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Insufficient immune tolerance during pregnancy is associated with pathological conditions such as preeclampsia (PE). Soluble fms-like tyrosine kinase-1 (sFLT1), which exerts a role in the late stage of PE, has shown its beneficial anti-inflammatory effects in inflammation-associated diseases. Macrophage migration inhibitory factor (MIF) was reported to upregulate sFLT1 production in experimental congenital diaphragmatic hernia. However, the placental sFLT1 expression in early uncomplicated pregnancy and whether MIF can regulate sFLT1 expression in uncomplicated and preeclamptic pregnancy are unclear. We collected first-trimester placentas and term placentas from uncomplicated and preeclamptic pregnancies to investigate sFLT1 and MIF expression in vivo. Primary cytotrophoblasts (CTBs) and a human trophoblast cell line (Bewo) were used to study the regulation of MIF on sFLT1 expression in vitro. In placentas from first-trimester pregnancy, we observed a high expression of sFLT1, specifically in extravillous trophoblasts (EVTs) and syncytiotrophoblast (STB) cells. MIF mRNA levels strongly correlated with sFLT1 expression in term placentas from preeclamptic pregnancies. In in vitro experiments, sFLT1 and MIF levels increased significantly in CTBs during their differentiation to EVTs and STBs, and MIF inhibitor (ISO-1) significantly reduced sFLT1 expression in a dose-dependent manner during this process. sFLT1 showed significant upregulation with increasing doses of MIF in Bewo cells. Our results show that sFLT1 is highly expressed at the maternal–fetal interface during early pregnancy and that MIF can increase sFLT1 expression in early uncomplicated pregnancy and PE, which suggests that sFLT1 plays an essential role in the modulation of inflammation in pregnancy.

(1) Background: Soluble Fms-like tyrosine kinase 1 (sFLT1) is an endogenous VEGF inhibitor. sFLT1 has been described as an anti-inflammatory treatment for diabetic nephropathy and heart fibrosis. However, sFLT1 has also been related to peritubular capillary (PTC) loss, which promotes fibrogenesis. Here, we studied whether transfection with sFlt1 aggravates experimental AKI-to-CKD transition and whether sFLT1 is increased in human kidney fibrosis. (2) Methods: Mice were transfected via electroporation with sFlt1. After confirming transfection efficacy, mice underwent unilateral ischemia/reperfusion injury (IRI) and were sacrificed 28 days later. Kidney histology and RNA were analyzed to study renal fibrosis, PTC damage and inflammation. Renal sFLT1 mRNA expression was measured in CKD biopsies and control kidney tissue. (3) Results: sFlt1 transfection did not aggravate renal fibrosis, PTC loss or macrophage recruitment in IRI mice. In contrast, higher transfection efficiency was correlated with reduced expression of pro-fibrotic and pro-inflammatory markers. In the human samples, sFLT1 mRNA levels were similar in CKD and control kidneys and were not correlated with interstitial fibrosis or PTC loss. (4) Conclusion: As we previously found that sFLT1 has therapeutic potential in diabetic nephropathy, our findings indicate that sFLT1 can be administered at a dose that is therapeutically effective in reducing inflammation, without promoting maladaptive kidney damage.

Contains fulltext : 240021.pdf (Publisher’s version ) (Open Access) A promising avenue for health behavior change is to influence conversational valence, that is, the extent to which people talk negatively or positively about health behaviors. However, no research to date has experimentally manipulated conversational valence, thereby inhibiting conclusions about causal inferences. This study aims to fill this gap by investigating the influence of conversational valence instructions on perceived conversational valence and subsequent binge drinking determinants. College students (N = 138) read either negative or positive conversational valence instructions. Subsequently, dyads engaged in a 5-min conversation about drinking, before self-reporting perceived conversational valence and binge drinking determinants (i.e., attitudes, norms, perceived behavioral control, and intentions). Results revealed that valence instructions influenced binge drinking determinants via perceived conversational valence. Those instructed to talk negatively about binge drinking reported healthier binge drinking determinants than those instructed to talk positively. Furthermore, this effect on binge drinking determinants was mediated by perceived conversational valence. These findings demonstrate that conversational valence about health can be manipulated through simple instructions and confirm the idea that conversational valence is causally linked to binge drinking determinants. Thereby, these findings show the potential that interpersonal communication in general, and conversational valence instructions, in particular, have when integrated in health interventions. 7 p.

