Maternal perception of decreased fetal movements is independent of infant size.

OBJECTIVE: Fetal movements are often used as a surrogate for fetal wellbeing. Previous research suggests a link between maternal perception of decreased fetal movements (DFM) and small for gestational age (SGA) infants. The aim of this study was to investigate the association between maternal presentation with DFM and birthweight centile categories at a large Australian perinatal center. METHODS: This was a 5-year cohort study (January 2016 to October 2020) of non-anomalous singleton infants born at the Mater Mothers' Hospital in Brisbane, Australia at 28+0 weeks gestation or later. The primary outcome for this study was the rate of DFM by birthweight centile categories. Maternal demographics included age, body mass index, ethnicity, parity, medical conditions, and previous stillbirths. The effect of decreased fetal movements on birthweight centile was evaluated with adjusted multinomial regression models. Adjusted logistic regression models were then used to evaluate whether decreased fetal movements resulted in birthweight centiles <5 and <10. Robust standard errors were used to account for clustering at the patient level. Wald tests, Hosmer and Lemeshow's goodness of fit tests, Akaike's and Bayesian Information Criteria were used to evaluate models. RESULTS: Over the 5-year study period, 45042 women met the inclusion criteria. Of these, 6690 (14.9%) women presented with DFM. Of the DFM cohort, 80.9% (5411/6690) had only one presentation with DFM, whilst 19.1% (1279/6690) had >2 presentations. The overall stillbirth rate was similar in women with DFM (0.1%, 8/6690) and without DFM (0.1%, 50/38352). There was no difference in rates of DFM (either single or multiple) vs. no DFM and infant birthweight centile categories. There was no association between DFM (either single or multiple) and infant birth weight centile. CONCLUSION: The results of this study suggest that presentation with DFM is not associated with infant size. Clinicians should consider additional risk factors and the overall clinical context in deciding appropriate management. DFM is not necessarily an indication for an immediate or urgent ultrasound scan to assess fetal size. This article is protected by copyright. All rights reserved.

Placental biomarkers and fetoplacental Dopplers in combination reliably predict preterm birth in pregnancies complicated by fetal growth restriction.

OBJECTIVE: To assess the association between placental biomarkers (placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio) and fetoplacental Dopplers - Umbilical Artery Pulsatility Index (UA PI) and Uterine Artery Pulsatility Index (UtA PI) in various combinations for the likelihood of preterm birth (PTB) in women with fetal growth restriction (FGR). METHODS: A prospective cohort study of pregnancies complicated by FGR. Maternal serum PlGF levels, sFlt-1/PlGF ratio, UA PI and UtA PI were measured at 4-weekly intervals from recruitment to delivery. Harrell's concordance statistic was used to evaluate various combinations of placental biomarkers and fetoplacental Dopplers to ascertain the ideal combination to predict PTB (<37 weeks). Multivariable Cox regression was used as time-varying covariates. RESULTS: There were 320 pregnancies in the study cohort - 179 (55.9%) were FGR and 141 (44.1%) were AGA. In the FGR cohort, both low PlGF levels and elevated sFlt-1/PlGF ratio significantly affected time to PTB. Low PlGF was a better predictor of PTB than either sFlt-1/PlGF ratio or combination of PlGF and sFlt-1/PlGF ratio (Harrell's C 0.81, 0.79, 0.75 respectively). Similarly, although both UA PI and UtA PI >95th centile for gestation significantly affected the time to PTB, in combination, they were better predictors than either measure alone (Harrell's C 0.82, 0.75, 0.76 respectively). The predictive utility was highest when PlGF <100ng/L, UA PI and UtA PI >95th centile was combined (Harrell's C 0.88) (HR 32.99 95% CI 10.74, 101.32). CONCLUSIONS: Low maternal PlGF levels (<100ng/L) and abnormal fetoplacental Dopplers (UA PI and UtA PI >95th centile) in combination have greatest predictive utility for PTB in pregnancies complicated with FGR and may help guide clinical management of these complex pregnancies. This article is protected by copyright. All rights reserved.

The Mars 2020 Perseverance Rover Mast Camera Zoom (Mastcam-Z) Multispectral, Stereoscopic Imaging Investigation.

