DNA repair and oxidative stress defense systems in radiation-resistant Deinococcus murrayi.

Deinococcus murrayi is a bacterium isolated from hot springs in Portugal, and named after Dr. Robert G.E. Murray in recognition of his research on the genus Deinococcus. Like other Deinococcus species, D. murrayi is extremely resistant to ionizing radiation. Repair of massive DNA damage and limitation of oxidative protein damage are two important factors contributing to the robustness of Deinococcus bacteria. Here, we identify, among others, the DNA repair and oxidative stress defense proteins in D. murrayi, and highlight special features of D. murrayi. For DNA repair, D. murrayi does not contain a standalone uracil-DNA glycosylase (Ung), but it encodes a protein in which Ung is fused to a DNA photolyase domain (PhrB). UvrB and UvrD contain large insertions corresponding to inteins. One of its endonuclease III enzymes lacks a [4Fe-4S] cluster. Deinococcus murrayi possesses a homolog of the error-prone DNA polymerase IV. Concerning oxidative stress defense, D. murrayi encodes a manganese catalase in addition to a heme catalase. Its organic hydroperoxide resistance protein Ohr is atypical because the redox active cysteines are present in a CXXC motif. These and other characteristics of D. murrayi show further diversity among Deinococcus bacteria with respect to resistance-associated mechanisms.

Root responses to aluminium and iron stresses require the SIZ1 SUMO ligase to modulate the STOP1 transcription factor.

STOP1, an Arabidopsis transcription factor favouring root growth tolerance against Al toxicity, acts in the response to iron under low Pi (-Pi). Previous studies have shown that Al and Fe regulate the stability and accumulation of STOP1 in roots, and that the STOP1 protein is sumoylated by an unknown E3 ligase. Here, using a forward genetics suppressor screen, we identified the E3 SUMO (small ubiquitin-like modifier) ligase SIZ1 as a modulator of STOP1 signalling. Mutations in SIZ1 increase the expression of ALMT1 (a direct target of STOP1) and root growth responses to Al and Fe stress in a STOP1-dependent manner. Moreover, loss-of-function mutations in SIZ1 enhance the abundance of STOP1 in the root tip. However, no sumoylated STOP1 protein was detected by Western blot analysis in our sumoylation assay in Escherichia coli, suggesting the presence of a more sophisticated mechanism. We conclude that the sumo ligase SIZ1 negatively regulates STOP1 signalling, at least in part by modulating STOP1 protein in the root tip. Our results will allow a better understanding of this signalling pathway.

Comparison of national surveillance systems for Lyme disease in humans in Europe and North America: a policy review.

BACKGROUND: Lyme disease incidence is increasing in Europe, the USA, and Canada. In 2010, a comparison of surveillance systems for Lyme disease (LD) in humans in 28 European countries showed that systems highly varied, making epidemiological comparisons difficult. Details by country were not published. In 2018, one of LD clinical manifestations, neuroborreliosis, was added under European Union (EU) surveillance to standardise definitions. In this study, we identified and compared, 10 years after the European inventory, the characteristics of national surveillance systems and policies for LD in humans, with additional countries. METHODS: Thirty-four European and North American countries were included. Information on national "traditional" systems (which compile data reported by clinicians and laboratories) and "public participatory" websites and mobile applications (which collect information directly from the public) were searched in MEDLINE, a systematic evidence map, and Google. An existing framework on LD surveillance was adapted to capture information on the administration level, indicators, reporting entities, coverage, and obligation to report. RESULTS: A surveillance system was found for 29 (85%) countries. Twenty-four had a traditional system alone, one had a public participatory system alone, and the remaining had both. Among countries with traditional systems, 23 (82%) administered them at the national level. Nineteen (68%) required mandatory reporting. Sixteen (57%) used both clinicians and laboratories as reporting entities. Eighteen (64%) employed case definitions, most of which considered both neuroborreliosis and erythema migrans (n = 14). Others monitored the number of positive laboratory tests and/or patient consultations. Public participatory systems were only implemented in countries employing either also sentinels or voluntary surveys, or no traditional system, suggesting their use as a complementary tool. Only 56% of EU countries had neuroborreliosis as an indicator. CONCLUSION: The situation remains similar to 2010 with persisting heterogeneity between systems, suggesting that countries prioritise different surveillance objectives for LD. Without a common indicator in Europe, it is difficult to get a clear epidemiological picture. We discuss four factors that potentially influence LD surveillance strategies: perceptions of severity, burden on resources, two-way communication, and the medical conflicts about LD. Addressing these with countries might help moving towards the adoption of common practices.