Biomedical imaging is unequivocally dependent on the ability to reconstruct interpretable and high-quality images from acquired sensor data. This reconstruction process is pivotal across many applications, spanning from magnetic resonance imaging to ultrasound imaging. While advanced data-adaptive reconstruction methods can recover much higher image quality than traditional approaches, their implementation often poses a high computational burden. In ultrasound imaging, this burden is significant, especially when striving for low-cost systems, and has motivated the development of high-resolution and high-contrast adaptive beamforming methods. Here we show that deep neural networks, that adopt the algorithmic structure and constraints of adaptive signal processing techniques, can efficiently learn to perform fast high-quality ultrasound beamforming using very little training data. We apply our technique to two distinct ultrasound acquisition strategies (plane wave, and synthetic aperture), and demonstrate that high image quality can be maintained when measuring at low data-rates, using undersampled array designs. Beyond biomedical imaging, we expect that the proposed deep learning based adaptive processing framework can benefit a variety of array and signal processing applications, in particular when data-efficiency and robustness are of importance.

Diabetic nephropathy is the leading cause of end-stage renal disease. Diabetic patients have increased plasma concentrations of apolipoprotein C-I (apoCI), and meta-analyses found that a polymorphism in APOC1 is associated with an increased risk of developing nephropathy. To investigate whether overexpressing apoCI contributes to the development of kidney damage, we studied renal tissue and peritoneal macrophages from APOC1 transgenic (APOC1-tg) mice and wild-type littermates. In addition, we examined renal material from autopsied diabetic patients with and without diabetic nephropathy and from autopsied control subjects. We found that APOC1-tg mice, but not wild-type mice, develop albuminuria, renal dysfunction, and glomerulosclerosis with increased numbers of glomerular M1 macrophages. Moreover, compared to wild-type macrophages, stimulated macrophages isolated from APOC1-tg mice have increased cytokine expression, including TNF-alpha and TGF-beta, both of which are known to increase the production of extracellular matrix proteins in mesangial cells. These results suggest that APOC1 expression induces glomerulosclerosis, potentially by increasing the cytokine response in macrophages. Furthermore, we detected apoCI in the kidneys of diabetic patients, but not in control kidneys. Moreover, patients with diabetic nephropathy have significantly more apoCI present in glomeruli compared to diabetic patients without nephropathy, suggesting that apoCI could be involved in the development of diabetic nephropathy. ApoCI co-localized with macrophages. Therefore, apoCI is a promising new therapeutic target for patients at risk of developing nephropathy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Contains fulltext : 160641.pdf (Publisher’s version ) (Open Access) Health-promoting messages can be framed in terms of the beneficial consequences of healthy behaviour (gain-framed messages) or the detrimental consequences of unhealthy behaviour (loss-framed messages). An influential notion holds that the perceived risk associated with the recommended behaviour determines the relative persuasiveness of gain- and loss-framed messages. This 'risk-framing hypothesis', which was derived from prospect theory, has been central to health message-framing research for the better part of two decades and has enduring appeal to researchers and practitioners. It has found its way into several health communication handbooks and is communicated to the general public. The present article examines the validity of the risk-framing hypothesis anew by providing a review of the health message-framing literature. In spite of its ongoing appeal, we conclude that the hypothesis has severe theoretical flaws. In addition, we find that the empirical evidence in favour of the hypothesis is weak and inconsistent. It seems that, in applying prospect theory's tenets to a health-promotion context, some of the theory's key aspects have been lost in translation. At the close of the article, we offer a research agenda for the future, arguing that, above all, new methodology is needed to bring the message-framing literature further. 13 p.

Objective To investigate the incidence of malignancies during longitudinal followup of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and to examine the effect of immunosuppressive therapy on malignancy risk in these patients. Methods The study population consisted of patients with histopathologically confirmed AAV, diagnosed between 1991 and 2013 at a large university hospital. The mean duration of followup was 10 years. Malignancy incidence was assessed using the Dutch National Pathology Database. Incidence rates from the Netherlands Cancer Registry were used to compare malignancy incidence in the AAV cohort to that in the general Dutch population. Results Thirty-six of 138 patients with AAV developed a total of 85 malignancies during a mean followup of 9.7 years. The sex-, age-, and calendar year–adjusted malignancy risk was 2.21-fold higher (95% confidence interval [95% CI] 1.64–2.92) than that in the general population. Non-melanoma skin cancers occurred most frequently (standardized incidence ratio 4.23 [95% CI 2.76–6.19]). The incidence rates of other malignancies were not significantly increased. Malignancy risk was associated with the duration of cyclophosphamide (CYC) therapy and, interestingly, was not increased in patients who had received CYC for