Mastcam-Z is a multispectral, stereoscopic imaging investigation on the Mars 2020 mission's Perseverance rover. Mastcam-Z consists of a pair of focusable, 4:1 zoomable cameras that provide broadband red/green/blue and narrowband 400-1000 nm color imaging with fields of view from 25.6° × 19.2° (26 mm focal length at 283 µrad/pixel) to 6.2° × 4.6° (110 mm focal length at 67.4 µrad/pixel). The cameras can resolve (≥ 5 pixels) ∼0.7 mm features at 2 m and ∼3.3 cm features at 100 m distance. Mastcam-Z shares significant heritage with the Mastcam instruments on the Mars Science Laboratory Curiosity rover. Each Mastcam-Z camera consists of zoom, focus, and filter wheel mechanisms and a 1648 × 1214 pixel charge-coupled device detector and electronics. The two Mastcam-Z cameras are mounted with a 24.4 cm stereo baseline and 2.3° total toe-in on a camera plate ∼2 m above the surface on the rover's Remote Sensing Mast, which provides azimuth and elevation actuation. A separate digital electronics assembly inside the rover provides power, data processing and storage, and the interface to the rover computer. Primary and secondary Mastcam-Z calibration targets mounted on the rover top deck enable tactical reflectance calibration. Mastcam-Z multispectral, stereo, and panoramic images will be used to provide detailed morphology, topography, and geologic context along the rover's traverse; constrain mineralogic, photometric, and physical properties of surface materials; monitor and characterize atmospheric and astronomical phenomena; and document the rover's sample extraction and caching locations. Mastcam-Z images will also provide key engineering information to support sample selection and other rover driving and tool/instrument operations decisions.

A systematic review of the outcomes of using voice hearing simulation in the education of health care professionals and those in training.

OBJECTIVES: To identify and synthesise data from studies that have evaluated the outcomes of voice hearing simulation as an educational intervention with health care professionals and those in training. DESIGN: The research employed a systematic review that was informed by Centre for Reviews and Dissemination DATA SOURCES: The databases Web of Science, Medline, Embase, PsycINFO, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials Register and CINAHL were systematically searched to January 2020. REVIEW METHODS: Identified studies were screened by title (n = 509), abstract (n = 246) and full text (n = 56) using the following inclusion criteria: studies employing either qualitative and/or quantitative research methods, which have evaluated voice hearing simulation as a principal educational intervention with health care professionals during training or post-qualification. RESULTS: Twenty six studies were included in the review. Eleven studies adopted mixed methods, five adopted quantitative methods and ten used qualitative methods. Although most of the studies were of low to medium quality the findings were encouraging and suggest that voice hearing simulation may be a useful educational intervention. Positive outcomes of simulation included improvements in empathy, attitudes, knowledge, understanding about voice hearing experiences and increased confidence in practice. The majority of participants that took part in voice hearing simulation thought that it was a powerful learning experience that should be offered to other health care professionals and those in training. CONCLUSIONS: Voice hearing simulation is a valuable educational intervention that should be routinely used by academics when teaching health professionals and those in training about the experiences of people who hear voices. However, to confirm its true effects and optimum mode of delivery further better quality research is needed.

Tributyltin disrupts fin development in Fundulus heteroclitus from both PCB-sensitive and resistant populations: Investigations of potential interactions between AHR and PPARγ.

