The effects of alcohol consumption, psychological distress and smoking status on emergency department presentations in New South Wales, Australia

BACKGROUND: Despite clear links between risky alcohol consumption, mental health problems and smoking with increased morbidity and mortality, there is inconclusive evidence about how these risk factors combine and if they are associated with increased attendance at emergency departments. This paper examines the population-level associations and interactions between alcohol consumption, psychological distress and smoking status with having presented to an emergency department in the last 12 months. METHODS: This study uses data from a representative sample of 34,974 participants aged 16 years and over from the New South Wales Population Health Survey, administered between 2002 and 2004. Statistical analysis included univariate statistics, cross-tabulations, and the estimation of prevalence rate ratios using Cox's proportional hazard regression model. RESULTS: Results show that high-risk alcohol consumption, high psychological distress and current smoking were all significantly and independently associated with a greater likelihood of presenting to an emergency department in the last year. Presenting to an emergency department was found to be three times more likely for women aged 30 to 59 years with all three risk factors and ten times more likely for women aged 60 years or more who reported high risk alcohol consumption and high psychological distress than women of these age groups without these risk factors. For persons aged 16 to 29 years, having high-risk alcohol consumption and being a current smoker doubles the risk of presenting to an emergency department. CONCLUSION: The combination of being a high-risk consumer of alcohol, having high psychological distress, and being a current smoker are associated with increased presentations to emergency departments, independent of age and sex. Further research is needed to enhance recognition of and intervention for these symptoms in an emergency department setting in order to improve patient health and reduce future re-presentations to emergency departments

The Spatial and Temporal Deployment of Voluntary Attention across the Visual Field

Several studies have addressed the question of the time it takes for attention to shift from one position in space to another. Here we present a behavioural paradigm which offers a direct access to an estimate of voluntary shift time by comparing, in the same task, a situation in which subjects are required to re-engage their attention at the same spatial location with a situation in which they need to shift their attention to another location, all other sensory, cognitive and motor parameters being equal. We show that spatial attention takes on average 55 ms to voluntarily shift from one hemifield to the other and 38 ms to shift within the same hemifield. In addition, we show that across and within hemifields attentional processes are different. In particular, attentional spotlight division appears to be more difficult to operate within than across hemifields

Flagellin-Induced Corneal Antimicrobial Peptide Production and Wound Repair Involve a Novel NF-κB–Independent and EGFR-Dependent Pathway

The bacterial protein flagellin plays a major role in stimulating mucosal surface innate immune response to bacterial infection and uniquely induces profound cytoprotection against pathogens, chemicals, and radiation. This study sought to determine signaling pathways responsible for the flagellin-induced inflammatory and cytoprotective effects on human corneal epithelial cells (HCECs).Flagellin purified from Pseudomonas aeruginosa (strain PAK) or live bacteria were used to challenge cultured HCECs. The activation of signaling pathways was assessed with Western blot, and the secretion of cytokine/chemokine and production of antimicrobial peptides (AMPs) were measured with ELISA and dot blot, respectively. Effects of flagellin on wound healing were assessed in cultured porcine corneas. L94A (a site mutation in TLR5 binding region) flagellin and PAK expressing L94A flagellin were unable to stimulate NF-kappaB activation, but were potent in eliciting EGFR signaling in a TGF-alpha-related pathway in HCECs. Concomitant with the lack of NF-kappaB activation, L94A flagellin was ineffective in inducing IL-6 and IL-8 production in HCECs. Surprisingly, the secretion of two inducible AMPs, LL-37 and hBD2, was not affected by L94A mutation. Similar to wild-type flagellin, L94A induced epithelial wound closure in cultured porcine cornea through maintaining EGFR-mediated signaling.Our data suggest that inflammatory response mediated by NF-kappaB can be uncoupled from epithelial innate defense machinery (i.e., AMP expression) and major epithelial proliferation/repair pathways mediated by EGFR, and that flagellin and its derivatives may have broad therapeutic applications in cytoprotection and in controlling infection in the cornea and other mucosal tissues

Increased Secreted Amyloid Precursor Protein-α (sAPPα) in Severe Autism: Proposal of a Specific, Anabolic Pathway and Putative Biomarker

