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AIMS: In 2019, the Australian Academy of Science in collaboration with the nutrition community published the decadal plan for the science of nutrition. This article aims to review progress towards each of its pillar goals (societal determinants, nutrition mechanisms, precision and personalised nutrition, and education and training) and two enabling platforms (a national data capability and a trusted voice for nutrition science), prioritise actions, and conceptualise program logic implementation models. This process also brought together public health nutrition researchers to reflect on societal determinants of health, and advise how the next 5 years of the decadal plan could reflect contemporary issues. METHODS: Two engagement events, in 2023, brought together experienced and mid- and early-career nutrition professionals for co-creation of implementation logic models. RESULTS: One hundred and nine early and mid-career professionals were involved. A revised model for the decadal plan pillars emerged from synthesis of all logic models. This new model integrated the precision and personalised nutrition pillar with nutrition mechanisms pillar. These combined pillars build towards the national data capability enabling platform and created new cross-cutting themes for education and training. The need arose for greater focus on respectful engagement with Aboriginal and Torres Strait Islander communities and sustained effort to build cross-disciplinary collaboration to realise the plan's societal determinants goals. A new alliance for nutrition science is proposed to become a unified advocacy voice and build trust in nutrition professionals. CONCLUSIONS: A programmatic approach provides a road map for implementing the decadal plan for the final 5 years.

Background: There are numerous guidelines developed for bone health. Yet, it is unclear whether the differences in guideline development methods explain the variability in the recommendations for vitamin D and calcium intake. The objective of this systematic review was to collate and compare recommendations for vitamin D and calcium across bone health guidelines, assess the methods used to form the recommendations, and explore which methodological factors were associated with these guideline recommendations. Methods: We searched MEDLINE, EMBASE, CINAHL, and other databases indexing guidelines to identify records in English between 2009 and 2019. Guidelines or policy statements on bone health or osteoporosis prevention for generally healthy adults aged ≥40 years were eligible for inclusion. Two reviewers independently extracted recommendations on daily vitamin D and calcium intake, supplement use, serum 25 hydroxyvitamin D [25(OH)D] level, and sunlight exposure. They assessed guideline development methods against 25 recommended criteria in the World Health Organization (WHO) handbook for guideline development. Additionally, they identified types of evidence underpinning the recommendations. Results: we included 47 eligible guidelines from 733 records: 74% of the guidelines provided vitamin D (200~600–4000 IU/day) and 70% provided calcium (600–1200 mg/day) recommendations, 96% and 88% recommended vitamin D and calcium supplements, respectively, and 70% recommended a specific 25(OH)D concentration. On average, each guideline met 10 (95% CI: 9–12) of the total of 25 methodological criteria for guideline development recommended by the WHO Handbook. There was uncertainty in the association between the methodological criteria and the proportion of guidelines that provided recommendations on daily vitamin D or calcium. Various types of evidence, including previous bone guidelines, nutrient reference reports, systematic reviews, observational studies, and perspectives/editor

Nutrition interventions can support Aboriginal and Torres Strait Islander peoples to reduce their risk of cardiovascular disease (CVD). This review examines nutritional interventions aiming to improve CVD outcomes and appraises peer-reviewed interventions using an Aboriginal and Torres Strait Islander Quality Appraisal Tool. Five electronic databases and grey literature were searched, applying no time limit. Two reviewers completed the screening, data extraction and quality assessment independently. The study quality was assessed using the South Australian Health and Medical Research Institute and the Centre of Research Excellence in Aboriginal Chronic Disease Knowledge Translation and Exchange Aboriginal and Torres Strait Islander Quality Appraisal Tool (QAT). Twenty-one nutrition programs were included in this review. Twelve reported on anthropometric measurements, ten on biochemical and/or hematological measurements and sixteen on other outcome domains. Most programs reported improvements in measurable CVD risk factors, including reduced body mass index (BMI), waist circumference (WC), weight, blood pressure and improved lipid profiles. Most programs performed well at community engagement and capacity strengthening, but many lacked the inclusion of Indigenous research paradigms, governance and strengths-based approaches. This review highlights the need for contemporary nutrition programs aimed at improving cardiovascular health outcomes to include additional key cultural components.

