Partner gaze shapes the relationship between symptoms of psychopathology and interpersonal coordination.

Interpersonal coordination is a key determinant of successful social interaction but can be disrupted when people experience symptoms related to social anxiety or autism. Effective coordination rests on individuals directing their attention towards interaction partners. Yet little is known about the impact of the attentional behaviours of the partner themselves. As the gaze of others has heightened salience for those experiencing social anxiety or autism, addressing this gap can provide insight into how symptoms of these disorders impact coordination. Using a novel virtual reality task, we investigated whether partner gaze (i.e., direct vs. averted) influenced the emergence of interpersonal coordination. Results revealed: (i) spontaneous coordination was diminished in the averted (cf. direct) gaze condition; (ii) spontaneous coordination was positively related to symptoms of social anxiety, but only when partner gaze was averted. This latter finding contrasts the extant literature and points to the importance of social context in shaping the relationship between symptoms of psychopathology and interpersonal coordination.

A Multicenter Collaborative to Improve Postoperative Pain Management in the NICU.

OBJECTIVES: This quality improvement initiative aimed to decrease unrelieved postoperative pain and improve family satisfaction with pain management. METHODS: NICUs within the Children's Hospitals Neonatal Consortium that care for infants with complex surgical problems participated in this collaborative. Each of these centers formed multidisciplinary teams to develop aims, interventions, and measurement strategies to test in multiple Plan-Do-Study-Act cycles. Centers were encouraged to adopt evidence-based interventions from the Clinical Practice Recommendations, which included pain assessment tools, pain score documentation, nonpharmacologic treatment measures, pain management guidelines, communication of a pain treatment plan, routine discussion of pain scores during team rounds, and parental involvement in pain management. Teams submitted data on a minimum of 10 surgeries per month, spanning from January to July 2019 (baseline), August 2019 to June 2021 (improvement work period), and July 2021 to December 2021 (sustain period). RESULTS: The percentage of patients with unrelieved pain in the 24-hour postoperative period decreased by 35% from 19.5% to 12.6%. Family satisfaction with pain management measured on a 3-point Likert scale with positive responses ≥2 increased from 93% to 96%. Compliance with appropriate pain assessment and numeric documentation of postoperative pain scores according to local NICU policy increased from 53% to 66%. The balancing measure of the percentage of patients with any consecutive sedation scores showed a decrease from 20.8% at baseline to 13.3%. All improvements were maintained during the sustain period. CONCLUSIONS: Standardization of pain management and workflow in the postoperative period across disciplines can improve pain control in infants.

A Pre-implementation Study of Volumetric Modulated Arc Therapy for Same-day Planning and Treatment of Vertebral Bone Metastases Within a Rapid-access Palliative Radiotherapy Programme.

AIMS: We aimed to develop a process for same-day contouring, planning, quality assurance and delivery of volumetric modulated arc therapy (VMAT) for vertebral bone metastases within our institution's rapid-access palliative radiotherapy programme. MATERIALS AND METHODS: Two thoracic (T6-7, T3-7) and two lumbar (L2-3, L1-5) targets were contoured on computed tomography images acquired from an anthropomorphic phantom and five patient scans. Inverse planning aimed to provide coverage of a prescribed dose of 8 Gy with a combined lung V2Gy < 25% and a combined kidney mean dose <2 Gy. Serial plans were created to identify an efficient combination of six main planning variables specific to our treatment planning system: (i) voxel size (3 mm versus 5 mm), (ii) Monte Carlo statistical uncertainty (1% per calculation versus 3% per control point), (iii) fluence smoothing (medium versus high), (iv) number of iterations of segment shape changes during optimisation (1 versus 5), (v) dose calculation algorithm (Monte Carlo versus pencil beam) and (vi) number of arcs (single versus multiple). Contouring, planning, quality assurance and treatment delivery were timed. RESULTS: The combination of planning variables deemed efficient and appropriate was: a 3 mm voxel size, statistical uncertainty of 1% per calculation, medium fluence smoothing, five iterations of segment shape changes, Monte Carlo dose calculation and single full arc delivery. Patient scan contouring times ranged from 7 to 9 min (T6-7), 11-13 min (T3-7), 5-7 min (L2-3) and 8-10 min (L1-5) and planning times ranged from 9 to 15 min (T6-7), 13-25 min (T3-7), 18-25 min (L2-3) and 21-31 min (L1-5). Physics quality assurance times ranged from 15 to 21 min and beam-on times ranged from 3 to 6 min. CONCLUSIONS: The combined elements of VMAT for thoracic and lumbar vertebral bone metastases were completed in under 2 h. This new process makes same-day contouring, planning, quality assurance and treatment delivery of VMAT feasible within our rapid-access palliative radiotherapy programme.

