208 research outputs found
Regional grey matter volume and concentration in at-risk adolescents: Untangling associations with callous-unemotional traits and conduct disorder symptoms
Structural Magnetic Resonance Imaging studies have reported volume reductions in several brain regions implicated in social cognition and emotion recognition in juvenile antisocial populations. However, it is unclear whether these structural abnormalities are specifically related to antisocial features, or to co-occurring callous-unemotional (CU) traits. The present study employed voxel-based morphometry to assess both grey matter volume (GMV) and grey matter concentration (GMC) in a large representative at-risk sample of adolescents (n=134; mean age 17.7 yr), characterized by a broad range of CU trait and conduct disorder (CD) symptom scores. There was a significant interaction between CD symptom and CU trait scores in the prediction of GMV in the anterior insula, with a significant positive association between CU traits and GMV in youth low on CD symptoms only. In addition, we found a significant unique positive association between CD symptoms and GMC in the amygdala, and unique negative associations between CU traits and GMC in the amygdala and insula. These findings are in line with accumulating evidence of distinct associations of CD symptoms and CU traits with amygdala and insula GMC in juvenile antisocial populations
Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y Gastric Bypass on Neural Responsivity to Food Cues.
OBJECTIVE: It has been suggested that weight reduction and improvements in satiety after Roux-en-Y gastric bypass (RYGB) are partly mediated via postoperative neuroendocrine changes. Glucagon-like peptide-1 (GLP-1) is a gut hormone secreted after food ingestion and is associated with appetite and weight reduction, mediated via effects on the central nervous system (CNS). Secretion of GLP-1 is greatly enhanced after RYGB. We hypothesized that postoperative elevated GLP-1 levels contribute to the improved satiety regulation after RYGB via effects on the CNS. RESEARCH DESIGN AND METHODS: Effects of the GLP-1 receptor antagonist exendin 9-39 (Ex9-39) and placebo were assessed in 10 women before and after RYGB. We used functional MRI to investigate CNS activation in response to visual food cues (pictures) and gustatory food cues (consumption of chocolate milk), comparing results with Ex9-39 versus placebo before and after RYGB. RESULTS: After RYGB, CNS activation was reduced in the rolandic operculum and caudate nucleus in response to viewing food pictures (P = 0.03) and in the insula in response to consumption of palatable food (P = 0.003). GLP-1 levels were significantly elevated postoperatively (P < 0.001). After RYGB, GLP-1 receptor blockade resulted in a larger increase in activation in the caudate nucleus in response to food pictures (P = 0.02) and in the insula in response to palatable food consumption (P = 0.002). CONCLUSIONS: We conclude that the effects of RYGB on CNS activation in response to visual and gustatory food cues may be mediated by central effects of GLP-1. Our findings provide further insights into the mechanisms underlying the weight-lowering effects of RYGB
Brain reward responses to food stimuli among female monozygotic twins discordant for BMI
Obese individuals are characterized by altered brain reward responses to food. Despite the latest discovery of obesity-associated genes, the contribution of environmental and genetic factors to brain reward responsiveness to food remains largely unclear. Sixteen female monozygotic twin pairs with a mean BMI discordance of 3.96 ± 2.1 kg/m(2) were selected from the Netherlands Twin Register to undergo functional MRI scanning while watching high- and low-calorie food and non-food pictures and during the anticipation and receipt of chocolate milk. In addition, appetite ratings, eating behavior and food intake were assessed using visual analog scales, validated questionnaires and an ad libitum lunch. In the overall group, visual and taste stimuli elicited significant activation in regions of interest (ROIs) implicated in reward, i.e. amygdala, insula, striatum and orbitofrontal cortex. However, when comparing leaner and heavier co-twins no statistically