Improving outcomes for donation after circulatory death kidney transplantation: Science of the times

The use of kidneys donated after circulatory death (DCD) remains controversial due to concerns with regard to high incidences of early graft loss, delayed graft function (DGF), and impaired graft survival. As these concerns are mainly based on data from historical cohorts, they are prone to time-related effects and may therefore not apply to the current timeframe. To assess the impact of time on outcomes, we performed a time-dependent comparative analysis of outcomes of DCD and donation after brain death (DBD) kidney transplantations. Data of all 11,415 deceased-donor kidney transplantations performed in The Netherlands between 1990-2018 were collected. Based on the incidences of early graft loss, two eras were defined (1998-2008 [n = 3,499] and 2008-2018 [n = 3,781]), and potential time-related effects on outcomes evaluated. Multivariate analyses were applied to examine associations between donor type and outcomes. Interaction tests were used to explore presence of effect modification. Results show clear time-related effects on posttransplant outcomes. The 1998-2008 interval showed compromised outcomes for DCD procedures (higher incidences of DGF and early graft loss, impaired 1-year renal function, and inferior graft survival), whereas DBD and DCD outcome equivalence was observed for the 2008-2018 interval. This occurred despite persistently high incidences of DGF in DCD grafts, and more adverse recipient and donor risk profiles (recipients were 6 years older and the KDRI increased from 1.23 to 1.39 and from 1.35 to 1.49 for DBD and DCD donors). In contrast, the median cold ischaemic period decreased from 20 to 15 hours. This national study shows major improvements in outcomes of transplanted DCD kidneys over time. The time-dependent shift underpins that kidney transplantation has come of age and DCD results are nowadays comparable to DBD transplants. It also calls for careful interpretation of conclusions based on historical cohorts, and emphasises that retrospective studies should correct for time-related effects.Transplant surger

Perceived risk, anxiety, and behavioural responses of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands: Results of three consecutive online surveys

Background: Research into risk perception and behavioural responses in case of emerging infectious diseases is still relatively new. The aim of this study was to examine perceptions and behaviours of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands. Methods. Two cross-sectional and one follow-up online survey (survey 1, 30 April-4 May; survey 2, 15-19 June; survey 3, 11-20 August 2009). Adults aged 18 years and above participating in a representative Internet panel were invited (survey 1, n = 456; survey 2, n = 478; follow-up survey 3, n = 934). Main outcome measures were 1) time trends in risk perception, feelings of anxiety, and behavioural responses (survey 1-3) and 2) factors associated with taking preventive measures and strong intention to comply with government-advised preventive measures in the future (survey 3). Results. Between May and August 2009, the level of knowledge regarding Influenza A (H1N1) increased, while perceived severity of the new flu, perceived self-efficacy, and intention to comply with preventive measures decreased. The perceived reliability of information from the government decreased from May to August (62% versus 45%). Feelings of anxiety decreased from May to June, and remained stable afterwards. From June to August 2009, perceived vulnerability increased and more respondents took preventive measures (14% versus 38%). Taking preventive measures was associated with no children in the household, high anxiety, high self-efficacy, more agreement with statements on avoidance, and paying much attention to media information regarding Influenza A (H1N1). Having a strong intention to comply with government-advised preventive measures in the future was associated with higher age, high perceived severity, high anxiety, high perceived efficacy of measures, high self-efficacy, and finding governmental information to be reliable. Conclusions. Decreasing tren

Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure

PCA3 molecular urine assay for prostate cancer: association with pathologic features and impact of collection protocols

IntroductionPCA3 is a non-coding mRNA molecule that is overexpressed in prostate cancer. The purpose of this study is to evaluate the utility of the PCA3 molecular urine test scores to predict adverse pathologic features and catheterized specimen collection.MethodsHundred men with clinically localized prostate cancer scheduled to undergo robotic prostatectomy were enrolled in the study following a standard consent process. The study protocol consisted of providing four urine samples. Voided urine obtained following digital rectal examination (DRE) pre-operatively (Vl), catheterized urine without DRE (V2), and l0-day and 6-week postoperative voided (V3 and V4) urine samples were collected and analyzed. These four urine specimens underwent target capture, transcription-mediated amplification, and hybridization in order to quantify both PCA3 and PSA mRNA. The PCA3 score was calculated as the ratio of PCA3 to PSA.ResultsInformative rates (sufficient mRNA for analysis) for VI, V2, V3 and V4 were 91, 85, 0 and 2%, respectively. There was no significant associations with pathological stage, Gleason score >6. Higher PCA3 scores at V1 correlated with increased risk for perineural invasion (P = 0.0479).ConclusionsInformative PCA3 scores can be obtained from post-DRE voided urine as well as catheterized urine without a DRE. The PCA3 test does not seem to predict adverse pathologic features, though, may have an association with perineural invasion. The ability of PCA3 score to predict clinical outcome remains to be determined

