Systems thinking for local food environments: a participatory approach identifying leverage points and actions for healthy and sustainable transformations.

Background: Current local food environments encourage poor diets, posing a significant threat to public and planetary health. Acknowledging and addressing its inherent complexity is vital to making meaningful improvements to the food environment. Using a participatory approach with local stakeholders, this study aims to gain insight into the factors and mechanisms underlying the local food environment and to identify leverage points and system-based actions to foster healthy and sustainable local food environments.

Mutant TP53 switches therapeutic vulnerability during gastric cancer progression within interleukin-6 family cytokines.

Although aberrant activation of the KRAS and PI3K pathway alongside TP53 mutations account for frequent aberrations in human gastric cancers, neither the sequence nor the individual contributions of these mutations have been clarified. Here, we establish an allelic series of mice to afford conditional expression in the glandular epithelium of Kras;Pik3ca or Trp53 and/or ablation of Pten or Trp53. We find that Kras;Pik3ca is sufficient to induce adenomas and that lesions progress to carcinoma when also harboring Pten deletions.

Unveiling viewpoints on national food environment policies in the Dutch newspaper discourse: an interpretative media content analysis.

Background: National food environment policies can contribute to the reduction of diet-related non-communicable diseases. Yet, their implementation in the Netherlands remains low. It has been hypothesized that the media can play a pivotal role in inducing spikes in policy attention, thereby shaping political action.

Applying systems thinking in youth-centred participatory action research for health promotion in an underserved neighbourhood.

Purpose: Childhood overweight is considered a complex problem influenced by a range of factors, including energy balance-related behaviours (EBRBs) and interacting drivers of these behaviours. There is growing support that applying a systems approach is required to tackle complex problems resulting in actions that attempt to change the system's dynamics. Additionally, a participatory approach is advocated to include the lived experience of the population of interest both in the understanding of the system as well as the development, implementation and evaluation of relevant actions.

Development of an action programme tackling obesity-related behaviours in adolescents: a participatory system dynamics approach.

System dynamics approaches are increasingly addressing the complexity of public health problems such as childhood overweight and obesity. These approaches often use system mapping methods, such as the construction of causal loop diagrams, to gain an understanding of the system of interest. However, there is limited practical guidance on how such a system understanding can inform the development of an action programme that can facilitate systems changes.

TCF-1 limits intraepithelial lymphocyte antitumor immunity in colorectal carcinoma.

Intraepithelial lymphocytes (IELs), including αβ and γδ T cells (T-IELs), constantly survey and play a critical role in maintaining the gastrointestinal epithelium. We show that cytotoxic molecules important for defense against cancer were highly expressed by T-IELs in the small intestine. In contrast, abundance of colonic T-IELs was dependent on the microbiome and displayed higher expression of TCF-1/ and a reduced effector and cytotoxic profile, including low expression of granzymes.

Real-life experiments in supermarkets to encourage healthy dietary-related behaviours: opportunities, challenges and lessons learned.

Background: Supermarkets are the primary source of food for many people yet their full potential as a setting to encourage healthy dietary-related behaviours remains underutilised. Sharing the experiences from research groups who have worked with supermarket chains to evaluate strategies that promote healthy eating could improve the efficiency of building such relationships and enhance the design quality of future research studies.

Methods: A collective case study approach was used to synthesise experiences of engaging and sustaining research collaborations with national supermarket chains to test the effectiveness of health-focused in-store interventions.

Is the transition from primary to secondary school a risk factor for energy balance-related behaviours? A systematic review.

Objective: The substantial changes in the physical and social environment during the transition from primary to secondary school may significantly impact adolescents' energy balance-related behaviours (i.e. dietary behaviour, sedentary behaviour, sleep behaviour and physical activity (PA)).

Discovering a pregnancy after 30 weeks: a qualitative study on explanations for unperceived pregnancy.

"Unperceived pregnancy" names the phenomenon when a person becomes pregnant unintentionally and is not aware of being pregnant. Scientific explanations are roughly based on two hypotheses: psychological and physiological. We aim to gain a better understanding of unperceived pregnancy by studying the perspectives of people who experienced an unperceived pregnancy and obstetric professionals.

Women with unwanted pregnancies, their psychosocial problems, and contraceptive use in primary care in Northern Netherlands: insights from a primary care registry database.

Introduction: Globally an estimated 1 in 16 women per year experience an unwanted pregnancy (UWP). In the Netherlands, general practitioners (GPs) play an important role in providing care for women with UWP; however, it is unknown how many of these women consult their GP about the pregnancy. UWPs are a major life experience with a possible influence on mental health.

Generation of gene-of-interest knockouts in murine organoids using CRISPR-Cas9.

Gene-of-interest knockout organoids present a powerful and versatile research tool to study a gene's effects on many biological and pathological processes. Here, we present a straightforward and broadly applicable protocol to generate gene knockouts in mouse organoids using CRISPR-Cas9 technology. We describe the processes of transient transfecting organoids with pre-assembled CRISPR-Cas9 ribonucleoprotein complexes, organoid cell sorting, and establishing clonal organoid culture pairs.

Tumor Growth Remains Refractory to Ablation in Host Macrophages.

Aberrant expression of the oncoprotein c-Myc (Myc) is frequently observed in solid tumors and is associated with reduced overall survival. In addition to well-recognized cancer cell-intrinsic roles of Myc, studies have also suggested tumor-promoting roles for Myc in cells of the tumor microenvironment, including macrophages and other myeloid cells. Here, we benchmark inactivation in tumor cells against the contribution of its expression in myeloid cells of murine hosts that harbor endogenous or allograft tumors.

