Physiological reactivity to spontaneously occurring seizure activity in dogs with epilepsy and their carers

There is a complex bidirectional relationship between stress and epilepsy. Stressful stimuli and subsequent cortisol release act as a trigger for seizure activity in some individuals with epilepsy, and seizure activity itself may act as a stressor to the affected individual. Epilepsy is the most common chronic neurological condition in domestic dogs and requires chronic management by their human carers, impacting upon the quality of life of both dog and carer. Seizures occur unpredictably and may be stressful for carers to witness and manage. In the present study we investigated the role of seizure activity as a stressor, measuring the effect of spontaneously occurring seizure activity in dogs with epilepsy upon their own cortisol levels and that of their carers. Furthermore, we tested whether individual differences in HPA reactivity were associated with owner personality characteristics and the quality of the dog carer relationship. Saliva samples were obtained from sixteen dog carer dyads in the home setting 20 and 40 minute post-seizure, and at time-matched points on the following (non-seizure) day. Significant differences in cortisol levels were found in dogs at 40 minute post-seizure (265.1% increase), and at 20 minute post-seizure in their carers (40.5% increase). No associations were found between cortisol reactivity and the strength of the dog-carer bond. Carers with higher neuroticism scores exhibited higher cortisol levels at both post-seizure sampling points. As there was a gender bias in the carer sample (15/16 were female), and there are known sex differences in cortisol reactivity in response to psychological stress, the conclusions of this study may be limited to female carers. These findings are the first to objectively demonstrate the acutely stressful effects of seizures in dogs with epilepsy and their carers

A smart driving smartphone application : real-world effects on driving performance and glance behaviours

A smart driving Smartphone application – which offers real-time fuel efficiency and safety feedback to the driver in the vehicle – was evaluated in a real-world driving study. Forty participants drove an instrumented vehicle over a 50 minute mixed route driving scenario, with 15 being selected for video data analysis. Two conditions were adopted, one a control, the other with smart driving advice being presented to the driver. Key findings from the study showed a 4.1% improvement in fuel efficiency when using the smart driving system, and an almost 3-fold reduction in time spent travelling closer than 1.5 seconds to the vehicle in front. Glance behavior results showed that drivers spent an average of 4.3% of their time looking at the system, at an average of 0.43 seconds per glance, with no glances of greater than two seconds. In conclusion this study has shown that a smart driving system specifically developed and designed with the drivers’ information requirements in mind can lead to significant improvements in real-world driving behaviours, whilst limiting visual distraction, with the task being integrated into normal driving

Maturity effects in concrete dams

Model equations for determining the coupled heat, moisture and maturity changes within a concrete block are introduced and briefly examined. Preliminary results are obtained for the heat exchange between concrete slabs in contact driven by maturity differences

PMI: A Delta Psi(m) Independent Pharmacological Regulator of Mitophagy

Mitophagy is central to mitochondrial and cellular homeostasis and operates via the PINK1/Parkin pathway targeting mitochondria devoid of membrane potential (ΔΨm) to autophagosomes. Although mitophagy is recognized as a fundamental cellular process, selective pharmacologic modulators of mitophagy are almost nonexistent. We developed a compound that increases the expression and signaling of the autophagic adaptor molecule P62/SQSTM1 and forces mitochondria into autophagy. The compound, P62-mediated mitophagy inducer (PMI), activates mitophagy without recruiting Parkin or collapsing ΔΨm and retains activity in cells devoid of a fully functional PINK1/Parkin pathway. PMI drives mitochondria to a process of quality control without compromising the bio-energetic competence of the whole network while exposing just those organelles to be recycled. Thus, PMI circumvents the toxicity and some of the nonspecific effects associated with the abrupt dissipation of ΔΨm by ionophores routinely used to induce mitophagy and represents a prototype pharmacological tool to investigate the molecular mechanisms of mitophagy

Hormonal Regulation of Glucocorticoid Inactivation and Reactivation in aT3-1 and LßT2 Gonadotroph Cells

The regulation of reproductive function by glucocorticoids occurs at all levels of the hypothalamo-pituitary-gonadal axis. Within the pituitary, glucocorticoids have been shown to directly alter gene expression in gonadotrophs, indicating that these cell types are sensitive to regulation by the glucocorticoid receptor. Whilst the major glucocorticoid metabolising enzymes, 11β-hydroxysteroid dehydrogenase (11βHSD; HSD11B1 and HSD11B2), have been described in human pituitary adenomas, the activity of these enzymes within different pituitary cell types has not been reported. Radiometric conversion assays were performed in αT3-1, LβT2 (gonadotrophs), AtT-20 (corticotrophs) and GH3 (somatolactotrophs) anterior pituitary cell lines, using tritiated cortisol, corticosterone, cortisone or 11-dehydrocorticosterone as substrates. The net oxidation of cortisol/corticosterone and net reduction of cortisone/11-dehydrocorticosterone were significantly higher in the two gonadotroph cells lines compared with the AtT-20 and GH3 cells after 4 h. Whilst these enzyme activities remained the same in αT3-1 and LβT2 cells over a 24 h period, there was a significant increase in glucocorticoid metabolism in both AtT-20 and GH3 cells over this same period, suggesting cell-type specific activity of the 11βHSD enzyme(s). Stimulation of both gonadotroph cell lines with either 100 nM GnRH or PACAP (known physiological regulators of gonadotrophs) resulted in significantly increased 11β-dehydrogenase (11βDH) and 11-ketosteroid reductase (11KSR) activities, over both 4 and 24 h. These data reveal that gonadotroph 11βHSD enzyme activity can act to regulate local glucocorticoid availability to mediate the influence of the HPA axis on gonadotroph function

