Prevalence of the thioamide {···H-N-C=S}2 synthon-solid-state (X-ray crystallography), solution (NMR) and gas-phase (theoretical) structures of O-methyl-N-aryl-thiocarbamides

Structural investigations, i.e. solid-state (X-ray), solution (¹H NMR) and gas-phase (theoretical), on molecules with the general formula MeOC(S)N(H)C₆H₄-4-Y: Y = H (1), NO₂ (2), C(O)Me (3), Cl (4) have shown a general preference for the adoption of an E-conformation about the central C–N bond. Such a conformation allows for the formation of a dimeric hydrogen-bonded {H–N–C=S}₂ synthon as the building block. In the cases of 1–3, additional C–H^...O interactions give rise to the formation of tapes of varying topology. A theoretical analysis shows that the preference for the E-conformation is about the same as the crystal packing stabilisation energy and consistent with this, the compound with Y = C(O)OMe, (5), adopts a Z-conformation in the solid-state that facilitates the formation of N–H^...O, C–H^...O and C–H^...S interactions, leading to a layer structure. Global crystal packing considerations are shown to be imperative in dictating the conformational form of molecules 1–5.

Outcome data from the LEAP (Live, Eat and Play) trial: a randomized controlled trial of a primary care intervention for childhood overweight/mild obesity

OBJECTIVES: To reduce gain in body mass index (BMI) in overweight/mildly obese children in the primary care setting.
DESIGN: Randomized controlled trial (RCT) nested within a baseline cross-sectional BMI survey.
SETTING: Twenty nine general practices, Melbourne, Australia.
PARTICIPANTS: (1) BMI survey: 2112 children visiting their general practitioner (GP) April-December 2002; (2) RCT: individually randomized overweight/mildly obese (BMI z-score <3.0) children aged 5 years 0 months-9 years 11 months (82 intervention, 81 control).
INTERVENTION: Four standard GP consultations over 12 weeks, targeting change in nutrition, physical activity and sedentary behaviour, supported by purpose-designed family materials.
MAIN OUTCOME MEASURES: Primary: BMI at 9 and 15 months post-randomization. Secondary: Parent-reported child nutrition, physical activity and health status; child-reported health status, body satisfaction and appearance/self-worth.
RESULTS: Attrition was 10%. The adjusted mean difference (intervention-control) in BMI was -0.2 kg/m(2) (95% CI: -0.6 to 0.1; P=0.25) at 9 months and -0.0 kg/m(2) (95% CI: -0.5 to 0.5; P=1.00) at 15 months. There was a relative improvement in nutrition scores in the intervention arm at both 9 and 15 months. There was weak evidence of an increase in daily physical activity in the intervention arm. Health status and body image were similar in the trial arms.
CONCLUSIONS: This intervention did not result in a sustained BMI reduction, despite the improvement in parent-reported nutrition. Brief individualized solution-focused approaches may not be an effective approach to childhood overweight. Alternatively, this intervention may not have been intensive enough or the GP training may have been insufficient; however, increasing either would have significant cost and resource implications at a population level.

The prevalence and selected characteristics of non-fatal opioid overdoses attended by ambulance in Australia

Key Points
1. Ambulance attendance at non-fatal opioid overdose is a common event in mainland Australia (among heroin users in particular).
2. The monthly rate of non-fatal opioid overdose attended by ambulance was generally highest in Victoria (Melbourne) followed by NSW with the rates substantially lower in the remaining mainland states over the period Jan  1999 - Feb 2001.
3. Non-fatal opioid overdose victims were most likely to be male in all states with the proportion of males highest in Victoria (77%).
4. Non-fatal opioid overdose victims were aged around 28 years with ages lowest in WA (26) and highest in NSW (30).
5. The rates of transportation varied according to ambulance service practice across the states with around 94% of cases transported in WA and around 19% and 30% of cases transported in Melbourne and NSW respectively.

Pathways for algal recolonization in seasonally-flowing streams

1. In semi-arid climates, seasonally-flowing streams provide most of the water required for human use, but knowledge of how water extraction affects ecological processes is limited. Predicted alterations in stream flows associated with the impacts of climate change further emphasize the need to understand these processes. Benthic algae are an important base for stream food webs, but we have little knowledge of how algae survive dry periods or respond to altered flow regimes.