Barriers and facilitators to the implementation of Health-Promoting School programmes targeting bullying and violence: a systematic review.

Health-Promoting School (HPS) interventions aim to reduce bullying and violence via curriculum, environmental and family/community-engagement components. Despite evidence of their effectiveness, factors influencing the implementation of such interventions are poorly understood. This systematic review aims to examine such factors by assessing qualitative process evaluations of HPS interventions aiming to reduce bullying, aggression or violence. A comprehensive systematic search of 12 databases was carried out, and 20 reports from 17 studies were included. Thematic synthesis was used to identify factors affecting implementation. Factors that enable implementation were related to programme characteristics and stakeholder buy-in, including support from leadership, teachers, students and parents. Good communication and staff climate were important. Interventions were better implemented when they framed health promotion as a core school business, were supported by a national policy, used local data to show need and effectiveness and provided high-quality, pragmatic and accessible staff training. The results of this review can serve to guide and facilitate the design and implementation of future bullying and violence prevention programmes. Since there is significant overlap in terms of the important pillars and guiding principles for all interventions guided by the HPS framework, the findings may apply to outcomes beyond bullying and violence.

Crystal structure of the transcriptional repressor DdrO: insight into the metalloprotease/repressor-controlled radiation response in Deinococcus.

Exposure to harmful conditions such as radiation and desiccation induce oxidative stress and DNA damage. In radiation-resistant Deinococcus bacteria, the radiation/desiccation response is controlled by two proteins: the XRE family transcriptional repressor DdrO and the COG2856 metalloprotease IrrE. The latter cleaves and inactivates DdrO. Here, we report the biochemical characterization and crystal structure of DdrO, which is the first structure of a XRE protein targeted by a COG2856 protein. DdrO is composed of two domains that fold independently and are separated by a flexible linker. The N-terminal domain corresponds to the DNA-binding domain. The C-terminal domain, containing three alpha helices arranged in a novel fold, is required for DdrO dimerization. Cleavage by IrrE occurs in the loop between the last two helices of DdrO and abolishes dimerization and DNA binding. The cleavage site is hidden in the DdrO dimer structure, indicating that IrrE cleaves DdrO monomers or that the interaction with IrrE induces a structural change rendering accessible the cleavage site. Predicted COG2856/XRE regulatory protein pairs are found in many bacteria, and available data suggest two different molecular mechanisms for stress-induced gene expression: COG2856 protein-mediated cleavage or inhibition of oligomerization without cleavage of the XRE repressor.

Variability in the redox status of plant 2-Cys peroxiredoxins in relation to species and light cycle.

Plant 2-Cys peroxiredoxins (2-CysPRXs) are abundant plastidial thiol-peroxidases involved in key signaling processes such as photosynthesis deactivation at night. Their functions rely on the redox status of their two cysteines and on the enzyme quaternary structure, knowledge of which remains poor in plant cells. Using ex vivo and biochemical approaches, we thoroughly characterized the 2-CysPRX dimer/monomer distribution, hyperoxidation level, and thiol content in Arabidopsis, barley, and potato in relation to the light cycle. Our data reveal that the enzyme hyperoxidization level and its distribution as a dimer and monomer vary through the light cycle in a species-dependent manner. A differential susceptibility to hyperoxidation was observed for the two Arabidopsis 2-CysPRX isoforms and among the proteins of the three species, and was associated to sequence variation in hyperoxidation resistance motifs. Alkylation experiments indicate that only a minor fraction of the 2-CysPRX pool carries one free thiol in the three species, and that this content does not change during the light period. We conclude that most plastidial 2-CysPRX forms are oxidized and propose that there is a species-dependent variability in their functions since dimer and hyperoxidized forms fulfill distinct roles regarding direct oxidation of partners and signal transmission.

Assessing the applicability of public health intervention evaluations from one setting to another: a methodological study of the usability and usefulness of assessment tools and frameworks.

