To evaluate relationships between HIV-associated neurocognitive disorder and metabolic variables in a subgroup of HIV+ participants examined in a prospective, observational, multicenter cohort study.
...In a cross-sectional substudy of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort, 130 HIV+ participants provided fasting blood samples. Neurocognitive impairment (NCI) was defined by performance on neuropsychological tests adjusting for age, education, gender, and race/ethnicity. Global ratings and global deficit scores were determined. Demographics, biomarkers of HIV disease, metabolic variables, combination antiretroviral therapy (CART) history, other drug exposures, and self-reported diabetes were examined in multivariate models predicting NCI. Separate models were used for body mass index (BMI) alone (n = 90) and BMI and waist circumference (WC) together (n = 55).
NCI (global impairment rating ≥5) was diagnosed in 40%. In univariate analyses, age, longer duration of HIV infection, obesity, and WC, but not BMI, were associated with NCI. Self-reported diabetes was associated with NCI in the substudy and in those >55 in the entire CHARTER cohort. Multivariate logistic regression analyses demonstrated that central obesity (as measured by WC) increased the risk of NCI and that greater body mass may be protective if the deleterious effect of central obesity is accounted for.
As in HIV-uninfected persons, central obesity, but not more generalized increases in body mass (BMI), was associated with a higher prevalence of NCI in HIV+ persons. Diabetes appeared to be associated with NCI only in older patients. Avoidance of antiretroviral drugs that induce central obesity might protect from or help to reverse neurocognitive impairment in HIV-infected persons.
The complexity of oxytocin-mediated functions is strongly associated with its modulatory effects on other neurotransmission systems, including the serotonin (5-hydroxytryptamine, 5-HT) system. ...Signalling between oxytocin (OT) and 5-HT has been demonstrated during neurodevelopment and in the regulation of specific emotion-based behaviours. It is suggested that crosstalk between neurotransmitters is driven by interaction between their specific receptors, particularly the oxytocin receptor (OTR) and the 5-hydroxytryptamine 2C receptor (5-HTR2C), but evidence for this and the downstream signalling consequences that follow are lacking. Considering the overlapping central expression profiles and shared involvement of OTR and 5-HTR2C in certain endocrine functions and behaviours, including eating behaviour, social interaction and locomotor activity, we investigated the existence of functionally active OTR/5-HTR2C heterocomplexes. Here, we demonstrate evidence for a potential physical interaction between OTR and 5-HTR2Cin vitro in a cellular expression system using flow cytometry-based FRET (fcFRET). We could recapitulate this finding under endogenous expression levels of both receptors via in silico analysis of single cell transcriptomic data and ex vivo proximity ligation assay (PLA). Next, we show that co-expression of the OTR/5-HTR2C pair resulted in a significant depletion of OTR-mediated Gαq-signalling and significant changes in receptor trafficking. Of note, attenuation of OTR-mediated downstream signalling was restored following pharmacological blockade of the 5-HTR2C. Finally, we demonstrated a functional relevance of this novel heterocomplex, in vivo, as 5-HTR2C antagonism increased OT-mediated hypoactivity in mice. Overall, we provide compelling evidence for the formation of functionally active OTR/5-HTR2C heterocomplexes, adding another level of complexity to OTR and 5-HTR2C signalling functionality.
This article is part of the special issue on Neuropeptides.
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•Novel OTR/5-HTR2C heteroreceptor complex identified in vitro in cellular expression system and ex vivo in rodent brain.•Depletion of OTR-mediated Gαq signalling upon OTR/5-HTR2C co-expression in cells.•Restoration of OTR-mediated downstream signalling following 5-HTR2C antagonism in cells co-expressing both receptors.•5-HTR2C antagonism augments OT-mediated hypoactivity of mice in vivo.
► Early-life stress is correlated with vulnerability to psychopathologies. ► Adult hippocampal neurogenesis is involved in cognition and emotional regulation. ► We discuss immediate and lasting ...effects of adverse early-life experience on neurogenesis. ► To understand programming of neurogenesis by early-life is critical for intervention.
Early life is a period of unique sensitivity during which experience can confer enduring effects on brain structure and function. During early perinatal life the quality of the surrounding environment and experiences, in particular the parent–child relationship, is associated with emotional and cognitive development later in life. For instance, adverse early-life experience is correlated with an increased vulnerability to develop psychopathologies and aging-related cognitive decline. These are thought to be mediated by acute and long-lasting effects on the, at that time still developing, stress-neuroendocrine and cognitive systems. Adult hippocampal neurogenesis is involved in learning and memory while both regulation of the stress response as well as early-life stress is known to permanently reduce neurogenesis, and to be implicated in these functional deficits.