In occasione dei sessant'anni di Massimo Recalcati, sono stata invitata a partecipare a una giornata di studio sulla sua opera (23 novembre 2019); il contributo presente è una rielaborazione del mio intervento. La mia formazione è stata segnata da due eredità, tra loro intrecciate: il debito simbolico che mi lega a Riccardo Massa (e mi ha reso la pedagogista che sono) e l'interesse per la psicoanalisi che, ancora, alimenta la mia ricerca. Nello scritto discuto, a partire dalle riflessioni di Massimo Recalcati, il tema dell'eredità, l'importanza della separazione e la riconquista di quanto ereditato. Infine, esploro la categoria massiana di sadomasochismo pedagogico alla luce delle riflessioni di Recalcati sulla perversione e su desiderio, facendo emergere l'importanza dell'eros pedagogico nella trasmissione del sapere in pedagogia quanto in psicoanalisi.

Introduction Current recommendations for vitamin D and calcium in dietary guidelines and bone health guidelines vary significantly among countries and professional organisations. It is unknown whether the methods used to develop these recommendations followed a rigourous process and how the differences in methods used may affect the recommended intakes of vitamin D and calcium. The objectives of this study are (1) collate and compare recommendations for vitamin D and calcium across guidelines, (2) appraise methodological quality of the guideline recommendations and (3) identify methodological factors that may affect the recommended intakes for vitamin D and calcium. This study will make a significant contribution to enhancing the methodological rigour in public health guidelines for vitamin D and calcium recommendations. Methods and analyses We will conduct a systematic review to evaluate vitamin D and calcium recommendations for osteoporosis prevention in generally healthy middle-aged and older adults. Methodological assessment will be performed for each guideline against those outlined in the 2014 WHO handbook for guideline development. A systematic search strategy will be applied to locate food-based dietary guidelines and bone health guidelines indexed in various electronic databases, guideline repositories and grey literature from 1 January 2009 to 28 February 2019. Descriptive statistics will be used to summarise the data on intake recommendation and on proportion of guidelines consistent with the WHO criteria. Logistic regression, if feasible, will be used to assess the relationships between the methodological factors and the recommendation intakes. Ethics and dissemination Ethics approval is not required as we will only extract published data or information from the published guidelines. Results of this review will be disseminated through conference presentations and peer-reviewed publications. PROSPERO registration number CRD42019126452.

Introduction Maintaining fluid intake sufficient to reduce arginine vasopressin (AVP) secretion has been hypothesised to slow kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). However, evidence to support this as a clinical practice recommendation is of poor quality. The aim of the present study is to determine the long-term efficacy and safety of prescribed water intake to prevent the progression of height-adjusted total kidney volume (ht-TKV) in patients with chronic kidney disease (stages 1-3) due to ADPKD. Methods and analysis A multicentre, prospective, parallel-group, open-label, randomised controlled trial will be conducted. Patients with ADPKD (n=180; age ≤65 years, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m 2) will be randomised (1:1) to either the control (standard treatment+usual fluid intake) or intervention (standard treatment+prescribed fluid intake) group. Participants in the intervention arm will be prescribed an individualised daily fluid intake to reduce urine osmolality to ≤270 mOsmol/kg, and supported with structured clinic and telephonic dietetic review, self-monitoring of urine-specific gravity, short message service text reminders and internet-based tools. All participants will have 6-monthly follow-up visits, and ht-TKV will be measured by MRI at 0, 18 and 36 months. The primary end point is the annual rate of change in ht-TKV as determined by serial renal MRI in control vs intervention groups, from baseline to 3 years. The secondary end points are differences between the two groups in systemic AVP activity, renal disease (eGFR, blood pressure, renal pain), patient adherence, acceptability and safety. Ethics and dissemination The trial was approved by the Human Research Ethics Committee, Western Sydney Local Health District. The results will inform clinicians, patients and policy-makers regarding the long-term safety, efficacy and feasibility of prescribed fluid intake as an approach to reduce kidn

