A DFT study on the heterolytic bond cleavage of hydrazones under cathodic conditions in acetonitrile.

CONTEXT: Hydrazones have been studied for a myriad of chemical and physiochemical properties, such as sensors, chelators and numerous biological activities. Experimental data indicates that hydrazones are unstable under cathodic potentials irrespective of the solvent. The single electron reduction of hydrazones to produce radical anions result in unstable species that cleaves at the N-N bond in a heterolytic manner. The literature has proposed a mechanism favouring the radical on the imine moiety, however in this study DFT calculations suggest the radical on the amine product is more likely upon bond cleavage. This has implications on electrochemical mechanisms, and the active molecule in biological studies viz the method of delivery to target areas. METHODS: Density functional theory calculations were carried out using the GAMESS software package. The structures were optimized in the gas phase (B3LYP/6-31G(d,p)) as indicated by the absence of imaginary frequencies in the Hessian, and in CH3CN (B3LYP/6-31G(d,p)/SMD) with the Pople polarization functions. As a comparison, selected pathways were fully optimized using PBE0/6-31G(d,p) and PBE0/6-31G(d,p)/SMD for gas phase and CH3CN, respectively with the Pople polarization functions. The values were not significantly different (< 5% difference). As such only the B3LYP is evaluation is discussed.

Non-nutritive sweetener regulation and health: analysing applications to vary Australian and New Zealand food standards.

We aimed to understand the process of setting or varying food standards related to non-nutritive sweeteners (NNS) in Australia and New Zealand. Overconsumption of added sugars is a risk factor for non-communicable diseases. Limiting added sugar consumption is recommended by the World Health Organization. NNS are sweet substances with little to no energy that can be used to maintain the sweetness of packaged food when added sugar is reduced. The health and dietary pattern impacts of NNS are contested. Understanding how and why applications for NNS are submitted, assessed and approved within food regulatory systems is important to contextualize the increasing availability of NNS in the food supply. We completed an interpretive content analysis of applications to change the Food Standards Australia and New Zealand (FSANZ) Code, risk assessments and stakeholder submissions. Literature used in risk assessments were drawn from a mixture of documents supplied by industry and peer-reviewed studies. Risk assessments were primarily focussed on toxicological outcomes, while broader public health outcomes were not explicitly considered. Consumption data available to FSANZ were collected several years prior to dietary exposure assessments, and thus may not accurately represent current intakes. The study findings raise questions about whether the scope of what constitutes a 'risk' to public health in the setting of food standards needs to extend beyond immediate toxicological and food safety concerns, to include longer-term dietary balance considerations.

Global trends in added sugars and non-nutritive sweetener use in the packaged food supply: drivers and implications for public health.

OBJECTIVE: The health implications of excessive added sugar intakes have led to national policy actions to limit their consumption. Subsequently, non-nutritive sweeteners (NNS) may be used to maintain product sweetness. We aimed to assess trends in quantities of added sugars and NNS sold in packaged food and beverages worldwide, and the association between these trends and the number of national policy actions across regions to reduce added sugar consumption. DESIGN: (i) Longitudinal analysis of Euromonitor sales data (2007-2019) to assess the quantity of added sugars (kg) and NNS (g) sold in packaged foods and beverages globally, across regions, and across country income categories; (ii) policy-mapping of policy actions targeting added sugar consumption globally from the NOURISHING database; and (iii) Spearman's correlations to assess the association between national policy actions across regions and changes in added sugar/NNS sales. SETTING: Worldwide. PARTICIPANTS: Not applicable. RESULTS: Per capita volumes of NNS from beverage sales increased globally (36 %). Added sugars from beverage sales decreased in high-income countries (22 %) but increased in upper-middle-income countries (UMIC) and lower-middle-income countries (LMIC) (13-40 %). Added sugars from packaged food sales increased globally (9 %). Regions with more policy actions had a significant increase in NNS quantities from beverage sales (r = 0·68, P = 0·04). The sweetness of the packaged food supply (the sweetness of each NNS and added sugar, relative to sucrose, multiplied by sales volume) increased over time. CONCLUSIONS: The increasing use of NNS to sweeten beverages globally, and in packaged food in UMIC and LMIC, may have health and dietary implications in the future. Their use as a substitute for added sugar should be considered in public health nutrition policymaking.

