Perineuronal net structure as a non-cellular mechanism contributing to affective state: A scoping review.

Affective state encompasses emotional responses to our physiology and influences how we perceive and respond within our environment. In affective disorders such as depression, cognitive adaptability is challenged, and structural and functional brain changes have been identified. However, an incomplete understanding persists of the molecular and cellular mechanisms at play in affective state. An exciting area of newly appreciated importance is perineuronal nets (PNNs); a specialised component of extracellular matrix playing a critical role in neuroprotection and synaptic plasticity. A scoping review found 24 studies demonstrating that PNNs are still a developing field of research with a promising general trend for stress in adulthood to increase the intensity of PNNs, whereas stress in adolescence reduced (potentially developmentally delayed) PNN numbers and intensity, while antidepressants correlated with reduced PNN numbers. Despite promising trends, limited research underscores the need for further exploration, emphasizing behavioral outcomes for validating affective states. Understanding PNNs' role may offer therapeutic insights for depression and inform biomarker development, advancing precision medicine and enhancing well-being.

Antenatal care of women who use opioids: a qualitative study of practitioners' perceptions of strengths and challenges of current service provision in Scotland.

BACKGROUND: The increasing rise of women using opioids during pregnancy across the world has warranted concern over the access and quality of antenatal care received by this group. Scotland has particularly high levels of opioid use, and correspondingly, pregnancies involving women who use opioids. The purpose of this study was to investigate the different models of antenatal care for women using opioids during pregnancy in three Scottish Health Board Areas, and to explore multi-disciplinary practitioners' perceptions of the strengths and challenges of working with women who use opioids through these specialist services. METHODS: Thirteen semi-structured interviews were conducted with health and social care workers who had experience of providing antenatal and postnatal care to women who use drugs across three Scottish Health Board Areas: NHS Greater Glasgow and Clyde, NHS Lothian, and NHS Tayside. Framework Analysis was used to analyse interview data. The five stages of framework analysis were undertaken: familiarisation, identifying the thematic framework, indexing, charting, and mapping and interpretation. RESULTS: Each area had a specialist antenatal pathway for women who used substances. Pathways varied, with some consisting of specialist midwives, and others comprising a multidisciplinary team (e.g. midwife, mental health nurse, social workers, and an obstetrician). Referral criteria for the specialist service differed between health board areas. These specialised pathways presented several key strengths: continuity of care with one midwife and a strong patient-practitioner relationship; increased number of appointments, support and scans; and highly specialised healthcare professionals with experience of working with substance use. In spite of this, there were a number of limitations to these pathways: a lack of additional psychological support for the mother; some staff not having the skills to engage with the complexity of patients who use substances; and problems with patient engagement. CONCLUSIONS: Across the three areas, there appears to be high-quality multi-disciplinary antenatal services for women who use opioids during pregnancy. However, referral criteria vary and some services appear more comprehensive than others. Further research is needed into the perceptions of women who use opioids on facilitators and barriers to antenatal care, and provision in rural regions of Scotland.

The power of effective study design in animal experimentation: Exploring the statistical and ethical implications of asking multiple questions of a data set.

One of the chief advantages of using highly standardised biological models including model organisms is that multiple variables can be precisely controlled so that the variable of interest is more easily studied. However, such an approach often obscures effects in sub-populations resulting from natural population heterogeneity. Efforts to expand our fundamental understanding of multiple sub-populations are in progress. However, such stratified or personalised approaches require fundamental modifications of our usual study designs that should be implemented in Brain, Behavior and Immunity (BBI) research going forward. Here we explore the statistical feasibility of asking multiple questions (including incorporating sex) within the same experimental cohort using statistical simulations of real data. We illustrate and discuss the large explosion in sample numbers necessary to detect effects with appropriate power for every additional question posed using the same data set. This exploration highlights the strong likelihood of type II errors (false negatives) for standard data and type I errors when dealing with complex genomic data, where studies are too under-powered to appropriately test these interactions. We show this power may differ for males and females in high throughput data sets such as RNA sequencing. We offer a rationale for the use of alternative experimental and statistical strategies based on interdisciplinary insights and discuss the real-world implications of increasing the complexities of our experimental designs, and the implications of not attempting to alter our experimental designs going forward.

