Epidemiology of Chlamydia psittaci infections in pregnant Thoroughbred mares and foals.

Late-term foal loss due to the traditional avian pathogen Chlamydia psittaci recently emerged as a threat to the Australian Thoroughbred industry. A longitudinal study of 14 stud farms was undertaken to better understand C. psittaci infection in pregnant mares and their foals by evaluating C. psittaci prevalence, equine herpesvirus-1 (EHV-1) co-infection, avian reservoirs, and potential risk factors. Mucosal swabs taken from 228 healthy pregnant mares and their foals were tested for C. psittaci and EHV-1 using species-specific qPCR assays. No foal loss was recorded due to either pathogen, and no mare tested positive to either C. psittaci or EHV-1. However, healthy newborn foals tested positive to both pathogens, at low levels, with 13.2% (n = 30/228) and 14.5% (n = 33/228) prevalence for C. psittaci and EHV-1, respectively. Co-infection occurred in 1.3% (n = 3/228) of foals. In avian environmental faecal samples collected from the same studs, C. psittaci was detected at 5.3% (n = 5/94). Multiple logistic regression modelling found that foals born in winter were more likely to be infected with C. psittaci (adjusted odds ratio = 15.83; P < 0.001; Confidence Interval 5.12-48.49). Being a maiden mare, absence of prophylactic vaginal suture, interventions in the last trimester and residing on a farm with prior history of C. psittaci abortion posed no higher risk to infection in the newborn. Analysis of all reported C. psittaci abortion cases (Hunter Valley, 2016-2019) revealed a dominant C. psittaci sequence type (denoted ST24) and a significant correlation with frost events (Spearmans' rho = 0.44; P = 0.002).

Markers of vitamin D metabolism and premenstrual symptoms in healthy women with regular cycles.

STUDY QUESTION: Are insufficient 25-hydroxyvitamin D (25(OH)D) concentrations, and other markers of vitamin D metabolism, associated with premenstrual symptoms in healthy women with regular menstrual cycles? SUMMARY ANSWER: 25(OH)D insufficiency was associated with specific physical premenstrual symptoms, while no associations were observed with psychological symptoms or with other markers of vitamin D metabolism. WHAT IS KNOWN ALREADY: Prior studies evaluating vitamin D and premenstrual symptoms have yielded mixed results, and it is unknown whether 25(OH)D insufficiency and other markers of vitamin D metabolism are associated with premenstrual symptoms. STUDY DESIGN, SIZE, DURATION: We used two cohorts of women with regular menstrual cycles; 1191 women aged 18-40 years in EAGeR (cross-sectional analysis of a prospective cohort within a randomized trial) and 76 women aged 18-44 years in BioCycle (prospective cohort). In EAGeR, premenstrual symptoms over the previous year were assessed at baseline, whereas in BioCycle, symptoms were assessed prospectively at multiple points over two menstrual cycles with symptoms queried over the previous week. In both cohorts, symptomatology was assessed via questionnaire regarding presence and severity of 14 physical and psychological symptoms the week before and after menses. Both studies measured 25(OH)D in serum. We also evaluated the association of additional markers of vitamin D metabolism and calcium homeostasis, including intact parathyroid hormone (iPTH), calcium (Ca), fibroblast growth factor 23 (FGF23), and 1,25 dihydroxyvitamin D (1,25(OH)2D) with premenstrual symptoms in the BioCycle cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: One cohort of women actively seeking pregnancy (Effects of Aspirin in Gestation and Reproduction (EAGeR)) and one cohort not seeking pregnancy (BioCycle) were evaluated. Log-binomial regression was used to estimate risk ratios (RR) and 95% CIs for associations between insufficient 25(OH)D (<30 ng/ml) and individual premenstrual symptoms, adjusting for age, BMI, race, smoking, income, physical activity, and season of blood draw. MAIN RESULTS AND THE ROLE OF CHANCE: 25(OH)D insufficiency was associated with increased risk of breast fullness/tenderness (EAGeR RR 1.27, 95% CI 1.03, 1.55; BioCycle RR 1.37, 95% CI 0.56, 3.32) and generalized aches and pains (EAGeR RR 1.33, 95% CI 1.01, 1.78; BioCycle 1.36, 95% CI 0.41, 4.45), though results were imprecise in the BioCycle study. No associations were observed between insufficient 25(OH)D and psychological symptoms in either cohort. In BioCycle, iPTH, Ca, FGF23, and 1,25(OH) 2D were not associated with any premenstrual symptoms. LIMITATIONS, REASONS FOR CAUTION: Results from the EAGeR study were limited by the study design, which assessed both 25(OH)D at baseline and individual premenstrual symptoms over the past year at the baseline. As such, reverse causality is a potential concern. Though premenstrual symptoms were assessed prospectively in the BioCycle cohort, the power was limited due to small sample size. However, results were fairly consistent across both studies. WIDER IMPLICATIONS OF THE FINDINGS: Serum 25(OH)D may be associated with risk and severity of specific physical premenstrual symptoms. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract nos. HHSN267200603423, HHSN267200603424, and HHSN267200603426). JG.R. and D.L.K. have been funded by the NIH Medical Research Scholars Program, a public-private partnership jointly supported by the NIH and generous contributions to the Foundation for the NIH by the Doris Duke Charitable Foundation (Grant #2014194), the American Association for Dental Research, the Colgate Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih.org. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT00467363.

