ERMA (TMEM94) is a P-type ATPase transporter for Mg2+ uptake in the endoplasmic reticulum.

Intracellular Mg2+ (iMg2+) is bound with phosphometabolites, nucleic acids, and proteins in eukaryotes. Little is known about the intracellular compartmentalization and molecular details of Mg2+ transport into/from cellular organelles such as the endoplasmic reticulum (ER). We found that the ER is a major iMg2+ compartment refilled by a largely uncharacterized ER-localized protein, TMEM94. Conventional and AlphaFold2 predictions suggest that ERMA (TMEM94) is a multi-pass transmembrane protein with large cytosolic headpiece actuator, nucleotide, and phosphorylation domains, analogous to P-type ATPases. However, ERMA uniquely combines a P-type ATPase domain and a GMN motif for ERMg2+ uptake. Experiments reveal that a tyrosine residue is crucial for Mg2+ binding and activity in a mechanism conserved in both prokaryotic (mgtB and mgtA) and eukaryotic Mg2+ ATPases. Cardiac dysfunction by haploinsufficiency, abnormal Ca2+ cycling in mouse Erma+/- cardiomyocytes, and ERMA mRNA silencing in human iPSC-cardiomyocytes collectively define ERMA as an essential component of ERMg2+ uptake in eukaryotes.

Single-cell delineation of lineage and genetic identity in the mouse brain.

During neurogenesis, mitotic progenitor cells lining the ventricles of the embryonic mouse brain undergo their final rounds of cell division, giving rise to a wide spectrum of postmitotic neurons and glia1,2. The link between developmental lineage and cell-type diversity remains an open question. Here we used massively parallel tagging of progenitors to track clonal relationships and transcriptomic signatures during mouse forebrain development. We quantified clonal divergence and convergence across all major cell classes postnatally, and found diverse types of GABAergic neuron that share a common lineage. Divergence of GABAergic clones occurred during embryogenesis upon cell-cycle exit, suggesting that differentiation into subtypes is initiated as a lineage-dependent process at the progenitor cell level.

Loss of the endoplasmic reticulum protein Tmem208 affects cell polarity, development, and viability.

Nascent proteins destined for the cell membrane and the secretory pathway are targeted to the endoplasmic reticulum (ER) either posttranslationally or cotranslationally. The signal-independent pathway, containing the protein TMEM208, is one of three pathways that facilitates the translocation of nascent proteins into the ER. The in vivo function of this protein is ill characterized in multicellular organisms. Here, we generated a CRISPR-induced null allele of the fruit fly ortholog CG8320/Tmem208 by replacing the gene with the Kozak-GAL4 sequence. We show that Tmem208 is broadly expressed in flies and that its loss causes lethality, although a few short-lived flies eclose. These animals exhibit wing and eye developmental defects consistent with impaired cell polarity and display mild ER stress. Tmem208 physically interacts with Frizzled (Fz), a planar cell polarity (PCP) receptor, and is required to maintain proper levels of Fz. Moreover, we identified a child with compound heterozygous variants in TMEM208 who presents with developmental delay, skeletal abnormalities, multiple hair whorls, cardiac, and neurological issues, symptoms that are associated with PCP defects in mice and humans. Additionally, fibroblasts of the proband display mild ER stress. Expression of the reference human TMEM208 in flies fully rescues the loss of Tmem208, and the two proband-specific variants fail to rescue, suggesting that they are loss-of-function alleles. In summary, our study uncovers a role of TMEM208 in development, shedding light on its significance in ER homeostasis and cell polarity.

The role of breastfeeding support in racial/ethnic disparities in breastfeeding practices.

