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Pro-survival members of the BCL-2 family, including MCL-1, are emerging as important proteins during the development and therapeutic response of solid tumors. Notably, high levels of MCL-1 occur in breast cancer, where functional dependency has been demonstrated using cell lines and mouse models. The utility of restoring apoptosis in cancer cells through inhibition of pro-survival BCL-2 proteins has been realized in the clinic, where the first specific inhibitor of BCL-2 is approved for use in leukemia. A variety of MCL-1 inhibitors are now undergoing clinical trials for blood cancer treatment and application of this new class of drugs is also being tested in solid cancers. On-target compounds specific to MCL-1 have demonstrated promising efficacy in preclinical models of breast cancer and show potential to enhance the anti-tumor effect of conventional therapies. Taken together, this makes MCL-1 an extremely attractive target for clinical evaluation in the context of breast cancer. Abbreviations: ADC (antibody-drug conjugate); AML (Acute myeloid leukemia); APAF1 (apoptotic protease activating factor 1); bCAFs (breast cancer associated fibroblasts); BCL-2 (B-cell lymphoma 2); BH (BCL-2 homology); CLL (chronic lymphocytic leukemia); EGF (epidermal growth factor); EMT (epithelial to mesenchymal transition); ER (estrogen receptor); FDA (food and drug administration); GEMM (genetically engineered mouse model); HER2 (human epidermal growth factor 2); IL6 (interleukin 6); IMM (inner mitochondrial membrane); IMS (intermembrane space); MCL-1 (myeloid cell leukemia-1); MOMP (mitochondrial outer membrane permeabilisation); MM (multiple myeloma); PDX (patient-derived xenograft); OMM (outer mitochondrial membrane); PROTAC (proteolysis-targeting chimeras) TNBC (triple negative breast cancer); UPS (ubiquitin mediated proteolysis system).

Background: Mealtime television use has been cross-sectionally associated with suboptimal diets in children. This study aimed to assess the two-year prospective association between baseline mealtime television use and subsequent diets in young children, and identify socioeconomic differences., Methods: Parents reported their child's television use at meals, and fruit, vegetable, and discretionary food intakes. Multivariable linear and logistic regression analyses assessed the association between baseline mealtime television use and follow-up diet outcomes. Differences were assessed by socioeconomic position., Results: Participants were 352 Australian parents of children aged six months to six years. Daily mealtime television use (average frequency/day) was associated with higher daily frequency of discretionary food intakes (β 0.2, 95% confidence interval (CI) 0.07-0.67) at the 2-year follow-up. Individually, television use during breakfast and dinner (1-2 days/week compared to never) predicted higher daily intake frequency of discretionary food, β 0.36 (95% CI 0.12-0.60) and β 0.19 (95% CI 0.00-0.39), respectively. Similarly, 3-7 days/week of television use during breakfast and lunch predicted higher frequency of discretionary food intake, β 0.18 (95% CI 0.02-0.37) and β 0.31 (95% CI 0.07-0.55), respectively. Associations were not socioeconomically patterned., Conclusions: Investigating mealtime television use motivators across the socioeconomic spectrum could inform interventions targeting the high consumption of discretionary foods in children.

Objective: To explore government support service access, perceived barriers/enablers to menu planning and menu compliance in long day care (LDC) centres in Victoria, Australia, where the Victorian Government-funded Healthy Eating Advisory Service (HEAS) is available to provide free LDC menu planning support., Design: This is a cross-sectional study design. Data were collected from online surveys with the option of uploading 2 weeks of menus and recipes. Menu compliance was scored for quantity, quality and variety. Barriers/enablers to menu planning guideline implementation were determined using the Theoretical Domains Framework (TDF). Independent t tests, one-way ANOVA and chi-square tests assessed relationships between characteristics, barriers/enablers and menu scores., Setting: Eighty-nine LDC centres that prepare food onsite., Participants: LDC staff responsible for menu planning ( n 89) and menus from eighteen centres., Results: Fifty-five per cent of centres had accessed HEAS. Of eighteen provided menus, only one menu was compliant with menu planning guidelines. HEAS access was associated with higher average scores in four of seven TDF domains, namely knowledge/awareness, skills/role, reinforcement/influence and optimism/intent. There were no correlations between menu score and barriers/enablers; however, menu quality scores were higher for those accessing HEAS., Conclusions: Childcare-specific government support services may be an important public health nutrition strategy and may improve menu planning guideline implementation as well as menu quality; however, this does not necessarily translate into menu compliance. Research should confirm these findings in larger studies to ascertain uptake of these services. Public health efforts should focus on exploring barriers and enablers to uptake of government support services to increase reach and acceptability.

Mitochondrial dysfunction is interconnected with cancer. Nevertheless, how defective mitochondria promote cancer is poorly understood. We find that mitochondrial dysfunction promotes DNA damage under conditions of increased apoptotic priming. Underlying this process, we reveal a key role for mitochondrial dynamics in the regulation of DNA damage and genome instability. The ability of mitochondrial dynamics to regulate oncogenic DNA damage centers upon the control of minority mitochondrial outer membrane permeabilization (MOMP), a process that enables non-lethal caspase activation leading to DNA damage. Mitochondrial fusion suppresses minority MOMP and its associated DNA damage by enabling homogeneous mitochondrial expression of anti-apoptotic BCL-2 proteins. Finally, we find that mitochondrial dysfunction inhibits pro-apoptotic BAX retrotranslocation, causing BAX mitochondrial localization and thereby promoting minority MOMP. Unexpectedly, these data reveal oncogenic effects of mitochondrial dysfunction that are mediated via mitochondrial dynamics and caspase-dependent DNA damage., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Immigrant children from low- and middle-income countries (e.g. India) have higher obesity rates than children from high-income countries (e.g. Australia). Infant feeding practices are a key modifiable risk factor to prevent childhood obesity. This study compared infant feeding practices such as breastfeeding, infant formula feeding, timing of introduction to other liquids and solids of Indian-born versus Australian-born mothers living in Australia., Methods: Data of children aged between 0-24 months from the 2010-2011 Australian National Infant Feeding Survey were analysed. Infant feeding practices between Indian-born mothers (n = 501) and Australian-born mothers (n = 510) were compared. Multiple regression models with adjustments for covariates, such as maternal demographic factors, were conducted., Results: Compared to infants of Australian-born mothers, infants of Indian-born mothers were breastfed for 2.1 months longer, introduced solids 0.6 months later and water 0.4 months later (p < 0.001). Moreover, infants of Indian-born mothers were 2.7 times more likely to be currently breastfeeding, 70% less likely to currently consume solids and 67% less likely to consume solids before six months (p < 0.001). In contrast, infants of Indian-born mothers were introduced to fruit juice 2.4 months earlier, water-based drinks 2.8 months earlier and cow's milk 2.0 months earlier than infants of Australian-born mothers (p < 0.001). Additionally, infants of Indian-born mothers were 2.7 times more likely to consume fruit juice (p < 0.001) than the infants of Australian-born mothers., Conclusion: Significant differences exist in infant feeding practices of Indian-born and Australian-born mothers (some health promoting and some potentially obesogenic). The evidence of early introduction of sweetened fluids in infants of Indian-born mothers provides an opportunity to support parents to delay introduction to promote optimal infant growth.., (© 2022. The Author(s).)