Tributyltin (TBT) and dioxin-like polychlorinated biphenyls (PCBs) are environmental contaminants that are highly toxic to fish and co-occur in New Bedford Harbor (NBH), an estuarine Superfund site located in Massachusetts, USA. Atlantic killifish (Fundulus heteroclitus) that reside in NBH (and other highly contaminated sites along the east coast of the United States) have developed resistance to activation of the aryl hydrocarbon receptor (AHR) pathway and the toxicity of dioxin-like chemicals, such as 3,3',4,4',5-pentachlorobiphenyl, PCB126. In many biological systems, TBT disregulates adipose and bone development via the PPARγ-RXR pathway; AHR activation also disrupts adipose and bone homeostasis, potentially through molecular crosstalk between AHR and PPARγ. However, little is known about how co-exposure and the interaction of these pathways modulate the toxicological effects of these contaminants. Here, we tested the hypotheses that TBT would induce teratogenesis in killifish via activation of PPARγ and that PCB126 co-exposure would suppress PPARγ pathway activation in PCB-sensitive killifish from a reference site (Scorton Creek, SC, PCB-sensitive) but not in PCB-tolerant NBH killifish. Killifish embryos from both populations exposed to TBT (50 and 100 nM) displayed caudal fin deformities. TBT did not change the expression of pparg or its target genes related to adipogenesis (fabp11a and fabp1b) in either population. However, expression of osx/sp7, an osteoblast marker gene, and col2a1b, a chondroblast marker gene, was significantly suppressed by TBT only in SC killifish. An RXR-specific agonist, but not a PPARγ-specific agonist, induced caudal fin deformities like those observed in TBT-treated embryos. PCB126 did not induce caudal fin deformities and did not exacerbate TBT-induced fin deformities. Further, PCB126 increased expression of pparg in SC embryos and not NBH embryos, but did not change the expression of fabp1b. Taken together, these results suggest that in killifish embryos the PPARγ pathway is regulated in part by AHR, but is minimally active at least in this early life stage. In killifish, RXR activation, rather than PPARγ activation, appears to be the mechanism by which TBT induces caudal fin teratogenicity, which is not modulated by AHR responsiveness.

Assessment of Explicitly Stated Interval Change on Noncontrast Head CT Radiology Reports.

BACKGROUND AND PURPOSE: Consistent and standardized reporting of interval change for certain diagnoses may improve the clinical utility of radiology reports. The purpose of this study was to assess explicitly stated interval change of various findings in noncontrast head CT reports. MATERIALS AND METHODS: A retrospective review was performed on successive noncontrast head CT radiology reports from the first 2 weeks of January 2014. Reports with at least 1 prior comparison CT scan were included. Reports with normal examination findings and those that made comparison with only other types of examinations (eg, MR imaging) were excluded. Descriptive and subgroup statistical analyses were performed. RESULTS: In total, 200 patients with 230 reports and 979 radiographic findings were identified. The average interval between reports was 344.9 ± 695.9 days (range, 0-3556 days). Interval change was mentioned 67.3% (n = 659) of the time for all findings (n = 979). Explicitly stated interval change was significantly associated with nonremote findings (P < .001) and generalized statements of interval change (P < .001). The proportion of interval change reported ranged from 95.3% of the time for hemorrhagic to 36.4% for soft-tissue/osseous categorizations. CONCLUSIONS: Interval change reporting was variable, mentioned for 67.3% of noncontrast head CT report findings with a prior comparison CT scan. Structured radiology reports may improve the consistent and clear reporting of interval change for certain findings.

Superior immunogenicity of HCV envelope glycoproteins when adjuvanted with cyclic-di-AMP, a STING activator or archaeosomes.

Three decades after the discovery, hepatitis C virus (HCV) is still the leading cause of liver transplantation and poses a major threat to global health. In spite of recent advances in the development of direct acting antivirals, there is still a need for a prophylactic vaccine to limit the virus spread and protect at-risk populations, especially in developing countries, where the cost of the new treatments may severely limit access. The use of recombinant HCV glycoproteins E1E2 (rE1E2) in combination with the MF59, an oil-in-water emulsion-based adjuvant, has previously been shown to reduce the rate of chronicity in chimpanzees and to induce production of cross-neutralizing antibodies and cellular immune responses in human volunteers. To further improve neutralizing antibody responses in recipients along with robust T cell responses, we have explored the immunogenicity of different adjuvants when formulated with the HCV rE1E2 vaccine in mice. Our data show that cyclic di-adenosine monophosphate (c-di-AMP) and archaeosomes elicit strong neutralizing antibodies similar to those elicited using aluminum hydroxide/monophosphoryl lipid A (Alum/monophos. /MPLA) and MF59. However, both c-di-AMP and archaeosomes induced a more robust cellular immune response, which was confirmed by the detection of vaccine-specific poly-functional CD4+ T cells. We conclude that these adjuvants may substantially boost the immunogenicity of our E1E2 vaccine. In addition, our data also indicates that use of a partial or exclusive intranasal immunization regimen may also be feasible using c-di-AMP as adjuvant.