A realist evaluation of the feasibility of a randomised controlled trial of a digital music and movement intervention for older people living in care homes.

BACKGROUND: Low physical activity in care home residents brings about negative mental health consequences, such as higher levels of depression and loneliness. With advancements in communication technology, particularly during the COVID-19 pandemic, the feasibility and effectiveness of a randomised controlled trial (RCT) of a digital Physical Activity (PA) resource in care homes deserve more research attention. A realist evaluation was used to uncover influencing factors of a feasibility study implementation to inform how a digital music and movement programme would work and under what circumstances this would be most effective. METHODS: Participants were 49 older adults (aged 65 years +) recruited across ten care homes in Scotland. Surveys were administered at baseline and post-intervention comprising psychometric questionnaires on multidimensional health markers validated in older adults with possible cognitive impairment. The intervention comprised 12 weeks of four prescribed digitally delivered movement (n = 3) and music-only (n = 1) sessions per week. An activity coordinator delivered these online resources in the care home. Post-intervention focus groups with staff and interviews with a sub-sample of participants were conducted to gain qualitative data on the acceptability of the intervention. RESULTS: Thirty three care home residents started the intervention, but only 18 residents (84% female) completed both pre- and post-intervention assessments. Activity coordinators (AC) offered 57% of the prescribed sessions, with an average residents' adherence of 60%. Delivery of the intervention did not go as planned due to Covid restrictions in care homes and delivery challenges, including (1) motivation and engagement, (2) changes in cognitive impairment and disabilities of the participants, (3) death or hospitalisation of the participants and (4) limited staffing and technology resources to deliver the programme as intended. Despite this, group participation and encouragement of residents supported the delivery and acceptance of the intervention, with ACs and residents reporting improved mood, physical health, job satisfaction and social support. Improvements with large effect sizes were found for anxiety, depression, loneliness, perceived stress and sleep satisfaction, but no changes in fear of falling, domains of general health or appetite. CONCLUSION: This realist evaluation suggested that this digitally delivered movement and music intervention is feasible. From the findings, the initial programme theory was refined for future implementation of an RCT in other care homes but future research exploring how to tailor the intervention to those with cognitive impairment and/or lacking capacity to consent is needed. TRIAL REGISTRATION: Retrospectively registered at ClinicalTrials.gov NCT05559203.

Myeloperoxidase inhibitor AZD5904 enhances human sperm function in vitro.

STUDY QUESTION: Does AZD5904, a myeloperoxidase inhibitor (MPOi), have any effect on human sperm function in vitro? SUMMARY ANSWER: AZD5904 improves sperm function in an in vitro model of oxidative stress (OS) and potentially offers a novel treatment approach for male infertility. WHAT IS KNOWN ALREADY: Male infertility is an underlying or contributory cause in half of all couples experiencing difficulties conceiving, yet there is currently no effective treatment or cure. OS is a common pathology in a significant proportion of infertile men. It can negatively affect sperm motility and the ability to fertilize a mature oocyte, as well as DNA integrity, and therefore represents an attractive target for therapeutic intervention. STUDY DESIGN, SIZE, DURATION: This study included population-based samples from men (23-50 years) attending Ninewells Assisted Conception Unit, Dundee for diagnostic semen analysis, July 2017-September 2018. Semen samples (n = 47) from 45 patients were used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Neutrophils activated using zymosan were incubated with prepared human spermatozoa for 2 h (T2) and 24 h (T24) to create an in vitro model of OS. Parallel samples were co-incubated with AZD5904, an MPOi, to examine its effects. Sperm motility was assessed by computer-assisted sperm analysis at T2 and T24. Functional motility was assessed by sperm penetration assay. Statistical analysis was performed using GraphPad Prism. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in total or progressive sperm motility between any treatment and control groups at T2 or T24. Nonetheless, significant positive effects on sperm function were observed with AZD5904, with 16/45 (35.6%) samples (with both normal and abnormal baseline semen analysis characteristics) displaying a ≥20% increase in sperm penetrated through viscous media (P < 0.003). LIMITATIONS, REASONS FOR CAUTION: This was an in vitro study. WIDER IMPLICATIONS OF THE FINDINGS: Treatment with AZD5904 resulted in significant increased sperm penetration in one of three samples treated, which is likely to represent improvement in sperm function required for fertilization. We are now planning a clinical trial to validate these results and hope that this could represent a new treatment for male infertility. STUDY FUNDING/COMPETING INTEREST(S): AZD5904 was shared through the AstraZeneca Open Innovation program. The study was funded by AstraZeneca and sponsored by the University of Dundee. Additional funding was provided by Chief Scientist Office/NHS Research Scotland (S.J.M.d.S.). A.W. and H.J.S. are both full time employees of AstraZeneca. A.W. and H.J.S. are inventors on a patent filed by AstraZeneca titled MPOi for use in medicine which includes MPOi for use in the treatment of male infertility (WO 2019/016074 Al). S.J.M.d.S. is Associate Editor of Human Reproduction and Editorial Board member of Reproduction & Fertility. C.L.R.B. is Editor of RBMO and has received lecturing fees from Merck and Ferring and is on the Scientific Advisory Panel for Ohana BioSciences. C.L.R.B. was chair of the World Health Organization Expert Synthesis Group on Diagnosis of Male infertility (2012-2016). C.L.R.B. has a patent WO2013054111 A1 issued. The other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Blunted cardiovascular reactivity to acute psychological stress predicts low behavioral but not self-reported perseverance: A replication study.