2. We sampled 19 streams within the Grampians National Park, south-eastern Australia and included four components: a survey of different drought refuges (e.g. permanent pools, dry biofilm on stones and dry leaf packs) and associated algal taxa; a survey of algal regrowth on stones after flows recommenced to determine which refuges contributed to regrowth; reciprocal transplant experiments to determine the relative importance of algal drift and regrowth from dry biofilm in recolonization; direct measurement of algal drift to determine taxonomic composition in relation to benthic assemblage composition.

3. Algae showed little specificity for drought refuges but did depend on them; no species were found that were not present in at least one of the perennial pool, dry biofilm or leaf pack refuges. Perennial pools were most closely correlated with the composition of algal assemblages once flows resumed, but the loss or gain of perennial pools that might arise from stream regulation is unlikely to affect the composition of algal regrowth. However, regulated streams were associated with strong increases in algal density in dry biofilm, including increased densities of Cyanobacteria.

4. A model for algal recolonization in seasonally-flowing streams identified three pathways for algal recolonization (drift-dependent, dry biofilm-dependent and contributions from both), depending on whether streams are diatom-dominated or dominated by filamentous algae. The model predicted the effects of changes to stream flow regimes on benthic algal recolonization and provides a basis for hypotheses testable in streams elsewhere.

Consequences of maternal yolk testosterone for offspring development and survival : experimental test in a lizard

1. Hormone-mediated maternal effects and developmental plasticity are important sources of phenotypic variation, with potential consequences for trait evolution. Yet our understanding of the importance of maternal hormones for offspring fitness in natural populations is very limited, particularly in non-avian species.

2. We experimentally elevated yolk testosterone by injection of a physiological dose into eggs of the lizard Ctenophorus fordi Storr, to investigate its roles in offspring development, growth and survival.

3. Yolk testosterone did not influence incubation period, basic hatchling morphology or survival under natural conditions. However, there was evidence for increased growth in hatchlings from testosterone-treated eggs, suggesting that maternal hormones have potential fitness consequences in natural populations.

4. The positive effect of prenatal testosterone exposure on postnatal growth could represent a taxonomically widespread developmental mechanism that has evolved into an adaptive maternal effect in some taxa, but remains deleterious or selectively neutral in others.

5. A broader taxonomic perspective should increase our understanding of the role of physiological constraints in the evolution of endocrine maternal effects.

Exploring the possibilities of an expanded practice repertoire in child protection

Summary: This article discusses research that explored an alternative to proceduralized child protection practice informed by the risk paradigm, by expanding the repertoire available to practitioners through combining features of the risk paradigm with social constructionism. This approach incorporates three dimensions: theories of knowledge and power, related professional roles, and practice skills. In this article, we discuss and critically evaluate only the first dimension: theories of knowledge and power. Through dialogue facilitated by semi-structured questions, we explored practitioners' perspectives about the relevance and appropriateness of the alternative approach for practice.

Findings: The practitioners' participation and feedback offer insights into complex connections between `theory' and `practice' with the practitioner as a positioned subject and mediator of practical meanings of formal concepts.

Applications: 1) Recognition of each practitioner's interpretation of formal concepts and how they are applied in actual practice, even within shared organizational contexts. 2) The importance of dialogue to expand the range of possibilities that maintain openness to ongoing learning. 3) The value of theoretical pluralism that may offer greater opportunities for professional discretion, rather than single self-contained approaches that may constrain effective and ethical practice.

The sustainable farm families project: changing farmer attitudes to health

Farm health and safety has focussed on strategies such as injury prevention, audits and fulfilling legislative responsibilities. We know farmer injuries mask deeper health issues such as higher rates of cancer, suicides, cardiovascular disease and stress. The relationship between occupational health and safety and farming family health has not been investigated by other researchers either nationally or internationally. The Sustainable Farm Families (SFF) project attempts to make this connection in order to address the unacceptable rates of premature death, higher morbidity and injury on Australian farms.

The SFF focuses on the human resource in the triple bottom line and is working with farmers, families, industry, and university to collaboratively address and improve the health and well being of farming families. Based on a model of extension that engages farming families as active learners where they commit to healthy living and safe working practices the SFF is proving to be an effective model for engaging communities in learning and change. Health education and information is delivered to farming families using a workshop format with participants reporting positive impacts on their farming business. The SFF project sits across generations and sexes and has a high level of support with the overwhelming majority of participants saying they would recommend the program to others.