Examining the relationship between subclinical levels of social anxiety and the rubber hand illusion.

An embodied sense of self allows individuals to acquire moment-to-moment insight regarding the relationship between themselves and their environment. Fundamental to this experience is information regarding body ownership and self-location, which can inform both intrapersonal and interpersonal functioning. Although it is well documented that variation in mental health symptoms can impact the accuracy of bodily self-perception, little research has, to date, explored the influence of social anxiety on the embodied self. To address this issue, here we propose to examine the impact of social anxiety on the rubber hand illusion (RHI), a procedure which can distort perceptions of body location and ownership. Related literature points to competing predictions relative to how symptoms of social anxiety potentially impact susceptibility to the RHI. In the current manuscript we present the results of a pilot study indicating a positive relationship between the strength of the RHI and social anxiety, and detail a proposed registered report that seeks to replicate and extend this experiment.

Seeing synchrony: A replication of the effects of task-irrelevant social information on perceptions of interpersonal coordination.

The display of synchronous behaviour can be both an engaging spectacle and a source of important social information. When understood as a dynamical system, interpersonal synchrony has specific kinematic qualities that have been shown to shape social perceptions. Little research, however, has examined the converse relationship - are perceptions of the kinematics of interpersonal synchrony influenced by socially relevant, but task-irrelevant, information? To provide further insight to this question we conducted a pre-registered replication of Lumsden, Miles, and Macrae (2012). Participants (n = 191) rated the level of coordination present in dyads made up of individuals with either similar or dissimilar skin tones. Faithful to the original study, the results indicated that perceivers were sensitive to differing levels of interpersonal coordination, and judged dissimilar dyads to be less coordinated than dyads with a similar skin tone despite actual coordination levels being objectively equivalent. Extending Lumsden et al., the results also revealed a negative relationship between subclinical variation in social anxiety and the degree of perceived coordination. This work is discussed with respect to the perceptual and social factors that underlie judgements of interpersonal coordination.

Cardiorespiratory fitness and accelerometer-determined physical activity following one year of free-living high-intensity interval training and moderate-intensity continuous training: a randomized trial.

BACKGROUND: Free-living adherence to high-intensity interval training (HIIT) has not been adequately tested. This randomized trial examined changes in cardiorespiratory fitness (CRF) and accelerometer-measured purposeful physical activity over 12 months of free-living HIIT versus moderate-intensity continuous training (MICT). METHODS: Ninety-nine previously low-active participants with overweight/obesity were randomly assigned to HIIT (n = 47) or MICT (n = 52). Both interventions were combined with evidence-based behaviour change counselling consisting of 7 sessions over 2 weeks. Individuals in HIIT were prescribed 10 X 1-min interval-based exercise 3 times per week (totalling 75 min) whereas individuals in MICT were prescribed 150 min of steady-state exercise per week (50 mins 3 times per week). Using a maximal cycling test to exhaustion with expired gas analyses, CRF was assessed at baseline and after 6 and 12 months of free-living exercise. Moderate-to-vigorous physical activity of 10+ minutes (MVPA10+) was assessed by 7-day accelerometry at baseline, 3, 6, 9, and 12 months. Intention to treat analyses were conducted using linear mixed models. RESULTS: CRF was improved over the 12 months relative to baseline in both HIIT (+ 0.15 l/min, 95% CI 0.08 to 0.23) and MICT (+ 0.11 l/min, 95% CI 0.05 to 0.18). Both groups improved 12-month MVPA10+ above baseline (HIIT: + 36 min/week, 95% CI 17 to 54; MICT: + 69 min/week, 95% CI 49 to 89) with the increase being greater (by 33 min, 95% CI 6 to 60) in MICT (between group difference, P = 0.018). CONCLUSION: Despite being prescribed twice as many minutes of exercise and accumulating significantly more purposeful exercise, CRF improvements were similar across 12 months of free-living HIIT and MICT in previously low-active individuals with overweight/obesity.