BACKGROUND: Persistent racial/ethnic disparities in breastfeeding practices in the United States are well documented but the underlying causes remain unclear. While racial/ethnic disparities are often intertwined with socioeconomic disparities in breastfeeding, studies suggest that lack of breastfeeding support from family, health care organizations and workplaces may contribute to racial/ethnic disparities in breastfeeding rates. No studies have investigated the extent to which racial/ethnic disparities in breastfeeding practices can be explained by breastfeeding support. METHODS: We used survey data from participants of a federal nutrition assistance program in Los Angeles County, the most populous county in the United States, to examine causal mechanisms underlying racial/ethnic disparities in breastfeeding in five groups: Spanish-speaking Latina, English-speaking Latina, Non-Hispanic White (NHW), Non-Hispanic Black (NHB) and Non-Hispanic Asian (NHA). Applying causal mediation analysis, this study estimated the proportion of racial/ethnic differences in breastfeeding ('any' breastfeeding, i.e., partial or exclusive) rates at 6 months that could be explained by differential access to breastfeeding support from family, birth hospitals and workplaces. RESULTS: NHB and English-speaking Latina mothers were less likely, and Spanish-speaking Latina mothers more likely to breastfeed through 6 months than NHW mothers. Lack of breastfeeding support from family, hospitals and workplaces accounted for approximately 68% of the difference in any breastfeeding rates at 6 months between NHW and NHB mothers and 36% of the difference between NHW and English-speaking Latina mothers. CONCLUSION: These findings highlight the importance of improving support from family, hospitals and workplaces for breastfeeding mothers to reduce racial/ethnic disparities in breastfeeding.

Gender and Pathways to Leadership in Academic Anesthesiology: A Qualitative Content Analysis of US Chairpersons' Curricula Vitae.

BACKGROUND: Women are underrepresented in medicine and academic anesthesiology, and especially in leadership positions. We sought to characterize career achievement milestones of female versus male academic anesthesiology chairs to understand possible gender-related differences in pathways to leadership. METHODS: We conducted a retrospective observational cross-sectional analysis. In November 2019, curricula vitae (CVs) were requested from then-current members of the US Association of Academic Anesthesiology Chairs. Data reflecting accomplishments up to the time of chair appointment were systematically extracted from CVs and analyzed using a mixed methods approach with qualitative content analysis supplemented by descriptive statistics and bivariate statistical testing. Missing data were not imputed. RESULTS: Seventy-two CVs were received from eligible individuals (response rate 67.3%). The respondent sample was 12.5% women (n = 9), 87.5% men (n = 63), and no transgender or nonbinary people; this is similar to the known gender balance in anesthesiology chairs in the United States. No statistically significant differences in objective markers of academic achievement at the time of chair appointment were evident for female versus male chairs, including time elapsed between the first faculty appointment and assumption of the chair role (median 25 vs 18 years, P = .06), number of publications at the time the chair was assumed (101 vs 69, P = .28), or proportion who had ever held a National Institutes of Health (NIH) grant as principal investigator (44.4% vs 25.4%, 0.25). Four phenotypes of career paths were discernible in the data: the clinician-administrator, the educator, the investigator, and the well-rounded scholar; these did not differ by gender. CONCLUSIONS: Female chairpersons who were members of the Association of Academic Anesthesiology Chairs in the United States demonstrated similar patterns of academic achievement as compared to male chairpersons at the time the position of chair was assumed, suggesting that they were equally qualified for the role as compared to men. Four patterns of career achievements were evident in the chairperson group, suggesting multiple viable pathways to this leadership position.

Changing the default meal option at university events to reduce harmful environmental impacts: Six randomized controlled trials.

Animal agriculture is a leading contributor to greenhouse gas emissions and other harmful environmental impacts, which underscores the need to shift away from the consumption of animal-based products. One promising nudge intervention is making plant-based meals the default option, so we tested this approach at six different university events across four academic institutions for effecting sustainable dietary change. Event attendees pre-selected their meal on one of two randomly assigned RSVP forms: one with a plant-based default and one with a meal with meat default. The results from our randomized controlled trial showed that participants had a 43-percentage point greater probability of selecting the plant-based meal when it was indicated as the default option. This effect was similar across events and academic institutions, which indicates that this default intervention is generalizable and can be successfully implemented at university events. The combined effect of using plant-based defaults at these six events was an estimated reduction of 104,387 kg of CO2 emissions, 299.9 m2 of land use, 959.0 g of nitrogen use, and 259.5 g of phosphorus use, which represent roughly 45-46.2% reductions in harmful environmental impacts relative to the meals chosen when using a meat default. Given the significance and magnitude of these environmental benefits, our results support the widespread implementation of plant-based defaults for helping universities improve their sustainability.

