Regulation of the STARS signaling pathway in response to endurance and resistance exercise and training

The striated muscle activator of Rho signaling (STARS) protein and members of its downstream signaling pathway, including myocardin-related transcription factor-A (MRTF-A) and SRF, are increased in response to prolonged resistance exercise training but also following a single bout of endurance cycling. The aim of the present study was to measure and compare the regulation of STARS, MRTF-A and SRF mRNA and protein following 10 weeks of endurance training (ET) versus resistance training (RT), as well as before and following a single bout of endurance (EE) versus resistance exercise (RE). Following prolonged training, STARS, MRTF-A and SRF mRNA levels were all increased by similar magnitude, irrespective of training type. In the training-habituated state, STARS mRNA increased following a single-bout RE when measured 2.5 and 5 h post-exercise and had returned to resting level by 22 h following exercise. MRTF-A and SRF mRNA levels were decreased by 2.5, 5, and 22 h following a single bout of RE and EE exercise when compared to their respective basal levels, with no significant difference seen between the groups at any of the time points. No changes in protein levels were observed following the two modes of exercise training or a single bout of exercise. This study demonstrates that the stress signals elicited by ET and RT result in a comparable regulation of members of the STARS pathway. In contrast, a single bout of EE and RE, performed in the trained state, elicit different responses. These observations suggest that in the trained state, the acute regulation of the STARS pathway following EE or RE may be responsible for exercise-specific muscle adaptations.

A longitudinal evaluation of the resilient families randomized trial to prevent early adolescent depressive symptoms

This study aimed to evaluate whether an intervention prevented the development of depressive symptoms through the early years of secondary school (Grades 7 to 9 - mean ages 12.3 to 14.5 years) in Victoria, Australia. Twelve schools were randomized to a universal preventative intervention (including a student social relationship/emotional health curriculum, and parent/caregiver parenting education); 12 were randomized as control schools. Multivariate regression analyses used student self-report to predict depressive symptoms at 26-month follow-up (13-months after intervention completion) from baseline measures and intervention status (N = 2027). There was no overall intervention effect on depressive symptoms. However, intervention students with moderate symptoms whose parents attended parent education events had a significantly reduced risk of depressive symptoms at follow-up. Future evaluations of interventions of this type should investigate: therapeutic processes; methods to increase recruitment into effective parent education events; and the potential to target assistance to students with high depressive symptoms.

Barriers and enablers to healthcare access and use among Arabic-speaking and Caucasian English-speaking patients with type 2 diabetes mellitus: a qualitative comparative study

OBJECTIVE: The objective of this study was to explore the decision-making processes and associated barriers and enablers that determine access and use of healthcare services in Arabic-speaking and English-speaking Caucasian patients with diabetes in Australia. STUDY SETTING AND DESIGN: Face-to-face semistructured individual interviews and group interviews were conducted at various healthcare settings-diabetes outpatient clinics in 2 tertiary referral hospitals, 6 primary care practices and 10 community centres in Melbourne, Australia. PARTICIPANTS: A total of 100 participants with type 2 diabetes mellitus were recruited into 2 groups: 60 Arabic-speaking and 40 English-speaking Caucasian. DATA COLLECTION: Interviews were audio-taped, translated into English when necessary, transcribed and coded thematically. Sociodemographic and clinical information was gathered using a self-completed questionnaire and medical records. PRINCIPAL FINDINGS: Only Arabic-speaking migrants intentionally delayed access to healthcare services when obvious signs of diabetes were experienced, missing opportunities to detect diabetes at an early stage. Four major barriers and enablers to healthcare access and use were identified: influence of significant other(s), unique sociocultural and religious beliefs, experiences with healthcare providers and lack of knowledge about healthcare services. Compared with Arabic-speaking migrants, English-speaking participants had no reluctance to access and use medical services when signs of ill-health appeared; their treatment-seeking behaviours were straightforward. CONCLUSIONS: Arabic-speaking migrants appear to intentionally delay access to medical services even when symptomatic. Four barriers to health services access have been identified. Tailored interventions must be developed for Arabic-speaking migrants to improve access to available health services, facilitate timely diagnosis of diabetes and ultimately to improve glycaemic control.