Toward Precision and Reproducibility of Diffusion Tensor Imaging: A Multicenter Diffusion Phantom and Traveling Volunteer Study.

BACKGROUND AND PURPOSE: Precision medicine is an approach to disease diagnosis, treatment, and prevention that relies on quantitative biomarkers that minimize the variability of individual patient measurements. The aim of this study was to assess the intersite variability after harmonization of a high-angular-resolution 3T diffusion tensor imaging protocol across 13 scanners at the 11 academic medical centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury multisite study. MATERIALS AND METHODS: Diffusion MR imaging was acquired from a novel isotropic diffusion phantom developed at the National Institute of Standards and Technology and from the brain of a traveling volunteer on thirteen 3T MR imaging scanners representing 3 major vendors (GE Healthcare, Philips Healthcare, and Siemens). Means of the DTI parameters and their coefficients of variation across scanners were calculated for each DTI metric and white matter tract. RESULTS: For the National Institute of Standards and Technology diffusion phantom, the coefficients of variation of the apparent diffusion coefficient across the 13 scanners was <3.8% for a range of diffusivities from 0.4 to 1.1 × 10-6 mm2/s. For the volunteer, the coefficients of variations across scanners of the 4 primary DTI metrics, each averaged over the entire white matter skeleton, were all <5%. In individual white matter tracts, large central pathways showed good reproducibility with the coefficients of variation consistently below 5%. However, smaller tracts showed more variability, with the coefficients of variation of some DTI metrics reaching 10%. CONCLUSIONS: The results suggest the feasibility of standardizing DTI across 3T scanners from different MR imaging vendors in a large-scale neuroimaging research study.

Transitioning from caregiver to visitor in a long-term care facility: the experience of caregivers of people with dementia.

OBJECTIVES: Transitioning from the primary caregiver to the visitor in a long-term care facility may be challenging for the caregiver; they are required to surrender their caring duties to the medical and nursing staff. The aim of this study was to explore the experiences of caregivers during their transition from day-to-day caregiver of a person with dementia to a visitor in a long-term care facility. METHODS: This study utilised a qualitative descriptive design. Twenty caregivers of people with dementia were recruited from the one Aged Rehabilitation and Geriatric Evaluation and Management facility, located in Victoria, Australia. Semi-structured interviews were used to explore the caregiver's experiences. Interviews were analysed using thematic analysis. RESULTS: The interview data revealed that the participants were undergoing similar experiences. The findings revealed that it was difficult for the caregiver to transition to their new role of visitor; negative reactions of grief, loss of motivation and loneliness were also coupled with positive feelings of relief and the reassurance that their relative or friend would be well cared for and safe within the long-term care facility. CONCLUSION: The findings offer insight into the experiences felt by caregivers when their relative or friend with dementia is admitted to hospital. Implications of this study include the need to improve the transition process for the caregiver by allowing them to be involved in the decision-making process, keeping them informed of care decisions, and importantly, providing emotional support to help the caregiver positively adapt to this transition.

Evaluation of treatment outcomes for patients on first-line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses.