Food fussiness is associated with non-responsive parent feeding practices, such as persuasive and instrumental feeding. Although most children described as 'fussy eaters' are likely exhibiting developmentally typical behaviours, up to half of the parents of children 2-5 years old express concerns. Concern for fussy eating may mediate the use of non-responsive feeding practices and so must be addressed in parent feeding interventions. Therefore, it is critical to better understand parents' concerns and how they may relate to feeding practices. This study aimed to explore how parents' feeding practices and the social cognitive factors that may drive them clustered based on parents' concern for fussy eating. Data were collected from parent discussions of fussy eating on a Reddit forum (80,366 posts). Latent Dirichlet allocation was used to identify discussions of fussy eating. Relevant posts (1542) made by users who identified as a parent of a fussy eater (n = 630) underwent qualitative coding and thematic analysis. Five clusters of parents were identified, ranging in size from 53 to 189 users. These were primarily characterised by parents' degree of concern and feeding practices: (1) High concern, nonresponsive; (2) Concerned, nonresponsive; (3) Low concern, responsive; (4) Low concern, mixed strategies; (5) Low concern, indulgent. Parents who used responsive practices tended to be less concerned for fussy eating, have greater trust in their child's ability to self-regulate hunger, have longer-term feeding goals, and exhibit greater ability for personal self-regulation. Future research should further examine how these constructs may be leveraged in parent feeding interventions., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Introduction: Despite being an important period for the development of movement behaviours (physical activity, sedentary behaviour and sleep), few interventions commencing prior to preschool have been trialled. The primary aim of this trial is to assess the 12-month efficacy of the Let's Grow mHealth intervention, designed to improve the composition of movement behaviours in children from 2 years of age. Let's Grow is novel in considering composition of movement behaviours as the primary outcome, using non-linear dynamical approaches for intervention delivery, and incorporating planning for real-world implementation and scale-up from its inception., Methods and Analysis: A randomised controlled trial will test the effects of the 12-month parental support mHealth intervention, Let's Grow , compared with a control group that will receive usual care plus electronic newsletters on unrelated topics for cohort retention. Let's Grow will be delivered via a purpose-designed mobile web application with linked SMS notifications. Intervention content includes general and movement-behaviour specific parenting advice and incorporates established behaviour change techniques. Intervention adherence will be monitored by app usage data. Data will be collected from participants using 24-hour monitoring of movement behaviours and parent report at baseline (T 0 ), mid-intervention (T 1 ; 6 months post baseline), at intervention conclusion (T 2 ; 12 months post baseline) and 1-year post intervention (T 3 ; 2 years post baseline). The trial aims to recruit 1100 families from across Australia during 2021. In addition to assessment of efficacy, an economic evaluation and prospective scalability evaluation will be conducted., Ethics and Dissemination: The study was approved by the Deakin University Human Ethics Committee (2020-077). Study findings will be disseminated through publication in peer-reviewed journals, presentation at scientific and professional conferences, and via social and traditional media., Trial Registration Number: ACTRN12620001280998; U1111-1252-0599., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Ethiopia is affected by recurrent drought and food-insecurity crises, including El Niño. El Niño started in mid-2014, worsened in 2015, and continued in 2016, leading to a widespread food-insecurity emergency resulting in a surge in the rate of acute malnutrition in infants due to suboptimal feeding practices. This study explored how El Niño influenced complementary feeding practices in the eastern Ethiopia community from March to September 2016. It was an exploratory qualitative study with a basic interpretative qualitative approach. A general inductive approach was used for the analysis. The study involved 11 focus group discussions (FGD) with a total of 76 people, including three with mothers, three with Health Development Army (HDA) leaders, two with fathers, two with traditional birth attendants, and one with religious leaders. El Niño resulted in failed crops and loss of livestock, resulting in reduced dietary diversity and meal frequency. El Niño resulted in suboptimal complementary feeding practices by reducing food access and altering livelihood and coping strategies, reducing the time mothers allocated to child feeding, keeping them away from home, and stressing community health services. The maternal suboptimal time allocation is central to the poor complementary feeding practices. Thus, the women should be supported with climate-resilient livelihood options in their villages, allowing them to feed their children and attend education sessions with HDA leaders.

Background: The overall impact of interventions targeting multiple behaviours remains largely unexplored., Objectives: This study adopted an integrative lifestyle pattern analysis approach to assess the overall effectiveness of an early childhood intervention on change across multiple behaviours., Methods: The Melbourne INFANT program was a 15-month cluster-randomized controlled trial involving 4-month-old infants and their parents at baseline in 2008 (n = 542). The intervention included six education sessions helping parents to promote a healthy diet, physical activity and limit sedentary behaviour in their infants. Participants were followed-up twice post-intervention, at ages 3.6 (2011) and 5 years (2013), to assess sustained effects of the intervention. Previous principal component analyses identified two lifestyle patterns from dietary intake, outdoor time and television viewing time. Random effect linear regression models were conducted to assess the impact of the intervention on lifestyle patterns., Results: The intervention group had a lower 'Discretionary consumption and TV' lifestyle pattern score than the control group at all time points with adjusted mean difference: -0.29, 95% CI -0.49, -0.09, p = 0.004 post-intervention at age 1.5 years; -0.29, 95% CI -0.54, -0.04, p = 0.02 at the first follow-up (age 3.6 years); and -0.21, 95% CI -0.43, 0.01, p = 0.06 at the second follow-up (age 5.0 years). No evidence of between-group differences was found for the 'Fruit, vegetables and outdoor' lifestyle pattern score., Conclusion: This early childhood intervention designed to promote change in more than one obesity-related behaviour was effective in improving correlated unhealthy lifestyle behaviours. Lifestyle pattern analysis is a useful and interpretable approach for evaluating multi-behavioural interventions., (© 2021 World Obesity Federation.)

Informed by the Innocenti framework, this rapid review of systematic reviews ( n = 60) and sentinel grey literature ( n = 27) synthesises the evidence of what works to improve nutrition and food sustainability across the first 2000 days. Most systematic reviews focused on interventions targeting the behaviour of parents and caregivers ( n = 49), with fewer reviews focusing on the personal ( n = 7) and external ( n = 4) food environments. No reviews focused on food supply-chain activities. Most reviews were rated as critically low ( n = 28, 47%) or low ( n = 21, 35%) quality using AMSTAR 2. Evidence supports the effectiveness of multi-component breastfeeding interventions, interventions delivered in home and child-care settings, particularly when involving parents, interactive skill building and repeated exposure to vegetables. Food vouchers and access to local farmers markets and community gardens have potential for improving access and availability to healthier foods, while evidence supports interventions improving the external food environment, including fiscal strategies such as the SSB tax, restrictions on marketing and advertising of discretionary products and improved food labelling. Overall, this review highlights the importance of action across a range of settings and sectors at the international, national and local levels to improve young children's diets.

