Evidence for Recipient-Derived Cells in Peribiliary Glands and Biliary Epithelium of the Large Donor Bile Ducts After Liver Transplantation

Introduction Chimerism after orthotopic liver transplantation (OLT) has largely been investigated in intrahepatic cellular constituents. However, little is known about chimerism in the extrahepatic and large intrahepatic bile ducts. Our aim was to evaluate the presence and extent of chimerism after OLT in the peribiliary glands (PBG) and the luminal epithelium of the large donor bile ducts. Methods For this study, we examined six extrahepatic and large intrahepatic bile ducts from livers that were re-transplanted. In all cases there was a sex-mismatch between donor and recipient (female donor organ and male recipient), which allowed to discriminate between donor- and recipient-derived cells. Specimens from female to female transplants were used as negative controls and male to male transplants as positive controls. Fluorescencein situhybridization (FISH) for Y and X chromosomes was performed and the percentage of XY positive cells was determined among biliary epithelial cells. Immunohistochemistry was used to correlate chimerism with histological features. Results Cholangiocellular chimerism in all studied specimens ranged from 14 to 52%. The degree of chimerism was not associated with biliary damage. Marked chimerism was present at 5 days post-OLT. Ki-67-positivity was detected in 1-8% of the epithelial cells at the time of liver re-transplantation, and this correlated inversely with the degree of chimerism. Conclusion Recipient-derived cholangiocytes are present in the large bile ducts of the donor liver after OLT. The presence of chimerism in the large bile ducts suggests that recipient-derived cells may play a role in biliary regeneration following ischemia-induced injury during OLT

Tick Ecdysteroid Hormone, Global Microbiota/\u3ci\u3eRickettsia\u3c/i\u3e Signaling in the Ovary Versus Carcass During Vitellogenesis in Part-Fed (Virgin) American Dog Ticks, \u3ci\u3eDermacentor variabilis\u3c/i\u3e

The transovarial transmission of tick-borne bacterial pathogens is an important mechanism for their maintenance in natural populations and transmission, causing disease in humans and animals. The mechanism for this transmission and the possible role of tick hormones facilitating this process have never been studied. Injections of physiological levels of the tick hormone, 20-hydroxyecdysone (20E), into part-fed (virgin) adult females of the American dog tick, Dermacentor variabilis, attached to the host caused a reduction in density of Rickettsia montanensis in the carcass and an increase in the ovaries compared to buffer-injected controls. This injection initiates yolk protein synthesis and uptake by the eggs but has no effect on blood feeding. Francisella sp. and R. montanensis were the predominant bacteria based on the proportionality in the carcass and ovary. The total bacteria load increased in the carcass and ovaries, and bacteria in the genus Pseudomonas increased in the carcass after the 20E injection. The mechanism of how the Rickettsia species respond to changes in tick hormonal regulation needs further investigation. Multiple possible mechanisms for the proliferation of R. montanensis in the ovaries are proposed

Impact of modulation on CMB B-mode polarization experiments

We investigate the impact of both slow and fast polarization modulation strategies on the science return of upcoming ground-based experiments aimed at measuring the B-mode polarization of the CMB. Using simulations of the Clover experiment, we compare the ability of modulated and un-modulated observations to recover the signature of gravitational waves in the polarized CMB sky in the presence of a number of anticipated systematic effects. The general expectations that fast modulation is helpful in mitigating low-frequency detector noise, and that the additional redundancy in the projection of the instrument's polarization sensitivity directions onto the sky when modulating reduces the impact of instrumental polarization, are borne out by our simulations. Neither low-frequency polarized atmospheric fluctuations nor systematic errors in the polarization sensitivity directions are mitigated by modulation. Additionally, we find no significant reduction in the effect of pointing errors by modulation. For a Clover-like experiment, pointing jitter should be negligible but any systematic mis-calibration of the polarization coordinate reference system results in significant E-B mixing on all angular scales and will require careful control. We also stress the importance of combining data from multiple detectors in order to remove the effects of common-mode systematics (such as 1/f atmospheric noise) on the measured polarization signal. Finally we compare the performance of our simulated experiment with the predicted performance from a Fisher analysis. We find good agreement between the Fisher predictions and the simulations except for the very largest scales where the power spectrum estimator we have used introduces additional variance to the B-mode signal recovered from our simulations.Comment: Replaced with version accepted by MNRAS. Analysis of half-wave plate systematic (differential transmittance) adde

