How to use the videofluoroscopy swallow study in paediatric practice.

In paediatric practice feeding, eating, drinking and swallowing difficulties are present in up to 1% of children. Dysphagia is any disruption to the swallow sequence that results in compromise to the safety, efficiency or adequacy of nutritional intake. Swallowing difficulties may lead to pharyngeal aspiration, respiratory compromise or poor nutritional intake. It causes sensory and motor dysfunction impacting on a child's ability to experience normal feeding. Incoordination can result in oral pharyngeal aspiration where fluid or food is misdirected and enters the airway, or choking where food physically blocks the airway The incidence is much higher in some clinical populations, including children with neuromuscular disease, traumatic brain injury and airway malformations. The prevalence of dysphagia and aspiration-related disease is increasing secondary to the better survival of children with highly complex medical and surgical needs. This article aims to outline the indications for performing videofluoroscopy swallow (VFS). This includes the technical aspects of the study, how to interrupt a VFS report and some of the limitations to the study.

Cannabinoid type 2 receptors in dopamine neurons inhibits psychomotor behaviors, alters anxiety, depression and alcohol preference.

Cannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice. Using a novel sensitive RNAscope in situ hybridization, we detected CB2R mRNA expression in VTA DA neurons in wildtype and DAT-Cnr2 cKO heterozygous but not in the homozygous DAT-Cnr2 cKO mice. Here we report that the deletion of CB2Rs in dopamine neurons enhances motor activities, modulates anxiety and depression-like behaviors and reduces the rewarding properties of alcohol. Our data reveals that CB2Rs are involved in the tetrad assay induced by cannabinoids which had been associated with CB1R agonism. GWAS studies indicates that the CNR2 gene is associated with Parkinson's disease and substance use disorders. These results suggest that CB2Rs in dopaminergic neurons may play important roles in the modulation of psychomotor behaviors, anxiety, depression, and pain sensation and in the rewarding effects of alcohol and cocaine.

Demand for emergency department services in the elderly: an 11 year analysis of the Greater Sydney Area.

OBJECTIVE: To describe trends in population-based rates of ED presentations in the Greater Sydney Area (GSA) and compare these between the elderly and non-elderly age groups. METHODS: This was a retrospective study using ED presentation data from all public hospitals in the GSA and population data from the Australian Bureau of Statistics between 2001 and 2011. Age-specific ED presentation rates stratified by age group (<65 years, 65-79 years and ≥80 years of age) were presented and compared using negative binomial regression and generalised linear regression models. RESULTS: Over 11 million ED presentations were analysed. The annualised rate of increase in ED presentations per 1000 population was 1.8% per annum. The adjusted incidence rate ratio for patients aged 80 years and over was 3.6 times higher than patients younger than 65 years (95% CI 2.8, 4.7, P < 0.001) and 1.6 times higher for patients between 65 and 79 years of age (95% CI 1.4, 1.8, P < 0.001). There was an increase of 40 patients per 1000 population per year admitted to hospital from ED (ß = 40, 95% CI 29, 52 P < 0.001) in patients aged 80 years or older compared with those aged less than 65 years of age. CONCLUSIONS: A disproportionate increase in ED presentation rates and in-patient admission rates in patients aged 80 years and over was demonstrated over 11 years in the GSA. ED models of care and system wide strategies to address these demographic changes are required.

Evaluation of exercise on individuals with dementia and their carers: a randomised controlled trial.

BACKGROUND: Almost all of the 820,000 people in the UK with dementia will experience Behavioural and Psychological Symptoms of Dementia (BPSD). However, research has traditionally focused on treating cognitive symptoms, thus neglecting core clinical symptoms that often have a more profound impact on living with dementia. Recent evidence (Kales et al, 2007; Ballard et al, 2009) indicates that the popular approach to managing BPSD - prescription of anti-psychotic medication - can increase mortality and the risk of stroke in people with dementia as well as impair quality of life and accelerate cognitive decline. Consequently, there is a need to evaluate the impact that non-pharmacological interventions have on BPSD; we believe physical exercise is a particularly promising approach. METHODS/DESIGN: We will carry out a pragmatic, randomised, single-blind controlled trial to evaluate the effectiveness of exercise (planned walking) on the behavioural and psychological symptoms of individuals with dementia. We aim to recruit 146 people with dementia and their carers to be randomized into two groups; one will be trained in a structured, tailored walking programme, while the other will continue with treatment as usual. The primary outcome (BPSD) will be assessed with the Neuropsychiatric Inventory (NPI) along with relevant secondary outcomes at baseline, 6 and 12 weeks. DISCUSSION: Designing this study has been challenging both ethically and methodologically. In particular to design an intervention that is simple, measurable, safe, non-invasive and enjoyable has been testing and has required a lot of thought. Throughout the design, we have attempted to balance methodological rigour with study feasibility. We will discuss the challenges that were faced and overcome in this paper. TRIAL REGISTRATION: ISRCTN01423159.