Monitoring the level of government trust, risk perception and intention of the general public to adopt protective measures during the influenza A (H1N1) pandemic in the Netherlands

<p>Abstract</p> <p>Background</p> <p>During the course of an influenza pandemic, governments know relatively little about the possibly changing influence of government trust, risk perception, and receipt of information on the public's intention to adopt protective measures or on the acceptance of vaccination. This study aims to identify and describe possible changes in and factors associated with public's intentions during the 2009 influenza A (H1N1) pandemic in the Netherlands.</p> <p>Methods</p> <p>Sixteen cross-sectional telephone surveys were conducted (N = 8060) between April - November 2009. From these repeated measurements three consecutive periods were categorized based on crucial events during the influenza A (H1N1) pandemic. Time trends in government trust, risk perception, intention to adopt protective measures, and the acceptance of vaccination were analysed. Factors associated with an intention to adopt protective measures or vaccination were identified.</p> <p>Results</p> <p>Trust in the government was high, but decreased over time. During the course of the pandemic, perceived vulnerability and an intention to adopt protective measures increased. Trust and vulnerability were associated with an intention to adopt protective measures in general only during period one. Higher levels of intention to receive vaccination were associated with increased government trust, fear/worry, and perceived vulnerability. In periods two and three receipt of information was positively associated with an intention to adopt protective measures. Most respondents wanted to receive information about infection prevention from municipal health services, health care providers, and the media.</p> <p>Conclusions</p> <p>The Dutch response to the H1N1 virus was relatively muted. Higher levels of trust in the government, fear/worry, and perceived vulnerability were all positively related to an intention to accept vaccination. Only fear/worry was positively linked to an intention to adopt protective measures during the entire pandemic. Risk and crisis communication by the government should focus on building and maintaining trust by providing information about preventing infection in close collaboration with municipal health services, health care providers, and the media.</p

Neurogenic mechanisms in bladder and bowel ageing

The prevalence of both urinary and faecal incontinence, and also chronic constipation, increases with ageing and these conditions have a major impact on the quality of life of the elderly. Management of bladder and bowel dysfunction in the elderly is currently far from ideal and also carries a significant financial burden. Understanding how these changes occur is thus a major priority in biogerontology. The functions of the bladder and terminal bowel are regulated by complex neuronal networks. In particular neurons of the spinal cord and peripheral ganglia play a key role in regulating micturition and defaecation reflexes as well as promoting continence. In this review we discuss the evidence for ageing-induced neuronal dysfunction that might predispose to neurogenic forms of incontinence in the elderly

The effectiveness of adding cognitive behavioural therapy aimed at changing lifestyle to managed diabetes care for patients with type 2 diabetes: design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>In patients with type 2 diabetes, the risk for cardiovascular disease is substantial. To achieve a more favourable risk profile, lifestyle changes on diet, physical activity and smoking status are needed. This will involve changes in behaviour, which is difficult to achieve. Cognitive behavioural therapies focussing on self-management have been shown to be effective. We have developed an intervention combining techniques of Motivational Interviewing (MI) and Problem Solving Treatment (PST). The aim of our study is to investigate if adding a combined behavioural intervention to managed care, is effective in achieving changes in lifestyle and cardiovascular risk profile.</p> <p>Methods</p> <p>Patients with type 2 diabetes will be selected from general practices (n = 13), who are participating in a managed diabetes care system. Patients will be randomised into an intervention group receiving cognitive behaviour therapy (CBT) in addition to managed care, and a control group that will receive managed care only. The CBT consists of three to six individual sessions of 30 minutes to increase the patient's motivation, by using principles of MI, and ability to change their lifestyle, by using PST. The first session will start with a risk assessment of diabetes complications that will be used to focus the intervention.</p> <p>The primary outcome measure is the difference between intervention and control group in change in cardiovascular risk score. For this purpose blood pressure, HbA_1c, total and HDL-cholesterol and smoking status will be assessed. Secondary outcome measures are quality of life, patient satisfaction, physical activity, eating behaviour, smoking status, depression and determinants of behaviour change. Differences between changes in the two groups will be analysed according to the intention-to-treat principle, with 95% confidence intervals. The power calculation is based on the risk for cardiovascular disease and we calculated that 97 patients should be included in every group.</p> <p>Discussion</p> <p>Cognitive behavioural therapy may improve self-management and thus strengthen managed diabetes care. This should result in changes in lifestyle and cardiovascular risk profile. In addition, we also expect an improvement of quality of life and patient satisfaction.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN12666286</p