Use of focus groups to identify health promotion strategies for the early detection of diabetic retinopathy

BACKGROUND: People with diabetes do not regularly utilise eye services for the early prevention of vision loss due to diabetic eye disease. A community-based screening program has been initiated in Victoria to address this issue. To encourage people to take preventive eye health care measures, the most effective health promotion strategies were identified. METHODS: Thirty-three health professionals were invited to attend focus groups. A sample of 35 people with diabetes was approached by their GPs or diabetes educators because of their motivation to participate in diabetes activities. Each group consisted of 10 members. Discussion points included the type of education messages available to people with diabetes; use of eye services among the participants with diabetes; and strategies required promoting the screening service. RESULTS: Five focus groups were conducted. The discussions highlighted that a great deal could be achieved by using local community networks to promote the benefits of early detection of diabetic retinopathy and local screening program. The group members recommended that particular attention be directed to general practitioners and their distribution of materials to patients. Key issues for planning and implementing the program were highlighted. The groups urged development of strategies to encourage people with diabetes in rural Victoria to participate in a program for the early detection of diabetic retinopathy.

Early life environmental and pharmacological stressors result in persistent dysregulations of the serotonergic system

Dysregulations in the brain serotonergic system and exposure to environmental stressors have been implicated in the development of major depressive disorder. Here, we investigate the interactions between the stress and serotonergic systems by characterizing the behavioral and biochemical effects of chronic stress applied during early-life or adulthood in wild type (WT) mice and mice with deficient tryptophan hydroxylase 2 (TPH2) function. We showed that chronic mild stress applied in adulthood did not affect the behaviors and serotonin levels of WT and TPH2 knock-in (KI) mice. Whereas, maternal separation (MS) stress increased anxiety-and depressive-like behaviors of WT mice, with no detectable behavioral changes in TPH2, KI mice. Biochemically, we found that MS WT mice had reduced brain serotonin levels, which was attributed to increased expression of monoamine oxidase A (MAO A). The increased MAO A expression was detected in MS WT mice at 4 weeks old and adulthood. No change in TPH2 expression was detected. To determine whether a pharmacological stressor, dexamethasone (Dex), will result in similar biochemical results obtained from MS, we used an in vitro system, SH-SY5Y cells, and found that Dex treatment resulted in increased MAO A expression levels. We then treated WT mice with Dex for 5 days, either during postnatal days 7-11 or adulthood. Both groups of Dex treated WT mice had reduced basal corticosterone and glucocorticoid receptors expression levels. However, only Dex treatment during PND7-11 resulted in reduced serotonin levels and increased MAO A expression. Just as with MS WT mice, TPH2 expression in PND7-11, Dex-treated WT mice was unaffected. Taken together, our findings suggest that both environmental and pharmacological stressors affect the expression of MAO A, and not TPH2, when applied during the critical postnatal period. This leads to long-lasting perturbations in the serotonergic system, and results in anxiety-and depressive-like behaviors.

Cross-platform urine metabolomics of experimental hyperglycemia in type 2 diabetes

Hyperglycemia causes diabetic nephropathy, a condition for which there are no specific diagnostic markers thatpredict progression to renal failure. Here we describe a multiplatform metabolomic analysis of urine from individualswith type 2 diabetes, collected before and immediately following experimental hyperglycemia. We used targetednuclear magnetic resonance spectroscopy (NMR), liquid chromatography - mass spectrometry (LC-MS) and gaschromatography - MS (GC-MS) to identify markers of hyperglycemia. Following optimization of data normalisation andstatistical analysis, we identified a reproducible NMR and LC-MS based urine signature of hyperglycemia. Significantincreases of alanine, alloisoleucine, isoleucine, leucine, N-isovaleroylglycine, valine, choline, lactate and taurine anddecreases of arginine, gamma-aminobutyric acid, hippurate, suberate and N-acetylglutamate were observed. GC-MSanalysis identified a number of metabolites differentially present in post-glucose versus baseline urine, but these could not be identified using current metabolite libraries. This analysis is an important first step towards identifying biomarkers of early-stage diabetic nephropathy.

Epigenetic markers to predict conversion from gestational diabetes to type 2 diabetes