This paper discusses the progress of the research outlining the design of the project, the delivery and extension processes used to engage 321 farming families to date. The paper presents key learning’s on intersectoral collaboration, engaging farmers and families in health and the future for this project extending into agricultural industries across the nation.

Three key learnings: (1) The increased health risks faced by farmers and their families need social and political attention. (2) Joint ownership and collaborative partnerships where all partners have a key role within the development and delivery of the project to their relevant representative groups enables resources to be shared and encourages greater in-kind support to augment funding received. (3) Farming families are keen to understand more about their health and farmers who participate in health education programs based around industry collaboration with high levels of individual participation will engage with health professionals and obtain an improved health status if programs are presented to them in personally engaging and relevant ways

Do maternally derived antibodies and early immune experience shape the adult immune response?

1. Immunological imprinting by maternally derived antibodies has been proposed to have both positive and negative consequences for offspring immunity in early and adult life. However, few studies of maternal effects on immunity have followed individuals past the juvenile stages.

2. Using laboratory Japanese quail, we developed a novel method of directly manipulating yolk antibodies of neonates, and then followed individuals through a series of immune challenges until they were of reproductive age.

3. Our method of directly injecting purified antibodies into the yolk sac of newly hatched chicks successfully elevated the plasma titres of specific anti-KLH IgY in neonates. This allows us to test whether differences in neonatal anti-KLH IgY affect immunity at the juvenile and adult stages of life.

4. We found little evidence for an effect of maternal antibodies on juvenile stage immune response, in contrast to results from previous studies. Adult immune response depended largely on the magnitude of the juvenile immune response regardless of the identity of the antigen in the juvenile immune challenge, and did not depend on neonatal IgY titres. Our results are consistent with a priming effect of early immune experience on adult stage immune responsiveness, but we found no evidence of carryover effects of yolk-derived antibodies on adult immunity.

5. This study employs new methodology for investigation of maternal antibodies and presents results suggesting that further studies of maternal effects on immunity will require careful consideration of the numerous ways maternally derived yolk components can impact the different types of immune response.

Exercise and skeletal muscle glucose transporter 4 expression: molecular mechanisms

1.      Skeletal muscle is a highly plastic tissue that has a remarkable ability to adapt to external demands, such as exercise. Many of these adaptations can be explained by changes in skeletal muscle gene expression. A single bout of exercise is sufficient to induce the expression of some metabolic genes. We have focused our attention on the regulation of glucose transporter isoform 4 (GLUT-4) expression in human skeletal muscle.

2.      Glucose transporter isoform 4 gene expression is increased immediately following a single bout of exercise, and the GLUT-4 enhancer factor (GEF) and myocyte enhancer factor 2 (MEF2) transcription factors are required for this response. Glucose transporter isoform enhancer factor and MEF2 DNA binding activities are increased following exercise, and the molecular mechanisms regulating MEF2 in exercising human skeletal muscle have also been examined.

3.      These studies find possible roles for histone deacetylase 5 (HDAC5), adenosine monophosphate–activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and p38 mitogen-activated protein kinase (MAPK) in regulating MEF2 through a series of complex interactions potentially involving MEF2 repression, coactivation and phosphorylation.

4.      Given that MEF2 is a transcription factor required for many exercise responsive genes, it is possible that these mechanisms are responsible for regulating the expression of a variety of metabolic genes during exercise. These mechanisms could also provide targets for the treatment and management of metabolic disease states, such as obesity and type 2 diabetes, which are characterized by mitochondrial dysfunction and insulin resistance in skeletal muscle.

Histone modifications and skeletal muscle metabolic gene expression

1.      Skeletal muscle oxidative function and metabolic gene expression are co-ordinately downregulated in metabolic diseases such as insulin resistance, obesity and Type 2 diabetes. Altering skeletal muscle metabolic gene expression to favour enhanced energy expenditure is considered a potential therapy to combat these diseases.

2.      Histone deacetylases (HDACs) are chromatin-remodelling enzymes that repress gene expression. It has been shown that HDAC4 and 5 co-operatively regulate a number of genes involved in various aspects of metabolism. Understanding how HDACs are regulated provides insights into the mechanisms regulating skeletal muscle metabolic gene expression.