Prevalence and spatial distribution of Coxiella burnetii seropositivity in northern Australian beef cattle adjusted for diagnostic test uncertainty.

Q fever is a zoonotic disease caused by infection with Coxiella burnetii transmitted from animals including, but not limited to, cattle, sheep and goats. The infection in cattle is typically sub-clinical with some evidence suggesting associated reproductive loss. There is currently limited data on the true prevalence and distribution of coxiellosis in beef cattle across northern Australia. During this study, 2,012 sera samples from beef cattle managed on commercial farms located in Queensland and the Northern Territory were tested using an indirect immunofluorescent assay (IFA) for serological evidence of IgG antibodies against C. burnetii. Bayesian latent class models were used to estimate the true prevalence, adjusted for diagnostic test sensitivity and specificity and incorporating the hierarchical structure of the cattle within farms and regions. In this study, cattle in the Northern Territory had lower estimated true prevalence than cattle within most regions of Queensland with the exception of south-east Queensland. Results from this study have described the geographic distribution and estimated the true prevalence of antibodies to C. burnetii in a sample of extensively managed beef cattle located across the tropical grazing regions of northern Australia.

The effect of regional hypothermia on mechanical nociceptive thresholds in the equine distal forelimb.

Regional hypothermia has shown promise as analgesic in horses when used to manage painful conditions of the distal limb such as laminitis. In this prospective study, the analgesic effects of regional hypothermia were assessed using mechanical nociceptive thresholds during distal limb cooling. The study population consisted of eight healthy adult Standardbred horses, selected from a teaching herd. A distal forelimb of each horse was cooled using water immersion at the following sequential target water temperatures: 34 °C, 20 °C, 10 °C, 5 °C, 1 °C, 5 °C, 10 °C, 20 °C. Limb surface temperature was measured after 30 min at each target water temperature and the mechanical force required to elicit a response (mechanical nociceptive threshold) was determined using a pneumatic actuator. Both forelimbs of each horse were tested one week apart. At skin surface temperatures above 7 °C, there was little association between skin surface temperature and the mechanical force required to elicit a response. As the skin surface temperature decreased below 7 °C, there was a rapid increase in the force required to elicit a response (P = 0.036). Skin surface temperatures of <7 °C required water temperatures below 2 °C. The results of this study suggest that hypothermia has potential to provide distal limb analgesia in horses at skin surface temperatures below 7 °C. Further evaluation of the technique is warranted.

Cannabis use while trying to conceive: a prospective cohort study evaluating associations with fecundability, live birth and pregnancy loss.