Rifaximin alters gut microbiota profile, but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency.

Common variable immunodeficiency (CVID) patients have reduced gut microbial diversity compared to healthy controls. The reduced diversity is associated with gut leakage, increased systemic inflammation and ten "key" bacteria that capture the gut dysbiosis (dysbiosis index) in CVID. Rifaximin is a broad-spectrum non-absorbable antibiotic known to reduce gut leakage (lipopolysaccharides, LPS) in liver disease. In this study, we explored as a 'proof of concept' that altering gut microbial composition could reduce systemic inflammation, using CVID as a disease model. Forty adult CVID patients were randomized, (1:1) to twice-daily oral rifaximin 550 mg versus no treatment for 2 weeks in an open-label, single-centre study. Primary endpoints were reduction in plasma/serum levels of soluble (s) CD14, sCD25, sCD163, neopterin, CRP, TNF, LPS and selected cytokines measured at 0, 2 and 8 weeks. Secondary endpoint was changes in intra-individual bacterial diversity in stool samples. Rifaximin-use did not significantly change any of the inflammation or gut leakage markers, but decreased gut microbial diversity compared with no treatment (p = 0.002). Importantly, the gut bacteria in the CVID dysbiosis index were not changed by rifaximin. The results suggest that modulating gut microbiota by rifaximin is not the chosen intervention to affect systemic inflammation, at least not in CVID.

Current practice in total-body irradiation: results of a Canada-wide survey.

BACKGROUND: Total-body irradiation (tbi) is used to condition patients before bone marrow transplant. A variety of tbi treatment strategies have been described and implemented, but no consensus on best practice has been reached. We report on the results of a survey created to assess the current state of tbi delivery in Canada. RESULTS: A 19-question survey was distributed to 49 radiation oncology programs in Canada. Responses were received from 20 centres, including 12 centres that perform tbi. A variety of tbi dose prescriptions was reported, although 12 Gy in 6 fractions was used in 11 of the 12 centres performing tbi. Half of the centres also reported using a dose prescription unique to their facility. Most centres use an extended-distance parallel-opposed-pair technique, with the patient standing or lying on a stretcher against a wall. Others translate the patient under the beam, sweep the beam over the patient, or use a more complicated multi-field technique. All but 1 centre indicated that they attenuate the lung dose; only 3 centres indicated attenuating the dose for other organs at risk. The survey also highlighted the considerable resources used for tbi, including extra staff, prolonged planning and treatment times, and use of locally developed hardware or software. CONCLUSIONS: At transplant centres, tbi is commonly used, but there is no commonly accepted approach to planning and treatment delivery. The important discrepancies in practice between centres in Canada creates an opportunity to prompt more discussion and collaboration between centres, improving consistency and uniformity of practice.

Pharmacokinetics of ceftiofur sodium in equine pregnancy.