Emerging evidence suggests that individuals with poor behavioral perseverance show low or blunted physiological responses to acute psychological stress. For example, a recent preliminary laboratory study demonstrated that blunted responders give up sooner and take fewer attempts when endeavoring to complete an impossible puzzle, but do not self-report poor perseverance. This present research is a replication of the previous study with an increased sample size, longer recovery periods between tasks and addition of social evaluation to the cold pressor. Participants (147) completed a self-report perseverance questionnaire (Short Grit Scale) and behavioral perseverance tasks (impossible Euler puzzle and socially evaluated cold-pressor (SECPT)). The number of attempts and time spent trying to complete the unsolvable puzzle, and duration of hand submergent during the SECPT, were recorded as behavioral perseverance measures. Difference in blood pressure (BP) and pulse rate (PR) from baseline to a 10-min paced auditory serial addition task (PASAT) were computed as reactivity. As previously, reactivity did not relate to self-reported perseverance and blunted BP reactivity to the PASAT was associated with less time persevering at the unsolvable puzzle. Additionally, blunted BP and PR reactivity to the PASAT related to poorer perseverance during the SECPT. These findings, replicating the previous study, increase confidence that blunted reactivity is a physiological marker of poor behavioral perseverance. Moreover, given that self-reported perseverance does not relate to reactivity, this suggests that blunted responders are not conscious of this detriment in perseverance, but likely need additional support when persistence is critical (e.g., during behavior change).

Impact of 3D echocardiography on grading of mitral stenosis and prediction of clinical events

Background: The mitral valve orifice area (MVOA) is difficult to assess accurately by 2D echocardiography because of geometric assumptions; therefore, 3D planimetry may offer advantages. We studied the differences in MVOA measurements between the most frequently used methods, to determine if 3D planimetry would result in the re-grading of severity in any cases, and whether it was a more accurate predictor of clinical outcomes. Methods: This was a head-to-head comparison of the three most commonly used techniques to grade mitral stenosis (MS) by orifice area and to assess their impact on clinical outcomes. 2D measurements (pressure half-time (PHT), planimetry) and 3D planimetry were performed retrospectively on patients with at least mild MS. The clinical primary endpoint was defined as a composite of MV balloon valvotomy, mitral valve repair or replacement (MVR) and/or acute heart failure (HF) admissions. Results: Forty-one consecutive patients were included; the majority were female (35; 85.4%), average age 55 (17) years. Mean and peak MV gradients were 9.4 (4) mmHg and 19 (6) mmHg, respectively. 2D and 3D measures of MVOA differed significantly; mean 2D planimetry MVOA was 1.28 (0.40) cm2, mean 3D planimetry MVOA 1.15 (0.29) cm2 (P = 0.003). Mean PHT MVOA was 1.43 (0.44) cm2 (P = 0.046 and P < 0.001 in comparison to 2D and 3D planimetry methods, respectively). 3D planimetry reclassified 7 (17%) patients from mild-to-moderate MS, and 1 (2.4%) from moderate to severe. Overall, differences between the two methods were significant (X2, P < 0.001). Only cases graded as severe by 3D predicted the primary outcome measure compared with mild or moderate cases (odds ratio 5.7). Conclusion: 3D planimetry in MS returns significantly smaller measurements, which in some cases results in the reclassification of severity. Routine use of 3D may significantly influence the management of MS, with a degree of prediction of clinical outcomes.

