ß1/ß2/ß3-adrenoceptor knockout mice are obese and cold-sensitive but have normal lipolytic responses to fasting

Catecholamines are viewed as major stimulants of diet- and cold-induced thermogenesis and of fasting-induced lipolysis, through the β-adrenoceptors (β1/β2/β3). To test this hypothesis, we generated β1/β2/β3-adrenoceptor triple knockout (TKO) mice and compared them to wild type animals. TKO mice exhibited normophagic obesity and cold-intolerance. Their brown fat had impaired morphology and lacked responses to cold of uncoupling protein-1 expression. In contrast, TKO mice had higher circulating levels of free fatty acids and glycerol at basal and fasted states, suggesting enhanced lipolysis. Hence, β-adrenergic signalling is essential for the resistance to obesity and cold, but not for the lipolytic response to fasting.

Chemisorbed and physisorbed Structures for 1,10-Phenanthroline and Dipyrido[3,2-a:2',3'-c]phenazine on Au(111)

Scanning tunneling microscopy (STM) images of 1,10-phenanthroline (PHEN) and dipyrido[3,2-a:2‘,3‘-c]phenazine (DPPZ) on Au(111) are recorded using both in situ and ex situ techniques. The images of PHEN depict regimes of physisorption and chemisorption, whereas DPPZ is only physisorbed. All physisorbed structures are not pitted and fluctuate dynamically, involving aligned (4 × 4) surface domains with short-range (ca. 20 molecules) order for PHEN but unaligned chains with medium-range (ca. 100 molecules) order for DPPZ. In contrast, the chemisorbed PHEN monolayers remain stable for days, are associated with surface pitting, and form a (4 × √13)R46° lattice with long-range order. The density of pitted atoms on large gold terraces is shown to match the density of chemisorbed molecules, suggesting that gold adatoms link PHEN to the surface. For PHEN, chemisorbed and physisorbed adsorbate structures are optimized using plane-wave density-functional theory (DFT) calculations for the surface structure. Realistic binding energies are then obtained adding dispersive corrections determined using complete-active-space self-consistent field calculations using second-order perturbation theory (CASPT2) applied to cluster-interaction models. A fine balance between the large adsorbate−adsorbate dispersive forces, adsorbate−surface dispersive forces, gold ligation energy, and surface mining energy is shown to dictate the observed phenomena, leading to high surface mobility and substrate/surface lattice incommensurability. Increasing the magnitude of the dispersive forces through use of DPPZ, rather than PHEN, to disturb this balance produced physisorbed monolayers without pits and/or surface registration but with much longer-range order. Analogies are drawn with similar but poorly understood processes involved in the binding of thiols to Au(111).

A pilot study of a telephone-based parental intervention to increase fruit and vegetable consumption in 3-5 year old children

Objective : To examine the potential efficacy of a brief telephone-based parental intervention in increasing fruit and vegetable consumption in children aged 3–5 years and to examine the feasibility of intervention delivery and acceptability to parents.

Design : A pre–post study design with no comparison group. Telephone surveys were conducted approximately 1 week before and following intervention delivery.
Setting Participants were recruited through pre-schools in the Hunter region, New South Wales, Australia.

Subjects : Thirty-four parents of 3–5-year-olds received four 30-min interventional telephone calls over 4 weeks administered by trained telephone interviewers. The scripted support calls focused on fruit and vegetable availability and accessibility within the home, parental role modelling of fruit and vegetable consumption and on implementing supportive family eating routines.

Results : Following the intervention, the frequency and variety of fruit and vegetable consumption increased (P = 0·027), as measured by a subscale of the children's dietary questionnaire. The intervention was feasible to be delivered to parents, as all participants who started the intervention completed all four calls, and all aspects of the interventional calls, including the number, length, content, format and relevance, were considered acceptable by more than 90 % of parents.

Conclusions : A brief telephone-based parental intervention to encourage fruit and vegetable consumption in pre-school-aged children may be effective, feasible and acceptable. Further investigation is warranted in a randomised controlled trial.