Families face many barriers in providing nutritious home-cooked family meals. Meal kit subscription services are increasingly popular among families and may address obstacles to cooking at home and facilitate shared family meals. This study aimed to understand why families use meal kits and what they perceived to be the main impacts on family dynamics, nutrition, social and mental health. Sixteen primary meal providers with at least one child 18 years and under living at home, were recruited via social media (e.g., Facebook, Twitter) to participate in a semi-structured interview using Zoom videoconferencing. Interviews were conducted with participants who currently purchased and used commercially available meal kits in Australia (e.g., HelloFresh, Marley Spoon). Thematic analysis of interview transcripts revealed that women, as the primary carers responsible for family meals, primarily reported the role that meal kits played in reducing their mental load through reduced food-related decision making, enhanced family participation in meal preparation, and opportunities for food literacy. Additionally, meal kits were reported to reduce food eaten away-from-home with the majority of participants perceiving meal kits to provide nutritionally dense meals and appropriate portion sizes aligned with National dietary guidelines. This study provides important insights into the potential physical, mental and social health benefits of meal kits in supporting families to cook and eat meals together at home. While meal kits have the capacity to positively influence population health and wellbeing, it is necessary that meal kit subscription services address the nutritional quality of their meals and provide evidence-based nutrition messaging to facilitate improvements in food literacy and nutritional intake., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Gestational diabetes (GDM) impacts 8-18% of pregnancies and greatly increases both maternal and child risk of developing non-communicable diseases such as type 2 diabetes and obesity. Whilst lifestyle interventions in pregnancy and postpartum reduce this risk, a research translation gap remains around delivering implementable interventions with adequate population penetration and participation. Impact Diabetes Bump2Baby is an implementation project of an evidence-based system of care for the prevention of overweight and obesity. Bump2Baby and Me is the multicentre randomised controlled trial investigating the effectiveness of a mHealth coaching programme in pregnancy and postpartum for women at high risk of developing GDM., Methods: Eight hundred women will be recruited in early pregnancy from 4 clinical sites within Ireland, the UK, Spain, and Australia. Women will be screened for eligibility using the validated Monash GDM screening tool. Participants will be enrolled from 12 to 24 weeks' gestation and randomised on a 1:1 basis into the intervention or control arm. Alongside usual care, the intervention involves mHealth coaching via a smartphone application, which uses a combination of synchronous and asynchronous video and text messaging, and allows for personalised support and goal setting with a trained health coach. The control arm receives usual care. All women and their children will be followed from early pregnancy until 12 months postpartum. The primary outcome will be a difference in maternal body mass index (BMI) of 0.8 kg/m 2 at 12 months postpartum. Secondary maternal and infant outcomes include the development of GDM, gestational weight gain, pregnancy outcomes, improvements in diet, physical activity, sleep, and neonatal weight and infant growth patterns. The 5-year project is funded by the EU Commission Horizon 2020 and the Australian National Health and Medical Research Council. Ethical approval has been received., Discussion: Previous interventions have not moved beyond tightly controlled efficacy trials into routine service delivery. This project aims to provide evidence-based, sustainable support that could be incorporated into usual care for women during pregnancy and postpartum. This study will contribute evidence to inform the early prevention of non-communicable diseases like obesity and diabetes in mothers and the next generation., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12620001240932 . Registered on 19 November 2020., (© 2021. The Author(s).)

While the household in which a child grows up is considered a critical environment that influences nutrition outcomes, there is little research examining the influence of household composition and structure on complementary feeding practices. This study examined the influence of household structure and composition on complementary feeding practices, using the Ethiopian Demographic and Health Survey (EDHS), 2000 to 2016. The composition variables were calculated from the attributes of household members (alters) and the structure variables from their kinship status. A multilevel mixed-effects regression model, specifying survey rounds as the random effect, was used to examine the association between household structure/composition and the Minimum Meal Frequency (MMF) and Minimum Dietary Diversity (MDD). The average Marginal Effects (MEs) were calculated to facilitate practical interpretation. Children of caregivers with a higher number of alters (degree), unique number of kinship category (effect size), closely related (constraint), and mixed-age alters (age diversity) seemed to increase the probability of meeting the MDD. Degree and effective size decreased the probability of meeting MMF, while constraint increased it. Overall, this study revealed some associations between household structure and composition and complementary feeding practices. Hence, complementary feeding interventions could be adapted to account for the household structure and composition variations.

Damaged or superfluous cells are typically eliminated by apoptosis. Although apoptosis is a cell-autonomous process, apoptotic cells communicate with their environment in different ways. Here we describe a mechanism whereby cells under apoptotic stress can promote survival of neighbouring cells. We find that upon apoptotic stress, cells release the growth factor FGF2, leading to MEK-ERK-dependent transcriptional upregulation of pro-survival BCL-2 proteins in a non-cell autonomous manner. This transient upregulation of pro-survival BCL-2 proteins protects neighbouring cells from apoptosis. Accordingly, we find in certain cancer types a correlation between FGF-signalling, BCL-2 expression and worse prognosis. In vivo, upregulation of MCL-1 occurs in an FGF-dependent manner during skin repair, which regulates healing dynamics. Importantly, either co-treatment with FGF-receptor inhibitors or removal of apoptotic stress restores apoptotic sensitivity to cytotoxic therapy and delays wound healing. These data reveal a pathway by which cells under apoptotic stress can increase resistance to cell death in surrounding cells. Beyond mediating cytotoxic drug resistance, this process also provides a potential link between tissue damage and repair., (© 2021. The Author(s).)

Hematopoietic stem cells (HSCs) reside at the apex of the hematopoietic differentiation hierarchy and sustain multilineage hematopoiesis. Here, we show that the transcriptional regulator CITED2 is essential for life-long HSC maintenance. While hematopoietic-specific Cited2 deletion has a minor impact on steady-state hematopoiesis, Cited2-deficient HSCs are severely depleted in young mice and fail to expand upon aging. Moreover, although they home normally to the bone marrow, they fail to reconstitute hematopoiesis upon transplantation. Mechanistically, CITED2 is required for expression of key HSC regulators, including GATA2, MCL-1, and PTEN. Hematopoietic-specific expression of anti-apoptotic MCL-1 partially rescues the Cited2-deficient HSC pool and restores their reconstitution potential. To interrogate the Cited2→Pten pathway in HSCs, we generated Cited2;Pten compound heterozygous mice, which had a decreased number of HSCs that failed to reconstitute the HSC compartment. In addition, CITED2 represses multiple pathways whose elevated activity causes HSC exhaustion. Thus, CITED2 promotes pathways necessary for HSC maintenance and suppresses those detrimental to HSC integrity., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Promoting healthy eating and active play in early life is critical, however few interventions have been delivered or sustained at scale. The evaluation of interventions at scale is a crucial, yet under-researched aspect of modifying population-level health behaviours. INFANT is an evidence-based early childhood healthy lifestyle intervention that aims to improve parents' knowledge and skills around promoting optimal energy balance-related behaviours that, in turn, influence children's diet, activity and adiposity. It consists of: 1) Four group sessions delivered via first time parent groups across the first 12 months of life; 2) access to the My Baby Now app from birth to 18 months of age. This research aims to assess real-world implementation, effectiveness and cost-effectiveness of INFANT when delivered at scale across Victoria, Australia., Methods and Analysis: A hybrid type II implementation-effectiveness trial applying a mixed methods design will be conducted. INFANT will be implemented in collaboration with practice and policy partners including maternal and child health services, population health and Aboriginal health, targeting all local government areas (n=79) in Victoria, Australia. Evaluation is based on criteria from the 'Outcomes for Implementation Research' and 'RE-AIM' frameworks. Implementation outcomes will be assessed using descriptive quantitative surveys and qualitative interviews with those involved in implementation, and include intervention reach, organisational acceptability, adoption, appropriateness, cost, feasibility, penetration and sustainability. Process measures include organizational readiness, fidelity, and adaptation. Effectiveness outcomes will be assessed using a sample of INFANT participants and a non-randomized comparison group receiving usual care (1,500 infants in each group), recruited within the same communities. Eligible participants will be first time primary caregivers of an infant aged 0-3 months, owning a personal mobile phone and able to communicate in English. Effectiveness outcomes include infant lifestyle behaviours and BMIz at 12 and 18 months of age., Impact: This is the first known study to evaluate the scale up of an evidence based early childhood obesity prevention intervention under real world conditions. This study has the potential to provide generalisable implementation, effectiveness and cost-effectiveness evidence to inform the future scale up of public health interventions both in Australia and internationally., Clinical Trial Registration: Australian and New Zealand Clinical Trial Registry https://www.anzctr.org.au/, identifier ACTRN12620000670976., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Laws, Love, Hesketh, Koorts, Denney-Wilson, Moodie, Brown, Ong, Browne, Marshall, Lioret, Orellana and Campbell.)