Agnogenic practices and corporate political strategy: the legitimation of UK gambling industry-funded youth education programmes.

Agnogenic practices-designed to create ignorance or doubt-are well-established strategies employed by health-harming industries (HHI). However, little is known about their use by industry-funded organizations delivering youth education programmes. We applied a previously published framework of corporate agnogenic practices to analyse how these organizations used them in three UK gambling industry-funded youth education programmes. Evidential strategies adopted previously by other HHI are prominent in the programmes' practitioner-facing materials, evaluation design and reporting and in public statements about the programmes. We show how agnogenic practices are employed to portray these youth education programmes as 'evidence-based' and 'evaluation-led'. These practices distort the already limited evidence on these educational initiatives while legitimizing industry-favourable policies, which prioritize commercial interests over public health. Given the similarities in political strategies adopted by different industries, these findings are relevant to research and policy on other HHI.

Genome-Wide SNP and Indel Discovery in Abaca (Musa textilis Née) and among Other Musa spp. for Abaca Genetic Resources Management.

Abaca (Musa textilis Née) is an economically important fiber crop in the Philippines. Its economic potential, however, is hampered by biotic and abiotic stresses, which are exacerbated by insufficient genomic resources for varietal identification vital for crop improvement. To address these gaps, this study aimed to discover genome-wide polymorphisms among abaca cultivars and other Musa species and analyze their potential as genetic marker resources. This was achieved through whole-genome Illumina resequencing of abaca cultivars and variant calling using BCFtools, followed by genetic diversity and phylogenetic analyses. A total of 20,590,381 high-quality single-nucleotide polymorphisms (SNP) and DNA insertions/deletions (InDels) were mined across 16 abaca cultivars. Filtering based on linkage disequilibrium (LD) yielded 130,768 SNPs and 13,620 InDels, accounting for 0.396 ± 0.106 and 0.431 ± 0.111 of gene diversity across these cultivars. LD-pruned polymorphisms across abaca, M. troglodytarum, M. acuminata and M. balbisiana enabled genetic differentiation within abaca and across the four Musa spp. Phylogenetic analysis revealed the registered varieties Abuab and Inosa to accumulate a significant number of mutations, eliciting further studies linking mutations to their advantageous phenotypes. Overall, this study pioneered in producing marker resources in abaca based on genome-wide polymorphisms vital for varietal authentication and comparative genotyping with the more studied Musa spp.

NMIHBA results from hypomorphic PRUNE1 variants that lack short-chain exopolyphosphatase activity.

Neurodevelopmental disorder with microcephaly, hypotonia and variable brain anomalies (NMIHBA) is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by global developmental delay and severe intellectual disability. Microcephaly, progressive cortical atrophy, cerebellar hypoplasia and delayed myelination are neurological hallmarks in affected individuals. NMIHBA is caused by biallelic variants in PRUNE1 encoding prune exopolyphosphatase 1. We provide in-depth clinical description of two affected siblings harboring compound heterozygous variant alleles, c.383G > A (p.Arg128Gln), c.520G > T (p.Gly174*) in PRUNE1. To gain insights into disease biology, we biochemically characterized missense variants within the conserved N-terminal aspartic acid-histidine-histidine (DHH) motif and provide evidence that they result in the destabilization of protein structure and/or loss of exopolyphosphatase activity. Genetic ablation of Prune1 results in midgestational lethality in mice, associated with perturbations to embryonic growth and vascular development. Our findings suggest that NMIHBA results from hypomorphic variant alleles in humans and underscore the potential key role of PRUNE1 exopolyphoshatase activity in neurodevelopment.

Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease.

BACKGROUND: Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated in autoinflammatory disease, may define new disorders. METHODS: We analyzed peripheral-blood exome sequence data independent of clinical phenotype and inheritance pattern to identify deleterious mutations in ubiquitin-related genes. Sanger sequencing, immunoblotting, immunohistochemical testing, flow cytometry, and transcriptome and cytokine profiling were performed. CRISPR-Cas9-edited zebrafish were used as an in vivo model to assess gene function. RESULTS: We identified 25 men with somatic mutations affecting methionine-41 (p.Met41) in UBA1, the major E1 enzyme that initiates ubiquitylation. (The gene UBA1 lies on the X chromosome.) In such patients, an often fatal, treatment-refractory inflammatory syndrome develops in late adulthood, with fevers, cytopenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. Most of these 25 patients met clinical criteria for an inflammatory syndrome (relapsing polychondritis, Sweet's syndrome, polyarteritis nodosa, or giant-cell arteritis) or a hematologic condition (myelodysplastic syndrome or multiple myeloma) or both. Mutations were found in more than half the hematopoietic stem cells, including peripheral-blood myeloid cells but not lymphocytes or fibroblasts. Mutations affecting p.Met41 resulted in loss of the canonical cytoplasmic isoform of UBA1 and in expression of a novel, catalytically impaired isoform initiated at p.Met67. Mutant peripheral-blood cells showed decreased ubiquitylation and activated innate immune pathways. Knockout of the cytoplasmic UBA1 isoform homologue in zebrafish caused systemic inflammation. CONCLUSIONS: Using a genotype-driven approach, we identified a disorder that connects seemingly unrelated adult-onset inflammatory syndromes. We named this disorder the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. (Funded by the NIH Intramural Research Programs and the EU Horizon 2020 Research and Innovation Program.).

A qualitative framing analysis of how firearm manufacturers and related bodies communicate to the public on gun-related harms and solutions.

There is a growing understanding that the producers and sellers of harmful products directly and indirectly affect population health and policy, including through seeking to influence public understanding about the nature of harms and their solutions. However, the firearm industry and related organisations have not to date been the subject of this type of enquiry. This study sought to address this evidential gap through examining the ways in which the firearm industry and industry-associated organisations frame firearms, firearm-related harms and possible solutions to gun violence. This was a thematic qualitative documentary analysis of materials from 7 of the largest firearm manufacturers and associated organisations. Two authors independently extracted textual material from web articles, press releases, annual reports and shareholder communications between 1st April 2019 to 1st April 2020 (302 documents). A hybrid approach combining both deductive and inductive coding was adopted, guided by the literature on the commercial determinants of health and using NVivo version 12. The firearm industry and firearm industry-funded organisations use framings about the safety and role of guns, evidence on associated harms and solutions that align with the industry's business interests, consistent with evidence on other harmful product manufacturers. This study identified framing strategies employed by the firearm industry and related organisations. These included attempts to undermine evidence, linking regulation to a dystopian future, minimising some of the most common harms, placing the responsibility for harms on individuals, and attempting to foster a heightened sense of risk to personal safety.

A Qualitative Study of the Work Systems and Culture Around End-of-Day Intraoperative Anesthesia Handoffs in a Tertiary Care Center.

