Corticosterone Contributes to Diet-Induced Reprogramming of Post-Metamorphic Behavior in Spadefoot Toads.

Stressful experiences in early life can have phenotypic effects that persist into, or manifest during, adulthood. In vertebrates, such carryover effects can be driven by stress-induced secretion of glucocorticoid hormones, such as corticosterone, which can lead to developmental reprogramming of hypothalamic-pituitary-adrenal/interrenal axis activity and behavior. Nutritional stress in the form of early life nutrient restriction is well known to modify later life behaviors and stress activity through corticosterone-related mechanisms. However, it is not known whether corticosterone is also mechanistically involved in carryover effects induced by a different form of nutritional variation: the use of alternate or entirely novel types of dietary resources. The plains spadefoot (Spea bombifrons) presents an excellent system for testing this question, since larvae of this species have evolved to use 2 alternate diet types: an ancestral detritus-based diet and a more novel diet of live shrimp. While previous work has shown that feeding on the novel shrimp diet influences juvenile (i.e., post-metamorphic) behavior and corticosterone levels, it is unclear whether these diet-induced carryover effects are mediated by diet-induced corticosterone itself. To test for the mechanistic role of corticosterone in diet-induced carryover effects, we experimentally treated S. bombifrons larvae with exogenous corticosterone and measured subsequent effects on juvenile behavior and corticosterone levels. We found that while shrimp-fed larvae had elevated corticosterone levels, treatment of larvae with corticosterone itself had effects on juvenile behavior that partially resembled those carryover effects induced by the shrimp diet, such as altered food seeking and higher locomotor activity. However, unlike carryover effects caused by the shrimp diet, larval corticosterone exposure did not affect juvenile corticosterone levels. Overall, our study shows that corticosterone-related mechanisms are likely involved in carryover effects induced by a novel diet, yet such diet-induced carryover effects are not driven by corticosterone alone.

Prevalence and outcome of lymphopenia in the Paediatric Intensive Care Unit: A prospective observational study.

AIM: Leukopenia (lymphopenia or neutropenia) may be an important marker of altered immunity and risk in children with critical illness. We aimed to evaluate the prevalence, course, and outcome of leukopenia in children admitted to Paediatric Intensive Care Unit (PICU). METHODS: All consecutive children (n = 200) admitted to PICU for any reason except malignancy or pre-existing immune deficiency were enrolled during June-August 2018. RESULTS: Median (interquartile range) age was 2.2 (0.6-8.5) years. About 52% (n = 103) had undergone a surgical procedure; 34% (n = 68) being cardiac surgery. Among medical illnesses, respiratory disorders were the most common (n = 39, 20%). Laboratory confirmed infections were present in 63 (31.5%) children. Leukopenia was identified in 135 (67.5%) children in the first week; 117 (58.5%) had only lymphopenia, 16 (8%) had both lymphopenia and neutropenia, and 2 (1%) had only neutropenia. In 69 children who had follow-up blood counts, lymphopenia resolved in 33 (48%) within 48 h and in another 20 (29%) by 4 days, and in a further 10 (14%) by 7 days. Children with lymphopenia had higher frequency of cardiac surgery, longer cardiopulmonary bypass time, greater need for invasive ventilation and vasopressor/inotrope therapy, and a higher probability of organ failure on day 4 and longer hospital stay. CONCLUSION: In critically ill children, lymphopenia is very common, often transient, but may be associated with unfavourable outcomes. Further studies with follow-up of blood counts in a larger sample are required to determine the course and outcomes of lymphopenia.

Owners' views of canine nutrition, weight status and wellbeing and their implications for the veterinary consultation.

OBJECTIVES: To investigate owners' views around canine nutrition and wellbeing, how these beliefs may differ according to the weight status of the dog and the implications for owner support approaches. MATERIALS AND METHODS: A researcher-mediated questionnaire collected quantitative and qualitative data via structured interviews with dog owners (n=147) attending a country park in the East Midlands, UK, with a specific focus on views around canine nutrition and wellbeing. RESULTS: Forty-four percent of owners cited "past experience" when determining what to feed, and only 9% of owners cited the veterinarian as a source of this information. When comparing chosen verbal description versus non-sequential body condition score images of the dog, only 22% of owners with overweight animals matched perceived verbal and visual appraisals, compared with 89% of owners of ideal weight dogs. Owners cited a good diet and regular exercise as important factors for canine wellbeing, but companionship with other dogs as the least important factor. CLINICAL SIGNIFICANCE: Owners report being aware of the important association between canine nutrition and wellbeing, but their considered importance of factors influencing dog wellbeing may be influenced by their perceived weight status of the animal. Veterinarians may need to reframe owner discourse such that there is more routine discussion around weight and nutrition at every consultation. Furthermore, the use of non-sequential body condition score images could be a useful tool for a more considered opinion of canine weight status by owners.