AIM To investigate the relationship between 25-hydroxyvitamin D (25-OHD) deficiency and hepatic encephalopathy (HE) in patients with chronic liver disease (CLD). METHODS A retrospective analysis of the results of 392 adult patients with chronic liver disease who were assessed for liver transplantation between 2006 and 2010 was undertaken. HE, severity of CLD, nutritional status and 25-OHD were analysed in patients assessed for liver transplantation between 2006 and 2010. Patients who presented with acute, fulminant or subacute disease, with a primary diagnosis of liver cancer, were assessed for re-transplantation or who did not have a 25-OHD measurement were excluded from the analysis. RESULTS One hundred and sixty-five patients were included in this analysis. The mean age of all patients was 53 ± 8 years. Moderate to severe 25-OHD deficiency was identified in 49 patients of whom 36 had grade 2-3 HE compared with 13 patients who were not encephalopathic (p ≤ 0.0001). Mild 25-OHD deficiency was not associated with HE. There was a significant correlation between the severity of 25-OHD deficiency and the severity of liver disease (r = 0.39, p ≤ 0.0001) and disease severity and the presence of HE (p ≤ 0.0001). Importantly, individuals with 25-OHD deficiency were more likely to have a diagnosis of overt HE (OHE) at a significantly lower model for end stage liver disease (MELD) score than individuals without OHE (p ≤ 0.0001). This significant difference was observed with MELD scores from 10 to 38. CONCLUSION 25-OHD deficiency was observed in the majority of patients with CLD and for the first time was found to be significantly worse in patients with OHE.

BACKGROUND: Short food questions are appealing to measure dietary intakes. METHODS: A review of studies published between 2004 and 2016 was undertaken and these were included in the present study if they reported on a question or short item questionnaire (≤50 items, data presented as ≤30 food groups) measuring food intake or food-related habits, in children (aged 6 months to 18 years), and reported question validity or reliability. Thirty studies met the inclusion criteria. RESULTS: Most questions assessed foods or food groups (n = 29), with the most commonly assessed being fruit (n = 22) or vegetable intake (n = 23), dairy foods and discretionary foods (n = 20 studies each). Four studies assessed food habits, with the most common being breakfast and meal frequency (n = 4 studies). Twenty studies assessed reliability, and 25 studies determined accuracy and were most commonly compared against food records. Evaluation of question performance relied on statistical tests such as correlation. CONCLUSIONS: The present study has identified valid and reliable questions for the range of key food groups of interest to public health nutrition. Questions were more likely to be reliable than accurate, and relatively few questions were both reliable and accurate. Gaps in repeatable and valid short food questions have been identified that will provide direction for future tool development.

Introduction Community-based weight management programmes are important in addressing childhood obesity. However, the mechanisms that lead to behaviour change within the programmes are rarely studied within the context of the programmes themselves once they have been implemented. This means that further potential gains in the effectiveness of the programme are often not made and any potential losses of efficacy are often not noticed. Qualitative research alongside randomised controlled trials (RCTs) can tell us the context in which these programmes are implemented and elucidate potential mediators or modifiers of the programmes' effectiveness. The aim of this evaluation is to determine the barriers and enablers to the delivery and impact of an incentive-based behaviour change strategy targeting child obesity to inform future translation. Methods and analysis Qualitative analysis, including stakeholder and family interviews, focus groups and a survey, will be used. The research will be conducted in collaboration with policymakers, researchers and community health professionals. Participants will be selected from programme providers, and parents/carers and children participating in an Australian community weight management programme during an RCT examining the effectiveness of incentives for improving behaviour change. A maximum variation sampling method based on participant demographics and group characteristics will be used. Thematic analysis will be carried out inductively based on emergent themes, using NVivo V.9. Ethics and dissemination This research is approved by the South West Sydney Human Ethics Committee review body (HREC/14/LPOOL/480). The evaluation will provide information about the contextual and influencing factors related to the outcomes of the RCT. The results will assist researchers, community health practitioners and policymakers regarding the development, implementation and translation of behaviour change strategies in community initiatives for ob

