Effects of marketing claims on toddler food products on parents' product preferences, perceptions and purchasing intentions: an online experiment.

BACKGROUND: The retail market for toddler-specific packaged foods is growing. Many of these products are ultra-processed and high in nutrients of concern for health, yet marketed in ways that may make them appear wholesome. This study aims to assess parents' responses to claims on unhealthy, ultra-processed toddler food products and test whether removing such claims promotes more accurate product perceptions and healthier product preferences. METHODS: Parents of toddlers aged 12 to < 36 months (N = 838) were recruited for an online experiment testing four on-pack claim conditions: control (no claim); 'contains "good" ingredient'; 'free from "bad" ingredient'; and unregulated 'child-related' claim. Participants were randomly assigned to one condition, then viewed images of toddler food products that varied in nutrition content and the claims displayed. Participants completed tasks assessing product preferences (unhealthy product displaying claim vs. a healthier option with no claim, across four food categories (banana bars, strawberry snacks, blueberry yogurt snacks and veggie snacks)), purchase intentions and product perceptions. Poisson regression (count variable) and linear regression (continuous outcomes) analyses were employed to test for mean differences by marketing claim conditions. RESULTS: For the overall sample, brief exposure to 'free from "bad" ingredient' claims increased participant's intentions to purchase unhealthy food products for their toddlers, but there was no clear evidence that 'contains "good" ingredient' claims and 'child-related' claims significantly impacted parent's preferences, purchase intentions and perceptions of toddler foods. However, certain claims influenced particular parent subgroups. Notably, parents with three or more children chose more unhealthy products when these products displayed 'contains "good" ingredient' or 'free from "bad" ingredient' claims; the latter claims also promoted stronger purchase intentions and enhanced product perceptions among this subgroup. CONCLUSIONS: Findings indicate that 'free from "bad" ingredient' claims on unhealthy toddler foods are of most concern, as they boost the appeal of these products to parents. 'Contains "good" ingredient' claims and 'child-related' claims showed limited effects in this study. Considering available evidence, we recommend claims should not be permitted on child-oriented foods, as they may promote inaccurate product perceptions and unhealthy product choices by parents, that can detract from their children's diets and health.

KAP1 Recruitment of the 7SK snRNP Complex to Promoters Enables Transcription Elongation by RNA Polymerase II.

The transition from transcription initiation to elongation at promoters of primary response genes (PRGs) in metazoan cells is controlled by inducible transcription factors, which utilize P-TEFb to phosphorylate RNA polymerase II (Pol II) in response to stimuli. Prior to stimulation, a fraction of P-TEFb is recruited to promoter-proximal regions in a catalytically inactive state bound to the 7SK small nuclear ribonucleoprotein (snRNP) complex. However, it remains unclear how and why the 7SK snRNP is assembled at these sites. Here we report that the transcriptional regulator KAP1 continuously tethers the 7SK snRNP to PRG promoters to facilitate P-TEFb recruitment and productive elongation in response to stimulation. Remarkably, besides PRGs, genome-wide studies revealed that KAP1 and 7SK snRNP co-occupy most promoter-proximal regions containing paused Pol II. Collectively, we provide evidence of an unprecedented mechanism controlling 7SK snRNP delivery to promoter-proximal regions to facilitate "on-site" P-TEFb activation and Pol II elongation.

Structural basis for recognition of distinct deaminated DNA lesions by endonuclease Q.