OBJECTIVES: Viral load (VL) monitoring is recommended, but seldom performed, in resource-constrained countries. RV288 is a US President's Emergency Plan for AIDS Relief (PEPFAR) basic programme evaluation to determine the proportion of patients on treatment who are virologically suppressed and to identify predictors of virological suppression and recovery of CD4 cell count. Analyses from Uganda are presented here. METHODS: In this cross-sectional, observational study, patients on first-line antiretroviral therapy (ART) (efavirenz or nevirapine+zidovudine/lamivudine) from Kayunga District Hospital and Kagulamira Health Center were randomly selected for a study visit that included determination of viral load (HIV-1 RNA), CD4 cell count and clinical chemistry tests. Subjects were recruited by time on treatment: 6-12, 13-24 or >24 months. Logistic regression modelling identified predictors of virological suppression. Linear regression modelling identified predictors of CD4 cell count recovery on ART. RESULTS: We found that 85.2% of 325 subjects were virologically suppressed (viral load<47 HIV-1 RNA copies/ml). There was no difference in the proportion of virologically suppressed subjects by time on treatment, yet CD4 counts were higher in each successive stratum. Women had higher median CD4 counts than men overall (406 vs. 294 cells/µL, respectively; P<0.0001) and in each time-on-treatment stratum. In a multivariate logistic regression model, predictors of virological suppression included efavirenz use [odds ratio (OR) 0.47; 95% confidence interval (CI) 0.22-1.02; P=0.057], lower cost of clinic visits (OR 0.815; 95% CI 0.66-1.00; P=0.05), improvement in CD4 percentage (OR 1.06; 95% CI 1.014-1.107; P=0.009), and care at Kayunga vs. Kangulamira (OR 0.47; 95% CI 0.23-0.92; P=0.035). In a multivariate linear regression model of covariates associated with CD4 count recovery, time on highly active antiretroviral therapy (ART) (P<0.0001), patient satisfaction with care (P=0.038), improvements in total lymphocyte count (P<0.0001) and haemoglobin concentration (P=0.05) were positively associated, whereas age at start of ART (P=0.0045) was negatively associated with this outcome. CONCLUSIONS: High virological suppression rates are achievable on first-line ART in Uganda. The odds of virological suppression were positively associated with efavirenz use and improvements in CD4 cell percentage and total lymphocyte count and negatively associated with the cost of travel to the clinic. CD4 cell reconstitution was positively associated with CD4 count at study visit, time on ART, satisfaction with care at clinic, haemoglobin concentration and total lymphocyte count and negatively associated with age.

Is it necessary to perform week three dosimetric analysis in low-dose-rate brachytherapy for prostate cancer when day 0 dosimetry is done? A quality assurance assessment.

PURPOSE: To determine whether computed tomography/magnetic resonance imaging-based day 0 (d0) dosimetry is a meaningful predictor of day 21 (d21) dosimetry in low-dose-rate brachytherapy for localized prostate cancer. METHODS AND MATERIALS: The study population consisted of 277 men with localized (T1-2 N0 M0), low-/intermediate-risk prostate cancer treated with low-dose-rate brachytherapy. Computed tomography/magnetic resonance imaging fusion was used for postimplant dosimetry at d0 and d21. Logistic regression was used to construct receiver operating characteristic curves for achieving each constraint at d21, based on d0 D90 and V100, and Youden's index was used to evaluate cutpoints. Freedom from biochemical failure (FBCF) was estimated with the Kaplan-Meier method. RESULTS: The median d0 D90 increased from 133 to 150 Gy at d21, and median d0 V100 increased from 87% to 91%. For achieving the D90 constraint at d21, the optimal cut-point for d0 D90 was 135 Gy, with 84% of these patients maintaining a d21 D90 > 145 Gy. For achieving the D90 constraint at d21, the optimal cut-point for d0 V100 was 87%, with 83% of these patients maintained a d21 V100 > 90%. There was no improvement in FBCF in patients with a d0 D90 > 135 Gy or D90 > 145 Gy. Similarly, there was no improvement in FBCF in patients with a d0 V100 > 87% or V100 > 90%. CONCLUSIONS: Meeting dosimetric constraints on d0 does not obviate d21 dosimetric analysis. Constraints used for dose prescriptions on d0 are not the ideal predictors of d21 dosimetry.

Silver nanoparticle inhibition of polycyclic aromatic hydrocarbons degradation by Mycobacterium species RJGII-135.