STUDY QUESTION: Is cannabis use assessed via urinary metabolites and self-report during preconception associated with fecundability, live birth and pregnancy loss? SUMMARY ANSWER: Preconception cannabis use was associated with reduced fecundability among women with a history of pregnancy loss attempting pregnancy despite an increased frequency of intercourse. WHAT IS KNOWN ALREADY: Cannabis use continues to rise despite limited evidence of safety during critical windows of pregnancy establishment. While existing studies suggest that self-reported cannabis use is not associated with fecundability, self-report may not be reliable. STUDY DESIGN, SIZE, DURATION: A prospective cohort study was carried out including 1228 women followed for up to six cycles while attempting pregnancy (2006 to 2012), and throughout pregnancy if they conceived. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18-40 years with a history of pregnancy loss (n = 1228) were recruited from four clinical centers. Women self-reported preconception cannabis use at baseline and urinary tetrahydrocannabinol metabolites were measured throughout preconception and early pregnancy (up to four times during the study: at baseline, after 6 months of follow-up or at the beginning of the conception cycle, and weeks 4 and 8 of pregnancy). Time to hCG-detected pregnancy, and incidence of live birth and pregnancy loss were prospectively assessed. Fecundability odds ratios (FOR) and 95% CI were estimated using discrete time Cox proportional hazards models, and risk ratios (RRs) and 95% CI using log-binomial regression adjusting for age, race, BMI, education level, baseline urine cotinine, alcohol use and antidepressant use. MAIN RESULTS AND THE ROLE OF CHANCE: Preconception cannabis use was 5% (62/1228), based on combined urinary metabolite measurements and self-report, and 1.3% (11/789) used cannabis during the first 8 weeks of gestation based on urinary metabolites only. Women with preconception cannabis use had reduced fecundability (FOR 0.59; 95% CI 0.38, 0.92). Preconception cannabis use was also associated with increased frequency of intercourse per cycle (9.4 ± 7 versus 7.5 ± 7 days; P = 0.02) and higher LH (percentage change 64%, 95% CI 3, 161) and higher LH:FSH ratio (percentage change 39%, 95% CI 7, 81). There were also suggestive, though imprecise, associations with anovulation (RR 1.92, 95% CI 0.88, 4.18), and live birth (42% (19/45) cannabis users versus 55% (578/1043) nonusers; RR 0.80, 95% CI 0.57, 1.12). No associations were observed between preconception cannabis use and pregnancy loss (RR 0.81, 95% CI 0.46, 1.42). Similar results were observed after additional adjustment for parity, income, employment status and stress. We were unable to estimate associations between cannabis use during early pregnancy and pregnancy loss due to limited sample size. LIMITATIONS, REASONS FOR CAUTION: Owing to the relatively few cannabis users in our study, we had limited ability to make conclusions regarding live birth and pregnancy loss, and were unable to account for male partner use. While results were similar after excluding smokers, alcohol use and any drug use in the past year, some residual confounding may persist due to these potential co-exposures. WIDER IMPLICATIONS OF THE FINDINGS: These findings highlight potential risks on fecundability among women attempting pregnancy with a history of pregnancy loss and the need for expanded evidence regarding the reproductive health effects of cannabis use in the current climate of increasing legalization. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract numbers: HHSN267200603423, HHSN267200603424, HHSN267200603426, HHSN275201300023I). Jeannie G. Radoc has been funded by the National Institutes of Health Medical Research Scholars Program, a public-private partnership supported jointly by the National Institutes of Health and generous contributions to the Foundation for the National Institutes of Health from the Doris Duke Charitable Foundation (DDCF Grant # 2014194), Genentech, Elsevier, and other private donors. The authors report no conflict of interest in this work and have nothing to disclose. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT00467363.

Effects of topical treatment of cannabidiol extract in a unique manuka factor 5 manuka honey carrier on second intention wound healing on equine distal limb wounds: a preliminary study.

OBJECTIVE: Evaluate the effect of topical 1% cannabidiol on second intention wound healing in distal limb wounds of horses. DESIGN: Experimental. ANIMALS: Six Standardbred horses. METHODS: A total of five 2.5 cm × 2.5 cm full thickness skin wounds were created on the dorsomedial aspect of the metacarpi of 6 horses. Wounds were contaminated with faeces on the day of wound creation. Each wound was then assigned to a treatment group; compounded 1% cannabidiol in unique manuka factor (UMF) 5 manuka honey, UMF 5 manuka honey, UMF 20 manuka honey or saline. Each treatment was applied topically daily for a total of 42 days. Legs were bandaged and bandages were changed, daily, for 13 days postoperatively. Digital photographs of each wound were taken on day 1 then weekly for 6 weeks. Wound size, daily healing rate and total time to healing were recorded and compared statistically. RESULTS: Irrespective of the treatment, wounds did not retract as expected in the first 7 days after wound creation. There was no difference in wound area, daily healing rate, days to complete healing between treatment groups. CONCLUSIONS: This preliminary study failed to demonstrate any difference in wound healing variables between treatment groups in this model of second intention wound healing. This was unexpected due to the established effects of UMF 20 manuka honey on wound healing using the same model. This may be due to systemic effects of cannabidiol and study design. Further research into the use of cannabidiol in equine wounds is warranted.

Vitamin D and Reproductive Hormones Across the Menstrual Cycle.