Serum anti-Müllerian hormone concentrations before and after treatment of an ovarian granulosa cell tumour in a cat

Case summary A 15-year-old female cat was presented for investigation of progressive behavioural changes, polyuria, polydipsia and periuria. An ovarian granulosa cell tumour was identified and the cat underwent therapeutic ovariohysterectomy (OHE). The cat’s clinical signs resolved, but 6 months later it was diagnosed as having an anaplastic astrocytoma and was euthanased. Serum anti-Müllerian hormone (AMH) concentration prior to OHE was increased vs a control group of entire and neutered female cats. Following OHE, serum AMH concentration decreased to <1% of the original value. Relevance and novel information Serum AMH measurement may represent a novel diagnostic and monitoring tool for functional ovarian neoplasms in cats

Historical and recent tomato black ring virus and beet ringspot virus isolate genomes reveal interspecies recombination and plant health regulation inconsistencies

\ua9 2021 British Society for Plant Pathology. Tomato black ring virus (TBRV) and beet ringspot virus (BRSV) are closely related but distinct members of subgroup B of the genus Nepovirus. Both viruses have broad host ranges and are transmitted by seed, pollen, and ectoparasitic nematodes. Although 13 TBRV and 3 BRSV genome sequences were already available, no attempt has been made to link sequence data from these recent sequences with those of historical isolates studied in the pre-sequencing era. High-throughput sequencing was used to generate eight new TBRV and BRSV genome sequences from three historical &gt;60-year-old and two &gt;30-year-old isolates, and three more recent isolates. These eight isolates were from the Czech Republic, Germany, and the UK. We compared these with all genomes sequenced previously. Intraspecies recombination (three of four TBRV and two of four BRSV isolates) was frequent amongst the eight new genomes. Interspecies recombination was also present within the RNA1 of TBRV isolates BRSV-3393 SG GB and BRSV-9888 ST GB. No satellite RNAs were associated with the eight new genomes. Two commercial enzyme-linked immunosorbent assay (ELISA) kits used to detect TBRV during routine testing differed in that one detected only TBRV and the other only BRSV, so they are likely to provide incorrect but potentially complementary virus occurrence information. We suggest both ELISA kits, or appropriate molecular tests, be used by biosecurity authorities to avoid this problem. This study illustrates the value of sequencing historical isolates preserved from the pre-sequencing era

Optimal Scheduling of Trains on a Single Line Track

This paper describes the development and use of a model designed to optimise train schedules on single line rail corridors. The model has been developed with two major applications in mind, namely: as a decision support tool for train dispatchers to schedule trains in real time in an optimal way; and as a planning tool to evaluate the impact of timetable changes, as well as railroad infrastructure changes. The mathematical programming model described here schedules trains over a single line track. The priority of each train in a conflict depends on an estimate of the remaining crossing and overtaking delay, as well as the current delay. This priority is used in a branch and bound procedure to allow and optimal solution to reasonable size train scheduling problems to be determined efficiently. The use of the model in an application to a 'real life' problem is discussed. The impacts of changing demand by increasing the number of trains, and reducing the number of sidings for a 150 kilometre section of single line track are discussed. It is concluded that the model is able to produce useful results in terms of optimal schedules in a reasonable time for the test applications shown here

Glance behaviours when using an in-vehicle smart driving aid : a real-world, on-road driving study

In-vehicle information systems (IVIS) are commonplace in modern vehicles, from the initial satellite navigation and in-car infotainment systems, to the more recent driving related Smartphone applications. Investigating how drivers interact with such systems when driving is key to understanding what factors need to be considered in order to minimise distraction and workload issues while maintaining the benefits they provide. This study investigates the glance behaviours of drivers, assessed from video data, when using a smart driving Smartphone application (providing both eco-driving and safety feedback in real-time) in an on-road study over an extended period of time. Findings presented in this paper show that using the in-vehicle smart driving aid during real-world driving resulted in the drivers spending an average of 4.3% of their time looking at the system, at an average of 0.43 s per glance, with no glances of greater than 2 s, and accounting for 11.3% of the total glances made. This allocation of visual resource could be considered to be taken from ‘spare’ glances, defined by this study as to the road, but off-centre. Importantly glances to the mirrors, driving equipment and to the centre of the road did not reduce with the introduction of the IVIS in comparison to a control condition. In conclusion an ergonomically designed in-vehicle smart driving system providing feedback to the driver via an integrated and adaptive interface does not lead to visual distraction, with the task being integrated into normal driving