The spinal antinociceptive effects of cholinergic drugs in rats: receptor subtype specificity in different nociceptive tests

BACKGROUND: Several studies have shown that muscarinic cholinergic agonists cause antinociception in humans and animals when given by both spinal and non-spinal parenteral routes. It is uncertain which subtype of muscarinic receptor is involved in spinally mediated antinociceptive effects caused by these drugs. The cholinergic receptor agonists McN-A-343 (M(1 )selective; 3.89 to 389 nmol) and carbachol (non-selective; 0.029 to 29 nmol) were used in a rat acute pain model to investigate the involvement of M(1 )and non-M(1 )subtypes in spinally mediated antinociception. The drugs were injected intrathecally and results from experiments in which drug actions were carefully confined to the spinal cord were used to construct agonist dose response curves. RESULTS: McN-A-343 frequently diffused rostrally to the brain, away from the lumbosacral site of injection. Thus, in spite of its receptor subtype selectivity, McN-A-343 is a poor probe to use in attempting to identify receptor subtypes involved in spinal cord antinociceptive systems. However, in some experiments McN-A-343 caused spinally mediated antinociception assessed by the electrical current threshold test. Antinociception assessed by the tail flick latency test with intrathecal McN-A-343 was observed and found to involve supraspinal mechanisms. Carbachol caused spinally mediated antinociception assessed by both electrical current threshold and tail flick latency. CONCLUSIONS: The results suggest that M(1 )receptors are involved in spinally mediated antinociception revealed by electrical current threshold; other cholinergic receptors (non-M(1)) are involved in thermal antinociception at the spinal cord. This contrasts with previous work on spinally mediated cholinergic antinociception. These differences are believed to be due to difficulties in restricting the action of these drugs to the spinal cord

Human campylobacteriosis related to cross-contamination during handling of raw chicken meat: Application of quantitative risk assessment to guide intervention scenarios analysis in the Australian context

Quantitative Microbiological Risk Assessment (QMRA) is a methodology used to organize and analyze scientific information to both estimate the probability and severity of an adverse event as well as prioritize efforts to reduce the risk of foodborne pathogens. No QMRA efforts have been applied to Campylobacter in the Australian chicken meat sector. Hence, we present a QMRA model of human campylobacteriosis related to the occurrence of cross-contamination while handling raw chicken meat in Western Australia (WA). This work fills a gap in Campylobacter risk characterization in Australia and enables benchmarking against risk assessments undertaken in other countries. The model predicted the average probability of the occurrence of illness per serving of salad that became cross-contaminated from being handled following the handling of fresh chicken meat as 7.0 × 10−4 (90% Confidence Interval [CI] ± 4.7 × 10−5). The risk assessment model was utilized to estimate the likely impact of intervention scenarios on the predicted probability of illness (campylobacteriosis) per serving. Predicted relative risk reductions following changes in the retail prevalence of Campylobacter were proportional to the percentage desired in the reduction scenario; a target that is aiming to reduce the current baseline prevalence of Campylobacter in retail chicken by 30% is predicted to yield approximately 30% relative risk reduction. A simulated one-log reduction in the mean concentration of Campylobacter is anticipated to generate approximately 20% relative risk reductions. Relative risk reduction induced by a one-log decrease in the mean was equally achieved when the tail of the input distribution was affected—that is, by a change (one-log reduction) in the standard deviation of the baseline Campylobacter concentration. A scenario assuming a 5% point decrease in baseline probability of cross-contamination at the consumer phase would yield relative risk reductions of 14%, which is as effective as the impact of a strategic target of 10% reduction in the retail prevalence of Campylobacter. In conclusion, the present model simulates the probability of illness predicted for an average individual who consumes salad that has been cross-contaminated with Campylobacter from retail chicken meat in WA. Despite some uncertainties, this is the first attempt to utilize the QMRA approach as a scientific basis to guide risk managers toward implementing strategies to reduce the risk of human campylobacteriosis in an Australian context

Assessing the effects of the first 2 years of industry-led badger culling in England on the incidence of bovine tuberculosis in cattle in 2013–2015