Eleven pregnant pony mares (D270-326) were administered ceftiofur sodium intramuscularly at 2.2 mg/kg (n = 6) or 4.4 mg/kg (n = 5), once daily. Plasma was obtained prior to ceftiofur administration and at 0.5, 1, 2, 4, 8, 12, and 24 hr after administration. Eight pony mares were re-enrolled in the study at least 3 days from expected foaling to ensure steady-state concentrations of drug at the time of foaling. Mares were administered ceftiofur sodium (4.4 mg/kg, IM) daily until foaling. Parturition was induced using oxytocin 1 hr after ceftiofur sodium administration. Allantoic and amniotic fluid, plasma, and colostrum samples were collected at time of foaling. Serial foal plasma samples were obtained. Placental tissues were collected. Desfuroylceftiofur acetamide (DCA) concentrations were measured in samples by high-performance liquid chromatography (HPLC). Mean (±SD) peak serum concentrations of DCA were 3.97 ± 0.50 µg/ml (low dose) and 7.45 ± 1.05 µg/ml (high dose). Terminal half-life was significantly (p = .014) shorter after administration of the low dose (2.91 ± 0.59 hr) than after administration of the high dose (4.10 ± 0.72 hr). The mean serum concentration of DCA from mares at time of foaling was 7.96 ± 1.39 µg/ml. The mean DCA concentration in colostrum was 1.39 ± 0.70 µg/ml. DCA concentrations in allantoic fluid, amniotic fluid, placental tissues, and foal plasma were below the limit of quantification (<0.1 µg/ml) and below the minimum inhibitory concentration of ceftiofur against relevant pathogens. These results infer incomplete passage of DCA across fetal membranes after administration of ceftiofur sodium to normal pony mares.

Labour induction near term for women aged 35 or over: an economic evaluation.

OBJECTIVE: Induction of labour at 39 weeks for nulliparous women aged 35 years and over may prevent stillbirths and does not increase caesarean births, so it may be popular. But the overall costs and benefits of such a policy have not been compared. DESIGN: A cost-utility analysis alongside a randomised controlled trial (the 35/39 trial). SETTING: Obstetric departments of 38 UK National Health Service hospitals and one UK primary-care trust. POPULATION: Nulliparous women aged 35 years or over on their expected due date, with a singleton live fetus in a cephalic presentation. METHODS: Costs were estimated from the National Health Service and Personal Social Services perspective and quality-adjusted life-years (QALYs) were calculated based on patient responses to the EQ-5D at baseline and 4 weeks. MAIN OUTCOME MEASURES: Data on antenatal care, mode of delivery, analgesia in labour, method of induction, EQ-5D (baseline and 4 weeks postnatal) and participant-administered postnatal health resource use data were collected. RESULTS: The intervention was associated with a mean cost saving of £263 and a small additional gain in QALYs (though this was not statistically significant), even without considering any possible QALY gains from stillbirth prevention. CONCLUSION: A policy of induction of labour at 39 weeks for women of advanced maternal age would save money. TWEETABLE ABSTRACT: A policy of induction of labour at 39 weeks of gestation for women of advanced maternal age would save money.

Explaining trends in alcohol-related harms in Scotland, 1991-2011 (I): the role of incomes, effects of socio-economic and political adversity and demographic change.