Introduction: Prevention of falls and promotion of physical activity are essential for maximising well-being in older age. However, there is evidence that promoting physical activity among older people without providing fall prevention advice may increase fall rates. This trial aims to establish the impact of a physical activity and fall prevention programme compared with a healthy eating programme on physical activity and falls among people aged 60+ years. Methods and analysis: This cluster randomised controlled trial will involve 60 groups of community-dwelling people aged 60+ years. Participating groups will be randomised to: (1) a physical activity and fall prevention intervention (30 groups), involving written information, fall risk assessment and prevention advice, a pedometer-based physical activity tracker and telephone-based health coaching; or (2) a healthy eating intervention (30 groups) involving written information and telephone-based dietary coaching. Primary outcomes will be objectively measured physical activity at 12 months post-randomisation and self-reported falls throughout the 12-month trial period. Secondary outcomes include: the proportion of fallers, the proportion of people meeting the Australian physical activity guidelines, body mass index, eating habits, mobility goal attainment, mobility-related confidence, quality of life, fear of falling, risk-taking behaviour, mood, well-being, self-reported physical activity, disability, and health and community service use. The between-group difference in the number of falls per person-year will be analysed using negative binomial regression models. For the continuously scored primary and secondary outcome measures, linear regression adjusted for corresponding baseline scores will assess the effect of group allocation. Analyses will be preplanned, conducted while masked to group allocation, will take into account cluster randomisation, and will use an intention-to-treat approach. Ethics and dissemin

Background: TXT2BFiT was one of the first few innovative mHealth programs designed for young adults (18-35 years) with demonstrated efficacy in weight management. However, research is lacking to understand intervention effectiveness, especially in complex, multi-component mHealth programs. This paper investigates participant perceptions of and engagement with the mHealth program components in the TXT2BFiT to understand program effects. Methods: Process evaluation data were collected continuously for the study duration. The TXT2BFiT program was a multi-component lifestyle program delivered intensively for 3-month followed by a 6-month maintenance phase. Program components included personalised coaching calls, text messages, emails, smartphone apps and website access. Process evaluation measures included frequency of use of components and frequency for number of components used (online survey data); dose delivered and engagement with program components (researcher logs and web platform reports); frequency, timing and difficulties experienced with program components (online survey data) and overall perceptions of program components (online survey data and semi-structured telephone interviews). Qualitative data analysis was performed using NVivo10. Results: Over 80% of participants completed post-intervention (3-months, intervention, n = 110, control n = 104) and follow-up surveys (9-months, intervention, n = 96, control n = 104). Thirty intervention participants completed semi-structured telephone interviews. Participants reported high use of coaching calls, text messages and emails and no issues in content delivery from these components. These components were described as helping them to achieve their goals. Website and app use and engagement was low for the duration of the program. Participants would prefer incorporation of the self-monitoring apps and website resources into one smartphone application that can be individualised by entry of their personal data. Conclu

Animal-source foods (ASF) have the potential to enhance the nutritional adequacy of cereal-based diets in low- and middle-income countries, through the provision of high-quality protein and bioavailable micronutrients. The development of guidelines for including ASF in local diets requires an understanding of the nutrient content of available resources. This article reviews food composition tables (FCT) used in sub-Saharan Africa, examining the spectrum of ASF reported and exploring data sources for each reference. Compositional data are shown to be derived from a small number of existing data sets from analyses conducted largely in high-income nations, often many decades previously. There are limitations in using such values, which represent the products of intensively raised animals of commercial breeds, as a reference in resource-poor settings where indigenous breed livestock are commonly reared in low-input production systems, on mineral-deficient soils and not receiving nutritionally balanced feed. The FCT examined also revealed a lack of data on the full spectrum of ASF, including offal and wild foods, which correspond to local food preferences and represent valuable dietary resources in food-deficient settings. Using poultry products as an example, comparisons are made between compositional data from three high-income nations, and potential implications of differences in the published values for micronutrients of public health significance, including Fe, folate and vitamin A, are discussed. It is important that those working on nutritional interventions and on developing dietary recommendations for resource-poor settings understand the limitations of current food composition data and that opportunities to improve existing resources are more actively explored and supported.

