Interpretation of ambiguous interoceptive stimuli in panic disorder and nonclinical panic

Cognitive bias in the misinterpretation of ambiguous interoceptive stimuli has been demonstrated in panic disorder. This study investigated whether this cognitive bias also occurs in people with nonclinical panic who are at risk of developing panic disorder. The responses of 25 people with nonclinical panic were compared to those of 20 people with panic disorder and 69 nonpanic controls on a measure of interpretive bias, the Brief Body Sensations Interpretation Questionnaire. There was evidence for interpretive cognitive bias for ambiguous interoceptive stimuli among the nonclinical panickers which did not differ from that of the people with panic disorder, but which differed from the nonpanic controls. High anxiety sensitivity predicted interpretive bias toward both interoceptive and external stimuli. Results therefore suggest that interpretive cognitive bias for ambiguous interoceptive stimuli may be a risk factor for the development of panic disorder.

Internet cognitive behavioural therapy for panic disorder : does the inclusion of stress management information improve end-state functioning?

Previous research has established Internet-based cognitive behavioural therapy (CBT) for panic disorder (PD) as effective in reducing panic severity and frequency. There is evidence, however, that such programs are less effective at improving overall end-state functioning, defined by a PD clinician severity rating of ≤2 and panic free. In order to test the effect on end-state functioning of the incorporation of stress management material within a CBT program for PD, 32 people with PD were randomised to either Internet-based CBT (PO1), Internet-based CBT plus stress management (PO2) or an Internet-based information-only control condition (IC). Both CBT treatments were more effective at posttreatment assessment than the control condition in reducing PD severity, panic and agoraphobia-related cognition, negative affect and self-ratings of health. PO2 was more effective than PO1 at posttreatment assessment on PD severity and general anxiety, although at 3-month follow-up these differences were no longer apparent. This study provides further support for the efficacy of Internet-based CBT for PD and suggests that although the incorporation of stress management material confers short-term advantages over a standard program, it is not associated with any longer term improvements on panic severity and related cognitions, negative affect, general wellbeing and end-state functioning.

An impaired mitochondrial electron transport chain increases retention of the hypoxia imaging agent diacetylbis(4-methylthiosemicarbazonato)copper II

Radiolabeled diacetylbis(4-methylthiosemicarbazonato)copper^II [Cu^II(atsm)] is an effective positron-emission tomography imaging agent for myocardial ischemia, hypoxic tumors, and brain disorders with regionalized oxidative stress, such as mitochondrial myopathy, encephalopathy, and lactic acidosis with stroke-like episodes (MELAS) and Parkinson’s disease. An excessively elevated reductive state is common to these conditions and has been proposed as an important mechanism affecting cellular retention of Cu from Cu^II(atsm). However, data from whole-cell models to demonstrate this mechanism have not yet been provided. The present study used a unique cell culture model, mitochondrial xenocybrids, to provide whole-cell mechanistic data on cellular retention of Cu from Cu^II(atsm). Genetic incompatibility between nuclear and mitochondrial encoded subunits of the mitochondrial electron transport chain (ETC) in xenocybrid cells compromises normal function of the ETC. As a consequence of this impairment to the ETC we show xenocybrid cells upregulate glycolytic ATP production and accumulate NADH. Compared to control cells the xenocybrid cells retained more Cu after being treated with Cu^II(atsm). By transfecting the cells with a metal-responsive element reporter construct the increase in Cu retention was shown to involve a Cu^II(atsm)-induced increase in intracellular bioavailable Cu specifically within the xenocybrid cells. Parallel experiments using cells grown under hypoxic conditions confirmed that a compromised ETC and elevated NADH levels contribute to increased cellular retention of Cu from CuII(atsm). Using these cell culture models our data demonstrate that compromised ETC function, due to the absence of O2 as the terminal electron acceptor or dysfunction of individual components of the ETC, is an important determinant in driving the intracellular dissociation of Cu^II(atsm) that increases cellular retention of the Cu.