Health campaign effects may be improved by taking interpersonal communication processes into account. The current study, which employed an experimental, pretest-posttest, randomized exposure design (N = 208), investigated whether the emotions induced by anti-alcohol messages influence conversational valence about alcohol and subsequent persuasion outcomes. The study produced three main findings. First, an increase in the emotion fear induced a negative conversational valence about alcohol. Second, fear was most strongly induced by a disgusting message, whereas a humorous appeal induced the least fear. Third, a negative conversational valence elicited healthier binge drinking attitudes, subjective norms, perceived behavioral control, intentions, and behaviors. Thus, health campaign planners and health researchers should pay special attention to the emotional characteristics of health messages and should focus on inducing a healthy conversational valence.

The present study experimentally investigated the interplay between interpersonal communication and health message exposure in relation to alcohol consumption intentions. Participants were 174 students who took part in a study on the effects of an antialcohol message. At baseline, the authors assessed intention to refrain from binge drinking. At the second wave (2 weeks later), participants were assigned to the conditions of a 2 (antialcohol message or no-alcohol message) × 2 (alcohol conversation or control conversation) between-subjects design, after which intention was again assessed. Results showed that when participants talked about alcohol (instead of the control topic) and were not exposed to an antialcohol message, they were less inclined to refrain from binge drinking, an effect that was not visible when participants talked about alcohol after viewing an antialcohol message. These findings suggest that health campaign exposure moderates the influence of interpersonal communication on health variables.

To study the effects of framed messages on exercise intention and resolve.Two (type of frame: gain or loss) × 2 (type of kernel state: desirable or undesirable outcome) post-test study.Participants were recruited online and questioned about their previous exercise behaviour and their exercise risk perception. After this, they were randomly allocated to one of four messages that were different in terms of positive or negative outcomes (type of frame) and in terms of attained or avoided outcomes (type of kernel state). After reading the message, participants indicated their intention and resolve to engage in sufficient exercise.No effects were found for intention. For resolve, there was a significant interaction between type of frame, type of kernel state, and exercise adherence. Those who did not adhere to the exercise guideline and read the loss-framed message with attained outcomes reported significantly higher resolve than all other participants.This study indicates the relevance of including attained outcomes in message framing exercise interventions as well as a focus on exercise resolve.What is already known on this subject? Message framing is commonly used to increase exercise intentions and behaviour. Meta-analyses do not provide consistent support for this theory. Very little attention has been paid to resolve and message factors on framing effects. What does this study add? Framed messages have an effect on exercise resolve, but not on intention. Loss-framed messages with attained outcomes are most persuasive for those who do not adhere to exercise guidelines. Exercise framing studies should include behavioural resolve next to intention. .

Contains fulltext : 127707pre.pdf (Author’s version preprint ) (Open Access) Health-promoting messages can be framed in terms of the beneficial consequences of healthy behaviour (gain-framed messages) or the detrimental consequences of unhealthy behaviour (loss-framed messages). An influential notion holds that the perceived risk associated with the recommended behaviour determines the relative persuasiveness of gain- and loss-framed messages. This 'risk-framing hypothesis', as we call it, was derived from prospect theory, has been central to health message framing research for the last two decades, and does not cease to appeal to researchers. The present paper examines the validity of the risk-framing hypothesis. We performed six empirical studies on the interaction between perceived risk and message framing. These studies were conducted in two different countries and employed framed messages targeting skin cancer prevention and detection, physical activity, breast self-examination and vaccination behaviour. Behavioural intention served as the outcome measure. None of these studies found evidence in support of the risk-framing hypothesis. We conclude that the empirical evidence in favour of the hypothesis is weak and discuss the ramifications of this for future message framing research. 17 p.