Female rats display fewer optimistic responses in a judgment bias test in the absence of a physiological stress response.

Metabolic cages are a type of housing used in biomedical research. Metabolic cage housing has been demonstrated to elicit behavioural and physiological changes in rodents housed within them. The nature of this effect has been characterized as anxiogenic. However, few studies have evaluated positive affect in response to metabolic cage housing and the interaction between this, sex and traditional physiological measures of stress. Cognitive biasing, as measured through a judgment bias paradigm has proven a reliable measure of animal affective state, particularly through its ability to measure positive affect. The current study investigated differences in cognitive biasing between male and female rats when transferred from open-top, grouped housing to a metabolic cage. Rats (Rattus norvegicus) (n=60) were trained in a judgment bias paradigm previously validated for use in the rat model. Upon exposure to an intermediate, ambiguous probe rats responded with either an optimistic or pessimistic decision. The animals were also subjected to the sucrose preference test to identify the presence of anhedonia. Faecal corticosterone and changes in adrenal tyrosine hydroxylase were also measured to establish whether a stress-like state was experienced. There was a significant interaction between sex and metabolic cage housing on the number of optimistic decisions made F (1, 56)=7.461, p=0.008. Female rats that remained in control housing responded with a reduced number of days featuring an optimistic decision compared to males in control housing (p=0.036). However, both males and females responded with significantly fewer optimistic decisions in the metabolic cage compared to control (p<0.001). There was a significant negative correlation between treatment and sucrose consumption (rpb=-0.654, n=195, p<0.001). There was also a significant sex effect for faecal corticosterone concentrations F (1, 30)=6.305, p=0.018) with female rats (4.050±1.285), displaying greater corticosterone concentrations than males (2.291±0.495). No differences between treatment were observed for either corticosterone or tyrosine hydroxylase levels. This data demonstrates that movement into a metabolic cage resulted in rats displaying significantly greater pessimistic cognitive biases as determined through the judgment bias test. Interestingly, male rats that remained in control housing demonstrated cognitive biases that were not equivalent to female rats. Furthermore, despite a behavioural change being evident, a physiological change in corticosterone or tyrosine hydroxylase levels was not observed.

Effects of acute chemotherapy-induced mucositis on spontaneous behaviour and the grimace scale in laboratory rats.

Intestinal mucositis is a frequent side-effect of chemotherapy treatment. Many oncological research programs aim to identify novel treatments for this distressing condition, and these programs frequently use rat models. Little is known about the presence and progression of pain in these models and how this can best be treated by analgesic therapy. We used a number of behaviour-based methods of pain assessment to determine which tools were best suited for pain identification. Baseline measures for behavioural assessment, rat grimace score and sociability were determined through analysis of continuously recorded video data and an applied social interaction test (n = 16). Mucositis was then induced by intraperitoneal injection of 5-fluorouracil (150 mg/kg) and further behavioural analyses undertaken. An assessment of enrichment interaction was also made by determining the mass of a plastic chew toy gnawed both pre- and post-chemotherapy injection. Behavioural scoring was performed 1, 6, 12, 24 and 48 h after injection, with facial expression being scored at the 12, 24 and 48 h time-points. Sociability testing was performed once during the post-injection period. No significant differences were found in grimace scores between baseline and later daily measures. Behaviours similar to those previously reported post-laparotomy were observed. Writhing, twitching and back-arching behaviours were most evident in rats affected by mucositis and were increased in frequency (respective P values: 0.002, 0.004 and 0.008) 48 h after chemotherapy injection compared with baseline, implying that pain onset occurred around this time-point. Social investigatory behaviour was also increased (P = 0.002) following disease onset. Each day, rats post-5FU injection gnawed a greater percentage of their Nylabone enrichment by weight than the saline-injected control rats (P = 0.046). These data suggest that, of the tools tested, behavioural assessment scoring may find greatest utility in rodent models of intestinal mucositis and should be investigated further.