OBJECTIVE: This paper tests the extent to which differing trends in income, demographic change and the consequences of an earlier period of social, economic and political change might explain differences in the magnitude and trends in alcohol-related mortality between 1991 and 2011 in Scotland compared to England & Wales (E&W). STUDY DESIGN: Comparative time trend analyses and arithmetic modelling. METHODS: Three approaches were utilised to compare Scotland with E&W: 1. We modelled the impact of changes in income on alcohol-related deaths between 1991-2001 and 2001-2011 by applying plausible assumptions of the effect size through an arithmetic model. 2. We used contour plots, graphical exploration of age-period-cohort interactions and calculation of Intrinsic Estimator coefficients to investigate the effect of earlier exposure to social, economic and political adversity on alcohol-related mortality. 3. We recalculated the trends in alcohol-related deaths using the white population only to make a crude approximation of the maximal impact of changes in ethnic diversity. RESULTS: Real incomes increased during the 1990s but declined from around 2004 in the poorest 30% of the population of Great Britain. The decline in incomes for the poorest decile, the proportion of the population in the most deprived decile, and the inequality in alcohol-related deaths, were all greater in Scotland than in E&W. The model predicted less of the observed rise in Scotland (18% of the rise in men and 29% of the rise in women) than that in E&W (where 60% and 68% of the rise in men and women respectively was explained). One-third of the decline observed in alcohol-related mortality in Scottish men between 2001 and 2011 was predicted by the model, and the model was broadly consistent with the observed trends in E&W and amongst women in Scotland. An age-period interaction in alcohol-related mortality was evident for men and women during the 1990s and 2000s who were aged 40-70 years and who experienced rapidly increasing alcohol-related mortality rates. Ethnicity is unlikely to be important in explaining the trends or differences between Scotland and E&W. CONCLUSIONS: The decline in alcohol-related mortality in Scotland since the early 2000s and the differing trend to E&W were partly described by a model predicting the impact of declining incomes. Lagged effects from historical social, economic and political change remain plausible from the available data.

Explaining trends in alcohol-related harms in Scotland 1991-2011 (II): policy, social norms, the alcohol market, clinical changes and a synthesis.

OBJECTIVE: To provide a basis for evaluating post-2007 alcohol policy in Scotland, this paper tests the extent to which pre-2007 policy, the alcohol market, culture or clinical changes might explain differences in the magnitude and trends in alcohol-related mortality outcomes in Scotland compared to England & Wales (E&W). STUDY DESIGN: Rapid literature reviews, descriptive analysis of routine data and narrative synthesis. METHODS: We assessed the impact of pre-2007 Scottish policy and policy in the comparison areas in relation to the literature on effective alcohol policy. Rapid literature reviews were conducted to assess cultural changes and the potential role of substitution effects between alcohol and illicit drugs. The availability of alcohol was assessed by examining the trends in the number of alcohol outlets over time. The impact of clinical changes was assessed in consultation with key informants. The impact of all the identified factors were then summarised and synthesised narratively. RESULTS: The companion paper showed that part of the rise and fall in alcohol-related mortality in Scotland, and part of the differing trend to E&W, were predicted by a model linking income trends and alcohol-related mortality. Lagged effects from historical deindustrialisation and socio-economic changes exposures also remain plausible from the available data. This paper shows that policy differences or changes prior to 2007 are unlikely to have been important in explaining the trends. There is some evidence that aspects of alcohol culture in Scotland may be different (more concentrated and home drinking) but it seems unlikely that this has been an important driver of the trends or the differences with E&W other than through interaction with changing incomes and lagged socio-economic effects. Substitution effects with illicit drugs and clinical changes are unlikely to have substantially changed alcohol-related harms: however, the increase in alcohol availability across the UK is likely to partly explain the rise in alcohol-related mortality during the 1990s. CONCLUSIONS: Future policy should ensure that alcohol affordability and availability, as well as socio-economic inequality, are reduced, in order to maintain downward trends in alcohol-related mortality in Scotland.

Prevalence of metabolic syndrome and its risk factors in Canadian children and adolescents: Canadian Health Measures Survey Cycle 1 (2007-2009) and Cycle 2 (2009-2011).