Using the Hierarchies of Evidence Applied to Lifestyle Medicine (HEALM) Approach to Assess the Strength of Evidence on Associations between Dietary Patterns and All-Cause Mortality.

Dietary guidelines should be underpinned by high-quality evidence. Quality assessment methods that reflect traditional evidence hierarchies prioritise evidence from randomised controlled trials (RCTs). The Hierarchies of Evidence Applied to Lifestyle Medicine (HEALM) approach is an alternative quality assessment method for research questions that for practical and/or ethical reasons, cannot be answered using RCTs. The aim of this study was to investigate how the HEALM approach could be used to assess the strength of evidence on associations between dietary patterns and all-cause mortality (a research question that is difficult to answer using RCTs). Two data sources were used: an existing systematic review of dietary patterns and all-cause mortality that synthesised evidence from observational studies; and an overview of reviews that was conducted to summarise relevant evidence from mechanistic and intervention studies. A set of four criteria were developed and used in the application of HEALM. Using different datasets in combination, the strength of evidence was rated as 'Grade B: moderate/suggestive' or 'Grade C: insufficient/inconclusive'. HEALM is a novel approach for integrating and assessing the strength of evidence from mechanistic, intervention, and observational studies. Further research is needed to address the practical challenges that were identified in the application of HEALM.

A Systematic Review of the Methods Used to Assess and Report Dietary Patterns.

The use of dietary pattern assessment methods has increased over time. However, data from individual studies can be difficult to compare and synthesize when the dietary pattern assessment methods, and the dietary patterns that are identified are not described sufficiently. The aims of this systematic review were to analyze the application and reporting of dietary pattern assessment methods, and the reporting of the dietary patterns that were analyzed with health outcomes. Three electronic databases were searched (Medline, Embase, and Global Health). Cohort and nested case control studies published in English between January 1980 and March 2019 that examined associations between dietary patterns and health outcomes (including cardiovascular disease, cancer, diabetes and metabolic syndrome, and body weight) in apparently healthy, community dwelling adults (aged over 18 years) or children (aged 2-18 years) were eligible for inclusion. A narrative synthesis was conducted and descriptive statistics were used to summarize the application and reporting of each dietary pattern assessment method, and the reporting of the identified dietary patterns. Analysis of associations between dietary patterns and health outcomes was beyond the scope of this review. Of the included studies (n = 410), 62.7% used index-based methods, 30.5% used factor analysis or principal component analysis, 6.3% used reduced rank regression, and 5.6% used cluster analysis. Some studies (4.6%) used more than one method. There was considerable variation in the application and reporting of dietary pattern assessment methods. For example, the application of Mediterranean diet indices varied in terms of the nature of dietary components (foods only or foods and nutrients) and the rationale behind the cut-off points (absolute and/or data driven). In some cases, important methodological details were omitted. The level of detail used to describe the dietary patterns also varied, and food and nutrient profiles were often not reported. To ensure dietary patterns evidence can be synthesized and translated into dietary guidelines, standardized approaches for the application and reporting of dietary pattern assessment methods and the reporting of the identified dietary patterns would be beneficial.

Evidence Use in the Development of the Australian Dietary Guidelines: A Qualitative Study.