Factors associated with antiretroviral treatment uptake and adherence: a review. Perspectives from Australia, Canada, and the United Kingdom.

International focus on reducing onward HIV transmission emphasizes the need for routine HIV testing and early uptake of antiretroviral treatment (ART). Strategic targets have been set for 2020 to achieve the goal of 90% of people infected with HIV diagnosed, 90% of identified cases on treatment, and 90% of persons on treatment virally suppressed (90-90-90). It is vital to understand the complexity of factors influencing a person's treatment decisions over time and the context which may enable better adherence. In this paper we present findings from the review of published and gray literature (2003-2013) on the documented factors associated with treatment initiation and adherence in the general adult population of Australia, Canada, and the UK. A framework developed by Begley, McLaws, Ross, and Gold [2008. Cognitive and behavioural correlates of non-adherence to HIV anti-retroviral therapy: Theoretical and practical insight for clinical psychology and health psychology. Clinical Psychologist, 12(1), 9-17] in Australia was adapted to summarize the findings. A systematic database search using keywords and a set of inclusion criteria yielded 17 studies (Australia = 6; Canada = 8; UK = 3). In addition 11 reports were included in the review. We found that a person's abilities and motivations (intrapersonal factors, reported in 7 studies) to start and continue ART are influenced by a host of interconnected factors spanning relationship (interpersonal, 3 studies) and broader structural (extrapersonal, 15 studies) factors that are situated within social determinants of health. People therefore evaluate various costs and benefits of starting and staying on treatment, in which biomedical concerns play an important yet often subsidiary role. In this review the economic barriers to care were found to be significant and under-reported, highlighting the persistent health inequities in terms of access to services. Our understanding of the context around people's use of ART remains poor. Qualitative social research within HIV-positive communities is urgently needed to capture people's lived experiences and may address some of this deficit in understanding.

The assessment of general well-being using spontaneous burrowing behaviour in a short-term model of chemotherapy-induced mucositis in the rat.

Mucositis is a common and serious side-effect experienced by cancer patients during treatment with chemotherapeutic agents. Consequently, programmes of research focus on the elucidation of novel therapeutics for alleviation of mucositis symptoms, and these frequently use animal models. However, although these models are assumed to be painful and distressing to the animal, endpoints are difficult to determine. The aim of this study was to evaluate whether a change in burrowing behaviour could provide an indication of disease onset and potentially be applied as a humane endpoint. Baseline burrowing behaviour was measured in healthy animals on three occasions by determining the weight of gravel displaced from a hollow tube. Mucositis was then induced in the same animals by intraperitoneal injection of 5-fluorouracil (150 mg/kg) and burrowing behaviour recorded over three consecutive days. Standard measures of disease progression, including body weight loss and clinical score, were also made. The presence of mucositis was confirmed at necropsy by findings of decreased duodenal and colon lengths, and reduced liver, spleen and thymus weights in comparison with non-treated control animals. Histological score of the jejunum and ileum was also significantly increased. Mucositis onset coincided with a decrease in mean burrowing behaviour which was progressive, however this result did not achieve statistical significance (P = 0.66).We conclude that burrowing may be a useful indicator of inflammation in the mucositis model, although this requires further characterization. Pre-selection of animals into treatment groups based on their prior burrowing performance should be pursued in further studies.

Factors impacting HIV testing: a review--perspectives from Australia, Canada, and the UK.