Spontaneous deamination of DNA cytosine and adenine into uracil and hypoxanthine, respectively, causes C to T and A to G transition mutations if left unrepaired. Endonuclease Q (EndoQ) initiates the repair of these premutagenic DNA lesions in prokaryotes by cleaving the phosphodiester backbone 5' of either uracil or hypoxanthine bases or an apurinic/apyrimidinic (AP) lesion generated by the excision of these damaged bases. To understand how EndoQ achieves selectivity toward these structurally diverse substrates without cleaving undamaged DNA, we determined the crystal structures of Pyrococcus furiosus EndoQ bound to DNA substrates containing uracil, hypoxanthine, or an AP lesion. The structures show that substrate engagement by EndoQ depends both on a highly distorted conformation of the DNA backbone, in which the target nucleotide is extruded out of the helix, and direct hydrogen bonds with the deaminated bases. A concerted swing motion of the zinc-binding and C-terminal helical domains of EndoQ toward its catalytic domain allows the enzyme to clamp down on a sharply bent DNA substrate, shaping a deep active-site pocket that accommodates the extruded deaminated base. Within this pocket, uracil and hypoxanthine bases interact with distinct sets of amino acid residues, with positioning mediated by an essential magnesium ion. The EndoQ-DNA complex structures reveal a unique mode of damaged DNA recognition and provide mechanistic insights into the initial step of DNA damage repair by the alternative excision repair pathway. Furthermore, we demonstrate that the unique activity of EndoQ is useful for studying DNA deamination and repair in mammalian systems.

The big squeeze: a product content and labelling analysis of ready-to-use complementary infant food pouches in Australia.

BACKGROUND: Encouraging the early development of healthy eating habits prevents diet-related chronic disease. It is well understood that highly processed foods with high amounts of sugars, salt and fats are a risk factor for non-communicable diseases. Commercial baby foods in ready-to-use squeeze pouches emerged in the global food market around 2012. The long-term effects of this now ubiquitous packaging on the quality of infant diets, baby food consumption and marketing are unknown. This study aimed to conduct a rigorous mixed-methods audit of squeeze pouches in Australia to inform product regulation and policy. METHODS: Nutritional and marketing data were sourced from products available in Australian retailers. Analysis of nutritional content, texture and packaging labelling and serving size was conducted. Pouches were given a Nutrition Profile Index (NPI) score and compared with the Australian Infant Feeding Guidelines. Marketing text was thematically analysed and compared to existing infant nutrition policy around regulation of marketing claims. RESULTS: 276 products from 15 manufacturers were analysed, targeting infants from 4 + to 12 + months. Total sugar content ranged 0.8-17.5 g/100 g, 20% (n = 56) of products had added sugars, 17% (n = 46) had added fruit juice, 71% (n = 196) had added fruit puree. Saturated fat content ranged from 0.0 to 5.0 g/100 g, sodium 0.0-69 mg/100 g and dietary fibre 0.0-4.3 g/100 g. Only two products were nutritionally adequate according to a nutrient profiling tool. Marketing messages included ingredient premiumisation, nutrient absence claims, claims about infant development and health, good parenting, and convenience. Claims of 'no added sugar' were made for 59% of pouches, despite the addition of free sugars. CONCLUSIONS: Squeeze pouch products available in Australia are nutritionally poor, high in sugars, not fortified with iron, and there is a clear risk of harm tothe health of infant and young children if these products are fed regularly. The marketing messages and labelling on squeeze pouches are misleading and do not support WHO or Australian NHMRC recommendations for breastfeeding or appropriate introduction of complementary foods and labelling of products. There is an urgent need for improved regulation of product composition, serving sizes and labelling to protect infants and young children aged 0-36 months and better inform parents.

The ARF tumor suppressor targets PPM1G/PP2Cγ to counteract NF-κB transcription tuning cell survival and the inflammatory response.

Inducible transcriptional programs mediate the regulation of key biological processes and organismal functions. Despite their complexity, cells have evolved mechanisms to precisely control gene programs in response to environmental cues to regulate cell fate and maintain normal homeostasis. Upon stimulation with proinflammatory cytokines such as tumor necrosis factor-α (TNF), the master transcriptional regulator nuclear factor (NF)-κB utilizes the PPM1G/PP2Cγ phosphatase as a coactivator to normally induce inflammatory and cell survival programs. However, how PPM1G activity is precisely regulated to control NF-κB transcription magnitude and kinetics remains unknown. Here, we describe a mechanism by which the ARF tumor suppressor binds PPM1G to negatively regulate its coactivator function in the NF-κB circuit thereby promoting insult resolution. ARF becomes stabilized upon binding to PPM1G and forms a ternary protein complex with PPM1G and NF-κB at target gene promoters in a stimuli-dependent manner to provide tunable control of the NF-κB transcriptional program. Consistently, loss of ARF in colon epithelial cells leads to up-regulation of NF-κB antiapoptotic genes upon TNF stimulation and renders cells partially resistant to TNF-induced apoptosis in the presence of agents blocking the antiapoptotic program. Notably, patient tumor data analysis validates these findings by revealing that loss of ARF strongly correlates with sustained expression of inflammatory and cell survival programs. Collectively, we propose that PPM1G emerges as a therapeutic target in a variety of cancers arising from ARF epigenetic silencing, to loss of ARF function, as well as tumors bearing oncogenic NF-κB activation.

