Measuring Rural Food Environments Within Murrumbidgee Health Network, NSW: Methodology.

This document supplements the report on Measuring rural food environments within Murrumbidgee Local Health Network. This study has generated tools and protocols that can be disseminated and used in other locations, as well as information for the three study towns

Measuring Rural Food Environments Within Murrumbidgee Health Network, NSW.

This report presents the results of a study which mapped food availability in three small rural towns in New South Wales on the topic of Food Fairness in disadvantaged towns. This small study designed and tested simple, specifically-designed tools for assessing food availability, and has generated tools and protocols that can be disseminated and used in other locations, as well as information for the three study towns

Beyond static measures:A review of functional magnetic resonance spectroscopy and its potential to investigate dynamic glutamatergic abnormalities in schizophrenia

Abnormalities of the glutamate system are increasingly implicated in schizophrenia but their exact nature remains unknown. Proton magnetic resonance spectroscopy (1H-MRS), while fundamental in revealing glutamatergic alterations in schizophrenia, has, until recently, been significantly limited and thought to only provide static measures. Functional magnetic resonance spectroscopy (fMRS), which uses sequential scans for dynamic measurement of a range of brain metabolites in activated brain areas, has lately been applied to a variety of task or stimulus conditions, producing interesting insights into neurometabolite responses to neural activation. Here, we summarise the existing 1H-MRS studies of brain glutamate in schizophrenia. We then present a comprehensive review of research studies that have utilised fMRS, and lastly consider how fMRS methods might further the understanding of glutamatergic abnormalities in schizophrenia. </jats:p

Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats

Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either i.p. saline, mephedrone (10mg/kg), caffeine (10mg/kg) or combined caffeine and mephedrone twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day two), elevated plus maze (EPM, day eight) exploration, rectal temperature changes (day nine) and prepulse inhibition of acoustic startle (PPI, day 15) response were assessed. Seven days after the final injection, brain regions were collected for measurement of 5-hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs

Sarcopenia: Prevalence, and Impact on Operative and Oncologic Outcomes in the Multimodal Management of Locally Advanced Esophageal Cancer

Objective: The aim of this article was to study the prevalence and significance of sarcopenia in the multimodal management of locally advanced esophageal cancer (LAEC), and to assess its independent impact on operative and oncologic outcomes. Summary of background data: Sarcopenia in cancer may confer negative outcomes, but its prevalence and impact on modern multimodal regimens for LAEC have not been systematically studied. Methods: Two hundred fifty-two consecutive patients were studied. Lean body mass (LBM), skeletal muscle index (SMI), and fat mass (FM) were determined pre-treatment, preoperatively, and 1 year postoperatively. Sarcopenia was defined by computed tomography (CT) at L3 as SMI \u3c 52.4 cm/m for males and SMI \u3c 38.5 cm/m for females. All complications were recorded prospectively, including comprehensive complications index (CCI), Clavien-Dindo complication (CDC), and pulmonary complications (PPCs). Multivariable linear, logistic, and Cox regression analysis was performed. Results: In-hospital mortality was 1%, and CCI was 21 ± 19. Sarcopenia increased (P = 0.02) from 16% at diagnosis to 31% post-neoadjuvant therapy, with loss of LBM (-3.0 ± 5.4 kg, P \u3c 0.0001), but not FM (-0.3 ± 2.7 kg, P= 0.31) during treatment. On multivariable analysis, preoperative sarcopenia was associated with CCI (P = 0.043), and CDC ≥IIIb (P = 0.003). PPCs occurred in 36% nonsarcopenic versus 55% sarcopenic patients (P = 0.01). Sarcopenia did not impact disease-specific (P = 0.14) or overall survival (P = 0.11) after resection. At 1 year, 35% had sarcopenia, significantly associated with pre-treatment BMI (P = 0.013) but not complications (P = 0.20). Conclusions: Sarcopenia increases through multimodal therapy, is associated with an increased risk of major postoperative complications, and is prevalent in survivorship. These data highlight a potentially modifiable marker of risk that should be assessed and targeted in modern multimodal care pathways

Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

The psychoactive effects of mephedrone are commonly compared to those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action users often employ repeated administration to maintain its psychoactive actions. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels, and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1ml/kg, i.p.) or mephedrone HCl (10mg/kg) at 2h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (5,7-DHT, 150μg) or 6-hydroxydopamine (6-OHDA, 300μg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30min) with the 5-HT1A receptor antagonist WAY-100635 (0.5mg/kg), 5-HT1B receptor antagonist GR 127935 (3mg/kg) or the 5-HT7 receptor antagonist SB-258719 (10mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing), and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT1B and 5-HT1A receptors

Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

The psychoactive effects of mephedrone are commonly compared to those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action users often employ repeated administration to maintain its psychoactive actions. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels, and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1ml/kg, i.p.) or mephedrone HCl (10mg/kg) at 2h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (5,7-DHT, 150μg) or 6-hydroxydopamine (6-OHDA, 300μg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30min) with the 5-HT1A receptor antagonist WAY-100635 (0.5mg/kg), 5-HT1B receptor antagonist GR 127935 (3mg/kg) or the 5-HT7 receptor antagonist SB-258719 (10mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing), and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT1B and 5-HT1A receptors

Calbindin Deficits May Underlie Dissociable Effects of 5-HT6 and mGlu7 Antagonists on Glutamate and Cognition in a Dual-Hit Neurodevelopmental Model for Schizophrenia

© 2020, The Author(s). Despite several compounds entering clinical trials for the negative and cognitive symptoms of schizophrenia, few have progressed beyond phase III. This is partly attributed to a need for improved preclinical models, to understand disease and enable predictive evaluation of novel therapeutics. To this end, one recent approach incorporates “dual-hit” neurodevelopmental insults like neonatal phencyclidine plus isolation rearing (PCP-Iso). Glutamatergic dysfunction contributes to schizophrenia pathophysiology and may represent a treatment target, so we used enzyme-based microsensors to evaluate basal- and drug-evoked glutamate release in hippocampal slices from rats that received neonatal PCP and/or isolation rearing. 5-HT6 antagonist-evoked glutamate release (thought to be mediated indirectly via GABAergic disinhibition) was reduced in PCP-Iso, as were cognitive effects of a 5-HT6 antagonist in a hippocampal glutamate-dependent novel object discrimination task. Yet mGlu7 antagonist-evoked glutamatergic and cognitive responses were spared. Immunohistochemical analyses suggest these findings (which mirror the apparent lack of clinical response to 5-HT6 antagonists in schizophrenia) are not due to reduced hippocampal 5-HT input in PCP-Iso, but may be explained by reduced calbindin expression. This calcium-binding protein is present in a subset of GABAergic interneurons receiving preferential 5-HT innervation and expressing 5-HT6 receptors. Its loss (in schizophrenia and PCP-Iso) would be expected to reduce interneuron firing and potentially prevent further 5-HT6 antagonist-mediated disinhibition, without impacting on responses of VIP-expressing interneurons to mGlu7 antagonism. This research highlights the importance of improved understanding for selection of appropriate preclinical models, especially where disease neurobiology impacts on cells mediating the effects of potential therapeutics

Intercomparison of snow depth retrievals over Arctic sea ice from radar data acquired by Operation IceBridge

Since 2009, the ultra-wideband snow radar on Operation IceBridge (OIB; a NASA airborne mission to survey the polar ice covers) has acquired data in annual campaigns conducted during the Arctic and Antarctic springs. Progressive improvements in radar hardware and data processing methodologies have led to improved data quality for subsequent retrieval of snow depth. Existing retrieval algorithms differ in the way the air–snow (a–s) and snow–ice (s–i) interfaces are detected and localized in the radar returns and in how the system limitations are addressed (e.g., noise, resolution). In 2014, the Snow Thickness On Sea Ice Working Group (STOSIWG) was formed and tasked with investigating how radar data quality affects snow depth retrievals and how retrievals from the various algorithms differ. The goal is to understand the limitations of the estimates and to produce a well-documented, long-term record that can be used for understanding broader changes in the Arctic climate system. Here, we assess five retrieval algorithms by comparisons with field measurements from two ground-based campaigns, including the BRomine, Ozone, and Mercury EXperiment (BROMEX) at Barrow, Alaska; a field program by Environment and Climate Change Canada at Eureka, Nunavut; and available climatology and snowfall from ERA-Interim reanalysis. The aim is to examine available algorithms and to use the assessment results to inform the development of future approaches. We present results from these assessments and highlight key considerations for the production of a long-term, calibrated geophysical record of springtime snow thickness over Arctic sea ice

Next generation PCR microfluidic system

Stokes Bio, founded in 2005, develops innovative microfluidic technologies. In 2008 in collaboration with Monsanto, an application driven development for a high-throughput instrument in the detection and characterisation of Single Nucleotide Polymorphisms (SNPs) in agricultural crops was initiated. Stokes technology is designed to generate aqueous nanolitre scale droplets of reagents and samples, wrapped in a carrier fluid from standard microtitre plates and to mix them using Stokes Bio’s proprietary liquid bridge mixers. Following mixing the complete assay is transferred in the carrier fluid through the use of a continuous flow system, to a flow through thermal cycler and an optical reading station. This poster summarises results collated using the Stokes Bio genotyping platform currently based in Monsanto. Data will be presented to illustrate the dynamic capabilities of the instrument, highlighting the enhanced sensitivity and reproducibility of PCR in droplet format compared to well-based technologies