Hepatobiliary and pancreatic tuberculosis: A two decade experience

<p>Abstract</p> <p>Background</p> <p>Isolated hepatobiliary or pancreatic tuberculosis (TB) is rare and preoperative diagnosis is difficult. We reviewed our experience over a period two decades with this rare site of abdominal tuberculosis.</p> <p>Methods</p> <p>The records of 18 patients with proven histological diagnosis of hepatobiliary and pancreatic tuberculosis were reviewed retrospectively. The demographic features, sign and symptoms, imaging, cytology/histopathology, procedures performed, outcome and follow up data were obtained from the departmental records. The diagnosis of tuberculosis was based on granuloma with caseation necrosis on histopathology or presence of acid fast bacilli.</p> <p>Results</p> <p>Of 18 patients (11 men), 11 had hepatobiliary TB while 7 had pancreatic TB. Two-thirds of the patients were < 40 years (mean: 42 yrs; range 19–70 yrs). The duration of the symptoms varied between 2 weeks to 104 weeks (mean: 20 weeks). The most common symptom was pain in the abdomen (n = 13), followed by jaundice (n = 10), fever, anorexia and weight loss (n = 9). Five patients (28%) had associated extra-abdominal TB which helped in preoperative diagnosis in 3 patients. Imaging demonstrated extrahepatic bile duct obstruction in the patients with jaundice and in addition picked up liver, gallbladder and pancreatic masses with or without lymphadenopathy (peripancreatic/periportal). Preoperative diagnosis was made in 4 patients and the other 14 were diagnosed after surgery. Two patients developed significant postoperative complications (pancreaticojejunostomy leak <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> intraabdominal abscess <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>) and 3 developed ATT induced hepatotoxicity. No patient died. The median follow up period was 12 months (9 – 96 months).</p> <p>Conclusion</p> <p>Tuberculosis should be considered as a differential diagnosis, particularly in young patients, with atypical signs and symptoms coming from areas where tuberculosis is endemic and preoperative tissue and/or cytological diagnosis should be attempted before labeling them as hepatobiliary and pancreatic malignancy.</p

An Outer Membrane Receptor of Neisseria meningitidis Involved in Zinc Acquisition with Vaccine Potential

Since the concentration of free iron in the human host is low, efficient iron-acquisition mechanisms constitute important virulence factors for pathogenic bacteria. In Gram-negative bacteria, TonB-dependent outer membrane receptors are implicated in iron acquisition. It is far less clear how other metals that are also scarce in the human host are transported across the bacterial outer membrane. With the aim of identifying novel vaccine candidates, we characterized in this study a hitherto unknown receptor in Neisseria meningitidis. We demonstrate that this receptor, designated ZnuD, is produced under zinc limitation and that it is involved in the uptake of zinc. Upon immunization of mice, it was capable of inducing bactericidal antibodies and we could detect ZnuD-specific antibodies in human convalescent patient sera. ZnuD is highly conserved among N. meningitidis isolates and homologues of the protein are found in many other Gram-negative pathogens, particularly in those residing in the respiratory tract. We conclude that ZnuD constitutes a promising candidate for the development of a vaccine against meningococcal disease for which no effective universal vaccine is available. Furthermore, the results suggest that receptor-mediated zinc uptake represents a novel virulence mechanism that is particularly important for bacterial survival in the respiratory tract

Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation

Noncoding Y RNAs have recently been identified as essential factors for chromosomal DNA replication in human cell nuclei. Here, we investigate the expression of human Y RNAs in tumours and test their requirement for cell proliferation. Relative expression levels of all four human Y RNAs (hY1, hY3, hY4 and hY5 RNA) were determined by quantitative RT–PCR in extracts from human solid tumours, corresponding nonmalignant normal tissues and derived cultured cells. On average, all four hY RNAs are significantly overexpressed in solid tumours between 4- and 13-fold, compared to the corresponding normal tissues. In particular, hY1 and hY3 RNAs are overexpressed in carcinomas (and adenocarcinomas) of the bladder, cervix, colon, kidney, lung and prostate with extremely high statistical significance (ANOVA, between groups, P<10e-22). A functional requirement of all four hY RNAs for cell proliferation was investigated in a systematic survey for loss-of-function by RNA interference (RNAi). Degradation of hY1 and hY3 RNAs in human cell lines resulted in a significant cytostatic inhibition of cell proliferation. We conclude that noncoding hY RNAs have potential both as new cancer biomarkers and as molecular targets for anti-proliferative intervention