Toddler foods and milks don't stack up against regular foods and milks.

AIM: To compare the cost and nutritional profiles of toddler-specific foods and milks to 'regular' foods and milks. METHODS: Cross-sectional audit of non-toddler specific ('regular') foods and milks and secondary analysis of existing audit data of toddler specific (12-36 months) foods and milks in Australia. MAIN FINDINGS: The cost of all toddler-specific foods and milks was higher than the regular non-toddler foods. Foods varied in nutritional content, but toddler foods were mostly of poorer nutritional profile than regular foods. Fresh milk cost, on average, $0.22 less per 100 mL than toddler milk. Toddler milks had higher mean sugar and carbohydrate levels and lower mean protein, fat, saturated fat, sodium and calcium levels per 100 mL, when compared to fresh full fat cow's milk. CONCLUSIONS: Toddler specific foods and milks cost more and do not represent value for money or good nutrition for young children.

Regulated nutrition claims increase perceived healthiness of an ultra-processed, discretionary toddler snack food and ultra-processed toddler milks: A discrete choice experiment.

There has been a prolonged increase in the sale and consumption of ultra-processed, discretionary foods and ultra-processed milks for toddlers, which display numerous on-pack claims that influence health perceptions. This study investigated the relative impact of different regulated and unregulated claims on parent perceptions of the healthiness of a toddler snack food and milk in Australia. Participants aged 18+ years completed an online survey, including discrete choice experiments for an ultra-processed, discretionary toddler snack food and an ultra-processed toddler milk, which displayed combinations of claims across nutrition, health, and other domains. Participants were asked to choose the 'most and least healthy' products between three alternatives over seven choice sets. Data were analysed using an ordinal logistic regression model. Likelihood-ratio tests revealed the most important contribution was variation in regulated nutrition-content claims. For the toddler snack, participants were nearly 14 times more likely to perceive a product with the regulated nutrition-content claim "no added sugar, no added salt" as most healthy (OR 13.71, p < 0.001), compared to when no regulated nutrition-content claim was present. For the toddler milk, participants were more than two and a half times more likely to choose a product that contained the regulated nutrition-content claim "2 serves = up to 50% of RDI recommended dietary intake of 14 vitamins and minerals" as most healthy (OR 2.65, p < 0.001) compared to when no regulated nutrition-content claim was present. In Australia, regulated nutrition-content claims can be displayed on packaged foods regardless of healthiness. These results indicate that such claims increase perceptions of healthiness of ultra-processed, discretionary toddler snack foods and ultra-processed toddler milks. Further controls are required to regulate the use of nutrition-content and health claims to facilitate informed consumer choice.

Functional and Structural Insights into a Vif/PPP2R5 Complex Elucidated Using Patient HIV-1 Isolates and Computational Modeling.