Cell death is a natural process in organismal development, homeostasis and response to disease or infection that eliminates unnecessary or potentially dangerous cells and acts as an innate barrier to oncogenesis. Inactivation of cell death is a key step in tumour development and also impedes effective response to cancer therapy. Precise execution of unwanted cells is achieved through regulated cell death processes including the intrinsic apoptotic pathway that is governed by the BCL-2 (B-cell lymphoma 2) protein family. There is compelling evidence that intrinsic apoptosis is defective in prostate cancer, particularly in metastatic and castration resistant advanced disease, currently a lethal diagnosis. New therapeutics have been developed to target pro-survival BCL-2 proteins (including BCL-2, BCL-XL and MCL-1) and show promise in reinstating apoptosis to destroy tumour cells in haematological cancers. Here we discuss perturbation of cell death in prostate cancer and how new therapeutics could improve treatment outcome in prostate cancer., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Very few early childhood interventions have observed sustained effects regarding television viewing and none have examined the mechanisms behind sustained intervention effects at long-term follow-ups. Thus, the aim of this study was to investigate potential mechanisms relating to the maintained intervention effect on television viewing at two long-term follow-ups in the Melbourne Infant Feeding Activity and Nutrition Trial (INFANT). INFANT was a cluster-randomised controlled trial. At the 2- and 3.5-year follow-ups, a total of 262 infant/mother pairs had complete information. Television viewing was assessed via a questionnaire at both follow-ups and six potential mediators were measured post-intervention (i.e. 15 months after baseline). Causal mediation analysis was conducted. At the 2- and 3.5-year follow-ups, the positive impacts of INFANT on maternal television viewing knowledge were maintained (B = 0.34 units; 95% confidence interval (CI 95 ): 0.21, 0.48). An indirect effect of the intervention on reducing children's television viewing time was observed at the 2- and 3.5-year follow-ups (B = -11.73 min/day; CI 95 : -22.26, -3.28 and B = -4.78 min/day; CI 95 : -9.48, -0.99, respectively) via improved maternal television viewing knowledge.Conclusion: The positive impacts of INFANT on maternal television viewing knowledge were maintained at both follow-ups, with better maternal knowledge associated with less television viewing time in their children. These results have implications for paediatricians and healthcare professionals as educating new parents early on regarding screen time may lead to the development of healthier screen time habits that are sustained through to the pre-school years. What is Known: • Lifestyle behaviours inclusive of screen time have been found to be established before the pre-school years and track. • Few trials have evaluated the long-term mechanisms related to maintained intervention effectiveness. What is New: • This study shows the positive impacts of a low-dose intervention on maternal television viewing knowledge at two long-term follow-ups. • Better maternal television viewing knowledge was associated with less television viewing time in their children., (© 2021. The Author(s).)

Emerging evidence shows an association between protein intake during infancy and later obesity risk, and that association may differ by protein sources. This systematic review summarized and evaluated prospective cohort studies assessing the long-term association of total protein intake and protein sources during infancy (from birth to 2 y) with subsequent obesity outcomes in childhood or adolescence. Literature searches were conducted in Embase, Medline, Scopus, and Web of Science. Sixteen studies that reported associations between total protein intake and/or protein intake from different sources from birth to 2 y and ≥1 obesity outcomes in childhood or adolescence from 9 cohorts were identified. Most studies (11/16) were rated as high quality. The most frequently reported association was total protein intake and BMI (up to 10 y) with 6 out of 7 cohorts showing significant positive associations. Similar associations were found for animal protein, but not for plant protein. Limited studies examined the association between protein intake (both total and sources) and body composition (body fat, fat mass, and fat-free mass) and revealed inconsistent findings. Overall, higher intakes of total and animal protein during infancy were associated with higher BMI in childhood and adolescence. Future studies investigating the contribution of protein sources in long-term obesity development are needed. This review was registered at PROSPERO as CRD42020166540., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background/objectives: The role of infant feeding practices in longitudinal growth trajectories in children remains equivocal. This study utilised two longitudinal approaches to examine the associations of infant feeding mode (breastfeeding, mixed feeding, formula feeding), breastfeeding duration, and the timing of solid foods introduction with body mass index (BMI) z-score in early childhood., Subjects/methods: Secondary analyses of data from the Healthy Beginnings Trial were conducted. Infant feeding practices were reported by mothers at 6, 12, and 24 months of child age. Child weight and length were measured at birth, 12, 24, 42, and 60 months. Two longitudinal approaches: linear spline multilevel model (LSMM) and group-based trajectory modelling (GBTM) were used to describe BMI z-score trajectories and assess its associations with infant feeding practices., Results: The LSMM approach demonstrated that the breastfeeding group showed lower BMI z-scores from ages 12 to 60 months than the mixed feeding and formula feeding groups. Children who were breastfed for ≥ 6 versus < 6 months exhibited a lower BMI z-score trajectory from ages 12 to 60 months. Results from the GBTM approach revealed that the mixed feeding (OR: 1.83, 95%CI 1.04, 3.21) and the formula feeding group (OR: 2.00, 95%CI 0.67, 5.92) showed a tendency for higher odds of following the "High BMIz" trajectory than the breastfeeding group. Breastfeeding duration ≥6 versus < 6 months was linked with lower odds of following the "High BMIz" trajectory (OR 0.65, 95%CI 0.43, 0.98). Both approaches revealed no evidence of an association between the timing of solid foods introduction and BMI z-score trajectory., Conclusions: The two longitudinal approaches revealed similar findings that infant feeding mode and breastfeeding duration, but not the timing of solid foods introduction, were associated with BMI z-score trajectory in early childhood. The findings provide robust longitudinal evidence to encourage and support extended breastfeeding for childhood obesity prevention., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The link between high protein intake during infancy and obesity later in childhood has been much debated, and the association with differing protein sources remains unclear., Objective: This study aimed to examine the associations between total protein intake and protein from different sources (ie, nondairy animal, dairy, and plant) reported at age 9 months and development in body mass index (BMI) z scores until age 5 years., Design: This study involved a secondary data analysis of the Melbourne InFANT (Infant Feeding, Activity and Nutrition Trial) program, an observational prospective cohort study that was conducted from 2008 to 2013., Participants/setting: Participants were children (n = 345) who completed both the 9-month and 5-year follow-up visits within the Melbourne InFANT program., Main Outcome Measures: BMI z score was measured at age 5 years., Statistical Analyses Performed: Linear mixed models with a random effect for clusters of mother's group and with adjustment for baseline child and maternal covariates were conducted., Results: With adjustment for covariates, every 1 g or 1% energy increase in total protein intake at age 9 months was associated with a 0.016-unit (95% CI 0.003 to 0.029) or 0.034-unit (95% CI 0.005 to 0.063) increase in BMI z score at age 5 years, respectively. With respect to protein sources, associations of similar magnitude were found for nondairy animal protein. No evidence of an association with BMI z score was found for dairy (including milk, yogurt, cheese, breast milk, and infant formula) and plant proteins., Conclusions: High intakes of total protein, nondairy animal protein, but not dairy or plant proteins, during infancy were associated with higher BMI z score in early childhood. These findings can inform dietary recommendations regarding protein intakes during infancy., Clinical Trial Registration: The InFANT program was registered with Current Controlled Trials (ISRCTN81847050); http://www.isrctn.com/ISRCTN81847050., (Copyright © 2021 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

High levels of the anti-apoptotic BCL-2 family member MCL-1 are frequently found in breast cancer and, appropriately, BH3-mimetic drugs that specifically target MCL-1's function in apoptosis are in development as anti-cancer therapy. MCL-1 also has reported non-canonical roles that may be relevant in its tumour-promoting effect. Here we investigate the role of MCL-1 in clinically relevant breast cancer models and address whether the canonical role of MCL-1 in apoptosis, which can be targeted using BH3-mimetic drugs, is the major function for MCL-1 in breast cancer. We show that MCL-1 is essential in established tumours with genetic deletion inducing tumour regression and inhibition with the MCL-1-specific BH3-mimetic drug S63845 significantly impeding tumour growth. Importantly, we found that the anti-tumour functions achieved by MCL-1 deletion or inhibition were completely dependent on pro-apoptotic BAX/BAK. Interestingly, we find that MCL-1 is also critical for stem cell activity in human breast cancer cells and high MCL1 expression correlates with stemness markers in tumours. This strongly supports the idea that the key function of MCL-1 in breast cancer is through its anti-apoptotic function. This has important implications for the future use of MCL-1-specific BH3-mimetic drugs in breast cancer treatment., (© 2021. The Author(s).)

