Photo-antagonism of the GABAA receptor

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation

The role of mutation rate variation and genetic diversity in the architecture of human disease

Background We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified. Results Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless. Conclusions Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease

The Effect of Heat Waves on Mental Health in a Temperate Australian City

Objective: The goal of this study was to identify mental, behavioral, and cognitive disorders that may be triggered or exacerbated during heat waves, predisposing individuals to heat-related morbidity and mortality. Design: Using health outcome data from Adelaide, South Australia, for 1993–2006, we estimated the effect of heat waves on hospital admissions and mortalities attributed to mental, behavioral, and cognitive disorders. We analyzed data using Poisson regression accounting for overdispersion and controlling for season and long-term trend, and we performed threshold analysis using hockey stick regression. Results: Above a threshold of 26.7°C, we observed a positive association between ambient temperature and hospital admissions for mental and behavioral disorders. Compared with non–heat-wave periods, hospital admissions increased by 7.3% during heat waves. Specific illnesses for which admissions increased included organic illnesses, including symptomatic mental disorders ; dementia ; mood (affective) disorders ; neurotic, stress related, and somatoform disorders ; disorders of psychological development ; and senility. Mortalities attributed to mental and behavioral disorders increased during heat waves in the 65- to 74-year age group and in persons with schizophrenia, schizotypal, and delusional disorders. Dementia deaths increased in those up to 65 years of age. Conclusion: Our results suggest that episodes of extreme heat pose a salient risk to the health and well-being of the mentally ill. Relevance to Clinical or Professional Practice: Improvements in the management and care of the mentally ill need to be addressed to avoid an increase in psychiatric morbidity and mortality as heat waves become more frequent.Alana Hansen, Peng Bi, Monika Nitschke, Philip Ryan, Dino Pisaniello and Graeme Tucke

PainDroid: An android-based virtual reality application for pain assessment

Earlier studies in the field of pain research suggest that little efficient intervention currently exists in response to the exponential increase in the prevalence of pain. In this paper, we present an Android application (PainDroid) with multimodal functionality that could be enhanced with Virtual Reality (VR) technology, which has been designed for the purpose of improving the assessment of this notoriously difficult medical concern. Pain- Droid has been evaluated for its usability and acceptability with a pilot group of potential users and clinicians, with initial results suggesting that it can be an effective and usable tool for improving the assessment of pain. Participant experiences indicated that the application was easy to use and the potential of the application was similarly appreciated by the clinicians involved in the evaluation. Our findings may be of considerable interest to healthcare providers, policy makers, and other parties that might be actively involved in the area of pain and VR research

Soft Tissue Attenuation Patterns Associated with Upright Acquisition SPECT Myocardial Perfusion Imaging: A Descriptive Study

Abstract: Purpose: Soft-tissue attenuation patterns in SPECT-myocardial perfusion imaging (MPI) of supine acquisition systems are well recognized. Their prevalence and interaction with body-habitus and gender are ill-defined, which we sought to describe in this study. Methods: In a cross-sectional study, we described the prevalence of soft-tissue attenuation patterns in normal SPECT-MPI studies acquired with a supine patient-position SPECT system. Results: In 263 normal, clinically-indicated, supine-acquisition SPECT-MPIs the attenuation patterns observed were: anterior (35.4%), inferior (41.8%) and lateral (13.3%). Anterior attenuation was more prevalent among women (50.7 % vs. 15.7%, P<0.001) and was associated with chest circumference among men. Conversely, inferior attenuation was more prevalent among men (78.3 % vs. 13.5%, P<0.001) and was not affected by body-habitus. Lateral attenuation was more common among women (19.6 % vs. 5.2%, p=0.001) and was associated with obesity (p=0.015). Conclusions: Soft-tissue attenuation artifacts are common in supine-acquisition SPECT-MPI. The recognition of their prevalence and association with body-habitus and gender is critical for the accurate interpretation of SPECT-MPI

Extending colonic mucosal microbiome analysis - Assessment of colonic lavage as a proxy for endoscopic colonic biopsies

This study was supported through GI Research funds and MRC Grant Ref: MR/M00533X/1 to GH.Peer reviewedPublisher PD