UNLABELLED: Polycyclic aromatic hydrocarbons (PAH) are a common environmental contaminant originating from both anthropogenic and natural sources. Mycobacterium species are highly adapted to utilizing a variety of PAH. Silver nanoparticles (AgNP) are an emerging contaminant that possess bactericidal properties, interferes with the bacterial membrane and alters function. Mycobacterium sp. strain RJGII-135 provided a model bacterium to assess changes in carbon metabolism by focusing on PAH degradation, which is dependent upon passive uptake of hydrophobic molecules into the cell membrane. A mixture of 18 PAH served as a complex mixture of carbon sources for assessing carbon metabolism. At environmentally relevant PAH concentrations, RJGII-135 degraded two-, three-, and four-ring PAH within 72 h, but preferentially attacked phenanthrene and fluorene. Total cell growth and PAH degradation were successively reduced when exposed to 0·05-0·5 mg 1(-1) AgNP. However, 0·05 mg l(-1) AgNP inhibited degradation of naphthalene, acenaphthylene and acenaphthalene. RJGII-135 retained the ability to degrade the methylated naphthalenes regardless of AgNP concentration suggesting that proteins involved in dihydrodiol formation were inhibited. The reduced PAH metabolism of RJGII-135 when exposed to sublethal concentrations of AgNP provides evidence that nanoparticle pollution could alter carbon cycling in soils, sediment and aquatic environments. SIGNIFICANCE AND IMPACT OF THE STUDY: Silver nanoparticle (AgNP) pollution threatens bacterial-mediated processes due to their antibacterial properties. With the widespread commercial use of AgNP, continued environmental release is inevitable and we are just beginning to understand the potential environmental ramifications of nanoparticle pollution. This study examined AgNP inhibition of carbon metabolism through the polycyclic aromatic hydrocarbon degradation by Mycobacterium species RJGII-135. Sublethal doses altered PAH metabolism, which is dependent upon cell membrane properties and intracellular proteins. The changed carbon metabolism when exposed to sublethal doses of AgNP suggests broad impacts of this pollution on bacterial carbon cycling in diverse environments.

Serum haptoglobin concentrations in dogs with liver disease.

Dogs with liver disease have been shown to have increased serum C-reactive protein (CRP) concentrations. However, it is unclear whether dogs with liver disease also have increased serum haptoglobin concentrations. The aim of the study was to measure serum haptoglobin concentrations in healthy dogs, hospitalised dogs and dogs with liver diseases. Haptoglobin concentrations were measured in 30 healthy dogs, 47 hospitalised dogs with non-hepatic illness, 46 dogs with congenital portosystemic shunt (cPSS) and 11 dogs with primary hepatopathy. Haptoglobin concentrations were not significantly different between cPSS dogs with and without hepatic encephalopathy (HE), thus all cPSS dogs were considered as one group. Haptoglobin concentrations were significantly different between the remaining groups (P<0.0001). Hospitalised ill dogs had significantly higher haptoglobin concentrations than healthy dogs (P<0.001), dogs with cPSS (P<0.001) and dogs with primary hepatopathy (P<0.05). There was no significant difference between haptoglobin concentrations in healthy dogs, dogs with cPSS and dogs with primary hepatopathy. Haptoglobin concentrations were not significantly increased in dogs with liver diseases or in dogs with cPSS and HE. This is in contrast with the previously reported CRP results. This study demonstrates that liver function should be considered when interpreting haptoglobin concentrations in dogs.

No change in calreticulin with fetal growth restriction in human and rat pregnancies.

INTRODUCTION: Calreticulin is a ubiquitously expressed protein that was detected in the circulation and is significantly increased in maternal blood during human pregnancy compared to the non-pregnant state. Calreticulin is further increased in the plasma of women with the pregnancy-related disorder pre-eclampsia compared to normotensive pregnancy. The aims of this study were to compare calreticulin in human pregnancy with calreticulin in rat pregnancy, and to compare calreticulin during fetal growth restriction with normal control pregnancies. METHODS: Women were recruited who either had normal pregnancies or had pregnancies complicated with fetal growth restriction; maternal blood samples and placentas were collected. Blood was also taken from women who were not-pregnant. Growth restriction was induced in pregnant rats by uterine vessel ligation; blood and placental samples were collected. Blood was also taken from non-pregnant rats. Western blot was used to quantify the placental expression of calreticulin and the concentrations of calreticulin in plasma. RESULTS: Although calreticulin was significantly increased in maternal plasma during human pregnancy compared to the non-pregnant state; it did not increase in plasma during rat pregnancy. These results suggest that there may be differences in the role of extracellular calreticulin in human compared to rat pregnancy. Calreticulin was not significantly altered in either placental extracts or maternal plasma in both the human and rat pregnancies complicated by fetal growth restriction compared to gestational matched control pregnancies. CONCLUSION: This study found that there was no change in calreticulin during human pregnancy complicated with fetal growth restriction or when growth restriction is induced in rats.

Infectious agent screening in canine blood donors in the United Kingdom.

