Take it or leave it: prefrontal control in recreational cocaine users.

Though stimulant drugs such as cocaine are considered highly addictive, some individuals report recreational use over long periods without developing dependence. Difficulties in response inhibition have been hypothesized to contribute to dependence, but previous studies investigating response inhibition in recreational cocaine users have reported conflicting results. Performance on a stop-signal task was examined in 24 recreational cocaine users and 32 healthy non-drug using control participants matched for age, gender and verbal intelligence during functional magnetic resonance imaging scanning. The two groups were further matched on traumatic childhood histories and the absence of family histories of addiction. Results revealed that recreational cocaine users did not significantly differ from controls on any index of task performance, including response execution and stop-signal reaction time, with the latter averaging 198 ms in both groups. Functional magnetic resonance imaging analyses indicated that, compared with controls, stopping in the recreational users was associated with increased activation in the pre-supplementary motor area but not the right inferior frontal cortex. Thus, findings imply intact response inhibition abilities in recreational cocaine users, though the distinct pattern of accompanying activation suggests increased recruitment of brain areas implicated in response inhibition. This increased recruitment could be attributed to compensatory mechanisms that enable preserved cognitive control in this group, possibly relating to their hypothetical resilience to stimulant drug dependence. Such overactivation, alternatively, may be attributable to prolonged cocaine use leading to neuroplastic adaptations.This work was funded by a Medical Research Council (MRC) research grant to KDE, ETB and TWR (G0701497) and was conducted within the Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK, which is supported by a joint award from the MRC and the Wellcome Trust; Both KDE and PSJ were supported by the MRC, SM was supported by a Wellcome Trust grant (089589/Z/09/Z) awarded to TW Robbins.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/tp.2015.8

Screening families of patients with premature coronary heart disease to identify avoidable cardiovascular risk: a cross-sectional study of family members and a general population comparison group

<b>Background:</b> Primary prevention should be targeted at individuals with high global cardiovascular risk, but research is lacking on how best to identify such individuals in the general population. Family history is a good proxy measure of global risk and may provide an efficient mechanism for identifying high risk individuals. The aim was to test the feasibility of using patients with premature cardiovascular disease to recruit family members as a means of identifying and screening high-risk individuals. <b>Findings:</b> We recruited family members of 50 patients attending a cardiology clinic for premature coronary heart disease (CHD). We compared their cardiovascular risk with a general population control group, and determined their perception of their risk and current level of screening. 103 (36%) family members attended screening (27 siblings, 48 adult offspring and 28 partners). Five (5%) had prevalent CHD. A significantly higher percentage had an ASSIGN risk score >20% compared with the general population (13% versus 2%, p < 0.001). Only 37% of family members were aware they were at increased risk and only 50% had had their blood pressure and serum cholesterol level checked in the previous three years. <b>Conclusions:</b> Patients attending hospital for premature CHD provide a mechanism to contact family members and this can identify individuals with a high global risk who are not currently screened

Circuit Quantum Electrodynamics with a Spin Qubit

Circuit quantum electrodynamics allows spatially separated superconducting qubits to interact via a "quantum bus", enabling two-qubit entanglement and the implementation of simple quantum algorithms. We combine the circuit quantum electrodynamics architecture with spin qubits by coupling an InAs nanowire double quantum dot to a superconducting cavity. We drive single spin rotations using electric dipole spin resonance and demonstrate that photons trapped in the cavity are sensitive to single spin dynamics. The hybrid quantum system allows measurements of the spin lifetime and the observation of coherent spin rotations. Our results demonstrate that a spin-cavity coupling strength of 1 MHz is feasible.Comment: Related papers at http://pettagroup.princeton.edu

Fear of movement/(re)injury in Chinese patients with chronic pain: Factorial validity of the Chinese version of the Tampa Scale for Kinesiophobia

Objective: To assess the factor structure of the Chinese version of the Tampa Scale for Kinesiophobia (TSK). Design: Chinese patients with chronic pain attending either orthopaedic specialist services (n = 216) or multidisciplinary specialist pain services (n = 109) participated in this study. Methods: Subjects completed the Chinese version of TSK, The Chronic Pain Grade Questionnaire, Hospital Anxiety and Depression Scale, and questions assessing socio-demographic characteristics. Confirmatory factor analyses were used to compare hierarchical and correlated models of 5 different factor solutions previously reported in patients with chronic pain in the West. Results: Confirmatory factor analyses demonstrated inequality of the TSK factor structure, in that the TSK11 for the orthopaedics sample was best represented by a two-factor correlated model (S-Bχ2 = 49.593; comparative fit index (CFI) = 0.93; normed filt index (NFI) = 0.911; root mean square error of approximation (RMSEA) = 0.025) comprising 2 first-order factors, Somatic Focus (TSK11-SF) and Activity Avoidance (TSK-AA). The pain clinic sample showed a one-factor structure as best representing the TSK4’s underlying dimensions (CFI  = 0.971; NFI = 0.912; RMSEA = 0.048). There was no evidence to support a single overarching concept of kinesiophobia. Conclusion: The TSK appears to have utility in Chinese chronic pain populations. Elucidation of the TSK’s psychometrics properties in other Chinese/Asian pain populations with different diagnoses and presentations of pain problems is warranted