Inhibition of HCK in myeloid cells restricts pancreatic tumor growth and metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a low 5-year survival rate and is associated with poor response to therapy. Elevated expression of the myeloid-specific hematopoietic cell kinase (HCK) is observed in PDAC and correlates with reduced patient survival. To determine whether aberrant HCK signaling in myeloid cells is involved in PDAC growth and metastasis, we established orthotopic and intrasplenic PDAC tumors in wild-type and HCK knockout mice.

Differential temperature effects on photoperiodism in female voles: A possible explanation for declines in vole populations.

Many mammalian species use photoperiod as a predictive cue to time seasonal reproduction. In addition, metabolic effects on the reproductive axis may also influence seasonal timing, especially in female small, short-lived mammals. To get a better understanding of how annual cycling environmental cues impact reproductive function and plasticity in small, short-lived herbivores with different geographic origins, we investigated the mechanisms underlying integration of temperature in the photoperiodic-axis regulating female reproduction in a Northern vole species (tundra vole, Microtus oeconomus) and in a Southern vole species (common vole, Microtus arvalis).

The ENCOMPASS framework: a practical guide for the evaluation of public health programmes in complex adaptive systems.

Background: Systems thinking embraces the complexity of public health problems, including childhood overweight and obesity. It aids in understanding how factors are interrelated, and it can be targeted to produce favourable changes in a system. There is a growing call for systems approaches in public health research, yet limited practical guidance is available on how to evaluate public health programmes within complex adaptive systems.

Understanding obesity-related behaviors in youth from a systems dynamics perspective: The use of causal loop diagrams.

This paper reports how we applied systems dynamics methods to gain insight into the complexity of obesity-related behaviors in youth, including diet, physical activity, sedentary behavior, and sleep, by integrating a literature review into causal loop diagrams (CLDs). Results showed that the CLDs consisted of multiple subsystems and three types of dynamics appeared, including (1) feedback loops, (2) connections between feedback loops and subsystems, and (3) mechanisms. We observed clear similarities in the dynamics for the four behaviors in that they relate to "traditional" subsystems, such as home and school environments, as well as to newly added subsystems, including macroeconomics, social welfare, and urban systems.

Can Healthy Checkout Counters Improve Food Purchases? Two Real-Life Experiments in Dutch Supermarkets.

Most snacks displayed at supermarket checkouts do not contribute to a healthy diet. We investigated the effects of introducing healthier snack alternatives at checkouts in supermarkets on purchasing behavior. In Study 1, we investigated the effect of completely substituting less healthy with healthier snacks (one supermarket).

Prenatal Transfer of Gut Bacteria in Rock Pigeon.

Vertebrates evolved in concert with bacteria and have developed essential mutualistic relationships. Gut bacteria are vital for the postnatal development of most organs and the immune and metabolic systems and may likewise play a role during prenatal development. Prenatal transfer of gut bacteria is shown in four mammalian species, including humans.

IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization.

The contribution of mast cells in the microenvironment of solid malignancies remains controversial. Here we functionally assess the impact of tumor-adjacent, submucosal mast cell accumulation in murine and human intestinal-type gastric cancer. We find that genetic ablation or therapeutic inactivation of mast cells suppresses accumulation of tumor-associated macrophages, reduces tumor cell proliferation and angiogenesis, and diminishes tumor burden.

'Obesogenic' School Food Environments? An Urban Case Study in The Netherlands.

(1) Background: This study aimed to explore and define socio-economic (SES) differences in urban school food environments in The Netherlands. (2) Methods: Retail food outlets, ready-to-eat products, in-store food promotions and food advertisements in public space were determined within 400 m walking distance of all secondary schools in the 4th largest city of The Netherlands. Fisher's exact tests were conducted.

Interleukin 33 Signaling Restrains Sporadic Colon Cancer in an Interferon-γ-Dependent Manner.

Interleukin 33 (IL33) is an inflammatory cytokine released during necrotic cell death. The epithelium and stroma of the intestine express large amounts of IL33 and its receptor St2. IL33 is therefore continuously released during homeostatic turnover of the intestinal mucosa.

The CD40-CD40L Dyad in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis.

The CD40-CD40L dyad is an immune checkpoint regulator that promotes both innate and adaptive immune responses and has therefore an essential role in the development of inflammatory diseases, including multiple sclerosis (MS). In MS, CD40 and CD40L are expressed on immune cells present in blood and lymphoid organs, affected resident central nervous system (CNS) cells, and inflammatory cells that have infiltrated the CNS. CD40-CD40L interactions fuel the inflammatory response underlying MS, and both genetic deficiency and antibody-mediated inhibition of the CD40-CD40L dyad reduce disease severity in experimental autoimmune encephalomyelitis (EAE).

Serotonin: A mediator of the gut-brain axis in multiple sclerosis.

Background: The significance of the gut microbiome for the pathogenesis of multiple sclerosis (MS) has been established, although the underlying signaling mechanisms of this interaction have not been sufficiently explored.

Objectives: We address this point and use serotonin (5-hydroxytryptamine (5-HT))-a microbial-modulated neurotransmitter (NT) as a showcase to demonstrate that NTs regulated by the gut microbiome are potent candidates for mediators of the gut-brain axis in demyelinating disorders. Methods, Results, and Conclusion: Our comprehensive overview of literature provides evidence that 5-HT levels in the gut are controlled by the microbiome, both via secretion and through regulation of metabolites.

Sowing Seeds for Healthier Diets: Children's Perspectives on School Gardening.

School gardening programmes are among the most promising interventions to improve children's vegetable intake. Yet, low vegetable intake among children remains a persistent public health challenge. This study aimed to explore children's perspectives, experiences, and motivations concerning school gardening in order to better understand and increase its potential for health promotion.