INTRODUCTION: We investigated the prevalence of metabolic syndrome (MetS) and its risk factors, and the influence of socioeconomic status, in Canadian children and adolescents. METHODS: Canadian Health Measures Survey cycle 1 (2007-2009) and cycle 2 (2009-2011) respondents aged 10 to 18 years who provided fasting blood samples were included (n = 1228). The International Diabetes Federation (IDF) consensus definition for children and adolescents (10-15 years) and worldwide adult definition (≥ 16 years) were used to diagnose MetS. Prevalence of MetS and its risk factors were calculated and differences by socioeconomic status were examined using χ2 tests. RESULTS: The prevalence of MetS was 2.1%. One-third (37.7%) of participants had at least one risk factor, with the most prevalent being abdominal obesity (21.6%), low HDL-C (19.1%) and elevated triglyceride levels (7.9%). This combination of abdominal obesity, low HDL-C and elevated triglyceride levels accounted for 61.5% of MetS cases. Participants from households with the highest income adequacy and educational attainment levels had the lowest prevalence of one or more MetS risk factors, abdominal obesity and low HDL-C. CONCLUSION: The prevalence of MetS (2.1%) was lower than previously reported in Canada (3.5%) and the USA (4.2%¬-9.2%), potentially due to the strict application of the IDF criteria for studying MetS. One-third of Canadian children and adolescents have at least one risk factor for MetS. Given that the risk for MetS increases with age, these prevalence estimates, coupled with a national obesity prevalence of almost 10% among youth, point to a growing risk of MetS and other chronic diseases for Canadian youth.

TITRE: Prévalence du syndrome métabolique et de ses facteurs de risque chez les enfants et les adolescents canadiens : Enquête canadienne sur les mesures de la santé, cycle 1 (2007-2009) et cycle 2 (2009-2011). INTRODUCTION: Nous avons étudié la prévalence du syndrome métabolique (SMet) et de ses facteurs de risque ainsi que l'influence du statut socioéconomique chez les enfants et les adolescents canadiens. MÉTHODOLOGIE: Nous avons inclus dans notre étude les 1228 répondants de l'Enquête canadienne sur les mesures de la santé, cycle 1 (2007-2009) et cycle 2 (2009-2011), âgés de 10 à 18 ans et ayant fourni un échantillon de sang à jeun. Nous avons utilisé les définitions consensuelles du SMet proposées par la Fédération internationale du diabète (FID) pour les enfants et adolescents (10 à 15 ans) et pour les adultes (16 ans et plus). Nous avons mesuré la prévalence du SMet et de ses facteurs de risque ainsi que les différences en fonction du statut socioéconomique au moyen de tests du χ2. RÉSULTATS: La prévalence du SMet était de 2,1 %. Le tiers (37,7 %) des répondants présentaient au moins un facteur de risque, les plus répandus étant l'obésité abdominale (21,6 %), un faible taux de C-HDL (19,1 %) et un taux de triglycérides élevé (7,9 %). Cette combinaison d'obésité abdominale, de faible taux de C-HDL et de taux élevé de triglycérides correspondait à 61,5 % des cas de SMet. Les participants des ménages de la tranche supérieure de revenu et bénéficiant d'un niveau de scolarité élevé présentaient la plus faible prévalence d'un ou de plusieurs facteurs de risque du SMet, d'obésité abdominale et de faible taux de C-HDL. CONCLUSION : La prévalence du SMet (2,1 %) s'est révélée inférieure à celle mesurée auparavant pour le Canada (3,5 %) et les États-Unis (4,2 % à 9,2 %), sans doute en raison de l'application stricte des critères de la FID pour l'étude du SMet. Le tiers des enfants et des adolescents canadiens présentaient au moins un facteur de risque de SMet. Comme le risque de SMet augmente avec l'âge, ces estimations de la prévalence, couplées à une prévalence nationale de l'obésité d'environ 10 % chez les jeunes, laissent entrevoir un accroissement du risque de SMet et d'autres maladies chroniques chez les jeunes Canadiens.

Disposition of firocoxib in late pregnant and early postpartum mares.

Pregnancy induces several physiologic changes that might impact the bioavailability, distribution, metabolism, and excretion of drugs. The objective of this study was to determine the effects of pregnancy on the disposition of oral firocoxib in mares. Seven pony mares received oral firocoxib paste at a dose of 0.1 mg/kg during late pregnancy and again 12 to 33 days postpartum. Firocoxib concentrations were measured in plasma by HPLC with ultraviolet detection. Maximum plasma concentrations were significantly lower in pregnant (50.0 ± 21.8 ng/mL) than in postpartum (73.7 ± 25.6 ng/mL) mares. Plasma concentrations 24 h after administration, time to maximum plasma concentrations, and area under the plasma concentration versus time curve were not significantly different between late pregnancy and the postpartum period in mares.