Human immunodeficiency virus type 1 (HIV-1) Vif recruits a cellular ubiquitin ligase complex to degrade antiviral APOBEC3 enzymes (APOBEC3C-H) and PP2A phosphatase regulators (PPP2R5A to PPP2R5E). While APOBEC3 antagonism is the canonical function of HIV-1 Vif, this viral accessory protein is also known to trigger G2/M cell cycle arrest. Vif initiates G2/M arrest by degrading multiple PPP2R5 family members, an activity prevalent among diverse HIV-1 and simian immunodeficiency virus (SIV) isolates. Here, computational protein-protein docking was used to delineate a Vif/CBF-ß/PPP2R5 complex in which Vif is predicted to bind the same PPP2R5 surface as physiologic phosphatase targets. This model was tested using targeted mutagenesis of amino acid residues within or adjacent to the putative interface to show loss or retention, respectively, of Vif-induced PPP2R5 degradation activity. Additionally, expression of a peptide that mimics cellular targets of PPP2R5s robustly inhibited Vif-mediated degradation of PPP2R5A but not APOBEC3G. Moreover, live-cell imaging studies examining Vif-mediated degradation of PPP2R5A and APOBEC3G within the same cell revealed that PPP2R5A degradation kinetics are comparable to those of APOBEC3G with a half-life of roughly 6 h postinfection, demonstrating that Vif can concurrently mediate the degradation of distinct cellular substrates. Finally, experiments with a panel of patient-derived Vif isolates indicated that PPP2R5A degradation activity is common in patient-derived isolates. Taken together, these results support a model in which PPP2R5 degradation and global changes in the cellular phosphoproteome are likely to be advantageous for viral pathogenesis.IMPORTANCE A critical function of HIV-1 Vif is to counteract the family of APOBEC3 innate immune proteins. It is also widely accepted that Vif induces G2/M cell cycle arrest in several different cell types. Recently, it has been shown that Vif degrades multiple PPP2R5 phosphoregulators to induce the G2/M arrest phenotype. Here, computational approaches are used to test a structural model of the Vif/PPP2R5 complex. In addition, imaging studies are used to show that Vif degrades these PPP2R5 substrates in roughly the same time frame as APOBEC3 degradation and that this activity is prevalent in patient-derived Vif isolates. These studies are important by further defining PPP2R5 proteins as a bona fide substrate of HIV-1 Vif.

Nutrition and packaging characteristics of toddler foods and milks in Australia.

OBJECTIVE: To analyse nutritional and packaging characteristics of toddler-specific foods and milks in the Australian retail food environment to identify how such products fit within the Australian Dietary Guidelines (ADG) and the NOVA classification. DESIGN: Cross-sectional retail audit of toddler foods and milks. On-pack product attributes were recorded. Products were categorised as (1) food or milk; (2) snack food or meal and (3) snacks sub-categorised depending on main ingredients. Products were classified as a discretionary or core food as per the ADG and level of processing according to NOVA classification. SETTING: Supermarkets and pharmacies in Australia. RESULTS: A total of 154 foods and thirty-two milks were identified. Eighty percentage of foods were snacks, and 60 % of foods were classified as core foods, while 85 % were ultraprocessed (UP). Per 100 g, discretionary foods provided significantly more energy, protein, total and saturated fat, carbohydrate, total sugar and Na (P < 0·001) than core foods. Total sugars were significantly higher (P < 0·001) and Na significantly lower (P < 0·001) in minimally processed foods than in UP foods. All toddler milks (n 32) were found to have higher energy, carbohydrate and total sugar levels than full-fat cow's milk per 100 ml. Claims and messages were present on 99 % of foods and all milks. CONCLUSIONS: The majority of toddler foods available in Australia are UP snack foods and do not align with the ADG. Toddler milks, despite being UP, do align with the ADG. A strengthened regulatory approach may address this issue.

The DNA deaminase APOBEC3B interacts with the cell-cycle protein CDK4 and disrupts CDK4-mediated nuclear import of Cyclin D1.

Apolipoprotein B mRNA editing enzyme catalytic subunit-like protein 3B (APOBEC3B or A3B), as other APOBEC3 members, is a single-stranded (ss)DNA cytosine deaminase with antiviral activity. A3B is also overexpressed in multiple tumor types, such as carcinomas of the bladder, cervix, lung, head/neck, and breast. A3B generates both dispersed and clustered C-to-T and C-to-G mutations in intrinsically preferred trinucleotide motifs (TCA/TCG/TCT). A3B-catalyzed mutations are likely to promote tumor evolution and cancer progression and, as such, are associated with poor clinical outcomes. However, little is known about cellular processes that regulate A3B. Here, we used a proteomics approach involving affinity purification coupled to MS with human 293T cells to identify cellular proteins that interact with A3B. This approach revealed a specific interaction with cyclin-dependent kinase 4 (CDK4). We validated and mapped this interaction by co-immunoprecipitation experiments. Functional studies and immunofluorescence microscopy experiments in multiple cell lines revealed that A3B is not a substrate for CDK4-Cyclin D1 phosphorylation nor is its deaminase activity modulated. Instead, we found that A3B is capable of disrupting the CDK4-dependent nuclear import of Cyclin D1. We propose that this interaction may favor a more potent antiviral response and simultaneously facilitate cancer mutagenesis.