BACKGROUND: Public health interventions can be complicated, complex and context dependent, making the assessment of applicability challenging. Nevertheless, for them to be of use beyond the original study setting, they need to be generalisable to other settings and, crucially, research users need to be able to identify to which contexts it may be applicable. There are many tools with set criteria for assessing generalisability/applicability, yet few seem to be widely used and there is no consensus on which should be used, or when. This methodological study aimed to test these tools to assess how easy they were to use and how useful they appeared to be. METHODS: We identified tools from an existing review and an update of its search. References were screened on pre-specified criteria. Included tools were tested by using them to assess the applicability of a Swedish weight management intervention to the English context. Researcher assessments and reflections on the usability and utility of the tools were gathered using a standard pro-forma. RESULTS: Eleven tools were included. Their length, content, style and time required to complete varied. No tool was considered ideal for assessing applicability. Their limitations included unrealistic criteria (requiring unavailable information), a focus on implementation to the neglect of transferability (i.e. little focus on potential effectiveness in the new setting), overly broad criteria (associated with low reliability), and a lack of an explicit focus on how interventions worked (i.e. their mechanisms of action). CONCLUSION: Tools presenting criteria ready to be used may not be the best method for applicability assessments. They are likely to be either too long or incomplete, too focused on differences and fail to address elements that matter for the specific topic of interest. It is time to progress from developing lists of set criteria that are not widely used in the literature, to creating a new approach to applicability assessment. Focusing on mechanisms of action, rather than solely on characteristics, could be a useful approach, and one that remains underutilised in current tools. New approaches to assessing generalisability that evolve away from checklist style assessments need to be developed, tested, reported and discussed.

Physiological relevance of plant 2-Cys peroxiredoxin overoxidation level and oligomerization status.

Peroxiredoxins are ubiquitous thioredoxin-dependent peroxidases presumed to display, upon environmental constraints, a chaperone function resulting from a redox-dependent conformational switch. In this work, using biochemical and genetic approaches, we aimed to unravel the factors regulating the redox status and the conformation of the plastidial 2-Cys peroxiredoxin (2-Cys PRX) in plants. In Arabidopsis, we show that in optimal growth conditions, the overoxidation level mainly depends on the availability of thioredoxin-related electron donors, but not on sulfiredoxin, the enzyme reducing the 2-Cys PRX overoxidized form. We also observed that upon various physiological temperature, osmotic and light stress conditions, the overoxidation level and oligomerization status of 2-Cys PRX can moderately vary depending on the constraint type. Further, no major change was noticed regarding protein conformation in water-stressed Arabidopsis, barley and potato plants, whereas species-dependent up- and down-variations in overoxidation were observed. In contrast, both 2-Cys PRX overoxidation and oligomerization were strongly induced during a severe oxidative stress generated by methyl viologen. From these data, revealing that the oligomerization status of plant 2-Cys PRX does not exhibit important variation and is not tightly linked to the protein redox status upon physiologically relevant environmental constraints, the possible in planta functions of 2-Cys PRX are discussed.

Radiation response in Deinococcus deserti: IrrE is a metalloprotease that cleaves repressor protein DdrO.

Deinococcus bacteria are famous for their extreme radiation tolerance. The IrrE protein was shown to be essential for radiation tolerance and, in an unelucidated manner, for induction of a number of genes in response to radiation, including recA and other DNA repair genes. Earlier studies indicated that IrrE could be a zinc peptidase, but proteolytic activity was not demonstrated. Here, using several in vivo and in vitro experiments, IrrE from Deinococcus deserti was found to interact with DdrO, a predicted regulator encoded by a radiation-induced gene that is, like irrE, highly conserved in Deinococcus. Moreover, IrrE was found to cleave DdrO in vitro and when the proteins were coexpressed in Escherichia coli. This cleavage was not observed in the presence of metal chelator EDTA or when IrrE contains a mutation in the conserved active-site motif of metallopeptidases. In D. deserti, IrrE-dependent cleavage of DdrO was observed after exposure to radiation. Furthermore, DdrO-dependent repression of the promoter of a radiation-induced gene was shown. These results demonstrate that IrrE is a metalloprotease and we propose that IrrE-mediated cleavage inactivates repressor protein DdrO, leading to transcriptional induction of various genes required for repair and survival after exposure of Deinococcus to radiation.

The abundant and essential HU proteins in Deinococcus deserti and Deinococcus radiodurans are translated from leaderless mRNA.