Antitumor effects of TRAIL-expressing mesenchymal stromal cells in a mouse xenograft model of human mesothelioma.

Malignant mesothelioma (MM) remains a highly deadly malignancy with poor treatment option. The MM cells further promote a highly inflammatory microenvironment, which contributes to tumor initiation, development, severity and propagation. We reasoned that the anti-inflammatory actions of mesenchymal stromal cells (MSCs) and further antitumor effects of MSCs engineered to overexpress tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein (MSC-TRAIL) would effectively inhibit mesothelioma growth. Using a mouse xenograft model of intraperitoneal human mesothelioma, native mouse (mMSCs) or human (hMSC) MSCs were administered either systemically (intravenously or intraperitoneally) at various times following tumor inoculation. Both mMSCs and hMSCs localized at the sites of MM tumor growth in vivo and decreased local inflammation. Further, a trend towards decrease in tumor burden was observed. Parallel studies of in vitro exposure of nine primary human mesothelioma cell lines to mMSCs or hMSCs demonstrated reduced tumor cell migration. MSC-TRAIL exposure induced apoptosis of TRAIL-sensitive MM cells in vitro, and both mouse and human MSC-TRAIL significantly reduced the inflammatory tumor environment in vivo. Moreover, human MSC-TRAIL administration significantly reduced peritoneal tumor burden in vivo and increased tumor cell apoptosis. These proof-of-concept studies suggest that TRAIL-expressing MSCs may be useful against malignant mesothelioma.

Effects of topical application of misoprostol on cervical relaxation in mares.

Mares who have not delivered a foal early in life may experience limitations in cervical relaxation, primarily during oestrus. A closed cervix prevents intrauterine deposition of semen during natural breeding, may delay uterine clearance after insemination leading to intrauterine fluid accumulation in, and subsequent infertility. Therefore, a reliable pharmacological method of dilating the equine cervix would have practical application in veterinary medicine. The goal of this study was to investigate the effectiveness of topically applied, synthetic prostaglandin E1 analogue (PGE1 ) for stimulating dilation of the equine cervix. Ten mares in dioestrus were randomly assigned to one of two treatments in a single-blind crossover study: (treatment) PGE1 gel (1000 mcg compounded misoprostol cream) applied topically to the external cervical os (n = 5), and (control) a vehicle cream applied topically to the external cervical os (n = 5). Transrectal palpation and ultrasonographic measurements of the cervix were performed prior to, six and 24 h post-treatment. Digital measurements were taken, per vagina, at six and 24 h post-treatment. Mares were monitored through the subsequent oestrous cycle for ovulation. Mares were assigned to the opposite treatment group such that each mare served as her own control (crossover). Data were analysed using parametric (split-plot anova), as well as nonparametric (Kruskal-Wallis anova, Wilcoxon's rank-sum test) methods. At six and 24 h there were no significant differences for tone, length, height, degree of relaxation or echotexture between control and PGE1 treated groups at the measured time points (p > 0.05). Topical cervical application of PGE1 did not induce a measurable degree of cervical relaxation under the conditions of this experiment.

Acute and chronic effects of a contraceptive compound RTI-4587-073(l) on testicular histology and endocrine function in miniature horse stallions.

