in human pregnancies. Placentas from human pregnancies affected by FGR displayed lower gal-3 expression, which correlated with placental dysfunction. These data highlight the importance of gal-3 in the promotion of proper placental function, as its absence leads to placental disease and subsequent FGR.

Membrane interactions of the globular domain and the hypervariable region of KRAS4b define its unique diffusion behavior.

The RAS proteins are GTP-dependent switches that regulate signaling pathways and are frequently mutated in cancer. RAS proteins concentrate in the plasma membrane via lipid-tethers and hypervariable region side-chain interactions in distinct nano-domains. However, little is known about RAS membrane dynamics and the details of RAS activation of downstream signaling. Here, we characterize RAS in live human and mouse cells using single-molecule-tracking methods and estimate RAS mobility parameters. KRAS4b exhibits confined mobility with three diffusive states distinct from the other RAS isoforms (KRAS4a, NRAS, and HRAS); and although most of the amino acid differences between RAS isoforms lie within the hypervariable region, the additional confinement of KRAS4b is largely determined by the protein's globular domain. To understand the altered mobility of an oncogenic KRAS4b, we used complementary experimental and molecular dynamics simulation approaches to reveal a detailed mechanism.

Acculturation and Food Intake Among Ghanaian Migrants in Europe: Findings From the RODAM Study.

OBJECTIVE: This study examined the role of migration and acculturation in the diet of Ghanaian migrants in Europe by (1) comparing food intake of Ghanaian migrants in Europe with that of Ghanaians living in Ghana and (2) assessing the association between acculturation and food intake. DESIGN: Data from the cross-sectional multicenter study Research on Obesity and Diabetes among African Migrants were used. Food intake was assessed using a Ghana-specific food propensity questionnaire (134 items and 14 food groups); foods were grouped based on a model of dietary change proposed by Koctürk-Runefors. SETTING: Ghana, London, Amsterdam, and Berlin. PARTICIPANTS: A total of 4,534 Ghanaian adults living in Ghana and Europe, with complete dietary data. Of these, 1,773 Ghanaian migrants had complete acculturation data. MAIN OUTCOME MEASURE: Food intake (the weighted intake frequency per week of food categories). ANALYSIS: Linear regression. RESULTS: Food intake differed between Ghanaians living in Ghana and Europe. Among Ghanaian migrants in Europe, there were inconsistent and small associations between acculturation and food intake, except for ethnic identity, which was consistently associated with intake only of traditional staples. CONCLUSIONS AND IMPLICATIONS: Findings indicate that migration is associated with dietary changes that cannot be fully explained by ethnic, cultural, and social acculturation. The study provides limited support to the differential changes in diet suggested by the Koctürk-Runefors' model of dietary change.

A systematic scoping review of asset-based approaches to promote health in communities: development of a framework.

Asset-based approaches to health promotion have become increasingly popular as a way to tackle health inequalities by empowering people in more disadvantaged communities to use local resources and increase control over health and its determinants. However, questions remain about how they work in practice. This article presents the findings from a systematic scoping review of the empirical literature on asset-based approaches in communities. The aim was to identify the key elements of asset-based approaches, and how they are operationalised in interventions aimed at promoting health and reducing inequalities in local communities. Four databases were searched (Medline, PsycINFO, CINAHL, ASSIA) and papers were included if they described interventions explicitly adopting an asset-based approach but excluded if limited to asset identification. Thirty articles were included in the review. Data were extracted on the type of assets that the intervention built upon, how assets were mobilised, the expected outcomes and evaluation methods. A framework is presented that synthesises the key characteristics of asset-based interventions to promote health in communities. Three main approaches to mobilising assets were identified in the literature: (A) connecting assets, (B) raising awareness of assets and (C) enabling assets to thrive. It is argued that asset-based approaches to health promotion take a wide variety of forms, making it difficult to anticipate outcomes and to evaluate interventions. The framework presented here can be used to better understand the processes through which asset-based approaches work in practice to promote health and reduce inequalities.