ObjectivesIn the action control framework, intention-behaviour discordance is studied around public health guidelines. Although this framework has been applied to physical activity behaviours, it has only seen very limited attention regarding fruit intake. The purpose of this study was therefore to investigate distributions and predictors of fruit intake intention-behaviour discordance.DesignProspective correlational design.MethodsData were obtained from undergraduate students (n = 413) using validated questionnaires. Variables from the theory of planned behaviour, automaticity, and action planning were assessed at baseline, and fruit intake was assessed 2 weeks later. Data were analysed using discriminant function analyses and analyses of variance.ResultsThe proportion of unsuccessful intenders ranged from 39.2% to 80.8%. There was a larger proportion of fruit intake intenders amongst those who reported strong automatic fruit intake. Action control was predicted by fruit intake automaticity and affective attitudes, but the strongest predictor was perceived behavioural control. No action planning items were related to fruit intake action control.ConclusionsThere is considerable asymmetry in the intention-fruit intake relationship. An application of the action control framework may stimulate debate on the applicability of intention-based models at the public health level.Statement of contributionWhat is already known on this subject?Intention is theorized to be a key construct in fruit intake.Studies in the physical activity domain indicate that nearly half of the people with positive intentions fail to subsequently act.What does this study add?The proportion of unsuccessful intenders ranged from 39.2% to 80.8%.Holding positive intentions is not sufficient to consume fruit at suggested public health guidelines.Perceived behavioural control is the most important predictor of fruit intake action control.

BACKGROUND Pre-eclampsia has a clear familial component, suggesting that the condition may be partly attributable to genetic susceptibility. The search for susceptibility genes has led to a drastic increase in the number of published studies associating genetic factors with pre-eclampsia. However, attempts to replicate these findings have yielded inconsistent results. This meta-analysis assessed the pooled effect of each genetic variant that is reproducibly associated with pre-eclampsia. METHODS Studies that assessed the association between genes and pre-eclampsia were searched in PubMed, Embase and Web of Science. We selected all genetic variants that were significantly associated with pre-eclampsia in an initial study and were subsequently independently reproduced in at least one additional study. All studies that assessed these reproduced variants were then included. The association between genetic variants and pre-eclampsia was calculated at the allele level, and the main measure of effect was a pooled odds ratio in a random-effects model. RESULTS The literature search yielded 2965 articles, of which 542 investigated genetic associations in pre-eclampsia. We identified 22 replicated genetic variants, of which 7 remained significantly associated with pre-eclampsia following meta-analysis. These variants were in or near the following genes: ACE, CTLA4, F2, FV, LPL and SERPINE1. CONCLUSIONS This meta-analysis identified seven genetic variants associated with pre-eclampsia. Importantly, many of these variants are also risk factors for developing cardiovascular disease, revealing that pre-eclampsia and cardiovascular disease have shared genetic risk factors. The contribution of the identified genetic variants in the pathogenesis of pre-eclampsia should be the focus of future studies.

Preeclampsia is a significant cause of maternal and fetal morbidity and mortality worldwide. A clinically useful screening test that can predict development of preeclampsia at an early stage is urgently needed. The detection of podocyturia by immunohistochemistry after cell culture has been noted as a reliable marker for preeclampsia. However, this method is laborious and carries the risk of cell culture contamination. The aim of this study was to investigate the diagnostic value of quantitative polymerase chain reaction as a rapid method to detect preeclampsia. Clean-catch urine samples were collected from preeclamptic (n=35), healthy pregnant (n=34), and healthy nonpregnant (n=12) women. Furthermore, a control group of women with gestational hypertension (n=5) was included. Quantitative polymerase chain reaction analysis was performed for podocyte-specific markers. Receiver operating characteristic curve analyses were performed. Significantly elevated mRNA levels of nephrin, podocin, and vascular endothelial growth factor were detected in preeclamptic women compared with healthy pregnant and healthy nonpregnant controls. In addition, significantly elevated levels of nephrin mRNA were detected in urine of preeclamptic women compared with women with gestational hypertension. A positive correlation (ρ=0.82; P

BACKGROUND Allogeneic islets of Langerhans transplantation is hampered in its success as a curative treatment of type 1 diabetes by the absence of potent, specific, and nontoxic immunosuppressive drugs. Here, we assessed whether donor bone marrow-derived dexamethasone-treated dendritic cells (dexDCs) could prolong islet allograft survival in a full major histocompatibility complex mismatch rat model. METHODS Rodent allogeneic islet transplantation was performed from DA rats to Lewis rats and vice versa. Permanently immature dendritic cells were generated from the bone marrow of DA and Lewis rats by treatment with dexamethasone. Animals were either vehicle or donor dexDCs pretreated. Serum was used to monitor glucose, C-peptide, and alloreactive antibodies. RESULTS The transplantation of DA islets into Lewis recipients showed direct graft failure with reduced numbers of β-cells when rats were pretreated with donor dexDCs. In the reverse model (Lewis islets into DA recipients), dexDC-treated DA recipients even showed a significantly accelerated rejection of Lewis islets. Immunohistochemical analysis of allograft tissue of dexDC-treated recipients showed a predominant natural killer cell infiltration and a presence of antibody reactivity in the absence of complement deposition. Alloreactive antibodies were solely found in dexDC-treated recipients. CONCLUSION Our study shows that pretreatment with donor-derived dexDCs induces an antibody-mediated rejection in this islet transplantation rodent model.