Background: Behavioural patterns are typically derived using unsupervised multivariate methods such as principal component analysis (PCA), latent profile analysis (LPA) and cluster analysis (CA). Comparability and congruence between the patterns derived from these methods has not been previously investigated, thus it's unclear whether patterns from studies using different methods are directly comparable. This study aimed to compare behavioural patterns derived across diet, physical activity, sedentary behaviour and sleep domains, using PCA, LPA and CA in a single dataset., Methods: Parent-report and accelerometry data from the second wave (2011/12; child age 6-8y, n = 432) of the HAPPY cohort study (Melbourne, Australia) were used to derive behavioural patterns using PCA, LPA and CA. Standardized variables assessing diet (intake of fruit, vegetable, sweet, and savoury discretionary items), physical activity (moderate- to vigorous-intensity physical activity [MVPA] from accelerometry, organised sport duration and outdoor playtime from parent report), sedentary behaviour (sedentary time from accelerometry, screen time, videogames and quiet playtime from parent report) and sleep (daily sleep duration) were included in the analyses. For each method, commonly used criteria for pattern retention were applied., Results: PCA produced four patterns whereas LPA and CA each generated three patterns. Despite the number and characterisation of the behavioural patterns derived being non-identical, each method identified a healthy, unhealthy and a mixed pattern. Three common underlying themes emerged across the methods for each type of pattern: (i) High fruit and vegetable intake and high outdoor play ("healthy"); (ii) poor diet (either low fruit and vegetable intake or high discretionary food intake) and high sedentary behaviour ("unhealthy"); and (iii) high MVPA, poor diet (as defined above) and low sedentary time ("mixed")., Conclusion: Within this sample, despite differences in the number of patterns derived by each method, a good degree of concordance across pattern characteristics was seen between the methods. Differences between patterns could be attributable to the underpinning statistical technique of each method. Therefore, acknowledging the differences between the methods and ensuring thorough documentation of the pattern derivation analyses is essential to inform comparison of patterns derived through a range of approaches across studies., Competing Interests: The authors have declared that no competing interests exist.

Background: The respective contribution of total, daytime and nighttime sleep duration in childhood obesity remains unclear., Objectives: To assess the longitudinal association between developmental trajectories of sleep duration and BMI z-score in early childhood., Methods: Data were from the Melbourne INFANT program, a prospective cohort with 4-month-old infants being followed-up until age 60 months (n = 528). Sleep duration (total, daytime, nighttime) and BMI z-score were measured using questionnaire at ages 4, 9, 18, 43 and 60 months. Group-based trajectory modelling was used to describe longitudinal trajectories from ages 4 to 60 months. Multivariable logistic regression was conducted to assess the association between sleep duration and BMI z-score trajectories., Results: Three nighttime sleep duration trajectory groups were identified: "Long stable" (10.5 to 11.0 hours, 61%), "catchup long" (8.0 to 11.5 hours, 23%) and "short stable" (8.7 to 9.8 hours, 16%) nighttime sleepers. BMI z-score trajectory groups were classified as "low-BMIz" (-1.5 to -0.5 unit, 21%), "mid-BMIz" (-0.5 to 0.5 unit, 58%) and "high-BMIz" (0.8 to 1.4 unit, 21%). With adjustment for child and maternal covariates, both "catchup long" (OR 3.69 95%CI 1.74, 7.92) and "long stable" nighttime sleepers (OR 4.27 95%CI 2.21, 8.25) revealed higher odds of being in the "mid-BMIz" than the "high-BMIz" group. By contrast, total or daytime sleep duration trajectories were not associated with BMI z-score trajectories., Conclusions: Longer nighttime, but not total or daytime, sleep duration was associated with lower BMI z-score trajectories in early childhood. Our findings reinforce the importance of nighttime sleep for healthy body-weight development in early childhood., (© 2020 World Obesity Federation.)

Competing Interests: Competing interests: None declared.

Early intervention is critical for addressing the challenge of childhood obesity. Yet many preventive interventions do not target infants most at risk of future overweight or obesity. This systematic review examines interventions delivered before 2 years that aim to ameliorate excess weight gain among infants at high risk of overweight or obesity, due to sociodemographic characteristics, parental weight or health status, infant feeding or health behaviours. We searched six databases for interventions: (a) delivered before age two, (b) specifically aimed at infants at high risk of childhood obesity and (c) that reported outcomes by weight status beyond 28 days. The search identified over 27,000 titles, and 49 papers from 38 studies met inclusion criteria: 10 antenatal interventions, 16 postnatal and 12 conducted both before and after birth. Nearly all targeted infant and/or maternal nutrition. Studies varied widely in design, obesity risk factors, outcomes and quality. Overall, nine interventions of varying quality reported some evidence of significantly improved child weight trajectory, although effects tended to diminish over time. Interventions that improved weight outcomes tended to engage parents for a longer period, and most offered health professional input and support. Two studies of limited quality reported significantly worse weight outcomes in the intervention group., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Introduction: We evaluated the use of text messages to communicate information to patients whose surgeries were postponed because of the COVID-19 restriction on elective surgeries. Our hypothesis was that text messaging would be an effective way to convey updates., Methods: In this observational study, 295 patients received text messaging alerts. Eligibility included patients who had their surgery postponed and had a cell phone that received text messages. Engagement rates were determined using embedded smart links. Patient survey responses were collected., Results: A total of 3,032 texts were delivered. Engagement rates averaged 90%. Survey responses (n = 111) demonstrated that 98.2% of patients liked the text messages and 95.5% said that they felt more connected to their care team; 91.9% of patients agreed that the text updates helped them avoid calling the office. Patients with higher pain levels reported more frustration with their surgery delay (5.3 versus 2.8 on 1 to 10 scale, P value < 0.01). More frustrated patients wished they received more text messages (24.4% versus 4.6%, P value = 0.04) and found the content less helpful (8.2 versus 9.2 on 1 to 10 scale, P value = 0.01)., Conclusion: Text messaging updates are an efficient way to communicate with patients during the COVID-19 pandemic., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: Understanding the mechanisms (mediators) of behavior change is crucial to designing more effective interventions. However, this is rarely reported. This paper investigates the mechanisms that explain the lack of intervention effect on physical activity and the significant effect on television viewing time from an early childhood trial., Methods: Secondary analyses were undertaken of data from a cluster randomized controlled trial. The Melbourne Infant Feeding, Activity and Nutrition Trial (INFANT) was a 15-month group program promoting obesity-protective behaviors from the age of 4 months. Outcomes relevant to the current study were child physical activity (accelerometer), television viewing time (maternal report) and 12 potential mediator scales (maternal report). Linear regression models used the product of coefficients method with a joint significance test., Results: Complete data were from 398 mother-child dyads. Despite weak evidence of an intervention effect on the mother's physical activity knowledge and optimism, there was no effect on children's physical activity, and no clear mechanisms were identified. An intervention effect was observed for the mothers' television knowledge (unstandardized regression coefficient for a path ( a ) = 0.34, 95% confidence interval (CI 95 ) = 0.22, 0.45), with weak evidence for maternal efficacy ( a = 0.11, CI 95 = -0.02, 0.24) and the use of television ( a = -0.10, CI 95 = -0.22, 0.01). The intervention impact on television knowledge explained 75% of the difference between the intervention and control groups in children's television viewing., Conclusions: In the very early childhood period, as mothers are commencing their parenting journey, improving their behavioral knowledge appears to be the biggest contributor to reducing child television viewing, constituting a relatively simple strategy that could be implemented across clinical and public health settings. In contrast, it remains unclear what mechanisms may increase physical activity levels in this age group.