BACKGROUND: Intraoperative handoffs have been implicated as a contributing factor in many perioperative adverse events. Despite conflicting data around their impact on perioperative outcomes, they remain a vulnerable point in the perioperative system with significant attention focused on improving them. This study aimed to understand the processes in place surrounding the point of information transfer in intraoperative handoffs. METHODS: We used semistructured interviews with anesthesia clinicians to understand the processes and systems surrounding intraoperative handoffs. Interview data were coded deductively using the Systems Engineering Initiative for Patient Safety model as a framework, with subthemes developed inductively. RESULTS: Clinicians do a significant amount of work before and after the point of information transfer to ensure a smooth handoff and safe patient care. Despite not having standardization of handoffs, most clinicians have a typical handoff organization and largely agree on content that should be included. However, there is variability based on clinician and patient characteristics, including clinician discipline and patient acuity. These handoffs are additionally impacted by the overall culture in the operating room, including the teamwork and hierarchies present among the surgical and anesthesia teams. Finally, the broader operating room logistics, including scheduling practices for surgical cases and anesthesia teams, impact the quality of intraoperative handoffs and the ability of clinicians to prepare for these handoffs. CONCLUSIONS: Handoffs involve processes beyond the point of information transfer and are embedded in the systems and culture of the operating rooms. These considerations are important when seeking to improve the quality of intraoperative handoffs.

Drinking on an empty stomach: a scoping review of the evidence on how consuming food with alcohol affects short-term outcomes.

BACKGROUND: Alcohol is a leading risk factor for death worldwide. Governments issue official guidelines on reducing the short-term risks associated with alcohol as do alcohol industry-funded organizations. Both sources frequently recommend consuming food with alcohol, however, it is unclear what evidence these recommendations are based on. The aim of this scoping review was to map and summarize evidence on the short-term effects of consuming food and alcohol. METHODS: A scoping review, following PRISMA Extension for Scoping Reviews, searched CINAHL, Cochrane Library, Embase, Medline, PsychINFO and NICE Evidence Search (published inception to June 2021). Studies in English, investigating co-consumption of food and alcohol and reporting short-term health outcomes or acute effects, were included. RESULTS: Of the 15 246 studies identified, 10 met the inclusion criteria. There was little evidence on the effects of food co-consumption on most short-term alcohol-related outcomes. Included studies were low in quality and inconsistent in their reported outcomes. CONCLUSIONS: Despite a weak and inconsistent evidence base, food co-consumption is often recommended by both official guidance and alcohol industry-funded sources. Food co-consumption as a harm reduction measure, while plausible, requires a stronger evidence base and more nuanced messaging due to the risk of encouraging heavier, sustained drinking.

Effects of dexmedetomidine on kidney and brain tissue microcirculation and histology in ovine cardiopulmonary bypass: a randomised controlled trial.

Cardiac surgery requiring cardiopulmonary bypass is associated with postoperative acute kidney injury and neurocognitive disorders, including delirium. Intra-operative inflammation and/or impaired tissue perfusion/oxygenation are thought to be contributors to these outcomes. It has been hypothesised that these problems may be ameliorated by the highly selective α2 -agonist, dexmedetomidine. We tested the effects of dexmedetomidine on renal and cerebral microcirculatory tissue perfusion, oxygenation and histology in a clinically relevant ovine model. Sixteen sheep were studied while conscious, after induction of anaesthesia and during 2 h of cardiopulmonary bypass. Eight sheep were allocated randomly to receive an intravenous infusion of dexmedetomidine (0.4-0.8 µg.kg-1 .h-1 ) from induction of anaesthesia to the end of cardiopulmonary bypass, and eight to receive an equivalent volume of matched placebo (0.9% sodium chloride). Commencement of cardiopulmonary bypass decreased renal medullary tissue oxygenation in the placebo group (mean (95%CI) 5.96 (4.24-7.23) to 1.56 (0.84-2.09) kPa, p = 0.001), with similar hypoxic levels observed in the dexmedetomidine group (6.33 (5.33-7.07) to 1.51 (0.33-2.39) kPa, p = 0.002). While no differences in kidney function (i.e. reduced creatinine clearance) were evident, a greater incidence of histological renal tubular injury was observed in sheep receiving dexmedetomidine (7/8 sheep) compared with placebo (2/8 sheep), p = 0.041. Graded on a semi-quantitative scale (0-3), median (IQR [range]) severity of histological renal tubular injury was higher in the dexmedetomidine group compared with placebo (1.5 (1-2 [0-3]) vs. 0 (0-0.3 [0-1]) respectively, p = 0.013). There was no difference in cerebral tissue microglial activation (neuroinflammation) between the groups. Dexmedetomidine did not reduce renal medullary hypoxia or cerebral neuroinflammation in sheep undergoing cardiopulmonary bypass.

