Altered functional connectivity within the central reward network in overweight and obese women.

Background/objectivesNeuroimaging studies in obese subjects have identified abnormal activation of key regions of central reward circuits, including the nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to examine whether women with elevated body mass index (BMI) show structural and resting state (RS) functional connectivity alterations within regions of the reward network.Subjects/methodsFifty healthy, premenopausal women, 19 overweight and obese (high BMI=26-38 kg m(-2)) and 31 lean (BMI=19-25 kg m(-2)) were selected from the University of California Los Angeles' Oppenheimer Center for Neurobiology of Stress database. Structural and RS functional scans were collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation dynamics of intrinsic brain activity and functional connectivity of the NAcc to regions within the reward network were examined.ResultsGMV of the left NAcc was significantly greater in the high BMI group than in the lean group (P=0.031). Altered frequency distributions were observed in women with high BMI compared with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and in bilateral anterior cingulate cortex (ACC) (P=0.014, <0.001) and ventro-medial prefrontal cortex (vmPFC) (P=0.034, <0.001) in a high-frequency band. Subjects with high BMI had greater connectivity of the left NAcc with bilateral ACC (P=0.024) and right vmPFC (P=0.032) in a MF band and with the left ACC (P=0.03) in a high frequency band.ConclusionsOverweight and obese women in the absence of food-related stimuli show significant structural and functional alterations within regions of reward-related brain networks, which may have a role in altered ingestive behaviors

The effect of the GLP-1 analogue Exenatide on functional connectivity within an NTS-based network in women with and without obesity.

ObjectiveThe differential effect of GLP-1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite-related behaviours was investigated in women with normal weight compared with women with obesity.MethodsFollowing an 8-h fast, 19 female subjects (11 lean, 8 obese) participated in a 2-d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30-min post subcutaneous injection of 5 μg of Exenatide or placebo. Functional connectivity was examined with the NTS. Drug-induced functional connectivity changes within and between groups and correlations with appetite measures were examined in a region of interest approach focusing on the thalamus and hypothalamus.ResultsWomen with obesity reported less hunger after drug injection. Exenatide administration increased functional connectivity of the left NTS with the left thalamus and hypothalamus in the obese group only and increased the correlation between NTS functional connectivity and hunger scores in all subjects, but more so in the obese.ConclusionsObesity can impact the effects of Exenatide on brain connectivity, specifically in the NTS and is linked to changes in appetite control. This has implications for the use of GLP-1 analogues in therapeutic interventions

History of early life adversity is associated with increased food addiction and sex-specific alterations in reward network connectivity in obesity.

Background:Neuroimaging studies have identified obesity-related differences in the brain's resting state activity. An imbalance between homeostatic and reward aspects of ingestive behaviour may contribute to obesity and food addiction. The interactions between early life adversity (ELA), the reward network and food addiction were investigated to identify obesity and sex-related differences, which may drive obesity and food addiction. Methods:Functional resting state magnetic resonance imaging was acquired in 186 participants (high body mass index [BMI]: ≥25: 53 women and 54 men; normal BMI: 18.50-24.99: 49 women and 30 men). Participants completed questionnaires to assess ELA (Early Traumatic Inventory) and food addiction (Yale Food Addiction Scale). A tripartite network analysis based on graph theory was used to investigate the interaction between ELA, brain connectivity and food addiction. Interactions were determined by computing Spearman rank correlations, thresholded at q < 0.05 corrected for multiple comparisons. Results:Participants with high BMI demonstrate an association between ELA and food addiction, with reward regions playing a role in this interaction. Among women with high BMI, increased ELA was associated with increased centrality of reward and emotion regulation regions. Men with high BMI showed associations between ELA and food addiction with somatosensory regions playing a role in this interaction. Conclusions:The findings suggest that ELA may alter brain networks, leading to increased vulnerability for food addiction and obesity later in life. These alterations are sex specific and involve brain regions influenced by dopaminergic or serotonergic signalling

Sex differences in the influence of body mass index on anatomical architecture of brain networks.

Background/objectivesThe brain has a central role in regulating ingestive behavior in obesity. Analogous to addiction behaviors, an imbalance in the processing of rewarding and salient stimuli results in maladaptive eating behaviors that override homeostatic needs. We performed network analysis based on graph theory to examine the association between body mass index (BMI) and network measures of integrity, information flow and global communication (centrality) in reward, salience and sensorimotor regions and to identify sex-related differences in these parameters.Subjects/methodsStructural and diffusion tensor imaging were obtained in a sample of 124 individuals (61 males and 63 females). Graph theory was applied to calculate anatomical network properties (centrality) for regions of the reward, salience and sensorimotor networks. General linear models with linear contrasts were performed to test for BMI and sex-related differences in measures of centrality, while controlling for age.ResultsIn both males and females, individuals with high BMI (obese and overweight) had greater anatomical centrality (greater connectivity) of reward (putamen) and salience (anterior insula) network regions. Sex differences were observed both in individuals with normal and elevated BMI. In individuals with high BMI, females compared to males showed greater centrality in reward (amygdala, hippocampus and nucleus accumbens) and salience (anterior mid-cingulate cortex) regions, while males compared to females had greater centrality in reward (putamen) and sensorimotor (posterior insula) regions.ConclusionsIn individuals with increased BMI, reward, salience and sensorimotor network regions are susceptible to topological restructuring in a sex-related manner. These findings highlight the influence of these regions on integrative processing of food-related stimuli and increased ingestive behavior in obesity, or in the influence of hedonic ingestion on brain topological restructuring. The observed sex differences emphasize the importance of considering sex differences in obesity pathophysiology

Moving from evidence-based medicine to evidence-based health.