Autism is a neurodevelopmental disorder characterized by deficits in verbal communication, social interactions, and the presence of repetitive, stereotyped and compulsive behaviors. Excessive early brain growth is found commonly in some patients and may contribute to disease phenotype. Reports of increased levels of brain-derived neurotrophic factor (BDNF) and other neurotrophic-like factors in autistic neonates suggest that enhanced anabolic activity in CNS mediates this overgrowth effect. We have shown previously that in a subset of patients with severe autism and aggression, plasma levels of the secreted amyloid-β (Aβ) precursor protein-alpha form (sAPPα) were significantly elevated relative to controls and patients with mild-to-moderate autism. Here we further tested the hypothesis that levels of sAPPα and sAPPβ (proteolytic cleavage products of APP by α- and β-secretase, respectively) are deranged in autism and may contribute to an anabolic environment leading to brain overgrowth. We measured plasma levels of sAPPα, sAPPβ, Aβ peptides and BDNF by corresponding ELISA in a well characterized set of subjects. We included for analysis 18 control, 6 mild-to-moderate, and 15 severely autistic patient plasma samples. We have observed that sAPPα levels are increased and BDNF levels decreased in the plasma of patients with severe autism as compared to controls. Further, we show that Aβ1-40, Aβ1-42, and sAPPβ levels are significantly decreased in the plasma of patients with severe autism. These findings do not extend to patients with mild-to-moderate autism, providing a biochemical correlate of phenotypic severity. Taken together, this study provides evidence that sAPPα levels are generally elevated in severe autism and suggests that these patients may have aberrant non-amyloidogenic processing of APP

Neurobiology of social behavior abnormalities in autism and Williams syndrome

Social behavior is a basic behavior mediated by multiple brain regions and neural circuits, and is crucial for the survival and development of animals and humans. Two neuropsychiatric disorders that have prominent social behavior abnormalities are autism spectrum disorders (ASD), which is characterized mainly by hyposociability, and Williams syndrome (WS), whose subjects exhibit hypersociability. Here we review the unique properties of social behavior in ASD and WS, and discuss the major theories in social behavior in the context of these disorders. We conclude with a discussion of the research questions needing further exploration to enhance our understanding of social behavior abnormalities

Transcriptome Analysis of Synaptoneurosomes Identifies Neuroplasticity Genes Overexpressed in Incipient Alzheimer's Disease

In Alzheimer's disease (AD), early deficits in learning and memory are a consequence of synaptic modification induced by toxic beta-amyloid oligomers (oAβ). To identify immediate molecular targets downstream of oAβ binding, we prepared synaptoneurosomes from prefrontal cortex of control and incipient AD (IAD) patients, and isolated mRNAs for comparison of gene expression. This novel approach concentrates synaptic mRNA, thereby increasing the ratio of synaptic to somal mRNA and allowing discrimination of expression changes in synaptically localized genes. In IAD patients, global measures of cognition declined with increasing levels of dimeric Aβ (dAβ). These patients also showed increased expression of neuroplasticity related genes, many encoding 3′UTR consensus sequences that regulate translation in the synapse. An increase in mRNA encoding the GluR2 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) was paralleled by elevated expression of the corresponding protein in IAD. These results imply a functional impact on synaptic transmission as GluR2, if inserted, maintains the receptors in a low conductance state. Some overexpressed genes may induce early deficits in cognition and others compensatory mechanisms, providing targets for intervention to moderate the response to dAβ

The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity

Anatomical structures and mechanisms linking genes to neuropsychiatric disorders are not deciphered. Reciprocal copy number variants at the 16p11.2 BP4-BP5 locus offer a unique opportunity to study the intermediate phenotypes in carriers at high risk for autism spectrum disorder (ASD) or schizophrenia (SZ). We investigated the variation in brain anatomy in 16p11.2 deletion and duplication carriers. Beyond gene dosage effects on global brain metrics, we show that the number of genomic copies negatively correlated to the gray matter volume and white matter tissue properties in cortico-subcortical regions implicated in reward, language and social cognition. Despite the near absence of ASD or SZ diagnoses in our 16p11.2 cohort, the pattern of brain anatomy changes in carriers spatially overlaps with the well-established structural abnormalities in ASD and SZ. Using measures of peripheral mRNA levels, we confirm our genomic copy number findings. This combined molecular, neuroimaging and clinical approach, applied to larger datasets, will help interpret the relative contributions of genes to neuropsychiatric conditions by measuring their effect on local brain anatomy

Functional parcellation of attentional control regions of the brain.

Recently, a number of investigators have examined the neural loci of psychological processes enabling the control of visual spatial attention using cued-attention paradigms in combination with event-related functional magnetic resonance imaging. Findings from these studies have provided strong evidence for the involvement of a fronto-parietal network in attentional control. In the present study, we build upon this previous work to further investigate these attentional control systems. In particular, we employed additional controls for nonattentional sensory and interpretative aspects of cue processing to determine whether distinct regions in the fronto-parietal network are involved in different aspects of cue processing, such as cue-symbol interpretation and attentional orienting. In addition, we used shorter cue-target intervals that were closer to those used in the behavioral and event-related potential cueing literatures. Twenty participants performed a cued spatial attention task while brain activity was recorded with functional magnetic resonance imaging. We found functional specialization for different aspects of cue processing in the lateral and medial subregions of the frontal and parietal cortex. In particular, the medial subregions were more specific to the orienting of visual spatial attention, while the lateral subregions were associated with more general aspects of cue processing, such as cue-symbol interpretation. Additional cue-related effects included differential activations in midline frontal regions and pretarget enhancements in the thalamus and early visual cortical areas