Culling badgers to control the transmission of bovine tuberculosis (TB) between this wildlife reservoir and cattle has been widely debated. Industry-led culling began in Somerset and Gloucestershire between August and November 2013 to reduce local badger populations. Industry-led culling is not designed to be a randomised and controlled trial of the impact of culling on cattle incidence. Nevertheless, it is important to monitor the effects of the culling and, taking the study limitations into account, perform a cautious evaluation of the impacts. A standardised method for selecting areas matched to culling areas in factors found to affect cattle TB risk has been developed to evaluate the impact of badger culling on cattle TB incidence. The association between cattle TB incidence and badger culling in the first two years has been assessed. Descriptive analyses without controlling for confounding showed no association between culling and TB incidence for Somerset, or for either of the buffer areas for the first two years since culling began. A weak association was observed in Gloucestershire for Year 1 only. Multivariable analysis adjusting for confounding factors showed that reductions in TB incidence were associated with culling in the first two years in both the Somerset and Gloucestershire intervention areas when compared to areas with no culling (IRR: 0.79, 95%CI: 0.72-0.87, p<0.001 and IRR: 0.42, 95%CI: 0.34-0.51, p<0.001 respectively). An increase in incidence was associated with culling in the 2 km buffer surrounding the Somerset intervention area (IRR: 1.38, 95%CI: 1.09-1.75, p=0.008), but not in Gloucestershire (IRR: 0.91, 95%CI: 0.77-1.07, p=0.243). As only two intervention areas with two years’ of data are available for analysis, and the biological cause-effect relationship behind the statistical associations is difficult to determine, it would be unwise to use these findings to develop generalisable inferences about the effectiveness of the policy at present

Somatostatin 2 receptors in the spinal cord tonically restrain thermogenic, cardiac and other sympathetic outflows

The anatomical and functional characterization of somatostatin (SST) and somatostatin receptors (SSTRs) within the spinal cord have been focused in the dorsal horn, specifically in relation to sensory afferent processing. However, SST is also present within the intermediolateral cell column (IML), which contains sympathetic preganglionic neurons (SPN). We investigated the distribution of SSTR2 within the thoracic spinal cord and show that SSTR2A and SSTR2B are expressed in the dorsal horn and on SPN and non-SPN in or near the IML. The effects of activating spinal SSTR and SSTR2 were sympathoinhibition, hypotension, bradycardia, as well as decreases in interscapular brown adipose tissue temperature and expired CO2, in keeping with the well-described inhibitory effects of activating SSTR receptors. These data indicate that spinal SST can decrease sympathetic, cardiovascular and thermogenic activities. Unexpectedly blockade of SSTR2 revealed that SST tonically mantains sympathetic, cardiovascular and thermogenic functions, as activity in all measured parameters increased. In addition, high doses of two antagonists evoked biphasic responses in sympathetic and cardiovascular outflows where the initial excitatory effects were followed by profound but transient falls in sympathetic nerve activity, heart rate and blood pressure. These latter effects, together with our findings that SSTR2A are expressed on GABAergic, presumed interneurons, are consistent with the idea that SST2R tonically influence a diffuse spinal GABAergic network that regulates the sympathetic cardiovascular outflow. As described here and elsewhere the source of tonically released spinal SST may be of intra- and/or supra-spinal origin

Linking Melodic Expectation to Expressive Performance Timing and Perceived Musical Tension

This article may not exactly replicate the final version published in the APA journal. It is not the copy of record

Spatially Explicit Data: Stewardship and Ethical Challenges in Science

Scholarly communication is at an unprecedented turning point created in part by the increasing saliency of data stewardship and data sharing. Formal data management plans represent a new emphasis in research, enabling access to data at higher volumes and more quickly, and the potential for replication and augmentation of existing research. Data sharing has recently transformed the practice, scope, content, and applicability of research in several disciplines, in particular in relation to spatially specific data. This lends exciting potentiality, but the most effective ways in which to implement such changes, particularly for disciplines involving human subjects and other sensitive information, demand consideration. Data management plans, stewardship, and sharing, impart distinctive technical, sociological, and ethical challenges that remain to be adequately identified and remedied. Here, we consider these and propose potential solutions for their amelioration

Occurrence and characterization of Salmonella isolated from table egg layer farming environments in Western Australia and insights into biosecurity and egg handling practices