HU proteins have an important architectural role in nucleoid organization in bacteria. Compared with HU of many bacteria, HU proteins from Deinococcus species possess an N-terminal lysine-rich extension similar to the eukaryotic histone H1 C-terminal domain involved in DNA compaction. The single HU gene in Deinococcus radiodurans, encoding DrHU, is required for nucleoid compaction and cell viability. Deinococcus deserti contains three expressed HU genes, encoding DdHU1, DdHU2 and DdHU3. Here, we show that either DdHU1 or DdHU2 is essential in D. deserti. DdHU1 and DdHU2, but not DdHU3, can substitute for DrHU in D. radiodurans, indicating that DdHU3 may have a non-essential function different from DdHU1, DdHU2 and DrHU. Interestingly, the highly abundant DrHU and DdHU1 proteins, and also the less expressed DdHU2, are translated in Deinococcus from leaderless mRNAs, which lack a 5'-untranslated region and, hence, the Shine-Dalgarno sequence. Unexpectedly, cloning the DrHU or DdHU1 gene under control of a strong promoter in an expression plasmid, which results in leadered transcripts, strongly reduced the DrHU and DdHU1 protein level in D. radiodurans compared with that obtained from the natural leaderless gene. We also show that the start codon position for DrHU and DdHU1 should be reannotated, resulting in proteins that are 15 and 4 aa residues shorter than initially reported. The expression level and start codon correction were crucial for functional characterization of HU in Deinococcus.

Comparative proteomics reveals key proteins recruited at the nucleoid of Deinococcus after irradiation-induced DNA damage.

The nucleoids of radiation-resistant Deinococcus species show a high degree of compaction maintained after ionizing irradiation. We identified proteins recruited after irradiation in nucleoids of Deinococcus radiodurans and Deinococcus deserti by means of comparative proteomics. Proteins in nucleoid-enriched fractions from unirradiated and irradiated Deinococcus were identified and semiquantified by shotgun proteomics. The ssDNA-binding protein SSB, DNA gyrase subunits GyrA and GyrB, DNA topoisomerase I, RecA recombinase, UvrA excinuclease, RecQ helicase, DdrA, DdrB, and DdrD proteins were found in significantly higher amounts in irradiated nucleoids of both Deinococcus species. We observed, by immunofluorescence microscopy, the subcellular localization of these proteins in D. radiodurans, showing for the first time the recruitment of the DdrD protein into the D. radiodurans nucleoid. We specifically followed the kinetics of recruitment of RecA, DdrA, and DdrD to the nucleoid after irradiation. Remarkably, RecA proteins formed irregular filament-like structures 1 h after irradiation, before being redistributed throughout the cells by 3 h post-irradiation. Comparable dynamics of DdrD localization were observed, suggesting a possible functional interaction between RecA and DdrD. Several proteins involved in nucleotide synthesis were also seen in higher quantities in the nucleoids of irradiated cells, indicative of the existence of a mechanism for orchestrating the presence of proteins involved in DNA metabolism in nucleoids in response to massive DNA damage. All MS data have been deposited in the ProteomeXchange with identifier PXD00196 (http://proteomecentral.proteomexchange.org/dataset/PXD000196).

Major soluble proteome changes in Deinococcus deserti over the earliest stages following gamma-ray irradiation.

BACKGROUND: Deinococcus deserti VCD115 has been isolated from Sahara surface sand. This radiotolerant bacterium represents an experimental model of choice to understand adaptation to harsh conditions encountered in hot arid deserts. We analysed the soluble proteome dynamics in this environmentally relevant model after exposure to 3 kGy gamma radiation, a non-lethal dose that generates massive DNA damages. For this, cells were harvested at different time lapses after irradiation and their soluble proteome contents have been analysed by 2-DE and mass spectrometry. RESULTS: In the first stage of the time course we observed accumulation of DNA damage response protein DdrB (that shows the highest fold change ~11), SSB, and two different RecA proteins (RecAP and RecAC). Induction of DNA repair protein PprA, DNA damage response protein DdrD and the two gyrase subunits (GyrA and GyrB) was also detected. A response regulator of the SarP family, a type II site-specific deoxyribonuclease and a putative N-acetyltransferase are three new proteins found to be induced. In a more delayed stage, we observed accumulation of several proteins related to central metabolism and protein turn-over, as well as helicase UvrD and novel forms of both gyrase subunits differing in terms of isoelectric point and molecular weight. CONCLUSIONS: Post-translational modifications of GyrA (N-terminal methionine removal and acetylation) have been evidenced and their significance discussed. We found that the Deide_02842 restriction enzyme, which is specifically found in D. deserti, is a new potential member of the radiation/desiccation response regulon, highlighting the specificities of D. deserti compared to the D. radiodurans model.