Objective: To prioritise and refine a set of evidence-informed statements into advice messages to promote vegetable liking in early childhood, and to determine applicability for dissemination of advice to relevant audiences., Design: A nominal group technique (NGT) workshop and a Delphi survey were conducted to prioritise and achieve consensus (≥70 % agreement) on thirty evidence-informed maternal (perinatal and lactation stage), infant (complementary feeding stage) and early years (family diet stage) vegetable-related advice messages. Messages were validated via triangulation analysis against the strength of evidence from an Umbrella review of strategies to increase children's vegetable liking, and gaps in advice from a Desktop review of vegetable feeding advice., Setting: Australia., Participants: A purposeful sample of key stakeholders (NGT workshop, n 8 experts; Delphi survey, n 23 end users)., Results: Participant consensus identified the most highly ranked priority messages associated with the strategies of: 'in-utero exposure' (perinatal and lactation, n 56 points) and 'vegetable variety' (complementary feeding, n 97 points; family diet, n 139 points). Triangulation revealed two strategies ('repeated exposure' and 'variety') and their associated advice messages suitable for policy and practice, twelve for research and four for food industry., Conclusions: Supported by national and state feeding guideline documents and resources, the advice messages relating to 'repeated exposure' and 'variety' to increase vegetable liking can be communicated to families and caregivers by healthcare practitioners. The food industry provides a vehicle for advice promotion and product development. Further research, where stronger evidence is needed, could further inform strategies for policy and practice, and food industry application.

Objective: This study examined the association between longitudinal trajectories of lifestyle patterns (LPs) and BMI z score in early childhood., Methods: Data of children (n = 439) who participated in the 18-, 42-, and 60-month follow-ups of the Melbourne InFANT Program were used. Multitrajectory modeling identified groups of children following similar LPs and BMI z score trajectories, and multinomial logistic regression assessed the determinants of the trajectory groups., Results: Three trajectory groups of child LPs and BMI z scores were identified: "Unhealthy LP, Low BMIz" (30%), "Healthy LP, Mid BMIz" (53%), and "Unhealthy LP, High BMIz" (17%). Relative to the "Unhealthy LP, Low BMIz" group, the maternal "Fruit and vegetables" dietary pattern was associated with higher odds (odds ratio [OR] 1.22, 95% CI: 1.01-1.47) of children following the "Healthy LP, Mid BMIz" group. Maternal prepregnancy BMI (≥25 kg/m 2 ) (OR 2.50, 95% CI: 1.31-4.75) and maternal TV-viewing time ≥130 min/d (OR 2.55, 95% CI: 1.13, 5.72) increased the odds of children following the "Unhealthy LP, High BMIz" group. Child sex, breastfeeding duration, and maternal physical activity were not associated with the identified trajectory groups., Conclusions: Three trajectory groups of LPs and BMI z scores in early childhood were revealed, with maternal prepregnancy BMI, dietary pattern, and TV-viewing time being identified as significant determinants., (© 2021 The Obesity Society.)

Background: Chinese Australian mothers are more likely than the general Australian mothers to introduce formula in the first month of age. A better understanding of the context of formula introduction in the early weeks of birth can provide a deeper insight into how Chinese Australian mothers can be supported to continue exclusive breastfeeding., Methods: An interpretative phenomenological analysis approach was used to examine the lived breastfeeding experiences of 11 first time Chinese mothers in Australia. The experiences of those who breastfed exclusively were compared to those who introduced formula in the first month after birth., Findings: An overarching theme across all participants' narratives was the meaning ascribed to breastfeeding in their emerging motherhood identity. Breastfeeding could be a pragmatic and a socially desirable method to nourish an infant but lacking personal identification to the mother. These mothers were more vulnerable to the early introduction of formula, especially when the support environment was lacking. Maternal identity conflict was common and negatively impacted exclusive breastfeeding and mothers' mental health. In contrast, mothers who identified closely with breastfeeding showed greater persistence and enjoyment in breastfeeding and were more likely to continue breastfeeding exclusively. Health professionals were perceived to have an important influence in strengthening maternal breastfeeding motivation and self-efficacy., Conclusion: Breastfeeding support to Chinese Australian mothers needs to consider how breastfeeding can be better integrated with their motherhood identity. Health professionals are well-positioned to facilitate this process through a better understanding of mothers' cultural and social contexts around breastfeeding., (Copyright © 2020 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

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.

Objective: This study aimed to assess whether the long-term effectiveness of the Melbourne Infant, Feeding, Activity and Nutrition Trial (INFANT) at 2 and 3·5 years post-intervention varied according to maternal education and age., Design: Two and 3·5 years post-intervention follow-up of the INFANT cluster-randomised controlled trial. Outcomes at both follow-ups included children's BMI z-scores, physical activity (ActiGraph), television viewing (parental report) and dietary intake (3 × 24-h dietary recalls). Dichotomous moderator variables included maternal education (university v. no university) and age (< 32 v. ≥ 32 years)., Setting: Population based., Participants: Families completing the 15-month programme (n 492) were invited to participate in the follow-ups when their child was 3·6 and 5 years old., Results: At the 2-year follow-up, the intervention effects on vegetable (positive) and sweet snack (negative) intake were greater in children with higher educated mothers, whereas water consumption (positive) was greater in children with lower educated mothers. At the 2-year follow-up, the intervention was more effective in increasing water consumption in children with younger mothers and decreasing sweet snack intake in children with older mothers (opposite result observed at the 3·5-year follow-up). At the 3·5-year follow-up, children with younger and older mothers increased and decreased their consumption of savoury snacks, respectively., Conclusions: Moderation by maternal education and age were observed for some outcomes; however, clear patterns were not evident at both follow-ups, with little consistency across outcomes. This indicates that INFANT was more-or-less equally effective in children irrespective of their mother's education level or age, which is important in community-based interventions.

Introduced rodent populations pose significant threats worldwide, with particularly severe impacts on islands. Advancements in genome editing have motivated interest in synthetic gene drives that could potentially provide efficient and localized suppression of invasive rodent populations. Application of such technologies will require rigorous population genomic surveys to evaluate population connectivity, taxonomic identification, and to inform design of gene drive localization mechanisms. One proposed approach leverages the predicted shifts in genetic variation that accompany island colonization, wherein founder effects, genetic drift, and island-specific selection are expected to result in locally fixed alleles (LFA) that are variable in neighboring nontarget populations. Engineering of guide RNAs that target LFA may thus yield gene drives that spread within invasive island populations, but would have limited impacts on nontarget populations in the event of an escape. Here we used pooled whole-genome sequencing of invasive mouse ( Mus musculus ) populations on four islands along with paired putative source populations to test genetic predictions of island colonization and characterize locally fixed Cas9 genomic targets. Patterns of variation across the genome reflected marked reductions in allelic diversity in island populations and moderate to high degrees of differentiation from nearby source populations despite relatively recent colonization. Locally fixed Cas9 sites in female fertility genes were observed in all island populations, including a small number with multiplexing potential. In practice, rigorous sampling of presumptive LFA will be essential to fully assess risk of resistance alleles. These results should serve to guide development of improved, spatially limited gene drive design in future applications., (© 2021 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Achieving the optimal transition to a family diet over the first two years of life has remained a challenge in Ethiopia. The use of amylase-rich flour (ARF) can improve complementary foods. However, utilisation requires an effective delivery strategy for upskilling the community to use ARF. The aim of this study was to explore facilitators and barriers of cascading ARF skills to improve complementary foods. The study was conducted in Gale Mirga kebele of Kersa district in Eastern Ethiopia in 2016. The study utilised exploratory qualitative research that used participatory action. Focus group discussions (FGDs) were conducted with the Health Development Army (HDA) leaders, religious leaders, and observation of participatory complementary food demonstrations. Cultural acceptability and the presence of HDA structure that supports skill development were identified as key facilitators to ARF use. On the other hand, the potential barriers to expanding ARF skill were lack of sustainability of external skill support for HDA leaders, perceived time constraints, unsuitable demonstration settings, cooking method, and large group size. The indigenous community's knowledge of germination has not been used to improve complementary foods. The universal use of ARF requires integration into the Health Extension Programme (HEP) with support and supervision for HDA leaders.