STUDY QUESTION: How do the calciotropic hormones (25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and intact parathyroid hormone (iPTH)) vary across the menstrual cycle and do cyclic patterns of reproductive hormones (estradiol, progesterone, LH, FSH) differ by vitamin D status? SUMMARY ANSWER: Calciotropic hormones vary minimally across the menstrual cycle; however, women with 25-hydroxyvitamin D below 30 ng/ml have lower mean estradiol across the menstrual cycle. WHAT IS KNOWN ALREADY: Prior human studies suggest that vitamin D status is associated with fecundability, but the mechanism is unknown. Exogenous estrogens and prolonged changes in endogenous estradiol (pregnancy or menopause) influence concentrations of 25-hydroxyvitamin D. In vitro, treatment with 1,25-dihydroxyvitamin D increases steroidogenesis in ovarian granulosa cells. There are little data about changes in calciotropic hormones across the menstrual cycle or cyclic patterns of reproductive hormones by categories of vitamin D status. STUDY DESIGN, SIZE, DURATION: A prospective cohort study of 89 self-identified white women aged 18-44, across two menstrual cycles. Participants were a subset of the BioCycle Study, a community-based study conducted at the University of Buffalo, 2005-2007. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible participants had self-reported regular menstrual cycles between 21 and 35 days and were not using hormonal contraception or vitamins. Early morning fasting blood samples were drawn at up to eight study visits per cycle. Visits were timed to capture information in all cycle phases. Serum samples for 89 women (N = 163 menstrual cycles) were analyzed for estradiol, progesterone, LH, FSH and 25-hydroxyvitamin D (25(OH)D). Variability in calciotropic hormones within and across menstrual cycles was assessed using intraclass correlation coefficients and non-linear mixed models. Given the relative stability of the calciotropic hormones across the menstrual cycle, non-linear mixed models were used to examine differences in the cyclic patterns of estradiol, progesterone, LH and FSH by categories of each calciotropic hormone (split at the median). These models were conducted for all ovulatory cycles (N = 142 ovulatory menstrual cycles) and were adjusted for age, BMI (measured in clinic) and self-reported physical activity. MAIN RESULTS AND THE ROLE OF CHANCE: Median 25(OH)D concentration was 29.5 ng/ml (SD 8.4), and only 6% of women had vitamin D deficiency (<20 ng/ml). The mean concentration of 25(OH)D did not differ between the luteal and follicular phase; however, both 1,25(OH)2D and iPTH showed small fluctuations across the menstrual cycle with the highest 1,25(OH)2D (and lowest iPTH) in the luteal phase. Compared with women who had mean 25(OH)D ≥30 ng/ml, women with lower 25(OH)D had 13.8% lower mean estradiol (95% confidence interval: -22.0, -4.7) and 10.8% lower free estradiol (95% CI: -0.07, -0.004). Additionally, compared to women with iPTH ≤36 pg/ml, women with higher concentrations of iPTH had 12.7% lower mean estradiol (95% CI: -18.7, -6.3) and 7.3% lower progesterone (95% CI: -13.3, -0.9). No differences in the cyclic pattern of any of the reproductive hormones were observed comparing cycles with higher and lower 1,25(OH)2D. LIMITATIONS, REASONS FOR CAUTION: Women included in this study had self-reported 'regular' menstrual cycles and very few were found to have 25(OH)D deficiency. This limits our ability to examine cycle characteristics, anovulation and the effects of concentrations of the calciotropic hormones found in deficient individuals. Additionally, the results may not be generalizable to women with irregular cycles, other races, or populations with a higher prevalence of vitamin D deficiency. WIDER IMPLICATIONS OF THE FINDINGS: These findings support current clinical practice that does not time testing for vitamin D deficiency to the menstrual cycle phase. We find that women with lower vitamin D status (lower 25(OH)D or higher iPTH) have lower mean concentrations of estradiol across the menstrual cycle. Although this study cannot identify a mechanism of action, further in vitro work or clinical trials may help elucidate the biologic mechanisms linking calciotropic and reproductive hormones. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract numbers: HHSN275200403394C, HHSN275201100002I and Task 1 HHSN27500001) and the National Institute of Environmental Health Sciences. There are no competing interests.

Elastic continuum stiffness of contractile tail sheaths from molecular dynamics simulations.

Contractile tails are key components of the biological nanomachinery involved in cell membrane puncturing, where they provide a means to deliver molecules and ions inside cells. Two intriguing examples of contractile tails are those from bacteriophage T4 and R2-pyocin. Although the two systems are different in terms of biological activity, they share a fascinatingly similar injection mechanism, during which the tail sheaths of both systems contract from a so-called extended state to around half of their length (the contracted state), accompanied by release of elastic energy originally stored in the sheath. Despite the great prevalence and biomedical importance of contractile delivery systems, many fundamental details of their injection machinery and dynamics are still unknown. In this work, we calculate the bending and torsional stiffness constants of a helical tail sheath strand of bacteriophage T4 and R2-pyocin, in both extended and contracted states, using molecular dynamics simulations of about one-sixth of the entire sheath. Differences in stiffness constants between the two systems are rationalized by comparing their all-atom monomer structures, changes in sheath architecture on contraction, and differences in interstrand interactions. The calculated coefficients indicate that the T4 strand is stiffer for both bending and torsion than the corresponding R2-pyocin strands in both extended and contracted conformations. The sheath strands also have greater stiffness in the contracted state for both systems. As the main application of this study, we describe how the stiffness constants can be incorporated in a model to simulate the dynamics of contractile nanoinjection machineries.