Does the availability of snack foods in supermarkets vary internationally?

BACKGROUND: Cross-country differences in dietary behaviours and obesity rates have been previously reported. Consumption of energy-dense snack foods and soft drinks are implicated as contributing to weight gain, however little is known about how the availability of these items within supermarkets varies internationally. This study assessed variations in the display of snack foods and soft drinks within a sample of supermarkets across eight countries. METHODS: Within-store audits were used to evaluate and compare the availability of potato chips (crisps), chocolate, confectionery and soft drinks. Displays measured included shelf length and the proportion of checkouts and end-of-aisle displays containing these products. Audits were conducted in a convenience sample of 170 supermarkets across eight developed nations (Australia, Canada, Denmark, Netherlands, New Zealand, Sweden, United Kingdom (UK), and United States of America (US)). RESULTS: The mean total aisle length of snack foods (adjusted for store size) was greatest in supermarkets from the UK (56.4 m) and lowest in New Zealand (21.7 m). When assessed by individual item, the greatest aisle length devoted to chips, chocolate and confectionery was found in UK supermarkets while the greatest aisle length dedicated to soft drinks was in Australian supermarkets. Only stores from the Netherlands (41%) had less than 70% of checkouts featuring displays of snack foods or soft drinks. CONCLUSION: Whilst between-country variations were observed, overall results indicate high levels of snack food and soft drinks displays within supermarkets across the eight countries. Exposure to snack foods is largely unavoidable within supermarkets, increasing the likelihood of purchases and particularly those made impulsively.

Youth involvement in policy processes in public health, education, and social work: Protocol for a scoping review.

The objective of this scoping review is to understand the extent and impact of youth involvement in policy processes within public health, education, and social work. Youth involvement in policy processes may enhance the relevance of policies and strengthen democratic practices. This scoping review aims to explore the nature, extent, and impact of youth involvement in policy processes in public health, education, and social work, with a focus on health, well-being, and obesity prevention. Empirical studies published from 1989 and evaluating involvement of youth aged 10 to 19 years old from all socioeconomic backgrounds and countries. Studies will be searched in seven databases. Data will be extracted and synthesized narratively by rights-based perspectives on youth involvement, practical processes of the involvement, and social experiences using descriptive statistics and visuals.

Associations between social media, adolescent mental health, and diet: A systematic review.

Social media use is integral to many adolescents' lives. It brings benefits but can also have detrimental effects on both physical and mental health. We conducted a systematic review examining associations between social media use, adolescent mental health (including body image, self-esteem, stress, interpersonal relationships and loneliness, anxiety, and depressive symptoms), and dietary outcomes. Quantitative studies published between 2019 and 2023 investigating both mental health and diet were searched in 11 databases. The risk of bias was appraised using ROBINS-E. Data were narratively synthesized by type of association, PROGRESS-Plus health equity characteristics, and related to social media influencers. Twenty-one studies were included, of which only one focused on influencers. Sex/gender was the only equity characteristic assessed (n = 8), with mixed results. The findings suggest significant positive correlations between social media use and both depressive and disordered eating symptoms, body dissatisfaction, and anxiety. Four studies identified body image, self-esteem, or anxiety as moderators acting between social media exposure and dietary outcomes. Policy interventions mitigating the impact of social media on adolescents-particularly body image and disordered eating-are needed, alongside follow-up studies on causal pathways, the role of influencers, equity impacts, dietary intake, and the best measurement tools to use.

Longitudinal relationship between adolescents' mental health, energy balance-related behavior, and anthropometric changes.