Stimulus-dependent maximum entropy models of neural population codes

Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. To be able to infer a model for this distribution from large-scale neural recordings, we introduce a stimulus-dependent maximum entropy (SDME) model---a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. The model is able to capture the single-cell response properties as well as the correlations in neural spiking due to shared stimulus and due to effective neuron-to-neuron connections. Here we show that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. As a result, the SDME model gives a more accurate account of single cell responses and in particular outperforms uncoupled models in reproducing the distributions of codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like surprise and information transmission in a neural population.Comment: 11 pages, 7 figure

Characterization of the ZBTB42 gene in humans and mice

A 12 kb haplotype upstream of the key signaling protein gene, AKT1, has been associated with insulin resistance and metabolic syndrome (Devaney et al. 2010). The region contains the first exon and promoter sequences of AKT1, but also includes the complete transcript unit for a highly conserved yet uncharacterized zinc finger-containing protein (ZBTB42). One of the component SNPs of the 12 kb haplotype metabolic syndrome haplotype changes a conserved amino acid in the predicted ZBTB42 protein, increasing the potential significance of the ZBTB42 transcript unit for contributing to disease risk. Using RT-PCR of human and mouse cells, we verified that the two exon ZBTB42 was expressed and correctly spliced in human skeletal muscle, and murine C2C12 cells. Production of peptide antibodies showed the expected protein in human (47 kD) and mouse (49 kD) immunoblots, and murine tissue distribution showed strongest expression in muscle and ovary. Immunostaining showed nuclear localization of the ZBTB42 protein in human muscle. Confocal imaging analyses of murine muscle showed ZBTB42 distributed in the nucleoplasm, with particular enrichment in nuclei underlying the neuromuscular junctions. The genetic association data of metabolic syndrome, coupled with the molecular characterization of the ZBTB42 transcript unit and encoded protein presented here, suggests that ZBTB42 may be involved in metabolic syndrome phenotypes

Positive psychology of Malaysian students: impacts of engagement, motivation, self-compassion and wellbeing on mental health

Malaysia plays a key role in education of the Asia Pacific, expanding its scholarly output rapidly. However, mental health of Malaysian students is challenging, and their help-seeking is low because of stigma. This study explored the relationships between mental health and positive psychological constructs (academic engagement, motivation, self-compassion, and wellbeing), and evaluated the relative contribution of each positive psychological construct to mental health in Malaysian students. An opportunity sample of 153 students completed the measures regarding these constructs. Correlation, regression, and mediation analyses were conducted. Engagement, amotivation, self-compassion, and wellbeing were associated with, and predicted large variance in mental health. Self-compassion was the strongest independent predictor of mental health among all the positive psychological constructs. Findings can imply the strong links between mental health and positive psychology, especially selfcompassion. Moreover, intervention studies to examine the effects of self-compassion training on mental health of Malaysian students appear to be warranted.N/

Characterisation of development and electrophysiological mechanisms underlying rhythmicity of the avian lymph heart

Despite significant advances in tissue engineering such as the use of scaffolds, bioreactors and pluripotent stem cells, effective cardiac tissue engineering for therapeutic purposes has remained a largely intractable challenge. For this area to capitalise on such advances, a novel approach may be to unravel the physiological mechanisms underlying the development of tissues that exhibit rhythmic contraction yet do not originate from the cardiac lineage. Considerable attention has been focused on the physiology of the avian lymph heart, a discrete organ with skeletal muscle origins yet which displays pacemaker properties normally only found in the heart. A functional lymph heart is essential for avian survival and growth in ovo. The histological nature of the lymph heart is similar to skeletal muscle although molecular and bioelectrical characterisation during development to assess mechanisms that contribute towards lymph heart contractile rhythmicity have not been undertaken. A better understanding of these processes may provide exploitable insights for therapeutic rhythmically contractile tissue engineering approaches in this area of significant unmet clinical need. Here, using molecular and electrophysiological approaches, we describe the molecular development of the lymph heart to understand how this skeletal muscle becomes fully functional during discrete in ovo stages of development. Our results show that the lymph heart does not follow the normal transitional programme of myogenesis as documented in most skeletal muscle, but instead develops through a concurrent programme of precursor expansion, commitment to myogenesis and functional differentiation which offers a mechanistic explanation for its rapid development. Extracellular electrophysiological field potential recordings revealed that the peak-to-peak amplitude of electrically evoked local field potentials elicited from isolated lymph heart were significantly reduced by treatment with carbachol; an effect that could be fully reversed by atropine. Moreover, nifedipine and cyclopiazonic acid both significantly reduced peak-to-peak local field potential amplitude. Optical recordings of lymph heart showed that the organ’s rhythmicity can be blocked by the HCN channel blocker, ZD7288; an effect also associated with a significant reduction in peak-to-peak local field potential amplitude. Additionally, we also show that isoforms of HCN channels are expressed in avian lymph heart. These results demonstrate that cholinergic signalling and L-type Ca2+ channels are important in excitation and contraction coupling, while HCN channels contribute to maintenance of lymph heart rhythmicity

Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals

$\textit{Rationale:}$ Biased attention towards drug-related cues and reduced inhibitory control over the regulation of drug-intake characterize drug addiction. The noradrenaline system has been critically implicated in both attentional and response inhibitory processes and is directly affected by drugs such as cocaine. $\textit{Objectives:}$ We examined the potentially beneficial effects of the noradrenaline reuptake inhibitor atomoxetine in improving cognitive control during two tasks that used cocaine- and non-cocaine-related stimuli. $\textit{Methods:}$ A double-blind, placebo-controlled, and cross-over psycho-pharmacological design was employed. A single oral dose of atomoxetine (40 mg) was administered to 28 cocaine-dependent individuals (CDIs) and 28 healthy controls. All participants performed a pictorial attentional bias task involving both cocaine- and non-cocaine-related pictures as well as a verbal go/no-go task composed of cocaine- and food-related words. $\textit{Results:}$ As expected, CDIs showed attentional bias to cocaine-related cues whilst controls did not. More importantly, however, atomoxetine, relative to placebo, significantly attenuated attentional bias in CDIs ($F_{26}$ = 6.73, $P$ = 0.01). During the go/no-go task, there was a treatment × trial × group interaction, although this finding only showed a trend towards statistical significance ($F_{26}$ = 3.38, $P$ = 0.07). $\textit{Conclusions:}$ Our findings suggest that atomoxetine reduces attentional bias to drug-related cues in CDIs. This may result from atomoxetine's modulation of the balance between tonic/phasic activity in the locus coeruleus and the possibly parallel enhancement of noradrenergic neurotransmission within the prefrontal cortex. Studying how cognitive enhancers such as atomoxetine influence key neurocognitive indices in cocaine addiction may help to develop reliable biomarkers for patient stratification in future clinical trials.This work was funded by a grant of the Medical Research Council (MR/J012084/1) to TWR, KDE, ETB, and BJS and conducted within the Behavioural and Clinical Neuroscience Institute at the University of Cambridge, which is jointly funded by the Medical Research Council and the Wellcome Trust. This study was jointly sponsored by the Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

Phenotypes of Non-Attached Pseudomonas aeruginosa Aggregates Resemble Surface Attached Biofilm

For a chronic infection to be established, bacteria must be able to cope with hostile conditions such as low iron levels, oxidative stress, and clearance by the host defense, as well as antibiotic treatment. It is generally accepted that biofilm formation facilitates tolerance to these adverse conditions. However, microscopic investigations of samples isolated from sites of chronic infections seem to suggest that some bacteria do not need to be attached to surfaces in order to establish chronic infections. In this study we employed scanning electron microscopy, confocal laser scanning microscopy, RT-PCR as well as traditional culturing techniques to study the properties of Pseudomonas aeruginosa aggregates. We found that non-attached aggregates from stationary-phase cultures have comparable growth rates to surface attached biofilms. The growth rate estimations indicated that, independently of age, both aggregates and flow-cell biofilm had the same slow growth rate as a stationary phase shaking cultures. Internal structures of the aggregates matrix components and their capacity to survive otherwise lethal treatments with antibiotics (referred to as tolerance) and resistance to phagocytes were also found to be strikingly similar to flow-cell biofilms. Our data indicate that the tolerance of both biofilms and non-attached aggregates towards antibiotics is reversible by physical disruption. We provide evidence that the antibiotic tolerance is likely to be dependent on both the physiological states of the aggregates and particular matrix components. Bacterial surface-attachment and subsequent biofilm formation are considered hallmarks of the capacity of microbes to cause persistent infections. We have observed non-attached aggregates in the lungs of cystic fibrosis patients; otitis media; soft tissue fillers and non-healing wounds, and we propose that aggregated cells exhibit enhanced survival in the hostile host environment, compared with non-aggregated bacterial populations