Background: Despite international efforts to arrest increasing rates of overweight and obesity, many population strategies have neglected young adults as a target group. Young adults are at high risk for unhealthy weight gain which tends to persist throughout adulthood with associated chronic disease health risks.Methods/design: TXT2BFiT is a nine month two-arm parallel-group randomized controlled trial aimed at improving weight management and weight-related dietary and physical activity behaviors among young adults. Participants are recruited via general practice (primary medical care) clinics in Sydney, New South Wales, Australia. All participants receive a mailed resource outlining national physical activity and dietary guidelines and access to the study website. Additional resources accessible to the intervention arm via the study website include Smartphone mobile applications, printable handouts, an interactive healthy weight tracker chart, and a community blog. The study consists of two phases: (1) Intensive phase (weeks 1 to 12): the control arm receives four short message service (SMS) text messages; the intervention arm receives eight SMS messages/week tailored to their baseline stage-of-change, one Email/week, and personalized coaching calls during weeks 0, 2, 5, 8, and 11; and (2) Maintenance phase (weeks 14 to 36): the intervention arm receives one SMS message/month, one Email/month and booster coaching calls during months 5 and 8. A sample of N = 354 (177 per arm) is required to detect differences in primary outcomes: body weight (kg) and body mass index (kg/m), and secondary outcomes: physical activity, sitting time, intake of specific foods, beverages and nutrients, stage-of-change, self-efficacy and participant well-being, at three and nine months. Program reach, costs, implementation and participant engagement will also be assessed.Discussion: This mobile phone based program addresses an important gap in obesity prevention efforts to date. The metho

The Get Healthy Information and Coaching Service® (GHS), a free government-funded telephone-delivered information and coaching service was launched in February 2009 by the Australian New South Wales state government. It represents the translation of research evidence applied in the real world (T4 or Phase 4 translation), aimed at addressing the modifiable risk factors associated with the overweight and obesity. In controlled settings, it has been established that telephone-based lifestyle counseling programs are efficacious in reducing anthropometric and behavioral risk factors. This article presents the GHS case study as a population-wide intervention and describes the quasi-experimental evaluation framework used to evaluate both the process (statewide implementation) and impact (effectiveness) of the GHS in a real-world environment. It details the data collection, measures, and statistical analysis required in assessing the process of implementation-reach and recruitment, marketing and promotion, service satisfaction, intervention fidelity, and GHS setting up and operations costs-and in assessing the impact of GHS-increasing physical activity, improving dietary practices, and reducing body weight and waist circumference. The comprehensive evaluation framework designed for the GHS provides a method for building effectiveness evidence of a rare translation of efficacy trial evidence into population-wide practice. © 2012 Society for Public Health Education.

Confidence in a professional role is a key element in the successful transition to competent practice. New graduate dietitians report that whilst they are confident about their general dietetic ability, they are not as confident when working with clients experiencing depression and anxiety. This study aimed to develop and validate a scale which measured confidence about working with clients with depression/anxiety. The 21-item Dietetics Collaborative Practice Scale was developed using research about dietetic practice in mental health, coping self-efficacy literature and collaboration with industry experts. A convenience sample of 189 Australian dietitians completed the questionnaire. Exploratory factor analysis suggests that dietetic confidence is best represented by a two dimensional solution consisting of (a) Client –focused practice (CFP, 50.8% variance) and (b) Advocacy for self and client care (ASC, 9.7% variance). The alpha coefficient of both dimensions (CFP ɑ=0.95, ASC ɑ=0.84) demonstrated the internal consistency of components. Combined, these two components account for 60.5% of variance. The scale components were not related to years of practice or working with mental health clients but were significantly related to overall dietetic confidence (ODC). Correlation coefficients between ODC and CFP were 0.501 (p<0.01), ODC and ASC were correlated at 0.465 (p<0.01) and CFP and number of years as a dietitian were weakly correlated at 0.24 (p<0.05). Results have implications for dietetic training and professional development. Client focus and advocacy for self and client appear to be important factors in overall confidence as a dietitian.