Protecting children and young people from contemporary marketing for gambling.

Around the world, children are being exposed to intensive marketing for gambling products. This normalizes perceptions that gambling is essentially a harmless form of entertainment, despite mounting evidence of the harms it causes. Young people and their parents are supportive of strategies to protect children from being exposed to gambling marketing. Yet existing regulatory efforts are inconsistent and inadequate, and have not protected children from exposure to the many forms of marketing now being developed and exploited by the gambling industry. We outline existing knowledge about strategies used by the gambling industry to market its products, with a specific focus on the potential impact of gambling marketing on young people. We provide a definition of gambling marketing and outline the different forms of promotion that are currently used to market gambling, current regulatory responses, and the impact of marketing on children and young people. We then argue that a comprehensive public health approach to gambling is urgently required, which must include effective action to limit the influence of marketing for gambling products, while recognizing that it is never possible to insulate children entirely from their reach.

• Gambling marketing has become particularly pervasive and aligned with major cultural activities such as sport. • Evidence clearly shows the normalizing impact of marketing on children and young people's gambling attitudes and consumption intentions. • Current regulatory efforts are inadequate and have not protected children and young people from exposure to a range of different forms of marketing. • Young people and their parents support the implementation of significant restrictions on gambling marketing. • The array of marketing mechanisms used by the gambling industry should be addressed as part of a comprehensive public health policy approach to protect children from gambling harms.

PUS7 deficiency in human patients causes profound neurodevelopmental phenotype by dysregulating protein translation.

Protein translation is a highly regulated process involving the interaction of numerous genes on every component of the protein translation machinery. Upregulated protein translation is a hallmark of cancer and is implicated in autism spectrum disorder, but the risks of developing each disease do not appear to be correlated with one another. In this study we identified two siblings from the NIH Undiagnosed Diseases Program with loss of function variants in PUS7, a gene previously implicated in the regulation of total protein translation. These patients exhibited a neurodevelopmental phenotype including autism spectrum disorder in the proband. Both patients also had features of Lesch-Nyhan syndrome, including hyperuricemia and self-injurious behavior, but without pathogenic variants in HPRT1. Patient fibroblasts demonstrated upregulation of protein synthesis, including elevated MYC protein, but did not exhibit increased rates of cell proliferation. Interestingly, the dysregulation of protein translation also resulted in mildly decreased levels of HPRT1 protein suggesting an association between dysregulated protein translation and the LNS-like phenotypic findings. These findings strengthen the correlation between neurodevelopmental disease, particularly autism spectrum disorders, and the rate of protein translation.

Robotic Resection of Type I Hilar Cholangiocarcinoma with Intrapancreatic Bile Duct Dissection.