The large-scale capture of eastern grey kangaroos (Macropus giganteus) and red kangaroos (Osphranter rufus) and its application to a population management project.

OBJECTIVE: A large-scale capture method was developed to enable sterilisation of a macropod population in western Sydney from 2005 to 2018. METHODS: Until March 2007, free ranging eastern grey kangaroos and red kangaroos were herded into purpose-built 15 m diameter capture yards (CYs) for darting with a projectile syringe. From March 2007 onwards, animals were free-range darted in large areas without herding. Kangaroos were darted with 1.33-5.10 mg/kg tiletamine/zolazepam and 0.01-0.02 mg/kg medetomidine, ± 0.03 mg/kg acepromazine. Deaths were monitored. Population counts were performed annually. RESULTS: There were 5825 capture events involving 3963 kangaroos. Over 85% of all captures occurred from 2005 to 2008. Of all reported deaths (n = 523), 135 were attributed to ill health. Musculoskeletal injuries incurred during capture were the main project-related cause of death (n = 116). Post capture myopathy was uncommonly diagnosed following capture (n = 19). CONCLUSION: The herding and capture method enabled a large number of kangaroos to be mobilised and captured with low mortality rates, and the use of CYs resulted in fewer capture-related injuries and deaths than free-range capture. The drug doses and combinations used for darting were safe and effective, and the capture technique was successfully applied to a population management project.

Ultrasound evaluation of small intestinal thickness and a comparison to body weight in normal chickens (Gallus gallus domesticus).

BACKGROUND: Ultrasound in avian patients is useful for identifying abnormalities within the coelomic cavity. A correlation between sonographic evaluation of jejunal thickness and body weight has been reported in mammals, but not the chicken (Gallus gallus domesticus). The purpose of this study was to prospectively assess the normal values of jejunal thickness in the chicken and compare this to body weight. METHODS: Coelomic ultrasound was performed on 89 clinically normal chickens with no history or signs of gastrointestinal disease. Two populations of hens (commercial layers and backyard purebred and mixed-breed hens) were used. Breed and ultrasonographically measured jejunal wall thickness were recorded in all hens. Body weight was recorded in 45 of the hens (mixed-breed and purebred backyard chickens). RESULTS AND CONCLUSION: There was no statistically significant correlation between body weight and ultrasonographically measured jejunal wall thickness. The mean thickness of the jejunal wall in healthy chickens was 2.1 ± 0.08 mm. Further studies comparing jejunal thickness in chickens with and without signs of GI disease would be useful.

Total intravenous anaesthesia with ketamine, medetomidine and guaifenesin compared with ketamine, medetomidine and midazolam in young horses anaesthetised for computerised tomography.

BACKGROUND: There is no information directly comparing midazolam with guaifenesin when used in combination with an alpha-2 agonist and ketamine to maintain anaesthesia via i.v. infusion in horses. OBJECTIVES: To compare ketamine-medetomidine-guaifenesin with ketamine-medetomidine-midazolam for total intravenous anaesthesia (TIVA) in young horses anaesthetised for computerised tomography. STUDY DESIGN: Prospective, randomised, blinded, crossover trial. METHODS: Fourteen weanlings received medetomidine 7 µg/kg bwt i.v. and anaesthesia was induced with ketamine 2.2 mg/kg bwt i.v. On two separate occasions horses each received infusions of ketamine 3 mg/kg bwt/h, medetomidine 5 µg/kg bwt/h, guaifenesin 100 mg/kg bwt/h (KMG) or ketamine 3 mg/kg bwt/h, medetomidine 5 µg/kg bwt/h, midazolam 0.1 mg/kg bwt/h (KMM) for 50 min. Cardiorespiratory variables and anaesthetic depth were assessed every 5-10 min. Recovery times after the infusions ceased were recorded and recovery quality was assessed using a composite score system (CSS), simple descriptive scale (SDS) and visual analogue scale (VAS). Multivariable models were used to generate mean recovery scores for each treatment and each recovery score system and provide P-values comparing treatment groups. RESULTS: Anaesthesia was uneventful with no difference in additional anaesthetic requirements and little clinically relevant differences in cardiopulmonary variables between groups. All horses recovered without incident with no significant difference in recovery times. Quality of the anaesthetic recovery was significantly better for the KMM group compared with the KMG group using the CSS (P<0.001), SDS (P<0.001) and VAS (P<0.001). MAIN LIMITATIONS: No surgical stimulus was applied and study animals may not represent general horse population. CONCLUSION: Midazolam is a suitable alternative to guaifenesin when co-infused with ketamine and medetomidine for anaesthesia in young horses undergoing noninvasive procedures. Both infusions produce a clinically comparable quality of anaesthesia; however, recovery from anaesthesia is of a better quality following an infusion of ketamine-medetomidine-midazolam.