While evidence-based medicine (EBM) has advanced medical practice, the health care system has been inconsistent in translating EBM into improvements in health. Disparities in health and health care play out through patients' limited ability to incorporate the advances of EBM into their daily lives. Assisting patients to self-manage their chronic conditions and paying attention to unhealthy community factors could be added to EBM to create a broader paradigm of evidence-based health. A perspective of evidence-based health may encourage physicians to consider their role in upstream efforts to combat socially patterned chronic disease

Socially sensitive lactation: Exploring the social context of breastfeeding

Many women report difficulties with breastfeeding and do not maintain the practice for as long as intended. Although psychologists and other researchers have explored some of the difficulties they experience, fuller exploration of the relational contexts in which breastfeeding takes place is warranted to enable more in-depth analysis of the challenges these pose for breastfeeding women. The present paper is based on qualitative data collected from 22 first-time breastfeeding mothers through two phases of interviews and audio-diaries which explored how the participants experienced their relationships with significant others and the wider social context of breastfeeding in the first five weeks postpartum. Using a thematic analysis informed by symbolic interactionism, we develop the overarching theme of ‘Practising socially sensitive lactation’ which captures how participants felt the need to manage tensions between breastfeeding and their perceptions of the needs, expectations and comfort of others. We argue that breastfeeding remains a problematic social act, despite its agreed importance for child health. Whilst acknowledging the limitations of our sample and analytic approach, we suggest ways in which perinatal and public health interventions can take more effective account of the social challenges of breastfeeding in order to facilitate the health and psychological well-being of mothers and their infants

IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection

IL-21 is produced predominantly by activated CD4(+) T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (gamma(c)) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8(+) T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4(+) and CD8(+) T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R(-/-) mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R(-/-) T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis.This work was supported by National Institutes of Health Grants R21 AI100766, R01 AI106725, and P01 AI073748

Tuning a Circular p-n Junction in Graphene from Quantum Confinement to Optical Guiding

The motion of massless Dirac-electrons in graphene mimics the propagation of photons. This makes it possible to control the charge-carriers with components based on geometrical-optics and has led to proposals for an all-graphene electron-optics platform. An open question arising from the possibility of reducing the component-size to the nanometer-scale is how to access and understand the transition from optical-transport to quantum-confinement. Here we report on the realization of a circular p-n junction that can be continuously tuned from the nanometer-scale, where quantum effects are dominant, to the micrometer scale where optical-guiding takes over. We find that in the nanometer-scale junction electrons are trapped in states that resemble atomic-collapse at a supercritical charge. As the junction-size increases, the transition to optical-guiding is signaled by the emergence of whispering-gallery modes and Fabry-Perot interference. The creation of tunable junctions that straddle the crossover between quantum-confinement and optical-guiding, paves the way to novel design-architectures for controlling electronic transport.Comment: 16 pages, 4 figure

The magic nature of 132Sn explored through the single-particle states of 133Sn

Atomic nuclei have a shell structure where nuclei with 'magic numbers' of neutrons and protons are analogous to the noble gases in atomic physics. Only ten nuclei with the standard magic numbers of both neutrons and protons have so far been observed. The nuclear shell model is founded on the precept that neutrons and protons can move as independent particles in orbitals with discrete quantum numbers, subject to a mean field generated by all the other nucleons. Knowledge of the properties of single-particle states outside nuclear shell closures in exotic nuclei is important for a fundamental understanding of nuclear structure and nucleosynthesis (for example the r-process, which is responsible for the production of about half of the heavy elements). However, as a result of their short lifetimes, there is a paucity of knowledge about the nature of single-particle states outside exotic doubly magic nuclei. Here we measure the single-particle character of the levels in 133Sn that lie outside the double shell closure present at the short-lived nucleus 132Sn. We use an inverse kinematics technique that involves the transfer of a single nucleon to the nucleus. The purity of the measured single-particle states clearly illustrates the magic nature of 132Sn.Comment: 19 pages, 5 figures and 4 table

Star forming dwarf galaxies

Star forming dwarf galaxies (SFDGs) have a high gas content and low metallicities, reminiscent of the basic entities in hierarchical galaxy formation scenarios. In the young universe they probably also played a major role in the cosmic reionization. Their abundant presence in the local volume and their youthful character make them ideal objects for detailed studies of the initial stellar mass function (IMF), fundamental star formation processes and its feedback to the interstellar medium. Occasionally we witness SFDGs involved in extreme starbursts, giving rise to strongly elevated production of super star clusters and global superwinds, mechanisms yet to be explored in more detail. SFDGs is the initial state of all dwarf galaxies and the relation to the environment provides us with a key to how different types of dwarf galaxies are emerging. In this review we will put the emphasis on the exotic starburst phase, as it seems less important for present day galaxy evolution but perhaps fundamental in the initial phase of galaxy formation.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon, September 2010, Springer Verlag, in pres