Position Paper on Critical Care Pharmacy Services (Executive Summary): 2020 Update.

OBJECTIVES: Provide a multiorganizational statement to update the statement from a paper in 2000 about critical care pharmacy practice and makes recommendations for future practice. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-Systems Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (> 66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting, and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: forty-four original recommendations and 38 new recommendation statements. Thirty-four recommendations were made for patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations are in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.

Position Paper on Critical Care Pharmacy Services: 2020 Update.

OBJECTIVES: To provide a multiorganizational statement to update recommendations for critical care pharmacy practice and make recommendations for future practice. A position paper outlining critical care pharmacist activities was last published in 2000. Since that time, significant changes in healthcare and critical care have occurred. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-Systems Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (> 66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: 44 original recommendations and 38 new recommendation statements. Thirty-four recommendations represent the domain of patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations were made in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: Critical care pharmacists are essential members of the multiprofessional critical care team. The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.

Mothers' and father's perceptions of the risks and benefits of screen time and physical activity during early childhood: a qualitative study.

BACKGROUND: This study sought to explore mothers' and fathers' perceptions of the risks and benefits of screen time and active play during early childhood. METHODS: In-depth semi structured telephone interviews were conducted with mothers and fathers (n = 28) of children aged 3-5 years who had earlier taken part in a larger quantitative study in Australia and identified willingness to be re-contacted were recruited. Interviews were audio recorded, transcribed verbatim, and analysed using NviVo. Coding was performed to produce themes. Quotes were extracted from the transcripts to illustrate common responses. COREQ guidelines for qualitative papers were followed. RESULTS: Parents reported active play was beneficial for many health and developmental outcomes such as imagination, enjoyment and socialisation, while reporting risks such as safety and stranger danger. There were mixed perceptions of screen time, with benefits such as learning, education and relaxation, and risks including habit formation, inappropriate content, negative cognitive and social outcome, and detriments to health being reported. A few differences between mothers' and fathers' perceptions were evident. CONCLUSION: This study identified that some parental perceptions of benefits and risks of screen time and active play were consistent with published evidence, while others were contradicted by current evidence. Future studies should consider evidence-based education to ensure parents are aware of evidence-based outcomes of children's behaviours. Interventions may wish to capitalise on parents perceived benefits to enhance engagement.

Australian Stakeholder Perspectives on Healthier Retail Food Environments for Toddlers-The Era of "Band Aids and Small Inroads".

Background: A healthy diet in young children is crucial for optimal growth and development. However, many toddlers (1-3 y) consume suboptimal diets, and as a result, are at a high risk of experiencing negative health outcomes. Moreover, minimal progress has been made to improve the healthiness of retail food environments for toddlers to date despite the potential and advocacy for the issue. Objectives: To gain insight into stakeholder perceptions and opinions on the healthiness of Australian retail food environments for toddlers, as well as perspectives on the options and barriers to improve their healthiness. Methods: Qualitative, online study utilizing semi-structured individual interviews with 27 key stakeholders from food industry, academia, nongovernment organizations, public health, and government in Australia. Results: Most stakeholders agreed that retail food environments for toddlers were not health promoting. Stakeholders identified that a multifaceted approach including nutrition education and strong government mandated regulation were essential to improve the healthiness of retail food environments for toddlers. Interviews also highlighted the main perceived barriers to progress, and reasons for policy inaction in this area are the food industry and government support. Many stakeholders were concerned that child health is being undermined due to the government favoring business needs over public health. Conclusions: Stakeholders in this study overwhelmingly agreed that there is more that can and should be done to create health promoting retail food environments for toddlers in Australia. Stakeholders identified a range of strategies that can be used to improve the healthiness of toddler food environments, but advocacy efforts are being undermined due to government inaction. Stakeholders believed that strong governance is required to create equitable, sustainable healthy retail food environments for young children. Improving the healthiness of retail food environments for young children will not only reduce diet related disease across the lifespan but will help to address financial and societal costs of a poor diet.