CONTEXT: Lifestyle factors mediate epigenetic changes that can cause chronic diseases. Although animal and laboratory studies link epigenetic changes to diabetes, epigenetic information in women with gestational diabetes (GDM) and type 2 diabetes is lacking. OBJECTIVE: To measure epigenetic markers across pregnancy and early postpartum and identify markers that could be used as predictors for conversion from GDM to type 2 diabetes. DESIGN: Global histone H3 dimethylation was measured at three time points: 30 weeks gestation, 8-10 weeks postpartum and 20 weeks postpartum, in white blood cells from four groups of women with and without diabetes. SETTING AND PARTICIPANTS: A total of 39 participants (six to nine in each group) were recruited including: non-diabetic women; women with GDM who developed postpartum type 2 diabetes; women with GDM without postpartum type 2 diabetes; and women with type 2 diabetes. MAIN OUTCOME MEASURE: Percentages of dimethylation of H3 histones relative to total H3 histone methylation were compared between diabetic/non-diabetic groups using appropriate comparative statistics. RESULTS: H3K27 dimethylation was 50-60% lower at 8-10 and 20 weeks postpartum in women with GDM who developed type 2 diabetes, compared with non-diabetic women. H3K4 dimethylation was 75% lower at 8-10 weeks postpartum in women with GDM who subsequently developed type 2 diabetes compared with women who had GDM who did not. CONCLUSIONS: The percentage of dimethylation of histones H3K27 and H3K4 varied with diabetic state and has the potential as a predictive tool to identify women who will convert from GDM to type 2 diabetes.

Taphonomy and palaeobiology of early Middle Triassic coprolites from the Luoping biota, southwest China: implications for reconstruction of fossil food webs

Abundant, exceptionally preserved coprolites are documented from the Luoping biota (Anisian, Middle Triassic) of Yunnan Province, southwest China. These coprolites can be categorized into fourmorphological types: A) bead to ribbon-shaped, B) short to long cylindrical-shaped, C) flattened, disk-like, and D) segmented faeces. Detailed multi-disciplinary studies reveal that coprolite type A was likely produced by invertebrate animals,while coprolite types B to D could be faeces generated by carnivorous fishes or marine reptiles, perhaps from different taxonomicgroups. When compared with coprolites reported from the Lower Triassic, the Luoping forms indicate more complicated predation-prey food web networks. These evidences, combined with body fossil discoveries fromLuoping, suggest the emergence of complex trophic ecosystems in the Anisian,marking the full biotic recovery following the Permian–Triassic Mass Extinction.

Systematic review of sedentary behavior and cognitive development in early childhood

OBJECTIVE: To comprehensively review observational and experimental studies examining the relationship between sedentary behavior and cognitive development during early childhood (birth to 5years). METHOD: Electronic databases were searched in July, 2014 and no limits were imposed on the search. Included studies had to be peer-reviewed, published, and meet the a priori determined population (apparently healthy children aged birth to 5years), intervention (duration, types, and patterns of sedentary behavior), comparator (various durations, types, or patterns of sedentary behavior), and outcome (cognitive development) study criteria. Data extraction occurred in October and November 2014 and study quality and risk of bias were assessed in December 2014. RESULTS: A total of 37 studies, representing 14,487 participants from nine different countries were included. Thirty-one studies used observational study designs and six studies used experimental study designs. Across study designs, increased or higher screen time (most commonly assessed as television viewing (TV)), reading, child-specific TV content, and adult-specific TV content had detrimental (negative) associations with cognitive development outcomes for 38%, 0%, 8%, and 25% of associations reported, respectively, and beneficial (positive) associations with cognitive development outcomes for 6%, 60%, 13%, and 3% of associations reported, respectively. Ten studies were moderate quality and 27 studies were weak quality. CONCLUSIONS: The type of sedentary behavior, such as TV versus reading, may have different impacts on cognitive development in early childhood. Future research with reliable and valid tools and adequate sample sizes that examine multiple cognitive domains (e.g., language, spatial cognition, executive function, memory) are needed. Registration no. CRD42014010004.

Cord blood monocyte-derived inflammatory cytokines suppress IL-2 and induce nonclassic "T(H)2-type" immunity associated with development of food allergy

Food allergy is a major health burden in early childhood. Infants who develop food allergy display a proinflammatory immune profile in cord blood, but how this is related to interleukin-4 (IL-4)/T helper 2 (T(H)2)-type immunity characteristic of allergy is unknown. In a general population-derived birth cohort, we found that in infants who developed food allergy, cord blood displayed a higher monocyte to CD4(+) T cell ratio and a lower proportion of natural regulatory T cell (nT(reg)) in relation to duration of labor. CD14(+) monocytes of food-allergic infants secreted higher amounts of inflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-α) in response to lipopolysaccharide. In the presence of the mucosal cytokine transforming growth factor-β, these inflammatory cytokines suppressed IL-2 expression by CD4(+) T cells. In the absence of IL-2, inflammatory cytokines decreased the number of activated nT(reg) and diverted the differentiation of both nT(reg) and naïve CD4(+) T cells toward an IL-4-expressing nonclassical TH2 phenotype. These findings provide a mechanistic explanation for susceptibility to food allergy in infants and suggest anti-inflammatory approaches to its prevention.