BACKGROUND: Type I hilar cholangiocarcinoma is a malignancy of the extrahepatic bile duct for which margin-negative resection with sufficient lymphadenectomy may provide curative treatment. The aim of this video is to highlight the advantages of optical magnification, articulating instruments, and indocyanine green fluorescent cholangiography to demonstrate extrahepatic bile duct resection from the biliary confluence to the intrapancreatic bile duct with comprehensive hilar lymphadenectomy for pathologic staging. METHODS: A 58-year-old male presented with obstructive jaundice and was found to have a biliary stricture arising from the cystic duct and bile duct junction. Endoscopic biopsy of the bile duct confirmed adenocarcinoma. His case was presented at a multidisciplinary tumor conference where consensus was to proceed with upfront robotic en bloc extrahepatic bile duct resection with hilar lymphadenectomy and Roux-en-Y hepaticojejunostomy. RESULTS: Final pathology demonstrated margin-negative resection of moderately differentiated adenocarcinoma, 1 out of 12 lymph nodes involved with disease, and pathologic stage T2N1M0 (stage IIIC). The patient had no postoperative complications and was discharged home on postoperative day 5. At 6 weeks from his operative date, he was initiated on four cycles of adjuvant gemcitabine/capecitabine, followed by 50 Gray external beam radiation therapy with capecitabine, then four cycles of gemcitabine/capecitabine, completed after 6 months of therapy. CONCLUSIONS: Robotic extrahepatic bile duct resection, hilar lymphadenectomy, and biliary enteric reconstruction is feasible and should be considered for selected cases of bile duct resection.

Setting the stage for speaking up: psychological safety and directing care in acute care collaboration.

Managing a safe and efficient anaesthetic induction within a team involves the challenge of when, if, and how to surface, discuss, and implement the best plan on how to proceed. The Lemke and colleagues study in this issue of the British Journal of Anaesthesia is a unique view into real-world conversations that naturally occur in anaesthesia teams in moments of high task and cognitive load, such as induction of anaesthesia. The study spotlights important small moments of physician, nurse, and trainee team coordination. It illuminates key patterns of conversation in naturally occurring anaesthesia teams, and raises important questions about what the speaking up standard should be and the psychological safety-shaping role consultants play in setting the norms for speaking up.

Understanding children's perspectives of the influences on their dietary behaviours.

OBJECTIVE: This study aimed to examine the intrapersonal, interpersonal, environmental and macrosystem influences on dietary behaviours among primary school children in Singapore. DESIGN: A qualitative interpretive approach was used in this study. Focus group discussions guided by the socio-ecological model (sem), of which transcripts were analysed deductively using the sem and inductively using thematic analysis to identify themes at each sem level. SETTING: Two co-educational public primary schools in Singapore. PARTICIPANTS: A total of 48 children (n 26 girls) took part in the semi-structured focus group discussions. Their mean age was 10·8 years (sd = 0·9, range 9-12 years), and the majority of the children were Chinese (n 36), along with some Indians (n 8) and Malays (n 4). RESULTS: Children's knowledge of healthy eating did not necessarily translate into healthy dietary practices and concern for health was a low priority. Instead, food and taste preferences were pivotal influences in their food choices. Parents had a large influence on children with regards to their accessibility to food, their attitudes and values towards food. Parental food restriction led to some children eating in secrecy. Peer influence was not frequently reported by children. Competitions in school incentivised children to consume fruits and vegetables, but reinforcements from teachers were inconsistent. The proximity of fast-food chains in the neighbourhood provided children easy access to less healthy foods. Health advertisements on social media rather than posters worked better in drawing children's attention. CONCLUSIONS: Findings highlighted important factors that should be considered in future nutrition interventions targeting children.

Back to our roots or sowing new seeds: thinking anew on the paradigms of health, harm and disease.

Health, harms and disease are intimately linked, and their promotion and distribution are determined by the social, political and physical worlds in which people live. Yet, the popular narrative on health is still dominated by a biological model that focuses on a disease-causing 'pathogen' or 'agent' that leads to pathology which is diagnosable and amenable to intervention at the individual level via measures delivered through the health care and public health systems. This model generally rests on understanding populations as a collection of individuals, with the pattern of disease seen as the sum of a series of risk factors acting on each of them. Too little attention is paid to the ways in which health, harm, disease, causation and risk are conceptualized and used as guiding concepts in research, policy debates and other fora. We often overlook the distribution of health and the regulatory regimes, norms, values and rights that promote or undermine health. By challenging our ways of thinking about health, harms and disease, we can start to appreciate with greater depth the ways in which health can be threatened and what should be seen as harmful, and conversely, opportunities for moving our systems towards promoting and protecting health.