Establishing and prioritizing research questions for the prevention, diagnosis and treatment of hair loss (excluding alopecia areata): the Hair Loss Priority Setting Partnership.

BACKGROUND: Hair and scalp problems are common. Unfortunately, many uncertainties exist around the most effective management and treatment strategies for these disorders. OBJECTIVES: To identify uncertainties in hair-loss management, prevention, diagnosis and treatment that are important to both people with hair loss and healthcare professionals. METHODS: A Hair Loss Priority Setting Partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in hair loss. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants; following exclusions 884 uncertainties relating to hair loss (excluding alopecia areata) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that was taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for hair loss (excluding alopecia areata) to guide researchers and funding bodies to support studies important to both patients and clinicians.

Establishing and prioritizing research questions for the treatment of alopecia areata: the Alopecia Areata Priority Setting Partnership.

BACKGROUND: Alopecia areata (AA) is a common hair loss disorder that results in patchy to complete hair loss. Many uncertainties exist around the most effective treatments for this condition. OBJECTIVES: To identify uncertainties in AA management and treatment that are important to both service users (people with hair loss, carers and relatives) and healthcare professionals. METHODS: An AA priority setting partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in AA. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants, of which 1012 uncertainties relating to AA (and variants) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that were taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for AA to guide researchers and funding bodies to support studies important to both patients and clinicians.

"Who's been a good dog?" - Owner perceptions and motivations for treat giving.

Complex relationships commonly exist between owners and their companion animals, particularly around feeding behaviour with an owner's affection or love for their animal most pronounced through the provision of food. It is notable that the pet food market is experiencing strong year-on-year growth in sales of dog and cat treats. Recognising the impact of treat giving in pet nutrition, the objective of the study was to investigate owner attitudes and motivations towards feeding treats (shop bought and other) to their dogs. A researcher-mediated questionnaire consisting of both quantitative and qualitative questions was used to interview dog owners (n=280) at two locations: an out-of-town retail park and a country park in the East Midlands. Owners almost unanimously viewed the word 'treat' within a nutritional context, as opposed to a new toy or other pleasure. The majority (96%) of owners interviewed reported feeding treats to their dog, with 69% feeding shop-bought treats on a daily basis. A wide range of treats was reportedly given by owners and the majority of owners interviewed fed multiple treat types. No association was found between owner age and frequency of shop-bought treats fed (P=0.659) nor between owner age and frequency of food given to the dog from the owner's plate (P=0.083). A wide range of foods which would not be considered balanced for the animal's nutritional requirements was viewed as a treat by some dog owners. A range of positive and negative views around the feeding of treats were expressed by dog owners, with some citing beneficial effects while others were clearly aware of the association between treat feeding and potential weight gain/obesity. Owner views included themes around positive reinforcement and responsibility but also reflected relational aspects of the human-animal bond. The results of the study show that treat giving is commonplace in feeding regimes and that treats are embedded in the feeding behaviour of many dog owners. However, the different views expressed around the motivations for, and feeding of, dog treats, reinforce the need to better understand owner psychology linked to this area, and the role this may play in the growing pet obesity epidemic.

Dysregulation of follicle development in a mouse model of premature ovarian insufficiency.

Premature ovarian insufficiency (POI) occurs in 1% of reproductive-age women. The ovarian manifestation ranges from the presence of a variable population of follicles (follicular) to the absence of follicles (afollicular), and in the majority of cases the cause is unknown. A transgenic mouse model of follicular POI, the Double Mutant (DM), arises from oocyte-specific deletion of Mgat1 and C1galt1 required for the generation of O- and N-glycans. DM females are subfertile at 6 weeks, infertile by 9 weeks and exhibit POI by 12 weeks of age. In this study we investigate the cause of the reduced fertility at 6 weeks and infertility at 9 weeks of DM females. Ovary sections were used to analyse follicle and corpora lutea (CL) numbers, apoptosis, and levels of laminin and 3ß-hydroxysteroid dehydrogenase using immunohistochemistry. After POI, DM females unexpectedly remained sexually receptive. At both 6 and 9 weeks, DM ovaries contained more primary follicles, however, at 9 weeks DM follicles were proportionally healthier, revealed by TUNEL analysis compared with Controls. In 9 week DM ovaries (collected post-mating), secondary follicles had theca and basal lamina structure abnormalities, whilst preovulatory follicles failed to ovulate resulting in the presence of numerous luteinised unruptured follicles, indicative of ovulation failure. Finally, DM ovaries contained more regressing CL with decreased luteal cell apoptosis indicative of a defect in CL regression. Identifying these follicular modifications have provided insight into the aetiology of a model of POI and highlight targets to investigate with the hope of developing new fertility treatments.