Comparison of conventional radiography and computed tomography as aids in the diagnosis of osteomyelitis in 11 foals.

BACKGROUND: Conventional radiography is currently the most common imaging modality used by veterinarians investigating foals with suspected osteomyelitis. Emerging evidence in adult horses and humans suggests computed tomography (CT) is a superior modality for evaluation of osseous changes in general. This study aimed to evaluate the potential benefits of CT versus conventional radiography in cases of osteomyelitis in foals. METHODS: Cases of osteomyelitis in foals under 6 months of age admitted over a 6-year period at a single referral hospital that had both CT and conventional radiography images were retrieved. Case details and measurements of the largest area of bone lysis identified in two planes (lateromedial/sagittal and dorsopalmar/dorsal) were evaluated by three veterinarians with a range of experience. RESULTS: A significant difference regarding lesion size was seen on the lateromedial (LM) radiographic projections compared with the equivalent sagittal plane CT image. The LM radiographic evaluation resulted in a 37% underestimation of the area of the lesion. Additionally, use of the LM radiographic projections were 2.5-fold more variable in the measurement area compared with CT. In general, regardless of projection, CT produced more information regarding lesion area and, in some cases, detected osseous changes that were not evident on the radiographs. CLINICAL RELEVANCE: LM radiographic projections are less reliable and commonly result in an under-appreciation of lesion size and extent. CT detected lesions that were difficult or impossible to identify on radiographs and may allow improved treatment planning.

Preconception antiphospholipid antibodies and risk of subsequent early pregnancy loss.

Objectives To prospectively estimate the association of preconception antiphospholipid antibodies (aPL) with subsequent pregnancy loss using a cohort design. aPL have been associated with recurrent early pregnancy loss (EPL) prior to 10 weeks in previous case-control studies. Prospective ascertainment of pregnancy loss is challenging, as most women do not seek care prior to EPL. Methods Secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial of preconception low-dose aspirin. Preconception anticardiolipin (aCL) and anti-ß2-glycoprotein-I (a-ß2-I) were assessed in 1208 women with one or two prior pregnancy losses and no more than two prior live births. Comparison cohorts were defined by positive aPL (+aPL) or negative aPL (-aPL) status. All women were followed for six menstrual cycles while trying to conceive; if successful, they underwent an ultrasound at 6-7 weeks' gestation. EPL was defined as loss prior to 10 weeks' gestation; embryonic loss was loss after visualization of an embryo but prior to 10 weeks; clinical loss was any loss after visualization of an embryo (with or without fetal cardiac activity detected). Results In total, 14/1208 (1%) tested positive for +aPL. 786/1208 (65%) women had positive human chorionic gonadotropin during the study period, of which 9/786 (1%) had +aPL. Of the 786 pregnant women, 589 (75%) had live births and 24% had pregnancy losses. Women with +aPL experienced EPL at similar rates as women with -aPL, 44% vs 21% (aRR 2.4, 95% confidence interval (CI) 0.5-10.9). Embryonic loss was more common in women with +aCL IgM (aRR 4.8, 95% CI 1.0-23.0) and in women with two positive aPL. Clinical pregnancy loss was more common in women with positive a-ß2-I IgM (50% vs 16.5%, aRR 3.7, 95% CI 1.3-10.8). Conclusion Positive levels of aPL are rare in women with one or two prior pregnancy losses and are not clearly associated with an increased rate of subsequent loss. Clinical trial registration The original source study was registered at ClinicalTrials.gov (#NCT00467363).

Effect of reducing inspired oxygen concentration on oxygenation parameters during general anaesthesia in horses in lateral or dorsal recumbency.

OBJECTIVE: To compare the effects of two concentrations of oxygen delivered to the anaesthetic breathing circuit on oxygenation in mechanically ventilated horses anaesthetised with isoflurane and positioned in dorsal or lateral recumbency. METHODS: Selected respiratory parameters and blood lactate were measured and oxygenation indices calculated, before and during general anaesthesia, in 24 laterally or dorsally recumbent horses. Horses were randomly assigned to receive 100% or 60% oxygen during anaesthesia. All horses were anaesthetised using the same protocol and intermittent positive pressure ventilation (IPPV) was commenced immediately following anaesthetic induction and endotracheal intubation. Arterial blood gas analysis was performed and oxygenation indices calculated before premedication, immediately after induction, at 10 and 45 min after the commencement of mechanical ventilation, and in recovery. RESULTS: During anaesthesia, the arterial partial pressure of oxygen was adequate in all horses, regardless of position of recumbency or the concentration of oxygen provided. At 10 and 45 min after commencing IPPV, the arterial partial pressure of oxygen was lower in horses in dorsal recumbency compared with those in lateral recumbency, irrespective of the concentration of oxygen supplied. Based on oxygenation indices, pulmonary function during general anaesthesia in horses placed in dorsal recumbency was more compromised than in horses in lateral recumbency, irrespective of the concentration of oxygen provided. CONCLUSION: During general anaesthesia, using oxygen at a concentration of 60% instead of 100% maintains adequate arterial oxygenation in horses in dorsal or lateral recumbency. However, it will not reduce pulmonary function abnormalities induced by anaesthesia and recumbency.