Somatization, but not depression, is characterized by disorders in the tryptophan catabolite (TRYCAT) pathway, indicating increased indoleamine 2,3-dioxygenase and lowered kynurenine aminotransferase activity

BACKGROUND: Reduced plasma tryptophan occurs in depression and somatization. Induction of indoleamine 2,3-dioxygenase (IDO) with consequent synthesis of tryptophan catabolites (TRYCATs) and lowered tryptophan are associated with the onset of depression in the puerperium and during interferon-alpha treatment. Depression is accompanied by lowered kynurenic acid, a neuroprotectant, or increased kynurenine, a neurotoxic TRYCAT.

AIMS AND METHODS: To examine plasma tryptophan; kynurenine; kynurenic acid; the kynurenine / tryptophan (KY/TRP) ratio, indicating IDO activity; and the kynurenine / kynurenic acid (KY/KA) ratio, indicating kynurenine aminotransferase (KAT) activity, in somatization; depression; somatization + depression; and controls. Illness severity is measured by the Somatic Symptom Index (SSI), the Screening for Somatoform Symptoms (SOMS), and the Beck Depression Inventory (BDI).

RESULTS: Tryptophan is significantly lower in patients than in controls and lower in somatization than in depression. KY/TRP is significantly increased in somatization. Kynurenic acid is significantly lower in patients than in controls, and lower in somatization than in depression. KY/KA is significantly higher in somatization and somatization + depression than in depression and controls. There are significant correlations between the severity of somatization, but not depression, and KY/TRP and KY/KA (positive) and tryptophan (negative). Kynurenine and kynurenic acid are significantly correlated in controls, somatization + depression, and depression, but not in somatization.

CONCLUSIONS: Somatization is characterized by increased IDO activity and disorders in KAT activity and an increased neurotoxic potential. The TRYCAT pathway may play a role in the pathophysiology of somatizing and “psychosomatic” symptoms through effects on pain, gut motility, the autonomic nervous system, peripheral NMDA receptors, etc. Even more, biological disorders, such as aberrations in the TRYCAT pathway, which are considered to be a hallmark for depression, are in fact attributable to somatization rather than to depression per se. Future research in depression on the TRYCAT pathway should always control for the possible effects of somatization.

The effects of apoptosis vulnerability markers on the myocardium in depression after myocardial infarction

Background : There is an increased incidence of major depressive disorder (MDD) in individuals after myocardial infarction (MI), but the pathophysiological processes mediating this association are unclear. Our previous study demonstrated an increase in pro-apoptotic pathways in the myocardium and hippocampus in MDD, which was reversed by venlafaxine. This study aimed to attempt to confirm the effects of apoptosis vulnerability markers on the myocardium in a model of depression after myocardial infarction.

Methods : Rats were divided into four groups: sham (N = 8), depression (N = 8, chronic mild unpredictable stress and separation were used in the depression group), MI (N = 13) and post-MI depression (N = 7). The rats in all four groups underwent the same open field and sucrose preference behavioral tests. Evan Blue staining was used to determine the area at risk of myocardial infarction in the left ventricle, and 2,3,5-triphenyl tetrazolium chloride (1.5% TTC) dye was used to detect the size of the myocardial infarction. The expression of bax and bcl-2 protein in the myocardium was investigated by immunohistochemistry, and the mRNA expression of bax, bcl-2 and caspase-3 in the myocardium was investigated by real time RT-PCR. Apoptosis was estimated in the myocardium by measuring the Bax:Bcl-2 ratio.

Results : In the depression and post-MI depression rats, there were significantly decreased movements and total sucrose consumption, modeling behavioral deficits and an anhedonic-like state. In terms of myocardial infarction size, no difference was seen between the MI and post-MI depression groups. There was an up-regulated Bax:Bcl-2 ratio in the depression, MI and post-MI depression groups. Furthermore, in the latter group, there was a greater up-regulated Bax:Bcl-2 ratio. However, caspase-3 did not differ among the four groups.

Conclusions : These results of this animal model suggest that active pro-apoptotic pathways may be involved in the nexus between myocardial infarction and depression. This mechanism may be germane to understanding this relationship in humans.