With the current global focus on strengthening HIV prevention through greater testing and treatment uptake, it is increasingly salient to identify and address barriers to testing. A review of the published, peer-reviewed literature and national reports from Australia, Canada, and the UK (2003-2013) on barriers to HIV testing was conducted to provide new information relevant to Australia and to complement earlier reviews from Canada and the UK. A systematic database search using keywords and a set of inclusion criteria yielded 36 studies (Australia = 13; Canada = 6; and the UK = 17). In addition 17 unpublished reports were included in the review. Our study uses a novel, comprehensive framework to describe barriers to HIV testing, and thus contributes to moving beyond the traditional patient-provider-system categorization. Within that framework, barriers are categorized as either intrapersonal (reported in 15 studies), interpersonal (21), or extrapersonal (16) and conceptualized within wider sociocultural and structural contexts. People's abilities and motivations to test (intrapersonal factors) are influenced by a host of interconnected factors spanning relationship (interpersonal) and broader socioeconomic, political and cultural (extrapersonal) factors. We suggest that the relative effects of interventions targeting barriers to HIV testing at the intrapersonal and interpersonal levels are limited by the extent to which the social determinants of health are addressed. The framework may also lend itself to thinking about the enabling factors for HIV testing, and future research may investigate the application of that framework for strategizing the most effective response. Future studies should also capture the lived experiences of barriers to HIV testing experienced by patients, especially in populations which are hard to reach based on social and geographic distance. Context-specific studies to evaluate the feasibility and effectiveness of various interventions proposed in the literature to address barriers to HIV testing are needed.

Women's expectations and experiences of hormone treatment for sexual dysfunction.

OBJECTIVES: There is a paucity of information regarding women's expectations of medical treatment for female sexual dysfunction (FSD) and their self-appraisal of treatment outcomes. The aims of this study were to explore women's perception and expectations of treatment and their experiences of treatment for FSD using a qualitative approach. METHODS: First-time attendees to an endocrinologist with the complaint of sexual difficulties were identified and were invited to take part in an in-depth interview on the same day as, but prior to, their medical consultation. Follow-up phone interview took place 3-4 months later. RESULTS: Seventeen women, aged 26-70 years, participated in the face-to-face interview. Ten of these participated in the follow-up interview. Four major themes emerged from the women's narrative stories: (1) personal psychological distress associated with FSD, (2) concern about the adverse effect of FSD on the relationship with their sexual partner, (3) a belief in a relationship between FSD and 'hormone deficiency', and (4) an expectation of treatment, which included positive physical and sexual changes. CONCLUSIONS: Health professionals should be aware of the high degree of psychological distress that can result from FSD and consider available treatment options, which may include hormone therapy.

Characterization of Khorasan wheat (Kamut) and impact of a replacement diet on cardiovascular risk factors: cross-over dietary intervention study.

BACKGROUND/OBJECTIVES: Khorasan wheat (Kamut) is an ancient grain with widely acclaimed beneficial effects on human health. The objective was to characterise Kamut and to examine the effect of a replacement diet with their products on cardiovascular risk parameters. SUBJECTS/METHODS: We conducted a randomized, single-blinded cross-over trial with two intervention phases on 22 healthy subjects (14 females; 8 males). The participants were assigned to consume products (bread, pasta and crackers) made either from Kamut or control semi-whole-grain wheat for 8 weeks in a random order. An 8-week washout period was implemented between the interventions. Laboratory analyses were performed both at the beginning and at the end of each intervention phase. RESULTS: At a general linear model for repeated measurements adjusted for several confounders, consumption of Kamut products showed a significant reduction of metabolic risk factors such as total cholesterol (mean reduction: -8.46 mg/dl; -4%), low-density lipoprotein cholesterol (-9.82 mg/dl; -7.8%) and blood glucose. Similarly, redox status was significantly improved only after the Kamut intervention phase, as measured by a reduction in both thiobarbituric acid reactive substances (-0.17 nmol/ml; -21.5%;) and carbonyl levels (-0.16 nmol/ml; -17.6%). The replacement diet with Kamut products also resulted in a significant increase of serum potassium and magnesium. Circulating levels of key pro-inflammatory cytokines (interleukin (IL)-6, IL-12, tumour necrosis factor-α and vascular endothelial growth factor) were significantly reduced after the consumption of Kamut products. CONCLUSIONS: The present results suggest that a replacement diet with Kamut products could be effective in reducing metabolic risk factors, markers of both oxidative stress and inflammatory status.