Dietary guidelines are important nutrition policy reference standards that should be informed by the best available evidence. The types of evidence that are reviewed and the evidence review methods that are used have implications for evidence translation. The aim of this study was to explore perceived advantages, disadvantages, and practicalities associated with the synthesis and translation of evidence from nutrient-based, food-based, and dietary patterns research in dietary guideline development. A qualitative descriptive study was conducted. Twenty-two semi-structured interviews were conducted with people involved in the development of the 2013 Australian Dietary Guidelines (ADGs). Transcripts were analysed thematically. To inform future ADGs, there was support for reviewing evidence on a range of dietary exposures (including dietary patterns, foods and food groups, nutrients and food components, and eating occasions) and health outcomes, as well as evidence on environmental sustainability and equity. At the evidence synthesis stage, practicalities associated with planning the evidence review and conducting original systematic reviews were discussed. At the evidence translation stage, practicalities associated with integrating the evidence and consulting stakeholders were described. To ensure that the best available evidence is translated into future ADGs, evidence review methods should be selected based on the exposures and outcomes of interest.

Dietary patterns, foods and nutrients: a descriptive analysis of the systematic reviews conducted to inform the Australian Dietary Guidelines.

Dietary guidelines should be underpinned by the best available evidence on relationships between diet and health, including evidence from nutrient-based, food-based and dietary patterns research. The primary aim of the present study was to analyse the systematic reviews conducted to inform the 2013 Australian Dietary Guidelines according to dietary exposure. The secondary aim was to analyse the reviews by health outcome, and design of included studies. To identify the systematic reviews, the dietary guidelines report was used as a starting point and relevant references were retrieved. The evidence report contained the data used in this analysis. Descriptive statistics were used to analyse reviews according to exposure, outcome, and design of included studies. A total of 143 systematic reviews were included in this analysis. Foods were the most common exposure (86·7 % of reviews), followed by nutrients (10·5 %) and dietary patterns (2·8 %). Chronic disease morbidity and/or mortality was the most common outcome (80·4 %), followed by chronic disease risk factors (19·6 %). Most reviews included evidence from cohort or nested case-control studies (92·3 %), many included evidence from case-control studies (61·5 %) and some included evidence from randomised controlled trials (28·7 %). These results reflect the research questions that were asked, the systematic review methods that were used, and the evidence that was available. In developing future iterations of the Australian Dietary Guidelines, there is an opportunity to review the latest evidence from dietary patterns research.

The drivers, trends and dietary impacts of non-nutritive sweeteners in the food supply: a narrative review.

Poor diets, including excess added sugar consumption, contribute to the global burden of disease. Subsequently, many nutrition policies have been implemented to reduce added sugar intake and improve population health, including taxes, education, labelling and environmental interventions. A potential consequence of these policy actions is the substitution of added sugars with non-nutritive sweeteners (NNS) in a variety of foods and beverages. NNS are used to reduce the energy and sugar content of foods and beverages while maintaining their palatability. Evidence of the toxicological risks of NNS is inconsistent, though concerns have been raised over the potential substitution effects of ultra-processed foods containing NNS for whole foods. This review aimed to provide an overview of current NNS food supply and consumption patterns, assess added sugar-reduction policies and their impact on NNS, and determine the impact of NNS on food choice, energy intake and diet quality. NNS are widely available in a variety of products, though most commonly in carbonated beverages, dairy products, confectionery, table-top sweeteners and fruit drinks. However, the longitudinal trends of different product categories, and differences between geographies and economy-income levels, require further study. Few studies have examined NNS consumption trends globally, though an increase in NNS consumption in beverages has been observed in some regions. Research examining how the increased availability of low-sugar, NNS-containing products affects global dietary patterns is limited, particularly in terms of their potential substitution effects.

Evaluating Nutrient-Based Indices against Food- and Diet-Based Indices to Assess the Health Potential of Foods: How Does the Australian Health Star Rating System Perform after Five Years?