significant differences in ROI-activations were observed after family wise error correction. Heavier versus leaner co-twins reported higher feelings of hunger (P = 0.02), cravings for sweet food (P = 0.04), body dissatisfaction (P < 0.05) and a trend towards more emotional eating (P = 0.1), whereas caloric intake was not significantly different between groups (P = 0.3). Our results suggest that inherited rather than environmental factors are largely responsible for the obesity-related altered brain responsiveness to food. Future studies should elucidate the genetic variants underlying the susceptibility to reward dysfunction and obesity. CLINICAL TRIAL REGISTRATION NUMBER: NCT02025595
First Emergence of Resistance to Macrolides and Tetracycline Identified in Mannheimia haemolytica and Pasteurella multocida Isolates from Beef Feedlots in Australia
Bovine respiratory disease (BRD) causes high morbidity and mortality in beef cattle worldwide. Antimicrobial resistance (AMR) monitoring of BRD pathogens is critical to promote appropriate antimicrobial stewardship in veterinary medicine for optimal treatment and control. Here, the susceptibility of Mannheimia haemolytica and Pasteurella multicoda isolates obtained from BRD clinical cases (deep lung swabs at post-mortem) among feedlots in four Australian states (2014-2019) was determined for 19 antimicrobial agents. The M. haemolytica isolates were pan-susceptible to all tested agents apart from a single macrolide-resistant isolate (1/88; 1.1%) from New South Wales (NSW). Much higher frequencies of P. multocida isolates were resistant to tetracycline (18/140; 12.9%), tilmicosin (19/140; 13.6%), tulathromycin/gamithromycin (17/140; 12.1%), and ampicillin/penicillin (6/140; 4.6%). Five P. multocida isolates (3.6%), all obtained from NSW in 2019, exhibited dual resistance to macrolides and tetracycline, and a further two Queensland isolates from 2019 (1.4%) exhibited a multidrug-resistant phenotype to ampicillin/penicillin, tetracycline, and tilmicosin. Random-amplified polymorphic DNA (RAPD) typing identified a high degree of genetic homogeneity among the M. haemolytica isolates, whereas P. multocida isolates were more heterogeneous. Illumina whole genome sequencing identified the genes msr(E) and mph(E)encoding macrolide resistance, tet(R)-tet(H) or tet(Y) encoding tetracycline resistance, and blaROB-1 encoding ampicillin/penicillin resistance in all isolates exhibiting a corresponding resistant phenotype. The exception was the tilmicosin-resistant, tulathromycin/gamithromycin-susceptible phenotype identified in two Queensland isolates, the genetic basis of which could not be determined. These results confirm the first emergence of AMR in M. haemolytica and P. multocida from BRD cases in Australia, which should be closely monitored
Cerebral effects of glucagonâlike peptideâ1 receptor blockade before and after RouxâenâY gastric bypass surgery in obese women: A proofâofâconcept restingâstate functional MRI study
Aim:
To assess the effects of RouxâenâY gastric bypass surgery (RYGB)ârelated changes in glucagonâlike peptideâ1 (GLPâ1) on cerebral restingâstate functioning in obese women.
Materials and Methods:
In nine obese females aged 40â54âyears in the fasted state, we studied the effects of RYGB and GLPâ1 on five a priori selected networks implicated in foodâ and rewardârelated processes as well as environment monitoring (default mode, right frontoparietal, basal ganglia, insula/anterior cingulate and anterior cingulate/orbitofrontal networks).
Results:
Before surgery, GLPâ1 receptor blockade (using exendin9â39) was associated with increased right caudate nucleus (basal ganglia network) and decreased right middle frontal (right frontoparietal network) connectivity compared with placebo. RYGB resulted in decreased right orbitofrontal (insula/anterior cingulate network) connectivity. In the default mode network, after surgery, GLPâ1 receptor blockade had a larger effect on connectivity in this region than GLPâ1 receptor blockade before RYGB (all PFWEâ<â.05). Results remained similar after correction for changes in body weight. Default mode and right frontoparietal network connectivity changes were related to changes in body mass index and food scores after RYGB.