Objective: With increasing rates of non-communicable disease, there is a need for implementing population-wide, evidence-based interventions for improving behavioural risk factors. Telephone-based interventions provide one option. This study reports on the evaluation of the Australia's Get Healthy Information and Coaching Service®, to improve lifestyle behaviours, amongst a population-wide sample who completed the 6-month coaching programme. Methods: Using a pre-post design, New South Wales participants who completed telephone-based coaching between February 2009 and December 2011 were included. Outcomes comprised self-reported weight, waist circumference, height, physical activity and dietary behaviours. Matched pair analyses and multivariate modelling were performed to assess behavioural changes. Results: Participants (n = 1440) reported statistically significant improvements in weight (-3.9. kg (5.1)); waist circumference (-5.0. cm (6.0)); and Body Mass Index (-1.4 BMI units (1.8)); number of walking and moderate-vigorous physical activity sessions of ≥ 30. min per week; number of vigorous physical activity sessions of ≥ 20. min per week and servings of vegetables; fruit; take-away meals and sweetened drinks (all p < 0.001). Improvements in weight, waist, moderate physical activity, fruit and vegetable and take-away meals consumption remained significant after adjusting for socio-demographic characteristics. Conclusions: These results support the effectiveness of replicating an evidence-based intervention in improving population risk factors for chronic disease. © 2012 Elsevier Inc.

Background: Maintaining a healthy weight and undertaking regular physical activity are important for the secondary prevention of cardiovascular disease (CVD). However, many people with CVD are overweight and insufficiently active. In addition, in Australia only 20-30% of people requiring cardiac rehabilitation (CR) for CVD actually attend. To improve outcomes of and access to CR the efficacy, effectiveness and cost-effectiveness of alternative approaches to CR need to be established.This research will determine the efficacy of a telephone-delivered lifestyle intervention, promoting healthy weight and physical activity, in people with CVD in urban and rural settings. The control group will also act as a replication study of a previously proven physical activity intervention, to establish whether those findings can be repeated in different urban and rural locations. The cost-effectiveness and acceptability of the intervention to CR staff and participants will also be determined.Methods/Design: This study is a randomised controlled trial. People referred for CR at two urban and two rural Australian hospitals will be invited to participate. The intervention (healthy weight) group will participate in four telephone delivered behavioural coaching and goal setting sessions over eight weeks. The coaching sessions will be on weight, nutrition and physical activity and will be supported by written materials, a pedometer and two follow-up booster telephone calls. The control (physical activity) group will participate in a six week intervention previously shown to increase physical activity, consisting of two telephone delivered behavioural coaching and goal setting sessions on physical activity, supported by written materials, a pedometer and two booster phone calls. Data will be collected at baseline, eight weeks and eight months for the intervention group (baseline, six weeks and six months for the control group). The primary outcome is weight change. Secondary outcomes incl

Alzheimer's disease (AD), the most common neurodegenerative disorder, goes along with extracellular amyloid-beta (Abeta) deposits. The cognitive decline observed during AD progression correlates with damaged spines, dendrites and synapses in hippocampus and cortex. Numerous studies have shown that Abeta oligomers, both synthetic and derived from cultures and AD brains, potently impair synaptic structure and functions. The cellular prion protein (PrP(C)) was proposed to mediate this effect. We report that ablation or overexpression of PrP(C) had no effect on the impairment of hippocampal synaptic plasticity in a transgenic model of AD. These findings challenge the role of PrP(C) as a mediator of Abeta toxicity.