Nutrient-based indices are commonly used to assess the health potential of individual foods for nutrition policy actions. This study aimed to evaluate the nutrient profile-informed Australian Health Star Rating (HSR), against NOVA and an index informed by the Australian Dietary Guidelines (ADGs), to determine the extent of alignment. All products displaying an HSR label in the Australian marketplace between June 2014 and June 2019 were extracted from the Mintel Global New Product Database, and classified into one of four NOVA categories, and either as an ADG five food group (FFG) food or discretionary food. Of 4451 products analysed, 76.5% were ultra-processed (UP) and 43% were discretionary. The median HSR of non-UP foods (4) was significantly higher than UP foods (3.5) (p < 0.01), and the median HSR of FFG foods (4) was significantly higher than discretionary foods (2.5) (p < 0.01). However, 73% of UP foods, and 52.8% of discretionary foods displayed an HSR ≥ 2.5. Results indicate the currently implemented HSR system is inadvertently providing a 'health halo' for almost ¾ of UP foods and ½ of discretionary foods displaying an HSR. Future research should investigate whether the HSR scheme can be reformed to avoid misalignment with food-and diet-based indices.

The Health Star Rating system - is its reductionist (nutrient) approach a benefit or risk for tackling dietary risk factors?

The Australian Government's voluntary Health Star Rating (HSR) system has potential to provide a user-friendly approach to help shoppers choose healthier packaged food options. However, despite evidence that it is dietary imbalances and excesses that are the predominant causes of diet-related noncommunicable diseases and obesity, the star-rating system's design is based on a reductionist (nutrient) world view of nutrition science which is not a fit-for-purpose solution to the cause of the problem. As a result, the HSR system frequently is inadvertently contradicting Australian Dietary Guidelines (ADG) recommendations, and promoting the marketing of discretionary and ultraprocessed foods. This perspective article looks at how the HSR system could be reformed to complement the ADG and stresses the overriding priority is to position it within, and not be a distraction from, a comprehensive national nutrition policy if dietary risk factors are to be effectively tackled.

Do Nutrient-Based Front-of-Pack Labelling Schemes Support or Undermine Food-Based Dietary Guideline Recommendations? Lessons from the Australian Health Star Rating System.

Food-based Dietary Guidelines (FBDGs) promote healthy dietary patterns. Nutrient-based Front-of-Pack Labelling (NBFOPL) schemes rate the 'healthiness' of individual foods. This study aimed to investigate whether the Australian Health Star Rating (HSR) system aligns with the Australian Dietary Guidelines (ADGs). The Mintel Global New Products Database was searched for every new food product displaying a HSR entering the Australian marketplace from 27 June 2014 (HSR system endorsement) until 30 June 2017. Foods were categorised as either a five food group (FFG) food or 'discretionary' food in accordance with ADG recommendations. Ten percent (1269/12,108) of new food products displayed a HSR, of which 57% were FFG foods. The median number of 'health' stars displayed on discretionary foods (2.5; range: 0.5-5) was significantly lower (p < 0.05) than FFG foods (4.0; range: 0.5-5), although a high frequency of anomalies and overlap in the number of stars across the two food categories was observed, with 56.7% of discretionary foods displaying ≥2.5 stars. The HSR system is undermining the ADG recommendations through facilitating the marketing of discretionary foods. Adjusting the HSR's algorithm might correct certain technical flaws. However, supporting the ADGs requires reform of the HSR's design to demarcate the food source (FFG versus discretionary food) of a nutrient.

Computational, electrochemical, and spectroscopic studies of two mononuclear cobaloximes: the influence of an axial pyridine and solvent on the redox behaviour and evidence for pyridine coordination to cobalt(i) and cobalt(ii) metal centres.