In order to increase our understanding of the influence of the perinatal environment on the long-lasting programming of neurogenesis, we here discuss immediate and lasting effects of various adverse early-life experiences on hippocampal neurogenesis and the associated behavioral alterations. Considering the persistence of these effects, the underlying molecular mechanisms, with focus on the potential epigenetic mechanisms will be discussed as well. Finally, special attention will be paid to the prominent sex differences in early-life stress-induced alterations in neurogenesis.
Despite the cultural ubiquity of ideas and images related to God, relatively little is known about the effects of exposure to God representations on behavior. Specific depictions of God differ across ...religions, but common to most is that God is (a) an omnipotent, controlling force and (b) an omniscient, all-knowing being. Given these 2 characteristic features, how might exposure to the concept of God influence behavior? Leveraging classic and recent theorizing on self-regulation and social cognition, we predict and test for 2 divergent effects of exposure to notions of God on self-regulatory processes. Specifically, we show that participants reminded of God (vs. neutral or positive concepts) demonstrate both decreased active goal pursuit (Studies 1, 2, and 5) and increased temptation resistance (Studies 3, 4, and 5). These findings provide the first experimental evidence that exposure to God influences goal pursuit and suggest that the ever-present cultural reminders of God can be both burden and benefit for self-regulation.
Five studies support the hypothesis that beliefs in societal fairness offer a self-regulatory benefit for members of socially disadvantaged groups. Specifically, members of disadvantaged groups are ...more likely than members of advantaged groups to calibrate their pursuit of long-term goals to their beliefs about societal fairness. In Study 1, low socioeconomic status (SES) undergraduate students who believed more strongly in societal fairness showed greater intentions to persist in the face of poor performance on a midterm examination. In Study 2, low SES participants who believed more strongly in fairness reported more willingness to invest time and effort to achieve desirable career outcomes. In Study 3, ethnic minority participants exposed to a manipulation suggesting that fairness conditions in their country were improving reported more willingness to invest resources in pursuit of long-term goals, relative to ethnic minority participants in a control condition. Study 4 replicated Study 3 using an implicit priming procedure, demonstrating that perceptions of the personal relevance of societal fairness mediate these effects. Across these 4 studies, no link between fairness beliefs and self-regulation emerged for members of advantaged (high SES, ethnic majority) groups. Study 5 contributed evidence from the World Values Survey and a representative sample (Inglehart, Basañez, Diez-Medrano, Halman, & Luijkx, 2004). Respondents reported more motivation to work hard to the extent that they believed that rewards were distributed fairly; this effect emerged more strongly for members of lower SES groups than for members of higher SES groups, as indicated by both self-identified social class and ethnicity.
Although women's underrepresentation in senior-level positions in the workplace has multiple causes, women's self-improvement or "empowerment" at work has recently attracted cultural attention as a ...solution. For example, the bestselling book Lean In states that women can tackle gender inequality themselves by overcoming the "internal barriers" (e.g., lack of confidence and ambition) that prevent success. We sought to explore the consequences of this type of women's empowerment ideology. Study 1 found that perceptions of women's ability to solve inequality were associated with attributions of women's responsibility to do so. Studies 2, 3, 5a, and 5b experimentally manipulated exposure to women's empowerment messages, finding that while such messages increase perceptions that women are empowered to solve workplace gender inequality, they also lead to attributions that women are more responsible both for creating and solving the problem. Study 4 found a similar pattern in the context of a specific workplace problem, and found that such messages also lead to a preference for interventions focused on changing women rather than changing the system. Studies 5a and 5b sought to replicate prior studies and document the weakened effects of messages that explicitly explain that women's "internal barriers" are the products of "external barriers" obstructing women's progress. This research suggests that self-improvement messages intended to empower women to take charge of gender inequality may also yield potentially harmful societal beliefs.
Sedentary behaviour is a public health concern that requires surveillance and epidemiological research. For such large scale studies, self-report tools are a pragmatic measurement solution. A large ...number of self-report tools are currently in use, but few have been validated against an objective measure of sedentary time and there is no comparative information between tools to guide choice or to enable comparison between studies. The aim of this study was to provide a systematic comparison, generalisable to all tools, of the validity of self-report measures of sedentary time against a gold standard sedentary time objective monitor.
Cross sectional data from three cohorts (N = 700) were used in this validation study. Eighteen self-report measures of sedentary time, based on the TAxonomy of Self-report SB Tools (TASST) framework, were compared against an objective measure of postural sitting (activPAL) to provide information, generalizable to all existing tools, on agreement and precision using Bland-Altman statistics, on criterion validity using Pearson correlation, and on data loss.