Genetically modified animals from life-science, socio-economic and ethical perspectives: examining issues in an EU policy context.

The interdisciplinary EC consortium (the PEGASUS project) aimed to examine the issues raised by the development, implementation and commercialisation of genetically modified (GM) animals, and derivative foods and pharmaceutical products. The results integrated existing social (including existing public perception) environmental and economic knowledge regarding GM animals to formulate policy recommendations relevant to new developments and applications. The use of GM in farmed animals (aquatic, terrestrial and pharmaceutical) was mapped and reviewed. A foresight exercise was conducted to identity future developments. Three case studies (aquatic, terrestrial and pharmaceutical) were applied to identify the issues raised, including the potential risks and benefits of GM animals from the perspectives of the production chain (economics and agri-food sector) and the life sciences (human and animal health, environmental impact, animal welfare and sustainable production). Ethical and policy concerns were examined through application of combined ethical matrix method and policy workshops. The case studies were also used to demonstrate the utility of public engagement in the policy process. The results suggest that public perceptions, ethical issues, the competitiveness of EU animal production and risk-benefit assessments that consider human and animal health, environmental impact and sustainable production need to be considered in EU policy development. Few issues were raised with application in the pharmaceutical sector, assuming ethical and economic issues were addressed in policy, but the introduction of agricultural GM animal applications should be considered on a case-by-case basis.

Prevalence and characterisation of, and producers' attitudes towards, hock lesions in UK dairy cattle.

The objectives of this paper were to characterise lesions found at the hock and to establish their prevalence across a large sample of dairy cows in the UK. In addition, the study aimed to examine farmers' perceptions of these lesions. Seventy-seven farms were visited; both hocks on a random sample of approximately 50 cows were scored on a categorical scale for hair loss, ulceration and swelling. In addition, the size and location of lesions were marked on a hock map. A questionnaire designed to explore attitudes towards lesions was conducted with the owner. Hair loss and ulceration were seen at five locations. Hair loss was identified on 5,619 of 6,896 hocks (mild: 43.7 per cent; moderate: 25.1 per cent; severe: 12.6 per cent) and 1,137 of 6,896 hocks had areas of ulceration (mild: 8.6 per cent; moderate: 5.8 per cent; severe: 2.1 per cent). The majority of lesions were small; however, a small proportion had extensive areas of hair loss (maximum size 113.3 cm2) and ulceration (maximum size 95.5 cm2). Moderate swelling was recorded on 20 per cent of hocks, and 2.0 per cent had severe swelling. Interview results suggested that more than 90 per cent of participants were aware of hock lesions and a third had sought treatment for them; most felt that lesions had at least some impact on productivity and welfare.

Canine obesity: is there a difference between veterinarian and owner perception?

OBJECTIVES: The overall aim of this study was to examine the nature of the relationship between dog-ownership and canine obesity, explored in two cohorts of overweight/obese or non-overweight dogs (n=125). This paper concentrates on the owners' perception of dog weight. METHODS: A researcher-mediated questionnaire was used to collect data from dog owners attending a small veterinary practice. Interviewees (n=121) were asked qualitative and quantitative questions, designed to examine the owners' views of their relationship with their dogs. RESULTS: Although a high proportion of owners claimed to have discussed the dog's weight with their veterinarian, some discrepancies were apparent between owner perception of animal weight and the veterinarian's evaluation of body condition score. Owner disagreement was significantly greater for the veterinarian-defined overweight dogs (P=0·005). Owners often provide personal narratives to account for their dog's weight status. CLINICAL SIGNIFICANCE: This study confirms the important role of the vet in providing information about the issue of dog weight but also suggests that providing verbal information is sometimes insufficient. The study also indicates the potential value of qualitative research methods to further understand client perception of complex animal care issues and highlights the need for further in-depth research.

Risk factors associated with hair loss, ulceration, and swelling at the hock in freestall-housed UK dairy herds.