Severe osteomyelitis caused by Myceliophthora thermophila after a pitchfork injury

BACKGROUND: Traumatic injuries occurring in agricultural settings are often associated with infections caused by unusual organisms. Such agents may be difficult to isolate, identify, and treat effectively. CASE REPORT: A 4-year-old boy developed an extensive infection of his knee and distal femur following a barnyard pitchfork injury. Ultimately the primary infecting agent was determined to be Myceliophthora thermophila, a thermophilic melanized hyphomycete, rarely associated with human infection, found in animal excreta. Because of resistance to standard antifungal agents including amphotericin B and caspofungin, therapy was instituted with a prolonged course of terbinafine and voriconazole. Voriconazole blood levels demonstrated that the patient required a drug dosage (13.4 mg/kg) several fold greater than that recommended for adults in order to attain therapeutic blood levels. CONCLUSION: Unusual pathogens should be sought following traumatic farm injuries. Pharmacokinetic studies may be of critical importance when utilizing antifungal therapy with agents for which little information exists regarding drug metabolism in children

Health-state utilities in a prisoner population : a cross-sectional survey

Background: Health-state utilities for prisoners have not been described. Methods: We used data from a 1996 cross-sectional survey of Australian prisoners (n = 734). Respondent-level SF-36 data was transformed into utility scores by both the SF-6D and Nichol's method. Socio-demographic and clinical predictors of SF-6D utility were assessed in univariate analyses and a multivariate general linear model. Results: The overall mean SF-6D utility was 0.725 (SD 0.119). When subdivided by various medical conditions, prisoner SF-6D utilities ranged from 0.620 for angina to 0.764 for those with none/mild depressive symptoms. Utilities derived by the Nichol's method were higher than SF-6D scores, often by more than 0.1. In multivariate analysis, significant independent predictors of worse utility included female gender, increasing age, increasing number of comorbidities and more severe depressive symptoms. Conclusion: The utilities presented may prove useful for future economic and decision models evaluating prison-based health programs

Inhibition of Toll-Like Receptor 4 Signaling Mitigates Microvascular Loss but Not Fibrosis in a Model of Ischemic Acute Kidney Injury

The development of chronic kidney disease (CKD) following an episode of acute kidney injury (AKI) is an increasingly recognized clinical problem. Inhibition of toll-like receptor 4 (TLR4) protects renal function in animal models of AKI and has become a viable therapeutic strategy in AKI. However, the impact of TLR4 inhibition on the chronic sequelae of AKI is unknown. Consequently, we examined the chronic effects of TLR4 inhibition in a model of ischemic AKI. Mice with a TLR4-deletion on a C57BL/6 background and wild-type (WT) background control mice (C57BL/6) were subjected to bilateral renal artery clamping for 19 min and reperfusion for up to 6 weeks. Despite the acute protective effect of TLR4 inhibition on renal function (serum creatinine 1.6 ± 0.4 mg/dL TLR4-deletion vs. 2.8 ± 0.3 mg/dL·WT) and rates of tubular apoptosis following ischemic AKI, we found no difference in neutrophil or macrophage infiltration. Furthermore, we observed significant protection from microvascular rarefaction at six weeks following injury with TLR4-deletion, but this did not alter development of fibrosis. In conclusion, we validate the acute protective effect of TLR4 signal inhibition in AKI but demonstrate that this protective effect does not mitigate the sequential fibrogenic response in this model of ischemic AKI

C-Band All-Sky Survey: A First Look at the Galaxy

We present an analysis of the diffuse emission at 5 GHz in the first quadrant of the Galactic plane using two months of preliminary intensity data taken with the C-Band All Sky Survey (C-BASS) northern instrument at the Owens Valley Radio Observatory, California. Combining C-BASS maps with ancillary data to make temperature-temperature plots we find synchrotron spectral indices of $\beta = -2.65 \pm 0.05$ between 0.408 GHz and 5 GHz and $\beta = -2.72 \pm 0.09$ between 1.420 GHz and 5 GHz for $-10^{\circ} < |b| < -4^{\circ}$, $20^{\circ} < l < 40^{\circ}$. Through the subtraction of a radio recombination line (RRL) free-free template we determine the synchrotron spectral index in the Galactic plane ($|b| < 4^{\circ}$) to be $\beta = -2.56 \pm 0.07$ between 0.408 GHz and 5 GHz, with a contribution of $53 \pm 8$ per cent from free-free emission at 5\,GHz. These results are consistent with previous low frequency measurements in the Galactic plane. By including C-BASS data in spectral fits we demonstrate the presence of anomalous microwave emission (AME) associated with the HII complexes W43, W44 and W47 near 30 GHz, at 4.4 sigma, 3.1 sigma and 2.5 sigma respectively. The CORNISH VLA 5 GHz source catalogue rules out the possibility that the excess emission detected around 30\;GHz may be due to ultra-compact HII regions. Diffuse AME was also identified at a 4 sigma level within $30^{\circ} < l < 40^{\circ}$, $-2^{\circ} < b < 2^{\circ}$ between 5 GHz and 22.8 GHz.Comment: 16 pages, 9 figures, submitted to MNRAS, referee's corrections made, awaiting for final approval for publicatio