Chromatin remodeling through histone posttranslational modifications (PTMs) and DNA methylation has recently been implicated in cognitive functions, but the mechanisms involved in such epigenetic regulation remain poorly understood. Here, we show that protein phosphatase 1 (PP1) is a critical regulator of chromatin remodeling in the mammalian brain that controls histone PTMs and gene transcription associated with long-term memory. Our data show that PP1 is present at the chromatin in brain cells and interacts with enzymes of the epigenetic machinery including HDAC1 (histone deacetylase 1) and histone demethylase JMJD2A (jumonji domain-containing protein 2A). The selective inhibition of the nuclear pool of PP1 in forebrain neurons in transgenic mice is shown to induce several histone PTMs that include not only phosphorylation but also acetylation and methylation. These PTMs are residue-specific and occur at the promoter of genes important for memory formation like CREB (cAMP response element-binding protein) and NF-kappaB (nuclear factor-kappaB). These histone PTMs further co-occur with selective binding of RNA polymerase II and altered gene transcription, and are associated with improved long-term memory for objects and space. Together, these findings reveal a novel mechanism for the epigenetic control of gene transcription and long-term memory in the adult brain that depends on PP1.

Much small-scale research has identified the role of physical activity in obesity prevention. This is the 'energy expenditure' side of the energy balance equation. Although around half an hour of daily moderate-intensity physical activity is required for cardiovascular health and disease prevention, the quantum of physical activity required for obesity prevention and weight loss is around 60-90 minutes per day. This amount of physical activity is difficult to achieve through leisure time physical activity (LTPA) alone, and additional energy expenditure is needed in the domains of active transport, occupation activity and in domestic settings. Modeling of 24-hour energy expenditures demonstrate the need for 'active living', namely energy expenditure over and above that due to LTPA, for weight loss and obesity prevention. The consequences of this for developing countries such as China are the need to focus on preventing the declines in energy expenditure attributable to urbanization, industrialization, and motor vehicle dependence. These will pose policy challenges in the developing world, if they are to be taken seriously as obesity prevention strategies. © 2007 The Authors.

Protein kinases and phosphatases can alter the impact of excitotoxicity resulting from ischemia by concurrently modulating apoptotic/survival pathways. Here, we show that protein phosphatase 1 (PP1), known to constrain neuronal signaling and synaptic strength (Mansuy et al., 1998; Morishita et al., 2001), critically regulates neuroprotective pathways in the adult brain. When PP1 is inhibited pharmacologically or genetically, recovery from oxygen/glucose deprivation (OGD) in vitro, or ischemia in vivo is impaired. Furthermore, in vitro, inducing LTP shortly before OGD similarly impairs recovery, an effect that correlates with strong PP1 inhibition. Conversely, inducing LTD before OGD elicits full recovery by preserving PP1 activity, an effect that is abolished by PP1 inhibition. The mechanisms of action of PP1 appear to be coupled with several components of apoptotic pathways, in particular ERK1/2 (extracellular signal-regulated kinase 1/2) whose activation is increased by PP1 inhibition both in vitro and in vivo. Together, these results reveal that the mechanisms of recovery in the adult brain critically involve PP1, and highlight a novel physiological function for long-term potentiation and long-term depression in the control of brain damage and repair.

Amyloid beta (Abeta) oligomers are derived from proteolytic cleavage of amyloid precursor protein (APP) and can impair memory and hippocampal long-term potentiation (LTP) in vivo and in vitro. They are recognized as the primary neurotoxic agents in Alzheimer's disease. The mechanisms underlying such toxicity on synaptic functions are complex and not fully understood. Here, we provide the first evidence that these mechanisms involve protein phosphatase 1 (PP1). Using a novel transgenic mouse model expressing human APP with the Swedish and Arctic mutations that render Abeta more prone to form oligomers (arcAbeta mice), we show that the LTP impairment induced by Abeta oligomers can be fully reversed by PP1 inhibition in vitro. We further demonstrate that the genetic inhibition of endogenous PP1 in vivo confers resistance to Abeta oligomer-mediated toxicity and preserves LTP. Overall, these results reveal that PP1 is a key player in the mechanisms of AD pathology.