What hispanic parents do to encourage and discourage 3-5 year old children to be active : a qualitative study using nominal group technique

Purpose : Hispanic preschoolers are less active than their non-Hispanic peers. As part of a feasibility study to assess environmental and parenting influences on preschooler physical activity (PA) (Niños Activos), the aim of this study was to identify what parents do to encourage or discourage PA among Hispanic 3-5 year old children to inform the development of a new PA parenting practice instrument and future interventions to increase PA among Hispanic youth.

Methods : Nominal Group Technique (NGT), a structured multi-step group procedure, was used to elicit and prioritize responses from 10 groups of Hispanic parents regarding what parents do to encourage (5 groups) or discourage (5 groups) preschool aged children to be active. Five groups consisted of parents with low education (less than high school) and 5 with high education (high school or greater) distributed between the two NGT questions.

Results : Ten NGT groups (n = 74, range 4-11/group) generated 20-46 and 42-69 responses/group for practices that encourage or discourage PA respectively. Eight to 18 responses/group were elected as the most likely to encourage or discourage PA. Parental engagement in child activities, modeling PA, and feeding the child well were identified as parenting practices that encourage child PA. Allowing TV and videogame use, psychological control, physical or emotional abuse, and lack of parental engagement emerged as parenting practices that discourage children from being active. There were few differences in the pattern of responses by education level.

Conclusions : Parents identified ways they encourage and discourage 3-5 year-olds from PA, suggesting both are important targets for interventions. These will inform the development of a new PA parenting practice scale to be further evaluated. Further research should explore the role parents play in discouraging child PA, especially in using psychological control or submitting children to abuse, which were new findings in this study.

Parental influences on the diets of 2- to 5-year-old children: systematic review of qualitative research

Parents have a major influence on young children's diets, food choices and habit formation. However, research concerning parental influence on children's diets is limited. Qualitative research informs quantitative research with a narrative of 'what works' and is a valuable tool to inform intervention design and practice. This article presents a systematic review of qualitative research with parents of preschool children and their influence on their child's diet. Nine studies were identified. Findings highlight the need to promote culturally tailored programmes to combat specific cultural differences such as attitudes; perceptions and concerns; address common barriers to providing healthy foods and challenges faced by lower income families; the use of food to shape a child's behaviour; that children will grow out of excess weight; common misconceptions such as a heavier child is healthier and depriving a child's food request could result in starvation. Research on parental understanding of healthy diets and feeding practices is lacking. Further insights into how to positively influence children's diets will come from research examining parent feeding practices and nutrition knowledge. © The Author(s) 2013.

Synthesis and preliminary investigations into novel 1,2,3-triazole-derived androgen receptor antagonists inspired by bicalutamide.

A versatile and high yielding synthesis of novel androgen receptor (AR) antagonists is presented. Using this methodology, six 1,4-substituted-1,2,3-triazole derived bicalutamide mimics were synthesised in five steps and in isolated overall yields from 41% to 85%. Evaluation of these compounds for their anti-proliferative properties against androgen dependent (LNCaP) and independent (PC-3) cells showed promising IC50 values of 34-45 μM and 29-151 μM, respectively. The data suggest that the latter compounds may be an excellent starting point for the development of prostate cancer therapeutics for both androgen dependent and independent forms of this disease. Docking of these compounds (each enantiomer) in silico into the T877A mutated androgen receptor, as possessed by LNCaP cells, was also undertaken.

Corrosion behavior of Mg-5Al-xZn alloys in 3.5 wt.% NaCl solution

Five types of Mg-5Al alloys with different weight percentages of Zn ranging from 0 to 4 wt.% were examined using electrochemical techniques and surface analysis. The electrochemical results indicated that the Mg-5Al alloys containing Zn have a lower corrosion and hydrogen evolution rates than the Mg-5Al based specimens with a decrease of value being observed with the decrease in Zn content. Zn addition induced the precipitation of Mg-Al and Mg-Zn phases in the Mg matrix along with grain refinement and increased an interaction of Zn oxide with Mg and Al products serving as a corrosion barrier. © 2014 Elsevier B.V. All rights reserved.