The objective of this study was to identify the risk factors associated with 3 presentations of hock lesions (hair loss, ulceration, and swelling) in freestall-housed lactating cattle. By independent identification and scoring of, and analysis of the factors associated with, hair loss, ulceration, and swelling, the aim was to identify whether risk factors were common to all 3, or differed among the presentations. A cross-sectional study was conducted on 76 herds in the UK during the winter housing period of 2007 to 2008, with a total of 3,691 cows examined for hock lesions. A randomly selected sample of approximately 50 cows in each herd were scored for body condition, lameness, cleanliness, rising behavior, and lesions at the hocks. For all cows, hair loss, ulceration, and swelling were scored separately on 4-point scales, with both left and right hocks scored. Based on a review of the literature, potential risk factors were identified and measured, collected from milk-recording data, or obtained through interviews with the farmers. Risk factors associated with hocks lesions in cattle were examined using data from the 2,982 cows housed in the 63 freestall-housed herds visited. Risk factors for each of the 3 lesion presentations were considered separately in multilevel logistic regression models, with moderate or severe hair loss, any degree of ulceration, and moderate or severe swelling as the outcome variables. Thirty risk factors were identified, none of which were common to all 3 lesion presentations. Five risk factors (locomotion score, number of days of winter housing, mean milk yield, freestall base material, and herd size) were common to both hair loss and ulceration. The stall bedding material was a common risk factor for both hair loss and swelling. A further 8, 5, and 11 risk factors were unique to hair loss, ulceration, and swelling, respectively. The existence of several differential risk factors between the 2 lesion presentations suggests that ulceration may not always be a direct extension of hair loss, as has been implied in previous scoring systems. Of the 12 risk factors associated with swelling, only 1 was common to another lesion presentation, which suggests that swelling may have a different etiology than hair loss and ulceration. The variables associated with the lesions indicate the importance of factors that affect the lying and rising behavior of the animal, including freestall structure and design, and the lying surface.

The effect of transmucosal 0.2 mg/kg midazolam premedication on dental anxiety, anaesthetic induction and psychological morbidity in children undergoing general anaesthesia for tooth extraction.

BACKGROUND: The project aims were to evaluate the benefit of transmucosal midazolam 0.2 mg/kg pre-medication on anxiety, induction behaviour and psychological morbidity in children undergoing general anaesthesia (GA) extractions. METHOD: One hundred and seventy-nine children aged 5-10 years (mean 6.53 years) participated in this randomised, double blind, placebo-controlled trial. Ninety children had midazolam placed in the buccal pouch. Dental anxiety was recorded preoperatively and 48 hours later using a child reported MCDAS-FIS scale. Behaviour at anaesthetic induction was recorded and psychological morbidity was scored by the parent using the Rutter Scale preoperatively and again one week later. Subsequent dental attendance was recorded at one, three and six months after GA. RESULTS: While levels of dental anxiety did not reduce overall, the most anxious patients demonstrated a reduction in anxiety after receiving midazolam premedication (p = 0.01). Neither induction behaviour nor psychological morbidity improved. Irrespective of group, parents reported less hyperactive (p = 0.002) and more pro-social behaviour (p = 0.002) after the procedure; older children improved most (p = 0.048). Post-GA dental attendance was poor and unaffected by premedication. CONCLUSION: 0.2 mg/kg buccal midazolam provided some evidence for reducing anxiety in the most dentally anxious patients. However, induction behaviour, psychological morbidity and subsequent dental attendance were not found to alter.

Balancing the needs and preferences of humans against concerns for fishes: how to handle the emerging ethical discussions regarding capture fisheries?

How can stakeholders within the fisheries community engage in constructive ethical discussions? Drawing on experiences from previous debates surrounding the human use of animals, this paper presents a proactive approach whereby stakeholders can create a framework for ethical discussion of capture fisheries.

The ethics and role of AI with fresh and frozen semen in dogs.

The use of artificial insemination (AI) with fresh semen has resulted in many benefits for the management of dog breeding, but there are disadvantages that can sometimes be overlooked. Furthermore, poorer quality semen arising as a result of cryopreservation necessitates uterine insemination, which raises the potential for surgical insemination. A number of significant ethical concerns have been raised by key stakeholders (such as The Kennel Club and the Royal College of Veterinary Surgeons) about AI per se, but particularly about the use of surgical insemination. This paper discusses the technological development of AI and explores a number of the ethical issues raised by its application to dog breeding. An Ethical Matrix method is used to map the potential ethical issues for key interest groups, namely dogs, breeders, owners, veterinarians and wider society. There are national variations in the way in which institutions have evaluated potential ethical impacts, and this is reflected in the different regulatory frameworks governing the use of AI in dogs. In order to facilitate decision-making and reduce some of the ethical risks associated with this technology, the veterinary research community could take several proactive steps including: (i) clarifying clinical decision-making processes, (ii) enhancing informed choice among clients and (iii) increasing the knowledge-base of potential impacts of AI.