Recent attempted and actual weight change in relation to pregnancy loss: a prospective cohort study.

OBJECTIVE: To assess weight change and attempted weight loss during the 12-18 months before spontaneous conception in relation to the risk of pregnancy loss. DESIGN: Prospective cohort study. SETTING: United States, 2007-2011. METHODS: Women (n = 629) who were attempting pregnancy reported at baseline any weight loss attempts over the past 12 months, and their minimum and maximum weights during that time. Follow up lasted one to six menstrual cycles and throughout pregnancy. Using bodyweight measured at 4 weeks' gestation, participants were categorised as having weight loss ≥5%, weight gain ≥5%, both, or neither, over the previous 12-18 months. Log-binomial models adjusted for potential confounders. MAIN OUTCOME MEASURES: Risk ratio (RR) and 95% confidence interval (CI) of pregnancy loss. RESULTS: Attempted weight loss was reported by 44% of women and actual weight loss by 11%, but neither was consistently associated with pregnancy loss. The RR for recent weight gain ≥5% was 1.65 (CI 1.09, 2.49). CONCLUSIONS: Weight gain over the period spanning 12-18 months pre-conception to 4 weeks' gestation may increase the risk of pregnancy loss among fertile women with prior pregnancy losses. Attempted and actual weight loss were not associated with pregnancy loss; however, replication is needed from larger studies with data on particular weight-loss methods. TWEETABLE ABSTRACT: Recent weight gain before and around the time of conception may increase the risk of pregnancy loss.

A pilot study comparing the effect of orally administered esomeprazole and omeprazole on gastric fluid pH in horses.

AIMS To compare the efficacy of an enteric coated esomeprazole paste with an enteric coated omeprazole paste to increase gastric pH after oral administration in horses. METHODS Nine adult Standardbred horses were randomly assigned to three groups, each containing three horses, for a study comprising three phases of 10 days, with an 18-day washout period between each phase. In each phase, three horses received either 0.5 mg/kg esomeprazole, 1 mg/kg omeprazole or a placebo, as an oral paste, once daily for 10 days (Days 0-9). Over the course of study all horses received all three treatments. Gastric fluid samples were collected using a gastroscope on Days 1, 3, 5, 8 and 10, with food and water withheld for 16 hours prior to collection of samples. The pH of all samples was measured immediately after collection. RESULTS Mean pH (3.38; SD 1.75) of the gastric fluid samples in the horses that received the placebo was lower than in the horses that received esomeprazole (6.28; SD 1.75) or omeprazole (6.13; SD 1.75) (p<0.001). There was no difference in the mean pH between horses receiving esomeprazole and those receiving omeprazole (p=0.56). CONCLUSIONS AND CLINICAL RELEVANCE Under these study conditions, esomeprazole paste was equally as effective as omeprazole paste in increasing gastric pH in horses. Enteric coated esomeprazole, may be a therapeutic alternative to omeprazole for the prevention of gastric ulcers in horses.

Comparison of the effects of topical application of UMF20 and UMF5 manuka honey with a generic multifloral honey on wound healing variables in an uncontaminated surgical equine distal limb wound model.

OBJECTIVE: To compare the effect of application of manuka honey with unique manuka factor (UMF) 5 or 20 with a generic multifloral honey on equine wound healing variables. METHODS: Two full-thickness skin wounds (2.5 × 2.5 cm) were created on the metatarsus of both hindlimbs of eight Standardbred horses. The wounds on each horse were assigned to 1 of 4 treatments: UMF20 (UMF20) and UMF5 (UMF5) manuka honey; generic multifloral honey (GH); and a saline control. Bandages were changed daily for 12 days, after which treatment was stopped and the bandages were removed. Wound area was measured on day 1, then weekly until day 42. Overall wound healing rate (cm2 /day) and time to complete healing were recorded. RESULTS: There was no difference in wound area for any of the treatments on any measurement day except for day 21, where the mean wound area for wounds treated with UMF20 was smaller than the mean wound area for the UMF5-treated wounds (P = 0.031). There was no difference in mean (± SE) overall healing rate (cm2 /day) among the treatment groups. There were differences in mean (± SE) days to complete healing. Wounds treated with UMF20 healed faster than wounds treated with GH (P = 0.02) and control wounds (P = 0.01). CONCLUSIONS: Treatment of wounds with UMF20 reduced overall wound healing time compared with wounds treated with GH and control wounds. However, using this model the difference in the overall time to complete healing was small.