The aim of this study was to investigate the occurrence and distribution of Salmonella in commercial layer farming environments of 26 flocks belonging to seven egg businesses (free-range and barn-laid) in Western Australia (WA). Between November 2017 and June 2018, a total of 265 environmental samples of dust, feed, water, pooled feces, and boot swabs were tested for detection of Salmonella according to standard culture-based methods. Isolates were assayed for serovar and subtyped by multilocus sequence typing (MLST). Salmonella spp. were recovered from 35% (93/265) of all tested samples. Dust (53.8%, 28/52) and pooled fecal (54.5%, 18/33) samples provided the highest Salmonella recovery rates. Nine different Salmonella serovars were characterized across the positive (n = 93) environmental samples, of which S. Typhimurium (60/93, 64.5%) and S. Infantis (21/93, 22.5%) were the most prevalent. MLST revealed that all S. Typhimurium isolates were of sequence type ST-19. Microbiological screening of Salmonella was not routinely practiced in any of the surveyed egg businesses. Some of the egg businesses exhibited variable levels of compliance with basic biosecurity measures as well as high-risk egg handling practices. Egg businesses in WA should be encouraged to adopt a voluntary program of environmental sampling and verification testing for Salmonella. Such voluntary programs will aid in supporting solutions for the management of this pathogen in the human food chain

A novel dielectric tensiometer enabling precision PID-based irrigation control of polytunnel-grown strawberries in coir

The benefits of closed-loop irrigation control have been demonstrated in grower trials which show the potential for improved crop yields and resource usage. Managing water use, by controlling irrigation in response to soil or substrate moisture changes, to meet crop water demands is a popular approach but requires substrate specific moisture sensor calibrations and knowledge of the moisture levels that result in water deficit or overwatering. The use of water tension sensors removes the need for substrate specific calibration and enables a more direct relationship with hydraulic conductivity. In this paper, we present a novel dielectric tensiometer that has been designed specifically for use in soil-free substrates such as coir, peat and Rockwool with a water tension measurement range of 0.7 kPa to 2.5 kPa. This new sensor design has also been integrated with a precision PID-based (drip) irrigation controller in a small-scale coir substrate strawberry growing trial: 32 strawberry plants in 4 coir growbags under a polytunnel. The data illustrates that excellent regulation of water tension in coir can be achieved which delivers robust and precise irrigation control - matching water delivery to the demands of the plants. During a 30-day growing period vapour pressure deficit (VPD) and daily water use data was collected and the irrigation controller set to maintain coir water tension at the following levels: 0.90 kPa, 0.95 kPa and 1 kPa for at least 7 consecutive days at each level. For each setpoint the coir water tension was maintained by the irrigation controller to within ±0.05 kPa. Meanwhile the polytunnel VPD varied diurnally from 0 to a maximum of 5 kPa over the trial period. Furthermore, the combination of the dielectric tensiometer and the method of PID-based irrigation control resulted in a linear relationship between daily average VPD and daily water use over 10 days during the cropping period

Elucidating the Binding Mechanism of a Novel Silica-Binding Peptide.

Linker-protein G (LPG) is a bifunctional fusion protein composed of a solid-binding peptide (SBP, referred as the "linker") with high affinity to silica-based compounds and a Streptococcus protein G (PG), which binds antibodies. The binding mechanisms of LPG to silica-based materials was studied using different biophysical techniques and compared to that of PG without the linker. LPG displayed high binding affinity to a silica surface (KD = 34.77 ± 11.8 nM), with a vertical orientation, in comparison to parent PG, which exhibited no measurable binding affinity. Incorporation of the linker in the fusion protein, LPG, had no effect on the antibody-binding function of PG, which retained its secondary structure and displayed no alteration of its chemical stability. The LPG system provided a milder, easier, and faster affinity-driven immobilization of antibodies to inorganic surfaces when compared to traditional chemical coupling techniques

Communities in university mathematics

This paper concerns communities of learners and teachers that are formed, develop and interact in university mathematics environments through the theoretical lens of Communities of Practice. From this perspective, learning is described as a process of participation and reification in a community in which individuals belong and form their identity through engagement, imagination and alignment. In addition, when inquiry is considered as a fundamental mode of participation, through critical alignment, the community becomes a Community of Inquiry. We discuss these theoretical underpinnings with examples of their application in research in university mathematics education and, in more detail, in two Research Cases which focus on mathematics students' and teachers' perspectives on proof and on engineering students' conceptual understanding of mathematics. The paper concludes with a critical reflection on the theorising of the role of communities in university level teaching and learning and a consideration of ways forward for future research