3.      Multiple kinases control phosphorylation-dependent nuclear export of HDACs, rendering them unable to repress transcription. We have found a major role for the AMP-activated protein kinase (AMPK) in response to energetic stress, yet metabolic gene expression is maintained in the absence of AMPK activity. Preliminary evidence suggests a potential role for protein kinase D, also a Class IIa HDAC kinase, in this response.

4.      The HDACs are also regulated by ubiquitin-mediated proteasomal degradation, although the exact mediators of this process have not been identified.

5.      Because HDACs appear to be critical regulators of skeletal muscle metabolic gene expression, HDAC inhibition could be an effective therapy to treat metabolic diseases.

6.      Together, these data show that HDAC4 and 5 are critical regulators of metabolic gene expression and that understanding their regulation could provide a number of points of intervention for therapies designed to treat metabolic diseases, such as insulin resistance, obesity and Type 2 diabetes.

Dual responsive chemosensors for anions : the combination of fluorescent PET (Photoinduced Electron Transfer) and colorimetric chemosensors in a single molecule

The design and synthesis of two novel fluorescent PET anion sensors is described, based on the principle of ‘fluorophore-spacer-(anion)receptor’. The sensors 1 and 2 employ simple diaromatic thioureas as anion receptors, and the fluorophore is a naphthalimide moiety that absorbs in the visible part of the spectrum and emits in the green. Upon recognition of anions such as F⁻ and AcO⁻ in DMSO, the fluorescence emission of 1 and 2 was ‘switched off’, with no significant changes in the UV–vis spectra. This recognition shows a 1:1 binding between the receptor and the anions. In the case of F⁻, further additions of the anion, gave rise to large changes in the UV–vis spectra, where the λ_max at 455 nm was shifted to 550 nm. These changes are thought to be due to the deprotonation of the 4-amino moiety of the naphthalimide fluorophore. This was in fact found to be the case, using simple naphthalimide derivatives such as 6. Sensors 1 and 2 can thus display dual sensing action; where at low concentrations, the fluorescence emission is quenched, and at higher concentrations the absorption spectra are modulated.

Assembly of 3-D network structures containing oxydiacetate and CeIII or CeIV

Reaction of CeCl₃·7H₂O with Na₂(oda) (oda = O(CH₂CO₂)₂²— oxydiacetate) in a 2:3 ratio gives the neutral cerium(III) complex [Ce₂(oda)₃(H₂O)₃]·9H₂O (1). Treatment of a 1:3 mixture of CeCl₃·7H₂O and H₂oda in water with 4 molar equivalents of NaOH also gives 1 but, with a larger excess of NaOH, the tri-sodium salt Na₃[Ce(oda)₃]·9H₂O (2) is isolated. Formation of a tri-ammonium analogue of 2 can be achieved by neutralisation of an aqueous solution of CeCl₃·7H₂O and H₂(oda) in a 1:3 ratio by NH₄OH, giving (NH₄)₃[Ce(oda)₃]·7H₂O (3). Use of the cerium(IV) reagent (NH₄)₂[Ce(NO₃)₆] with Na₂(oda) results in reduction to cerium(III) under ambient conditions and isolation of 1. However, in the absence of light this reaction yields crystals of the novel cerium(IV) heterobimetallic [Ce(oda)₃Na₄(NO₃)₂] (4). Each of these complexes exhibit a 3-D network structure having a common nine-coordinate [Ce(oda)₃]ⁿ— (n = 2 or 3) subunit, irrespective of the oxidation state of cerium. In 1, six [Ce(oda)₃]³— anions are connected, through bridging bidentate carboxylates, to a second Ce³⁺ site further coordinated by three water molecules. In contrast, the ammonium salt 2, displays isolated [Ce(oda)₃]³— anions, devoid of further carboxylate bonding, but enmeshed within a network of hydrogen-bonded NH₄⁺ cations and water molecules. The remarkable structure of 4 consists of infinite 2-D sheets of [Na₂(NO₃)]+ pillared by [Ce(oda)₃]^2— units, the connectivity arising by multidentate nitrate and carboxylate bridging.