Commissioning for health improvement following the 2012 health and social care reforms in England: what has changed?

BACKGROUND: The wide-ranging program of reforms brought about by the Health and Social Care Act (2012) in England fundamentally changed the operation of the public health system, moving responsibility for the commissioning and delivery of services from the National Health Service to locally elected councils and a new national public health agency. This paper explores the ways in which the reforms have altered public health commissioning. METHODS: We conducted multi-methods research over 33 months, incorporating national surveys of Directors of Public Health and local council elected members at two time-points, and in-depth case studies in five purposively selected geographical areas. RESULTS: Public health commissioning responsibilities have changed and become more fragmented, being split amongst a range of different organisations, most of which were newly created in 2013. There is much change in the way public health commissioning is done, in who is doing it, and in what is commissioned, since the reforms. There is wider consultation on decisions in the local council setting than in the NHS, and elected members now have a strong influence on public health prioritisation. There is more (and different) scrutiny being applied to public health contracts, and most councils have embarked on wide-ranging changes to the health improvement services they commission. Public health money is being used in different ways as councils are adapting to increasing financial constraint. CONCLUSIONS: Our findings suggest that, while some of the intended opportunities to improve population health and create a more joined-up system with clearer leadership have been achieved, fragmentation, dispersed decision-making and uncertainties regarding funding remain significant challenges. There have been profound changes in commissioning processes, with consequences for what health improvement services are ultimately commissioned. Time (and further research) will tell if any of these changes lead to improved population health outcomes and reduced health inequalities, but many of the opportunities brought about by the reforms are threatened by the continued flux in the system.

A RelA(p65) Thr505 phospho-site mutation reveals an important mechanism regulating NF-κB-dependent liver regeneration and cancer.

Post-translational modifications of nuclear factor (NF)-κB subunits provide a mechanism to differentially regulate their activity in response to the many stimuli that induce this pathway. However, the physiological significance of these modifications is largely unknown, and it remains unclear if these have a critical role in the normal and pathological functions of NF-κB in vivo. Among these, phosphorylation of the RelA(p65) Thr505 residue has been described as an important regulator of NF-κB activity in cell lines, but its physiological significance was not known. Therefore, to learn more about the role of this pathway in vivo, we generated a knockin mouse with a RelA T505A mutation. Unlike RelA knockout mice, the RelA T505A mice develop normally but exhibit aberrant hepatocyte proliferation following liver partial hepatectomy or damage resulting from carbon tetrachloride (CCl4) treatment. Consistent with these effects, RelA T505A mice exhibit earlier onset of cancer in the N-nitrosodiethylamine model of hepatocellular carcinoma. These data reveal a critical pathway controlling NF-κB function in the liver that acts to suppress the tumour-promoting activities of RelA.

Effect of Manuka honey gel on the transforming growth factor ß1 and ß3 concentrations, bacterial counts and histomorphology of contaminated full-thickness skin wounds in equine distal limbs.

OBJECTIVE: To investigate the effect of 66% Manuka honey gel on the concentrations of transforming growth factor (TGF)-ß1 and TGF-ß3, bacterial counts and histomorphology during healing of contaminated equine distal limb wounds. METHODS: In this experimental study of 10 Standardbred horses, five full-thickness skin wounds (2 × 1.5 cm) were created on one metacarpus and six similar wounds were created on the contralateral metacarpus. Wounds were assigned to three groups: non-contaminated control wounds; contaminated control wounds; contaminated wounds treated daily with 1 mL Manuka honey gel topically for 10 days. For the contaminated wounds, faeces were applied for 24 h after wound creation. In five horses wounds were bandaged and in the other five horses wounds were left without a bandage. Biopsies were taken on days 1, 2, 7 and 10 after wounding to evaluate the effects of Manuka honey gel, wound contamination and bandaging on TGF-ß1 and TGF-ß3 concentrations, aerobic and anaerobic bacterial counts, and histomorphology. RESULTS: Manuka honey gel had no significant effect on TGF-ß1 and TGF-ß3 concentrations or wound bacterial counts. Manuka honey gel decreased wound inflammation (days 7, 10), increased angiogenesis (days 2, 7, 10), increased fibrosis and collagen organisation (day 7) and increased epithelial hyperplasia (days 7, 10). CONCLUSIONS: Treatment with Manuka honey gel resulted in a more organised granulation tissue bed early in wound repair, which may contribute to enhanced healing of equine distal limb wounds.