The objective of this study was to evaluate acute endocrine effects as well as histological changes in testicular parenchyma induced by the contraceptive compound RTI-4587-073(l). Six miniature stallions were used in this experiment. The treatment group (n = 3) received one oral dose of 12.5 mg/kg of RTI-4587-073(l), and the control group (n = 3) received placebo only. The stallions' baseline parameters (semen, testicular dimensions, endocrine values) were collected and recorded for 5 weeks before treatment and for 6 weeks after treatment. Multiple blood samples were collected for endocrine analysis. Testicular biopsies were obtained before treatment, 1 day after treatment and every other week after treatment. Ultrasound exams were performed to monitor the dimensions of the stallions' testes. All stallions were castrated 6 weeks after treatment. Sperm numbers, motility and percentage of morphologically normal sperm decreased (p < 0.05), while the number of immature germ cells increased in ejaculates from treated animals (p < 0.05). Serum concentrations of inhibin and follicle-stimulating hormone did not change. Testosterone concentrations initially transiently decreased (p < 0.05) after administration of RTI-4587-073(l), and increased several days later (p < 0.05). Testicular content of testosterone and estradiol 17-ß was lower in treated stallions than in control stallions on Day 1 after treatment (p < 0.05). Severe disorganization of the seminiferous tubules, significant loss of immature germ cells and complete depletion of elongated spermatids were observed in testicular biopsies obtained from treated stallions 1 day, 2 and 4 weeks after treatment. These changes were still present in the testicular samples taken from treated stallions after castration. The results of this study confirmed that RTI-4587-073(l) has antispermatogenic effects in stallions. Furthermore, we concluded that this compound causes acute sloughing of immature germ cells from the seminiferous tubules. RTI-4587-073(l) has significant but transient effects on Leydig cell function in stallions.

Use of two conventional staining methods to assess the acrosomal status of stallion spermatozoa.

REASONS FOR PERFORMING STUDY: The acrosome is a highly specialised region of the spermatozoon that is essential for fertilisation. Defects or dysfunction of this structure have been associated with fertility problems in man and various domestic species including stallions. Current methods of evaluating the acrosome of stallion spermatozoa are time consuming and require specialised equipment, which is cost prohibitive to the average practitioner. OBJECTIVES: To evaluate 2 conventional stains (Dip Quick and Spermac) and determine their usefulness in assessing acrosome integrity in stallions as compared with specific acrosomal labelling with a fluorescein-conjugated lectin - a method that has been validated for acrosome status evaluation in stallions. STUDY DESIGN: In vivo experimental design. METHODS: Semen from 6 mature Miniature horse stallions of known fertility was collected on 5 separate occasions. To increase the number of reacted acrosomes, portions of each ejaculate were incubated with the calcium ionophore, A23187. Ejaculates were divided and semen samples were processed according to recommendations for fluorescein-conjugated peanut lectin, Pisum sativum agglutin, Dip Quick, and Spermac staining methods. Slides were evaluated independently by 2 separate investigators. Spermatozoa were classified as having intact, reacting, reacted or defective acrosomes. RESULTS: All parameters obtained by both investigators, using all 3 staining methods were highly correlated (P<0.001). There was no statistical difference (P>0.05) between investigators or staining method for the percentages of intact or reacted acrosomes. However, there was a significant difference between investigators and staining methods for determining reacting acrosome percentages (P<0.05). CONCLUSIONS: Dip Quick and Spermac stains are useful for determining intact vs. reacted acrosomes for stallion spermatozoa.

The CD11b-integrin (ITGAM) and systemic lupus erythematosus.

Variations at the ITGAM gene, which encodes for the CD11b chain of the Mac-1 (alphaMbeta2; CD11b/CD18; complement receptor-3) integrin, is one of the strongest genetic risk factors for systemic lupus erythematosus (SLE). More specifically, a genetic variant (rs1143679) which results in an arginine to histidine substitution at position 77 in the extracellular portion of the integrin is associated with disease. It has recently been shown that this amino acid substitution results in a dysfunctional integrin, which is deficient in mediating cell adhesion to integrin ligands, phagocytosis and in addition cannot restrict inflammatory cytokine production in macrophages. In this review, we discuss immunological functions of the Mac-1 integrin and how defects in the genetic variant of Mac-1 may relate to SLE development.