Conclusions:
These findings suggest GLPâ1 involvement in restingâstate networks related to food and reward processes and monitoring of the internal and external environment, pointing to a potential role for GLPâ1âinduced changes in restingâstate connectivity in RYGBâmediated weight loss and appetite control
Transient Cognitive Impairment and White Matter Hyperintensities in Severely Depressed Older Patients Treated With Electroconvulsive Therapy
BACKGROUND: Although electroconvulsive therapy (ECT) is a safe and effective treatment for patients with severe late life depression (LLD), transient cognitive impairment can be a reason to discontinue the treatment. The aim of the current study was to evaluate the association between structural brain characteristics and general cognitive function during and after ECT. METHODS: A total of 80 patients with LLD from the prospective naturalistic follow-up Mood Disorders in Elderly treated with Electroconvulsive Therapy study were examined. Magnetic resonance imaging scans were acquired before ECT. Overall brain morphology (white and grey matter) was evaluated using visual rating scales. Cognitive functioning before, during, and after ECT was measured using the Mini Mental State Examination (MMSE). A linear mixed-model analysis was performed to analyze the association between structural brain alterations and cognitive functioning over time. RESULTS: Patients with moderate to severe white matter hyperintensities (WMH) showed significantly lower MMSE scores than patients without severe WMH (F(1,75.54)âŻ=âŻ5.42, pâŻ=âŻ0.02) before, during, and post-ECT, however their trajectory of cognitive functioning was similar as no time Ă WMH interaction effect was observed (F(4,65.85)âŻ=âŻ1.9, pâŻ=âŻ0.25). Transient cognitive impairment was not associated with medial temporal or global cortical atrophy (MTA, GCA). CONCLUSION: All patients showed a significant drop in cognitive functioning during ECT, which however recovered above baseline levels post-ECT and remained stable until at least 6 months post-ECT, independently of severity of WMH, GCA, or MTA. Therefore, clinicians should not be reluctant to start or continue ECT in patients with severe structural brain alterations
The Minimal Scale Invariant Extension of the Standard Model
We perform a systematic analysis of an extension of the Standard Model that
includes a complex singlet scalar field and is scale invariant at the tree
level. We call such a model the Minimal Scale Invariant extension of the
Standard Model (MSISM). The tree-level scale invariance of the model is
explicitly broken by quantum corrections, which can trigger electroweak
symmetry breaking and potentially provide a mechanism for solving the gauge
hierarchy problem. Even though the scale invariant Standard Model is not a
realistic scenario, the addition of a complex singlet scalar field may result
in a perturbative and phenomenologically viable theory. We present a complete
classification of the flat directions which may occur in the classical scalar
potential of the MSISM. After calculating the one-loop effective potential of
the MSISM, we investigate a number of representative scenarios and determine
their scalar boson mass spectra, as well as their perturbatively allowed
parameter space compatible with electroweak precision data. We discuss the
phenomenological implications of these scenarios, in particular, whether they
realize explicit or spontaneous CP violation, neutrino masses or provide dark
matter candidates. In particular, we find a new minimal scale-invariant model
of maximal spontaneous CP violation which can stay perturbative up to
Planck-mass energy scales, without introducing an unnaturally large hierarchy
in the scalar-potential couplings.Comment: 71 pages, 34 eps figures, numerical error corrected, clarifying
comments adde
Higgs mass and vacuum stability in the Standard Model at NNLO
We present the first complete next-to-next-to-leading order analysis of the
Standard Model Higgs potential. We computed the two-loop QCD and Yukawa
corrections to the relation between the Higgs quartic coupling (lambda) and the
Higgs mass (Mh), reducing the theoretical uncertainty in the determination of
the critical value of Mh for vacuum stability to 1 GeV. While lambda at the
Planck scale is remarkably close to zero, absolute stability of the Higgs
potential is excluded at 98% C.L. for Mh < 126 GeV. Possible consequences of
the near vanishing of lambda at the Planck scale, including speculations about
the role of the Higgs field during inflation, are discussed.Comment: 35 pages, 8 figures. Final published version, misprints fixed,
figures update
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