OBJECTIVES: Transfusion of blood products is an important component of veterinary emergency medicine. Donors must be carefully selected to minimise risk of transmission of blood-borne infectious agents. This study was devised to assess the prevalence of such agents in healthy, non-travelled UK dogs screened as prospective donors. METHODS: Ethylenediaminetetraacetic acid blood samples from dogs donating blood between August 2007 and January 2012 were screened by polymerase chain reaction for haemotropic mycoplasmas, Bartonella, Babesia, Leishmania, Ehrlichia and Anaplasma spp. Dogs with positive or inconclusive results underwent repeat polymerase chain reaction testing. RESULTS: Four of 262 dogs had positive or inconclusive results at initial screening. Repeat polymerase chain reaction testing in each dog was negative, and none of the dogs developed clinical signs of disease. CLINICAL SIGNIFICANCE: The positive results on initial screening may have represented false positives from sample contamination or amplification of non-target DNA. It is also possible that dogs were infected at initial sampling but successfully cleared infection before repeat testing. The low number of positive results obtained suggests that prevalence of these agents in a population of healthy UK dogs is low and that use of blood products is unlikely to represent a significant risk of transmission of these diseases.

Calreticulin has opposing effects on the migration of human trophoblast and myometrial endothelial cells.

Calreticulin is a calcium binding, endoplasmic reticulum resident protein best known for its roles in intracellular calcium homeostasis and the quality control processes of the endoplasmic reticulum. There is evidence for a range of activities for calreticulin outside the endoplasmic reticulum, including in the cytosol, on the surface of different cells types and in the extracellular matrix. Recent evidence indicates that human pregnancy is a condition of elevated circulating calreticulin. Calreticulin was increased in the plasma of women throughout pregnancy compared to the non-pregnant state. Calreticulin was also further increased during the hypertensive disorder of human pregnancy, pre-eclampsia. To clarify the roles of circulating calreticulin in pregnancy and pre-eclampsia, the aim of this study was to determine the effects of exogenous calreticulin on two cell types that are relevant to normal human pregnancy and to pre-eclampsia. Human primary myometrial microvascular endothelial cells (UtMVEC-Myo) and the human trophoblast cell line, HTR8/SVneo, were cultured with exogenous calreticulin at concentrations (2 µg/ml and 5 µg/ml) comparable to that measured in maternal blood. The higher concentration of calreticulin significantly increased the migration of the UtMVEC-Myo cells, but significantly reduced the migration of the HTR8/SVneo cells. In the presence of only FGF, FBS and antibiotics calreticulin at 5 µg/ml significantly reduced the number of UtMVEC-Myo cells during in vitro culture for 120 h. These results demonstrate that exogenous calreticulin can alter both HTR8/SVneo and UtMVEC-Myo cell functions in vitro at a (patho-) physiologically relevant concentration. Increased calreticulin may also contribute to altered functions of both cell types during pre-eclampsia.

Dogs with congenital porto-systemic shunting (cPSS) and hepatic encephalopathy have higher serum concentrations of C-reactive protein than asymptomatic dogs with cPSS.

Hepatic encephalopathy (HE) is a cause of significant morbidity and mortality in patients with liver disorders and a wide range of rodent models of HE have been described to facilitate studies into the pathogenesis and treatment of HE. However, it is widely acknowledged that no individual model perfectly mimics human HE and there is a particular need for spontaneous, larger animal models. One common congenital abnormality in dogs is the portosystemic shunt (cPSS) which causes clinical signs that are similar to human HE such as ataxia, disorientation, lethargy and occasionally coma. As inflammation has recently been shown to be associated with HE in humans, we hypothesised that inflammation would similarly be associated with HE in dogs with cPSS. To examine this hypothesis we measured C-reactive protein (CRP) in 30 healthy dogs, 19 dogs with a cPSS and no HE and 27 dogs with a cPSS and overt HE. There was a significant difference in CRP concentration between healthy dogs and dogs with HE (p < 0.001) and between dogs with HE and without HE (p < 0.05). The novel finding that there is an association between inflammation and canine HE strengthens the concept that HE in dogs with cPSS shares a similar pathogenesis to humans with HE. Consequently, dogs with a cPSS may be a good spontaneous model of human HE in which to further examine the role of inflammation and development of HE.