Effects of early-life environment and epigenetics on cardiovascular disease risk in children: highlighting the role of twin studies

Cardiovascular disease (CVD) is the leading cause of death worldwide and originates in early life. The exact mechanisms of this early-life origin are unclear, but a likely mediator at the molecular level is epigenetic dysregulation of gene expression. Epigenetic factors have thus been posited as the likely drivers of early-life programming of adult-onset diseases. This review summarizes recent advances in epidemiology and epigenetic research of CVD risk in children, with a particular focus on twin studies. Classic twin studies enable partitioning of phenotypic variance within a population into additive genetic, shared, and nonshared environmental variances, and are invaluable in research in this area. Longitudinal cohort twin studies, in particular, may provide important insights into the role of epigenetics in the pathogenesis of CVD. We describe candidate gene and epigenome-wide association studies (EWASs) and transgenerational epigenetic inheritance of CVD, and discuss the potential for evidence-based interventions. Identifying epigenetic changes associated with CVD-risk biomarkers in children will provide new opportunities to unravel the underlying biological mechanism of the origins of CVD and enable identification of those at risk for early-life interventions to alter the risk trajectory and potentially reduce CVD incidence later in life.

A truncated fragment of Src protein kinase generated by calpain-mediated cleavage is a mediator of neuronal death in excitotoxicity

Excitotoxicity resulting from overstimulation of glutamate receptors is a major cause of neuronal death in cerebral ischemic stroke. The overstimulated ionotropic glutamate receptors exert their neurotoxic effects in part by overactivation of calpains, which induce neuronal death by catalyzing limited proteolysis of specific cellular proteins. Here, we report that in cultured cortical neurons and in vivo in a rat model of focal ischemic stroke, the tyrosine kinase Src is cleaved by calpains at a site in the N-terminal unique domain. This generates a truncated Src fragment of ?52 kDa, which we localized predominantly to the cytosol. A cell membrane-permeable fusion peptide derived from the unique domain of Src prevents calpain from cleaving Src in neurons and protects against excitotoxic neuronal death. To explore the role of the truncated Src fragment in neuronal death, we expressed a recombinant truncated Src fragment in cultured neurons and examined how it affects neuronal survival. Expression of this fragment, which lacks the myristoylation motif and unique domain, was sufficient to induce neuronal death. Furthermore, inactivation of the prosurvival kinase Akt is a key step in its neurotoxic signaling pathway. Because Src maintains neuronal survival, our results implicate calpain cleavage as a molecular switch converting Src from a promoter of cell survival to a mediator of neuronal death in excitotoxicity. Besides unveiling a new pathological action of Src, our discovery of the neurotoxic action of the truncated Src fragment suggests new therapeutic strategies with the potential to minimize brain damage in ischemic stroke.

In a city like Delhi: urban spirituality, sustainability and women

This paper is intended to be provocative as a way of exposing any fatal flaws in its logic. It advocates a pragmatic foundational role for spirituality upon which sustainable development can be built. It goes on to assert the importance of articulating spiritual dimensions of urban communities as integral to the spiritual and general sustainability of cities.

South west Victoria 2012-2050 : are the settlements sustainable?

Over the past few decades coastal cities around the world have grown at an incredible rate. With this growth have come major challenges relating to land use planning, social relationships, economic development, bio diversity and the ecological footprint. The following paper selects three regional coastal towns (Warrnambool, Portland and Port Fairy) situated in the Australian state of Victoria, and addresses the issues of: increasing population and population density, open space requirements, residential density issues, public transport coverage, employment and employment density, a shifting economic climate, environment and climate change, water quality issues and building energy consumption with subsequent C02 emissions. Through a series of simulations the nine issues for each of the three cities will be examined from 2012 through to 2030. The goal is to highlight the current and simulated future impacts of the selected issues and propose solutions that could mitigate those impacts.