Purpose: A comprehensive understanding of the biomechanical properties of the medial patellofemoral complex (MPFC) is necessary when performing an MPFC reconstruction. How components of the MPFC change over the course of flexion can influence the surgeon's choice of location for graft fixation along the extensor mechanism. The purpose of this study was to (1) determine native MPFC length changes throughout a 90° arc using an anatomically based attachment and using Schöttle's point, and (2) compare native MPFC length changes with different MPFC attachment sites along the extensor mechanism., Methods: Eight fresh-frozen (n = 8), cadaveric knees were dissected of all soft tissue structures except the MPFC. The distance between the femoral footprint (identified through anatomical landmarks and Schottle's point) and the MPFC was calculated at four attachment sites along the extensor mechanism [midpoint of the patella [MP], the center of the osseous footprint of the MPFC (FC), the superomedial corner of the patella at the quadriceps insertion (SM), and the proximal extent of the MPFC along the quadriceps tendon (QT)] at 0°, 20°, 40°, 60°, and 90° of flexion., Results: Length changes were investigated between the MPFL femoral attachment site and the radiographic surrogate of the MPFL attachment site, Schottle's Point (SP). Paired t tests at each of the four components showed no differences in length change from 0° to 90° when comparing SP to the anatomic MPFC insertion. MPFL length changes from 0° to 90° were greatest at the QT point (13.9 ± 3.0 mm) and smallest at the MP point (2.7 ± 4.4 mm). The FC and SM points had a length change of 6.6 ± 4.2 and 9.0 ± 3.8, respectively. Finally, when examining how the length of the MPFC components changed through flexion, the greatest differences were seen at QT where all comparisons were significant (p < 0.01) except when comparing 0° vs 20° (n.s.)., Conclusion: The MPFC demonstrates the most significant length changes between 0° and 20° of flexion, while more isometric behavior was seen during 20°-90°. The attachment points along the extensor mechanism demonstrate different length behaviors, where the more proximal components of the MPFC display greater anisometry through the arc of motion. When performing a proximal MPFC reconstruction, surgeons should expect increased length changes compared to reconstructions utilizing distal attachment sites.

Background: Chinese immigrants are the third largest immigrant group in Australia. Little is known about growth trajectories of their offspring when moving to a Western country. The aim was to describe the growth trajectories between birth to 3.5 years in children of Chinese-born immigrant mothers compared with Australian-born mothers living in Victoria, Australia., Methods: Ten nurse measured weights and lengths from birth to 3.5 years were used to examine growth trajectory using linear spline multilevel models. Five knot points were identified at visit 2 (0.5 months), visit 4 (2 months), visit 5 (4.5 months), visit 8 (18 months) and visit 9 (25 months)., Results: Ethnic disparities in growth trajectories between these two groups were revealed in models adjusted for birth weight, sex and level of socioeconomic disadvantage. Children of Chinese-born compared with Australian-born mothers revealed different growth rates and significant differences in predicted mean body mass index Z score (zBMI) at all time points from birth to 44 months, except for 12 months. Specifically, when compared with children of Australian-born mothers, children of Chinese-born mothers started with lower predicted zBMI from birth until 0.5 months, had a higher zBMI from 1 to 8 months and a lower zBMI from 12 to 44 months. Early and sharp acceleration of growth was also observed for children of Chinese-born mothers (0.5-2 months) when compared with children of Australian-born mothers (2-18 months)., Conclusion: Differences in growth trajectories exist between young children of Chinese-born and Australian-born mothers. Better understanding of these ethnically patterned growth trajectories is important for identifying key opportunities to promote healthy growth in early life., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In Sweden, there have been no interventions promoting the development of healthy lifestyle behaviors starting in infancy. Thus this paper aims to: (i) investigate Swedish parents' experiences regarding feeding of solid foods, screen time, and physical activity in healthy infants; (ii) investigate parents' needs and perceptions regarding information/support provided in primary child healthcare (CHC) and (iii) explore whether a parenting program focused on child diet and active play would be relevant and utilized. Semi-structured interviews were conducted with 20 parents. These were recorded, transcribed verbatim and analyzed using thematic analysis. Seven themes emerged: Feeling excited to enter a new phase; Parents' responsibility of doing it "right" can be stressful; Motivated to learn during specific time windows; Information to trust; The importance of social support from peers; Experiences of support received from CHC; and the Infant, Feeding, Activity, and Nutrition Trial (INFANT) for a Swedish context. Parents were excited to enter new phases in their child's development. However, this came with worry they were doing things "right", leading parents to want more information/support. Overall, Swedish parents were very positive about the prospects of engaging in a primary CHC delivered program to support them to promote healthy lifestyle behaviors from birth and felt this could complement the care currently provided.

Background: Childhood obesity is a global problem. Early obesity prevention interventions are complex and differ in effectiveness. Novel frameworks, taxonomies and experience from the Early Prevention of Obesity in CHildren (EPOCH) trials were applied to unpack interventions., Objectives: Deconstruct interventions into their components (target behaviours, delivery features and behaviour change techniques [BCTs]). Identify lessons learned and future recommendations for intervention planning, delivery, evaluation and implementation., Methods: This multi-methods study deconstructed the four EPOCH interventions into target behaviours, delivery features and BCTs from unpublished and published materials using systematic frameworks. Additionally, semi-structured interviews were conducted with intervention facilitators and principal investigators., Results: Each trial targeted between 10 and 14 obesity-related behaviours. Key variations in delivery features related to intensity, delivery mode and tailoring. BCTs consistently used across trials included goal-setting, social support, shaping knowledge, role-modelling and credible source. Recommendations from interview analyses include the importance of stakeholder collaboration and consideration of implementation throughout the study process., Conclusions: The combination of frameworks, methodologies and interviews used in this study is a major step towards understanding complex early obesity prevention interventions. Future work will link systematic intervention deconstruction with quantitative models to identify which intervention components are most effective and for whom., (© 2020 World Obesity Federation.)