Molecular neurobiological methods in marijuana-cannabinoid research.

Recent aggregation of evidence for the roles of endogenous agonist and receptor systems that are mimicked or activated by cannabanoid ligands has provided a focus for work that has elucidated details of some of the multiple physiological roles and pharmacological functions that these systems play in brain and peripheral tissues. This chapter reviews some of the approaches to improved elucidation of these systems, with special focus on the human genes that encode cannabanoid receptors and the variants in these receptors that appear likely to contribute to human addiction vulnerabilities.

Methods to study the behavioral effects and expression of CB2 cannabinoid receptor and its gene transcripts in the chronic mild stress model of depression.

Behavioral and molecular methods were used to study and determine whether there is a link between depression that may be a factor in drug/alcohol addiction, and the endocannabinoid hypothesis of substance abuse. Depression is a lack of interest in the pleasurable things of life (termed anhedonia) and depressed mood. It is unknown whether CB2 cannabinoid receptors are expressed in the brain and whether they are involved in depression and substance abuse. Therefore, mice were subjected daily for 4 wk to chronic mild stress (CMS), and anhedonia was measured by the consumption of 2% sucrose solution. Behavioral and rewarding effects of abused substances were determined in the CMS and control animals. The expression of CB2 receptors and their gene transcripts was compared in the brains of CMS and control animals by Western blotting using CB2 receptor antibody and reverse transcriptase-polymerase chain reaction (RT-PCR). Furthermore, the expression and immunocytochemical identification of CB2 cannabinoid receptor in the rat brain were determined. CMS induced gender-specific aversions, which were blocked by WIN55,212-2, a nonspecific CB1 and CB2 cannabinoid receptor agonist. Direct CB2 antisense oligonucleotide microinjection into the mouse brain induced anxiolysis, indicating that CB2 or CB2-like receptors are present in the brain and may influence behavior. The major finding from these studies was the expression of CB2 receptor and its gene transcript in the mouse brain, which was enhanced by CMS. These preliminary results, if confirmed, suggest that the CB2 receptors are expressed in the mammalian brain and may be involved in depression and substance abuse.

Endocannabinoids and cannabinoid receptor genetics.

This review presents the remarkable advances that have been achieved in marijuana (cannabinoid) research, with the discovery of specific receptors and the existence of naturally occurring cannabis-like substances in the human body and brain. The last decade has seen more rapid progress in marijuana research than any time in the thousands of years that marijuana has been used by humans, particularly in cannabinoid genomics. The cDNA and genomic sequences encoding G protein-coupled cannabinoid receptors (Cnrs) from several species have now been cloned. Endogenous cannabinoids (endocannabinoids), synthetic and hydrolyzing enzymes and transporters that define neurochemically-specific cannabinoid brain pathways have been identified. Endocannabinoid lipid signaling molecules alter activity at G protein-coupled receptors (GPCR) and possibly at anandamide-gated ion channels, such as vanilloid receptors. Availability of increasingly-specific CB1 and CB2 Cnr antagonists and of CB1 and CB2 Cnr knockout mice have increased our understanding of these cannabinoid systems and provides tantalizing evidence for even more G protein-coupled Cnrs. Initial studies of the Cnr gene structure, regulation and polymorphisms whet our appetite for more information about these interesting genes, their variants and roles in vulnerabilities to addictions and other neuropsychiatric disorders. Behavioral studies of cannabinoids document the complex interactions between rewarding and aversive effects of these drugs. Pursuing cannabinoid-related molecular, pharmacological and behavioral leads will add greatly to our understanding of endogenous brain neuromodulator systems, abused substances and potential therapeutics. This review of CB1 and CB2 Cnr genes in human and animal brain and their neurobiological effects provide a basis for many of these studies. Therefore, understanding the physiological cannabinoid control system in the human body and brain will contribute to elucidating this natural regulatory mechanism in health and disease.