All self-report measures showed poor accuracy compared with the objective measure of sedentary time, with very wide limits of agreement and poor precision (random error > 2.5 h). Most tools under-reported total sedentary time and demonstrated low correlations with objective data. The type of assessment used by the tool, whether direct, proxy, or a composite measure, influenced the measurement characteristics. Proxy measures (TV time) and single item direct measures using a visual analogue scale to assess the proportion of the day spent sitting, showed the best combination of precision and data loss. The recall period (e.g. previous week) had little influence on measurement characteristics.
Self-report measures of sedentary time result in large bias, poor precision and low correlation with an objective measure of sedentary time. Choice of tool depends on the research context, design and question. Choice can be guided by this systematic comparative validation and, in the case of population surveillance, it recommends to use a visual analog scale and a 7 day recall period. Comparison between studies and improving population estimates of average sedentary time, is possible with the comparative correction factors provided.
This research examines how the body type of consumers affects the food consumption of other consumers around them. We find that consumers anchor on the quantities others around them select but that ...these portions are adjusted according to the body type of the other consumer. We find that people choose a larger portion following another consumer who first selects a large quantity but that this portion is significantly smaller if the other is obese than if she is thin. We also find that the adjustment is more pronounced for consumers who are low in appearance self‐esteem and that it is attenuated under cognitive load.
The quarry at Kottavattom in the Trivandrum Block of southern India contains spectacular examples of fluid-assisted alteration of high-grade metamorphic rocks. Garnet-biotite gneiss has undergone a ...change in mineral assemblage to form submetre scale orthopyroxene-bearing patches, later retrogressed to form an amphibole-bearing lithology. These patches, often referred to as arrested or incipient charnockite, crosscut the original metamorphic foliation and are typically attributed to passage of a low
a
H
2
O fluid through the rock. Whilst this conversion is recognised as a late stage process, little detailed chronological work exists to link it temporally to metamorphism in the region. Zircon and monazite analysed from Kottavattom not only record metamorphism in the Trivandrum Block but also show internal, lobate textures crosscutting the original zoning, consistent with fluid-aided coupled dissolution-reprecipitation during formation of the orthopyroxene-bearing patches. High-grade metamorphism at the quarry occurred between the formation of metamorphic monazite at ~585 Ma and the growth of metamorphic zircon at ~523 Ma. The fluid-assisted alteration of the garnet-biotite gneiss is poorly recorded by altered zircon with only minimal resetting of the U–Pb system, whereas monazite has in some cases undergone complete U–Pb resetting and records an age for fluid infiltration at ~495 Ma. The fluid event therefore places the formation of the altered patches at least 25 Myr after the zircon crystallisation in the garnet-biotite gneiss. The most likely fluid composition causing the modification and U–Pb resetting of zircon and monazite is locally derived hypersaline brine.
Objective To assess the effectiveness of an integrated early child development intervention, combining stimulation and micronutrient supplementation and delivered on a large scale in Colombia, for ...children’s development, growth, and hemoglobin levels.Design Cluster randomized controlled trial, using a 2×2 factorial design, with municipalities assigned to one of four groups: psychosocial stimulation, micronutrient supplementation, combined intervention, or control.Setting 96 municipalities in Colombia, located across eight of its 32 departments.Participants 1420 children aged 12-24 months and their primary carers.Intervention Psychosocial stimulation (weekly home visits with play demonstrations), micronutrient sprinkles given daily, and both combined. All delivered by female community leaders for 18 months.Main outcome measures Cognitive, receptive and expressive language, and fine and gross motor scores on the Bayley scales of infant development-III; height, weight, and hemoglobin levels measured at the baseline and end of intervention.Results Stimulation improved cognitive scores (adjusted for age, sex, testers, and baseline levels of outcomes) by 0.26 of a standard deviation (P=0.002). Stimulation also increased receptive language by 0.22 of a standard deviation (P=0.032). Micronutrient supplementation had no significant effect on any outcome and there was no interaction between the interventions. No intervention affected height, weight, or hemoglobin levels.Conclusions Using the infrastructure of a national welfare program we implemented the integrated early child development intervention on a large scale and showed its potential for improving children’s cognitive development. We found no effect of supplementation on developmental or health outcomes. Moreover, supplementation did not interact with stimulation. The implementation model for delivering stimulation suggests that it may serve as a promising blueprint for future policy on early childhood development.Trial registration Current Controlled trials ISRCTN18991160.
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