Yeast Npl3 regulates replicative senescence outside of TERRA R-loop resolution and co-transcriptional processing.

Eukaryotic cells without telomerase experience progressively shorter telomeres with each round of cell division until cell cycle arrest is initiated, leading to replicative senescence. When yeast TLC1, which encodes the RNA template of telomerase, is deleted, senescence is accompanied by increased expression of TERRA (non-coding telomere repeat-containing RNA). Deletion of Npl3, an RNA-processing protein with telomere maintenance functions, accelerates senescence in tlc1Δ cells and significantly increases TERRA levels. Using genetic approaches, we set out to determine how Npl3 is involved in regulating TERRA expression and maintaining telomere homeostasis. Even though Npl3 regulates hyperrecombination, we found that Npl3 does not help resolve RNA:DNA hybrids formed during TERRA synthesis in the same way as RNase H1 and H2. Furthermore, Rad52 is still required for cells to escape senescence by telomere recombination in the absence of Npl3. Npl3 also works separately from the THO/TREX pathway for processing nascent RNA for nuclear export. However, deleting Dot1, a histone methyltransferase involved in tethering telomeres to the nuclear periphery, rescued the accelerated senescence phenotype of npl3Δ cells. Thus, our study suggests that Npl3 plays an additional role in regulating cellular senescence outside of RNA:DNA hybrid resolution and co-transcriptional processing.

Visual communication design: a neglected factor in nutrition promotion via packaged food labels.

Packaging design is a communication device and a critical component in branding strategy, and has relevance for food policy. Presently, packaging-related nutrition policy initiatives focus on the role of regulated claims, nutrition information panels and front-of-pack nutrition labels to help guide consumer food choices and address high prevalences of discretionary and ultra-processed food consumption in many countries. However, these nutrition labelling systems are not optimized as public health policy tools as many consumers do not use them to inform their food choices. Visual communication design theory posits that a designer orders the elements and principles of design into hierarchies that prioritize certain elements over others, and that some of these elements are more dominant and given more emphasis than others. The overall design of the package thereby directs consumer attention to some aspects of pack design (e.g., characters, contents of the package) and away from others (e.g., nutrition details). Dual processing frameworks propose that food decisions are made with the interplay between automatic and rational thinking processes. Packaging designs affect whether consumers rely predominantly on automatic or rational thinking to select a food. This narrative review outlines the role of food packaging design and how it impacts the clear communication of nutrition aspects of food products and how the use of nutrition information by consumers to make decisions may depend upon design structures in packaging. This article attests that nutrition scientists and policy makers should incorporate visual communication design into research on the food packaging as a public health promotion tool. A stronger focus on the communication of regulated front-of-pack nutrition information can be made with a re-evaluation of the hierarchy of elements in the front-of-pack design enabling consumers to make healthier decisions.

Effective recruitment and retention strategies in community health programs.

ISSUE ADDRESSED: The aim of this project was to identify effective recruitment and retention strategies used by health-promotion organisations that focus on increasing physical activity and improving nutrition within the local community. METHODS: Semistructured telephone or face-to-face interviews with 25 key informants from stakeholder organisations were conducted. Key informants discussed strategies used by their organisation to effectively recruit and retain participants into community-based healthy eating and/or physical activity programs. Transcribed data were analysed with NVivo software. RESULTS: Effective recruitment strategies included word of mouth, links with organisations, dissemination of printed materials, media, referrals, cross-promotion of programs and face-to-face methods. Effective retention strategies included encouraging a sense of community ownership, social opportunities, recruiting a suitable leader and offering flexibility and support. Fees and support for recruiting and retaining participants was also identified. CONCLUSION: This study provides novel insights to a greatly under researched topic in the field of health promotion. There are two key take-home messages from the present study that are applicable to health practitioners as well as developers and deliverers of community health-promotion programs: (1) it is imperative that all community health organisations report on the effectiveness of their recruitment and retention, both successes and failures; and (2) there is a clear need to tailor the recruitment and retention approach to the target population and the setting the program is occurring in. SO WHAT? These findings provide important insights for the development of future community-based healthy eating and physical activity programs.