Crystal structure of a ceIII/feIII heterobimetallic complex

A central μ₃—O moiety linking two Fe^III and one Ce^III sites supported by two distinct heterometallic carboxylate bridging modes features in self-assembled [CeFe₂(bpy)₂(μ₃—O)(μ—L)₂(μ—LH)₂(LH)(H₂O)₂]·0.5(bpy)·7H₂O (1) (LH₂ = glycolic acid), and the structure models potential bonding modes of the Rare Earth corrosion inhibitor Ce(glycolate)₃ to iron or iron oxide.

Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods

Objectives: To determine the efficacy on plasma cholesterol-lowering of plant sterol esters or non-esterified stanols eaten within low-fat foods as well as margarine.
Design: Randomised, controlled, single-blind study with sterol esters and non-esterified plant stanols provided in breakfast cereal, bread and spreads. Study 1 comprised 12 weeks during which sterol esters (2.4 g) and stanol (2.4 g) -containing foods were eaten during 4 week test periods of cross-over design following a 4 week control food period. In Study 2, in a random order cross-over design, a 50% dairy fat spread with or without 2.4 g sterol esters daily was tested.
Subjects: Hypercholesterolaemic subjects; 22 in study 1 and 15 in study 2.
Main outcome measures: Plasma lipids, plasma sterols, plasma carotenoids and tocopherols.
Results: Study 1¾median LDL cholesterol was reduced by the sterol esters (-13.6%; P<0.001 by ANOVA on ranks; P<0.05 by pairwise comparison) and by stanols (-8.3%; P=0.003, ANOVA and <0.05 pairwise comparison). With sterol esters plasma plant sterol levels rose (35% for sitosterol, 51% for campesterol; P<0.001); plasma lathosterol rose 20% (P=0.03), indicating compensatory increased cholesterol synthesis. With stanols, plasma sitosterol fell 22% (P=0.004), indicating less cholesterol absorption. None of the four carotenoids measured in plasma changed significantly. In study 2, median LDL cholesterol rose 6.5% with dairy spread and fell 12.2% with the sitosterol ester fortified spread (P=0.03 ANOVA and <5% pairwise comparison).
Conclusion: 1. Plant sterol esters and non-esterified stanols, two-thirds of which were incorporated into low-fat foods, contributed effectively to LDL cholesterol lowering, extending the range of potential foods. 2. The LDL cholesterol-raising effect of butter fat could be countered by including sterol esters. 3. Plasma carotenoids and tocopherols were not reduced in this study.

Are safety-related features of the road environment associated with smaller declines in physical activity among youth?

This study examined how objective measures of the local road environment related to safety were associated with change in physical activity (including active transport) among youth. Few longitudinal studies have examined the impact of the road environment on physical activity among children/adolescents in their neighborhoods. Participants were children aged 8–9 years (n=170) and adolescents aged 13–15 years (n=276) in 2004. Data were collected in 2004 and 2006 during followup of participants recruited initially in 2001 from 19 primary schools in Melbourne, Australia. Walking/cycling to local destinations was parent-reported for children and self-reported by adolescents. Moderate-to-vigorous physical activity (MVPA) during nonschool hours was recorded using accelerometers. Road environment features in each participant’s neighborhood (area within 800 m radius of their home) were measured objectively using a Geographical Information System. Linear regression analyses examined associations between road features and changes in active transport (AT) and MVPA over 2 years. Children’s AT increased but MVPA levels decreased in both age groups; on average, younger girls recorded the greatest declines. The number of traffic/pedestrian lights was associated with ΔAT among younger girls (B=0.45, p=0.004). The total length of walking tracks (in meters) was associated with ΔAT among younger girls (B=0.0016, p=0.015) and adolescent girls (B=0.0016, p=0.002). For adolescent boys, intersection density was associated with ΔAT (B=0.03, p=0.030). Slow points were associated with ΔMVPA among younger boys before school (B=1.55, p=0.021), while speed humps were associated with ΔMVPA among adolescent boys after school (B=0.23, p=0.015). There were many associations for adolescent girls: for example, the total length of local roads (B=0.49, p=0.005), intersection density (B=0.05, p=0.036), and number of speed humps (B=0.33, p=0.020) were associated with ΔMVPA during nonschool hours. Safety-related aspects of the built environment are conducive to physical activity among youth and may help stem age-related declines in physical activity. Passive road safety interventions may promote AT and physical activity among less active girls, in particular.