This study explored the views of participants who completed a 5-week, online, interactive, family-based, salt reduction education program (Digital Education to LImit Salt in the Home). A secondary aim was to explore the views of school staff on the delivery of food and nutrition education in schools. Children aged 7-10 years, their parents and principals/teachers from participating schools located in Victoria, Australia, completed a semi-structured evaluation interview. Audio-recordings of interviews were transcribed verbatim and analysed using NVivo. Twenty-eight interviews (13 children; 11 parents; 4 school staff) were included. Thematic analysis revealed that the program was well received by all groups. Children reported that the interactivity of the education sessions helped them to learn. Parents thought the program was interesting and important, and reported learning skills to reduce salt in the family diet. School staff supported the delivery of nutrition education in schools but indicated difficulties in sourcing well-packed nutrition resources aligned with the curriculum. It appears that there is support from parents and teachers in the delivery of innovative, engaging, nutrition education in schools, however such programs need to be of high quality, aligned with the school curriculum and readily available for incorporation within the school's teaching program., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Diet, physical activity, sedentary behaviour and sleep are typically examined independently with childhood adiposity; however, their combined influence remains uncertain. This review aims to systematically summarize evidence on the clustering of these behaviours through lifestyle patterns and evaluate associations with adiposity in children aged 5-12 years. Search strategies were run in six databases. Twenty-eight papers met the inclusion criteria, six of which included all four behaviours. A range of lifestyle patterns were identified (healthy, unhealthy and mixed). Mixed patterns were most frequently reported. Unhealthy patterns comprising low physical activity and high sedentary behaviour were also frequently observed. Mixed patterns comprising healthy diets, low physical activity and high sedentary behaviour were more commonly seen in girls, whereas boys were more physically active, similarly sedentary and had unhealthier diets. Children from lower socio-economic backgrounds tended to more frequently display unhealthy patterns. Unhealthy lifestyle patterns were more often associated with adiposity risk than healthy and mixed patterns. With few studies including all four behaviours, it is difficult to establish a clear picture of their interplay and associations with adiposity. Nonetheless, reliance on lifestyle patterns is likely more beneficial than individual behaviours in targeting adiposity and improving understanding of how these behaviours influence health., (© 2020 World Obesity Federation.)

Background: The few health behavior interventions commencing in infancy have shown promising effects. Greater insight into their longer-term benefits is required. This study aimed to assess post-intervention effects of the Melbourne INFANT Program to child age 5y on diet, movement and adiposity., Methods: Two and 3.5y post-intervention follow-up (2011-13; analyses completed 2019) of participants retained in the Melbourne INFANT Program at its conclusion (child age ~ 19 m; 2008-10) was conducted. The Melbourne INFANT Program is a 15-month, six session program delivered within first-time parent groups in Melbourne, Australia, between child age 4-19 m. It involves strategies to help parents promote healthy diet, physical activity and reduced sedentary behavior in their infants. No intervention was delivered during the follow-up period reported in this paper. At all time points height, weight and waist circumference were measured by researchers, children wore Actigraph and activPAL accelerometers for 8-days, mothers reported children's television viewing and use of health services. Children's dietary intake was reported by mothers in three unscheduled telephone-administered 24-h recalls., Results: Of those retained at program conclusion (child age 18 m, n = 480; 89%), 361 families (75% retention) participated in the first follow-up (2y post-intervention; age 3.6y) and 337 (70% retention) in the second follow-up (3.5y post-intervention; age 5y). At 3.6y children in the intervention group had higher fruit (adjusted mean difference [MD] = 25.34 g; CI 95 :1.68,48.99), vegetable (MD = 19.41; CI 95 :3.15,35.67) and water intake (MD = 113.33; CI 95 :40.42,186.25), than controls. At 5y they consumed less non-core drinks (MD = -27.60; CI 95 :-54.58,-0.62). Sweet snack intake was lower for intervention children at both 3.6y (MD = -5.70; CI 95 :-9.75,-1.65) and 5y (MD = -6.84; CI 95 :-12.47,-1.21). Intervention group children viewed approximately 10 min/day less television than controls at both follow-ups, although the confidence intervals spanned zero (MD = -9.63; CI 95 :-30.79,11.53; MD = -11.34; CI 95 :-25.02,2.34, respectively). There was no evidence for effect on zBMI, waist circumference z-score or physical activity., Conclusions: The impact of this low-dose intervention delivered during infancy was still evident up to school commencement age for several targeted health behaviors but not adiposity. Some of these effects were only observed after the conclusion of the intervention, demonstrating the importance of long-term follow-up of interventions delivered during early childhood., Trial Registration: ISRCTN Register ISRCTN81847050 , registered 7th November 2007.

Background: While exclusive breastfeeding is recommended to 6 months of age, just 15% of mothers in Australia achieve this. The rate appears to be even lower among mothers born in China, where 90% have introduced infant formula by this time. This study aimed to examine infant feeding patterns in the first 12 months of life and the factors associated with exclusive breastfeeding at 4 months of age and infant formula introduction by 1 month of age among Chinese Australian mothers., Methods: Chinese Australian women with a child aged 1 to 4 years born in Australia were recruited through social media and asked to complete an online survey. Chinese ethnicity was defined as the mother or her parents having been born in mainland China, Taiwan or Hong Kong. Infant feeding practices since birth and a range of psychosocial and cultural factors were assessed. A total of 289 Chinese Australian mothers completed the survey. The relationships between exposure variables and exclusive breastfeeding at 4 months or infant formula use by 1 month were examined using multivariable logistic regression., Results: Almost all (93%) mothers initiated breastfeeding, however by 1 month of age exclusive breastfeeding rates reduced to 44%, with a further decline to 33 and 18% at 4 and 6 months respectively. Concurrently, 7% of parents reported infant formula feeding at birth increasing to 55 and 63% at 1 and 6 months of age respectively. The rates of any breastfeeding were 81% at 6 months and 50% at 12 months of age. Breastfeeding intention, self-efficacy and awareness of the infant feeding guidelines were key factors associated with sustained exclusive breastfeeding to 4 months., Conclusions: While Chinese Australian mothers had comparable exclusive breastfeeding rates at 6 months to the general Australian population, twice as many had introduced infant formula by 1 month of age. There is an urgent need to support Chinese Australian mothers in the perinatal period to strengthen their knowledge, intention and confidence to delay early introduction of infant formula and promote exclusive breastfeeding in the early postpartum period.

The recurring association of specific genetic lesions with particular types of cancer is a fascinating and largely unexplained area of cancer biology. This is particularly true of clear cell renal cell carcinoma (ccRCC) where, although key mutations such as loss of VHL is an almost ubiquitous finding, there remains a conspicuous lack of targetable genetic drivers. In this study, we have identified a previously unknown protumorigenic role for the RUNX genes in this disease setting. Analysis of patient tumor biopsies together with loss-of-function studies in preclinical models established the importance of RUNX1 and RUNX2 in ccRCC. Patients with high RUNX1 (and RUNX2) expression exhibited significantly poorer clinical survival compared with patients with low expression. This was functionally relevant, as deletion of RUNX1 in ccRCC cell lines reduced tumor cell growth and viability in vitro and in vivo . Transcriptional profiling of RUNX1-CRISPR-deleted cells revealed a gene signature dominated by extracellular matrix remodeling, notably affecting STMN3, SERPINH1 , and EPHRIN signaling. Finally, RUNX1 deletion in a genetic mouse model of kidney cancer improved overall survival and reduced tumor cell proliferation. In summary, these data attest to the validity of targeting a RUNX1-transcriptional program in ccRCC. SIGNIFICANCE: These data reveal a novel unexplored oncogenic role for RUNX genes in kidney cancer and indicate that targeting the effects of RUNX transcriptional activity could be relevant for clinical intervention in ccRCC., (©2020 American Association for Cancer Research.)

Background : Early childhood (2-5 years) is acknowledged as a critical time for the establishment of healthy behaviours. The increasing number of children and amount of time spent in childcare provides strong rationale to explore the important role that childcare services and childcare educators play in influencing healthy eating behaviours of young children in their care. Methods : This study used a qualitative exploratory approach to describe the knowledge, attitudes and practices of Australian childcare trainee educators' regarding their role in the feeding of young children. Results : All participants agreed that feeding of young children was an important part of their role, but described challenges to the promotion of healthy eating and the adoption of responsive child feeding practices. These included personal beliefs and experiences with food, the bi-directional nature of child feeding, conflicting parental requests and/or unsupportive centre-based policies and procedures. Conclusion : Training about responsive child feeding practices within the childcare sector should include all childcare staff; aim to enhance relational efficacy and communication skills with parents; and empower childcare staff to lead organisational change. To support this, childcare centres need to provide coherent centre-based healthy eating policies inclusive of healthy food provision and desirable feeding practices.