[Co(dmgBF2)2(H2O)2] (where dmgBF2 = difluoroboryldimethylglyoximato) was used to synthesize [Co(dmgBF2)2(H2O)(py)]·0.5(CH3)2CO (where py = pyridine) in acetone. The formulation of complex was confirmed by elemental analysis, high resolution MS, and various spectroscopic techniques. The complex [Co(dmgBF2)2(solv)(py)] (where solv = solvent) was readily formed in situ upon the addition of pyridine to complex . A spectrophotometric titration involving complex and pyridine proved the formation of such a species, with formation constants, log K = 5.5, 5.1, 5.0, 4.4, and 3.1 in 2-butanone, dichloromethane, acetone, 1,2-difluorobenzene/acetone (4 : 1, v/v), and acetonitrile, respectively, at 20 °C. In strongly coordinating solvents, such as acetonitrile, the lower magnitude of K along with cyclic voltammetry, NMR, and UV-visible spectroscopic measurements indicated extensive dissociation of the axial pyridine. In strongly coordinating solvents, [Co(dmgBF2)2(solv)(py)] can only be distinguished from [Co(dmgBF2)2(solv)2] upon addition of an excess of pyridine, however, in weakly coordinating solvents the distinctions were apparent without the need for excess pyridine. The coordination of pyridine to the cobalt(ii) centre diminished the peak current at the Epc value of the Co(I/0) redox couple, which was indicative of the relative position of the reaction equilibrium. Herein we report the first experimental and theoretical (59)Co NMR spectroscopic data for the formation of Co(i) species of reduced cobaloximes in the presence and absence of py (and its derivatives) in CD3CN. From spectroelectrochemical studies, it was found that pyridine coordination to a cobalt(i) metal centre is more favourable than coordination to a cobalt(ii) metal centre as evident by the larger formation constant, log K = 4.6 versus 3.1, respectively, in acetonitrile at 20 °C. The electrosynthesis of hydrogen by complexes and in various solvents demonstrated the dramatic effects of the axial ligand and the solvent on the turnover number of the respective catalyst.

Formulating policy activities to promote healthy and sustainable diets.

OBJECTIVE: To develop a policy formulation tool for strategically informing food and nutrition policy activities to promote healthy and sustainable diets (HSD). DESIGN: A policy formulation tool consisting of two complementary components was developed. First, a conceptual framework of the environment-public health nutrition relationship was constructed to characterise and conceptualise the food system problem. Second, an 'Orders of Food Systems Change' schema drawing on systems dynamics thinking was developed to identify, assess and propose policy options to redesign food systems. SETTING: Food and nutrition policy activities to promote HSD have been politicised, fragmented and lacking a coherent conceptual and strategic focus to tackle complex food system challenges. RESULTS: The tool's conceptual framework component comprises three integrated dimensions: (i) a structure built around the environment and public health nutrition relationship that is mediated via the food system; (ii) internal mechanisms that operate through system dynamics; and (iii) external interactions that frame its nature and a scope within ecological parameters. The accompanying schema is structured around three orders of change distinguished by contrasting ideological perspectives on the type and extent of change needed to 'solve' the HSD problem. CONCLUSIONS: The conceptual framework's systems analysis of the environment-public health nutrition relationship sets out the food system challenges for HSD. The schema helps account for political realities in policy making and is a key link to operationalise the framework's concepts to actions aimed at redesigning food systems. In combination they provide a policy formulation tool to strategically inform policy activities to redesign food systems and promote HSD.

Spectroscopic and electrochemical properties of group 12 acetates of di-2-pyridylketone thiophene-2-carboxylic acid hydrazone (dpktch-H) complexes. The structure of [Cd(η³-N,N,O-dpktch-H)2].