A randomised placebo-controlled trial of the effects of midazolam premedication on children's postoperative cognition.

This randomised, placebo-controlled study assessed the effects of midazolam premedication on children's postoperative cognition and physical morbidity. In all, 179 children aged 5-10 years were randomly assigned to receive buccal midazolam (0.2 mg x kg(-1)) or placebo before sevoflurane-nitrous oxide anaesthesia for multiple dental extractions. They performed tests of choice reaction time, attention, psychomotor co-ordination and memory pre-operatively (baseline), before discharge and at 48 h. The reaction time of both groups was significantly slower before discharge compared to baseline, with the midazolam group being significantly slower than placebo. Psychomotor co-ordination was also significantly impaired postoperatively after midazolam. Performance on both tests had recovered to baseline by 48 h. Midazolam was also associated with significant anterograde amnesia, both postoperatively and at 48 h, for information presented in the interval between premedication and surgery. The results show significant short-term impairment of children's cognitive function and amnesia enduring for 48 h after low-dose midazolam premedication.

Glucocorticoid therapy for hypotension in the cardiac intensive care unit.

In recent years, it has been our practice to treat persistent hypotension in the cardiac intensive care unit with glucocorticoids. We undertook a retrospective review in an attempt to identify predictors of a hemodynamic response to steroids and of survival in these patients. Patients who had received glucocorticoids for hypotension over a 2-year period were identified retrospectively. Summary measures of blood pressure, heart rate, urine output, inotrope score, and volume of infused fluid were calculated for the 12 hours before and the 24 hours following initiation of glucocorticoid therapy. A hemodynamic response was defined as a > or =20% increase in mean blood pressure without an increase in inotrope score following initiation of steroid therapy. Fifty-one patients were included, of whom 6 (11.8%) died. Serum cortisol was measured in 43 patients (84.3%) and was below the lower limit of normal (<5 microg/dl) in 20 of these (46.5%). Following initiation of steroid therapy, blood pressure and urine output increased, whereas heart rate, inotrope score, and infused volume decreased. There were 21 (41.1%) hemodynamic responders, all of whom survived, whereas 6 of 30 (20%) nonresponders died (p = 0.036). No predictors of a hemodynamic response to steroid were identified. Some critically ill children with cardiac disease and inotrope refractory hypotension demonstrated hemodynamic improvement following glucocorticoid administration. An improvement in blood pressure following administration of glucocorticoid was associated with survival, but we were unable to identify predictors of that response.

The effects of brief sevoflurane-nitrous oxide anaesthesia upon children's postoperative cognition and behaviour.

This study assessed the effects of brief sevoflurane-nitrous oxide anaesthesia on children's postoperative cognition, behaviour and physical morbidity. Forty-eight children aged 5-10 years undergoing anaesthesia without premedication for multiple dental extractions, and 48 control children, performed tests of choice reaction time, attention, psychomotor co-ordination and memory pre-operatively (baseline), prior to discharge and at 48 h (anaesthesia group only). Physical and psychological morbidity were recorded at 1 week. Mean choice reaction time and psychomotor co-ordination were significantly impaired postoperatively but had recovered at 48 h. However, measures of performance variability suggested the presence of residual impairment. Profound retrograde amnesia affected postoperative and 48-h recall of pictorial stimuli presented prior to anaesthesia, but recognition memory was unimpaired. Attention-seeking, tantrums, crying and nightmares were occurring more frequently in some 8-20% of children 1 week after the procedure.

A partially blinded randomised controlled trial of patient-maintained propofol sedation and operator controlled midazolam sedation in third molar extractions.

Patient-maintained sedation using propofol has recently been shown to be effective for dental surgery. We compared this new technique to the established technique of operator administered midazolam. The two groups were compared before, during and after sedation. The two primary outcomes were time until discharge and oxygen saturation. Vital signs, anxiety and psychomotor skills were also compared. State anxiety was reduced to a greater extent in the propofol group (mean difference 10 (SD 4) mm; p = 0.010. Propofol patients recovered quicker (mean difference 7 (SD 1.4) min; p = 0.001). Propofol patients had a smaller reduction in arterial oxygen saturation (mean difference 0.8 (SD 0.3)%; p = 0.030), and a reduced increase in heart rate (mean difference 9 (SD 2) beats.min(-1); p < 0.001). Both techniques were well tolerated and safe. Propofol sedation offered superior anxiolysis, quicker recovery, less amnesia and less depression of simple psychomotor function.