Energy balance-related behaviors (EBRBs) are considered the immediate causes of adolescents' body weight increases, but adolescents have identified mental health as a contributor. Cross-sectional studies have reported associations between adolescents' mental health and obesity, but causal relationships and the role of EBRBs within this can only be established using longitudinal studies. This systematic review summarizes the findings of longitudinal studies investigating this relationship, in addition to the role of EBRB in the relationship. Multiple electronic databases were searched for longitudinal studies using keywords related to the adolescent population, mental health, EBRB, and body weight. In total, 1216 references were identified and screened based on previously defined eligibility criteria. Sixteen articles met the inclusion criteria. Most studies indicated that mental health-related measures like depression, anxiety, and body dissatisfaction were related to an increase in body weight later. As this review is focused on behavioral mediators, six studies reported associations between mental health-anthropometry dyad and EBRBs such as eating habits, screen time, physical activity, and sleep-as well as stressors like peer victimization. Future studies may focus on streamlining mental health measures and body weight outcomes to assess this relationship. Furthermore, more longitudinal investigations are needed to provide insight into the role of EBRBs in the mental health-body weight relationship during adolescence.

The Commercial Determinants of Health and Evidence Synthesis (CODES): methodological guidance for systematic reviews and other evidence syntheses.

BACKGROUND: The field of the commercial determinants of health (CDOH) refers to the commercial products, pathways and practices that may affect health. The field is growing rapidly, as evidenced by the WHO programme on the economic and commercial determinants of health and a rise in researcher and funder interest. Systematic reviews (SRs) and evidence synthesis more generally will be crucial tools in the evolution of CDOH as a field. Such reviews can draw on existing methodological guidance, though there are areas where existing methods are likely to differ, and there is no overarching guidance on the conduct of CDOH-focussed systematic reviews, or guidance on the specific methodological and conceptual challenges. METHODS/RESULTS: CODES provides guidance on the conduct of systematic reviews focussed on CDOH, from shaping the review question with input from stakeholders, to disseminating the review. Existing guidance was used to identify key stages and to provide a structure for the guidance. The writing group included experience in systematic reviews and other forms of evidence synthesis, and in equity and CDOH research (both primary research and systematic reviews). CONCLUSIONS: This guidance highlights the special methodological and other considerations for CDOH reviews, including equity considerations, and pointers to areas for future methodological and guideline development. It should contribute to the reliability and utility of CDOH reviews and help stimulate the production of reviews in this growing field.

Learning from the CO-CREATE project: A protocol for systems thinking across research (STAR).

The CO-CREATE project aimed to work with young people to create, inform, and disseminate obesity-preventive evidence-based policies using a complex systems perspective. This paper draws lessons from this experience and proposes a protocol for embedding systems thinking within a research project. We first draw on existing systems thinking frameworks to analyze how systems thinking was translated across CO-CREATE, including the flow and relationship between the work packages and in the methods used. We then take the lessons from CO-CREATE and the principles of existing systems thinking frameworks-which focus on various points of intervention planning and delivery but not on research projects as a whole-to formulate a protocol for embedding systems thinking across a research project. Key lessons for future planning and delivery of systems-oriented research projects include incorporating "boundary critique" by capturing key stakeholder (adolescent) values and concerns; working to avoid social exclusion; ensuring methodological pluralism to allow for reflection and responsiveness (with methods ranging from group model building, Photovoice, and small group engagement); getting policy recipients to shape key questions by understanding their views on the critical drivers of obesity early on in the project; and providing opportunity for intraproject reflection along the way.

Understanding the dynamics emerging from the interplay among poor mental wellbeing, energy balance-related behaviors, and obesity prevalence in adolescents: A simulation-based study.

Both obesity and poor mental wellbeing have a high prevalence in European youth. Adolescents in six countries identified mental wellbeing factors as main drivers of youth obesity through systems mapping. This study sought to (1) explore the dynamics of the interplay between poor mental wellbeing, energy balance-related behaviors, and adolescent overweight and obesity prevalence and (2) test the effect of intervention point scenarios to reduce adolescent obesity. Drawing on the youth-generated systems maps and a literature synthesis, we built a simulation model that represents the links from major feedback pathways for poor mental wellbeing to changes in dietary, physical activity, and sleep behaviors. The model was calibrated using survey data from Norway, expert input, and literature and shows a good fit between simulated behavior and available statistical data. The simulations indicate that adolescent mental wellbeing is harmed by socio-cultural pressures and stressors, which trigger reinforcing feedback mechanisms related to emotional/binge eating, lack of motivation to engage in physical activity, and sleep difficulty. Targeting a combination of intervention points that support a 25% reduction of pressure on body image and psychosocial stress showed potentially favorable effects on mental wellbeing-doubling on average for boys and girls and decreasing obesity prevalence by over 4%.