The reaction between [dpktch] and [M(OAc)2] (M=group 12 metal atom) in refluxing CH3CN gave [M(η(2)-O,O-OAc)(η(3)-N,N,O-dpktch-H)]·nH2O (n=0 or 1). The infrared and (1)H NMR spectra are consistent with the coordination of [η(2)-O,O-OAc] and [η(3)-N,N,O-dpktch-H](-) and the proposed formulations. The electronic absorption spectra of [M(η(2)-O,O-OAc)(η(3)-N,N,O-dpktch-H)]·nH2O measured in non-aqueous solvents revealed a highly intense intra-ligand-charge transfer (ILCT) transition due to π-π∗ of dpk followed by dpk→thiophene charge transfer. The electronic transitions of [M(η(2)-O,O-OAc)(η(3)-N,N,O-dpktch-H)]·nH2O are solvent and concentration dependent. Spectrophotometric titrations of dmso solutions of [M(η(2)-O,O-OAc)(η(3)-N,N,O-dpktch-H)]·nH2O with benzoic acid revealed irreversible inter-conversion between [M(η(2)-O,O-OAc)(η(3)-N,N,O-dpktch-H)]·nH2O and it conjugate acid [M(η(2)-O,O-OAc)(η(3)-N,N,O-dpktch)]·nH2O pointing to ligand exchange between the acetate and benzoate anions. When CH2Cl2 solutions of [M(η(2)-O,O-OAc)(η(3)-N,N,O-dpktch-H)]·nH2O were titrated with dmso, changes appeared pointing to solvolysis or ligand exchange reactions. Electrochemical measurements on dmso solutions of [M(η(2)-O,O-OAc)(η(3)-N,N,O-dpktch-H)]·nH2O divulged irreversible redox transformations consistent with electrochemical decomposition of [M(η(2)-O,O-OAc)(η(3)-N,N,O-dpktch-H)]·nH2O. The solid state structure of a single crystal of [Cd(η(3)-N,N,O-dpktch-H)2] obtained from a dmso solution of [Cd(η(2)-O,O-OAc)(η(3)-N,N,O-dpktch-H)]·nH2O confirmed the ligand scrambling of [M(η(2)-O,O-OAc)(η(3)-N,N,O-dpktch-H)]·nH2O. The extended structure of [Cd(η(3)-N,N,O-dpktch-H)2] revealed stacks of [Cd(η(3)-N,N,O-dpktch-H)2] locked via a network of hydrogen bonds. A significant amount of empty space (35.5%) was observed in the solid state structure of [Cd(η(3)-N,N,O-dpktch-H)2].

Functional neurons and melanocytes induced from immortal lines of postnatal neural crest-like stem cells.

Stem cells, that is, cells that can both reproduce themselves and differentiate into functional cell types, attract much interest as potential aids to healing and disease therapy. Embryonic neural crest is pluripotent and generates the peripheral nervous system, melanocytes, and some connective tissues. Neural-crest-related stem cells have been reported previously in postnatal skin: committed melanocytic stem cells in the hair follicle, and pluripotent cell types from the hair follicle and papilla that can produce various sets of lineages. Here we describe novel pluripotent neural crest-like stem cells from neonatal mouse epidermis, with different potencies, isolated as 3 independent immortal lines. Using alternative regulatory factors, they could be converted to large numbers of either Schwann precursor cells, pigmented melanocytes, chondrocytes, or functional sensory neurons showing voltage-gated sodium channels. Some of the neurons displayed abundant active TRPV1 and TRPA1 receptors. Such functional neurons have previously been obtained in culture only with difficulty, by explantation. The system was also used to generate comparative gene expression data for the stem cells, melanocytes, and melanoblasts that sufficiently explain the lack of pigment in melanoblasts and provide a rationale for some genes expressed apparently ectopically in melanomas, such as ephrin receptors.

Building global alliances for public health nutrition training.

The purpose of this paper is to present a review of opportunities and challenges for future progress in building intercountry, regional, and global alliances for public health nutrition training. Drawing on experiences from developing, implementing, and evaluating public health nutrition training in Australasia, Europe, and the Middle East, suggestions are provided for building a network of global training activities. Opportunities are described in areas such as standardization of course competencies and registration schemes, resource sharing, student and trainer exchange programs, and professional development. Challenges are identified and options presented for building global alliances in public health nutrition training into the future.

Examination of selected national policies towards mandatory folic acid fortification.

The purpose of this paper is to present an examination of the contrasting policies towards mandatory folic acid fortification in six countries from different regions of the world. Three questions are addressed: 1) What is the policy of the country? 2) Why was the policy adopted? 3) What lessons have been learned? Policy contrasts among countries were assessed as reflecting different interpretations of the potential risks and benefits associated with folic acid fortification. Although commonalities were identified, it was considered unlikely that there could be a standard policy response for all countries. Instead, a country-by-country policy response based on national circumstances is indicated.