Participation of ATM, SMG1, and DDX5 in a DNA Damage-Induced Alternative Splicing Pathway.

Altered cellular responses to DNA damage can contribute to cancer development, progression, and therapeutic resistance. Mutations in key DNA damage response factors occur across many cancer types, and the DNA damage-responsive gene, TP53, is frequently mutated in a high percentage of cancers. We recently reported that an alternative splicing pathway induced by DNA damage regulates alternative splicing of TP53 RNA and further modulates cellular stress responses. Through damage-induced inhibition of the SMG1 kinase, TP53 pre-mRNA is alternatively spliced to generate TP53b mRNA and p53b protein is required for optimal induction of cellular senescence after ionizing radiation-induced DNA damage. Herein, we confirmed and extended these observations by demonstrating that the ATM protein kinase is required for repression of SMG1 kinase activity after ionizing radiation. We found that the RNA helicase and splicing factor, DDX5, interacts with SMG1, is required for alternative splicing of TP53 pre-mRNA to TP53b and TP53c mRNAs after DNA damage, and contributes to radiation-induced cellular senescence. Interestingly, the role of SMG1 in alternative splicing of p53 appears to be distinguishable from its role in regulating nonsense-mediated RNA decay. Thus, ATM, SMG1, and DDX5 participate in a DNA damage-induced alternative splicing pathway that regulates TP53 splicing and modulates radiation-induced cellular senescence.

PARP inhibition and pharmacological ascorbate demonstrate synergy in castration-resistant prostate cancer.

Prostate cancer (PCa) is the second leading cause of cancer death for men in the United States. While organ-confined disease has reasonable expectation of cure, metastatic PCa is universally fatal upon recurrence during hormone therapy, a stage termed castration-resistant prostate cancer (CRPC). Until such time as molecularly defined subtypes can be identified and targeted using precision medicine, it is necessary to investigate new therapies that may apply to the CRPC population as a whole. The administration of ascorbate, more commonly known as ascorbic acid or Vitamin C, has proved lethal to and highly selective for a variety of cancer cell types. There are several mechanisms currently under investigation to explain how ascorbate exerts anti-cancer effects. A simplified model depicts ascorbate as a pro-drug for reactive oxygen species (ROS), which accumulate intracellularly and generate DNA damage. It was therefore hypothesized that poly(ADP-ribose) polymerase (PARP) inhibitors, by inhibiting DNA damage repair, would augment the toxicity of ascorbate. Results: Two distinct CRPC models were found to be sensitive to physiologically relevant doses of ascorbate. Moreover, additional studies indicate that ascorbate inhibits CRPC growth in vitro via multiple mechanisms including disruption of cellular energy dynamics and accumulation of DNA damage. Combination studies were performed in CRPC models with ascorbate in conjunction with escalating doses of three different PARP inhibitors (niraparib, olaparib, and talazoparib). The addition of ascorbate augmented the toxicity of all three PARP inhibitors and proved synergistic with olaparib in both CRPC models. Finally, the combination of olaparib and ascorbate was tested in vivo in both castrated and non-castrated models. In both cohorts, the combination treatment significantly delayed tumor growth compared to monotherapy or untreated control. Conclusions: These data indicate that pharmacological ascorbate is an effective monotherapy at physiological concentrations and kills CRPC cells. Ascorbate-induced tumor cell death was associated with disruption of cellular energy dynamics and accumulation of DNA damage. The addition of PARP inhibition increased the extent of DNA damage and proved effective at slowing CRPC growth both in vitro and in vivo. These findings nominate ascorbate and PARPi as a novel therapeutic regimen that has the potential to improve CRPC patient outcomes.