Effects of space allocation and housing density on measures of wellbeing in laboratory mice: a review.

In the majority of countries where there are legislative requirements pertaining to the use of animals in research, figures are quoted for minimum cage sizes or space allocation to be provided per animal. These figures are generally based on professional judgement and are in common usage. However, there is a growing trend and expectation that welfare science should inform regulatory decision-making. Given the importance of the potential welfare influences of cage size on the animals themselves, this paper presents the latest scientific knowledge on this topic in one of the most commonly used animals in research, the mouse. A comprehensive review of studies in laboratory mice was undertaken, examining the effects of space allocation per animal and animal density on established welfare indicators. To date, animal density studies have predominated, and the effects of space allocation per se are still relatively unclear. This information will guide those involved in facility management or legislative review, and provide a more solid foundation for further studies into the effects of routine husbandry practices on animal welfare.

Rayleigh theory of ultrasound scattering applied to liquid-filled contrast nanoparticles.

We present a novel modified theory based upon Rayleigh scattering of ultrasound from composite nanoparticles with a liquid core and solid shell. We derive closed form solutions to the scattering cross-section and have applied this model to an ultrasound contrast agent consisting of a liquid-filled core (perfluorooctyl bromide, PFOB) encapsulated by a polymer shell (poly-caprolactone, PCL). Sensitivity analysis was performed to predict the dependence of the scattering cross-section upon material and dimensional parameters. A rapid increase in the scattering cross-section was achieved by increasing the compressibility of the core, validating the incorporation of high compressibility PFOB; the compressibility of the shell had little impact on the overall scattering cross-section although a more compressible shell is desirable. Changes in the density of the shell and the core result in predicted local minima in the scattering cross-section, approximately corresponding to the PFOB-PCL contrast agent considered; hence, incorporation of a lower shell density could potentially significantly improve the scattering cross-section. A 50% reduction in shell thickness relative to external radius increased the predicted scattering cross-section by 50%. Although it has often been considered that the shell has a negative effect on the echogeneity due to its low compressibility, we have shown that it can potentially play an important role in the echogeneity of the contrast agent. The challenge for the future is to identify suitable shell and core materials that meet the predicted characteristics in order to achieve optimal echogenity.

Validation of a digital audio recording method for the objective assessment of cough in the horse.

AIM: To validate the use of digital audio recording and analysis for quantification of coughing in horses. MATERIALS AND METHODS: Part A: Nine simultaneous digital audio and video recordings were collected individually from seven stabled horses over a 1 h period using a digital audio recorder attached to the halter. Audio files were analysed using audio analysis software. Video and audio recordings were analysed for cough count and timing by two blinded operators on two occasions using a randomised study design for determination of intra-operator and inter-operator agreement. Part B: Seventy-eight hours of audio recordings obtained from nine horses were analysed once by two blinded operators to assess inter-operator repeatability on a larger sample. RESULTS AND CONCLUSIONS: Part A: There was complete agreement between audio and video analyses and inter- and intra-operator analyses. Part B: There was >97% agreement between operators on number and timing of 727 coughs recorded over 78 h. The results of this study suggest that the cough monitor methodology used has excellent sensitivity and specificity for the objective assessment of cough in horses and intra- and inter-operator variability of recorded coughs is minimal.

Investigation of the microstructure of milk protein concentrate powders during rehydration: alterations during storage.

The aim of this work was to use scanning electron microscopy to investigate the microstructure of rehydrated milk protein concentrate powder (MPC) particles. A sample preparation method for scanning electron microscopy analysis of rehydrated MPC particles is described and used to characterize the time course of dissolution and the effects of prior storage on the dissolution process. The results show that a combination of different types of interactions (e.g., bridges, direct contact) between casein micelles results in a porous, gel-like structure that restrains the dispersion of individual micelles into the surrounding liquid phase without preventing water penetration and solubilization of nonmicellar components. During storage of the powder, increased interactions occur between and within micelles, leading to compaction of micelles and the formation of a monolayer skin of casein micelles packed close together, the combination of which are proposed to be responsible for the slow dissolution of stored MPC powders.