Smoking and quit attempts during pregnancy and postpartum: a longitudinal UK cohort.

OBJECTIVES: Pregnancy motivates women to try stopping smoking, but little is known about timing of their quit attempts and how quitting intentions change during pregnancy and postpartum. Using longitudinal data, this study aimed to document women's smoking and quitting behaviour throughout pregnancy and after delivery. DESIGN: Longitudinal cohort survey with questionnaires at baseline (8-26 weeks' gestation), late pregnancy (34-36 weeks) and 3 months after delivery. SETTING: Two maternity hospitals in one National Health Service hospital trust, Nottingham, England. PARTICIPANTS: 850 pregnant women, aged 16 years or over, who were current smokers or had smoked in the 3 months before pregnancy, were recruited between August 2011 and August 2012. OUTCOME MEASURES: Self-reported smoking behaviour, quit attempts and quitting intentions. RESULTS: Smoking rates, adjusting for non-response at follow-up, were 57.4% (95% CI 54.1 to 60.7) at baseline, 59.1% (95% CI 54.9 to 63.4) in late pregnancy and 67.1% (95% CI 62.7 to 71.5) 3 months postpartum. At baseline, 272 of 488 current smokers had tried to quit since becoming pregnant (55.7%, 95% CI 51.3 to 60.1); 51.3% (95% CI 44.7 to 58.0) tried quitting between baseline and late pregnancy and 27.4% (95% CI 21.7 to 33.2) after childbirth. The percentage who intended to quit within the next month fell as pregnancy progressed, from 40.4% (95% CI 36.1 to 44.8) at baseline to 29.7% (95% CI 23.8 to 35.6) in late pregnancy and 14.2% (95% CI 10.0 to 18.3) postpartum. Postpartum relapse was lower among women who quit in the 3 months before pregnancy (17.8%, 95% CI 6.1 to 29.4) than those who stopped between baseline and late pregnancy (42.9%, 95% CI 24.6 to 61.3). CONCLUSIONS: Many pregnant smokers make quit attempts throughout pregnancy and postpartum, but intention to quit decreases over time; there is no evidence that smoking rates fall during gestation

Longitudinal cohort survey of women's smoking behaviour and attitudes in pregnancy: study methods and baseline data.

OBJECTIVES: To report the methods used to assemble a contemporary pregnancy cohort for investigating influences on smoking behaviour before, during and after pregnancy and to report characteristics of women recruited. DESIGN: Longitudinal cohort survey. SETTING: Two maternity hospitals, Nottingham, England. PARTICIPANTS: 3265 women who attended antenatal ultrasound scan clinics were offered cohort enrolment; those who were 8-26 weeks pregnant and were currently smoking or had recently stopped smoking were eligible. Cohort enrollment took place between August 2011 and August 2012. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of smoking at cohort entry and at two follow-up time points (34-36 weeks gestation and 3 months postnatally); response rate, participants' sociodemographic characteristics. RESULTS: 1101 (33.7%, 95% CI 32.1% to 35.4%) women were eligible for inclusion in the cohort, and of these 850 (77.2%, 95% CI 74.6% to 79.6%) were recruited. Within the cohort, 57.4% (N=488, 95% CI 54.1% to 60.7%) reported to be current smokers. Current smokers were significantly younger than ex-smokers (p<0.05), more likely to have no formal qualifications and to not be in current paid employment compared to recent ex-smokers (p<0.001). CONCLUSIONS: This contemporary cohort, which seeks very detailed information on smoking in pregnancy and its determinants, includes women with comparable sociodemographic characteristics to those in other UK cross-sectional studies and cohorts. This suggests that future analyses using this cohort and aimed at understanding smoking behaviour in pregnancy may produce findings that are broadly generalisable