Objectives. Although research has shown that whether people talk about health issues influences health campaign effects, no evidence exists on whether conversational valence fulfils a mediating role within health campaign effects. In the context of alcohol consumption, this two-wave experimental research studies the effects of exposure to an anti-alcohol message on conversational valence about alcohol. Further, it investigates whether valence subsequently affects alcohol consumption intentions. Design. Eighty-four undergraduate students, in dyads, were randomly assigned to one of two conditions (anti-alcohol message vs. no alcohol message exposure). Methods. A baseline measure of the intention to refrain from binge drinking was assessed in advance. Two weeks later, half of the participants were exposed to an anti-alcohol message, after which all pairs engaged in a conversation about alcohol and binge drinking followed by an assessment of conversational valence and again the intention to refrain from binge drinking. Results. An indirect effect of health message exposure on the intention to refrain from binge drinking through conversational valence was revealed. When participants viewed an anti-alcohol message, they reported significantly more negative conversations about alcohol. Subsequently, a more negative conversational valence about alcohol increased the intention to refrain from binge drinking. Conclusions. These findings suggest that conversational valence is relevant for health campaign effects. By demonstrating that health messages can influence this valence, important implications arise in terms of health promotion. Future research should focus on how to design effective health campaigns that are able to guide conversational valence in the desired direction.

Objectives. Repeated action can lead to the formation of habits and identification as 'the kind of person' that performs the behaviour. This has led to the suggestion that identity-relevance is a facet of habit. This study explores conceptual overlap between habit and identity, and examines where the two constructs fit into an extended Theory of Planned Behaviour (TPB) model of binge-drinking among university students. Design. Prospective, questionnaire-based correlational design. Methods. A total of 167 UK university students completed baseline measures of past behaviour, self-identity, the Self-Report Habit Index (SRHI), and TPB constructs. One week later, 128 participants completed a follow-up behaviour measure. Results. Factor analyses of the SRHI and four identity items revealed two correlated but distinct factors, relating to habit and identity, respectively. Hierarchical regression analyses of intention and behaviour showed that identity contributed over and above TPB constructs to the prediction of intention, whereas habit predicted behaviour directly, and interacted with intentions in predicting behaviour. Habits unexpectedly strengthened the intention-behaviour relation, such that strong intenders were more likely to binge-drink where they also had strong habits. Conclusions. Identity and habit are conceptually discrete and impact differently on binge-drinking. Findings have implications for habit theory and measurement. Recommendations for student alcohol consumption reduction initiatives are offered. Language: en

Recurrent miscarriage, fetal growth restriction and intrauterine fetal death are frequently occurring complications of pregnancy in patients with systemic lupus erythaematosus (SLE) and antiphospholipid syndrome (APS). Murine models show that complement activation plays a pivotal role in antiphospholipid antibody-mediated pregnancy morbidity, but the exact pathways of complement activation and their potential role in human pregnancy are insufficiently understood. We hypothesized that the classical pathway would play a major role in inducing fetal loss. Pregnant C57BL/6 mice and mice deficient in C1q and factor D were injected with antiphospholipid antibodies or normal human IgG. Mouse placentas were subsequently stained with an anti-C4 antibody and anti-normal human IgG to determine the presence of classical complement activation and IgG binding. Findings in mice were validated in 88 human placentae from 83 women (SLE and APS cases versus controls), which were immunohistochemically stained for C4d, C1q, properdin and MBL. Staining patterns were compared to pregnancy outcome. In murine placentae of mice pretreated with antiphospholipid antibodies, increased C4 deposition was observed, which was associated with adverse fetal outcome but not with IgG binding. In humans, diffuse C4d staining at the feto–maternal interface was present almost exclusively in patients with SLE and/or APS (p < 0.001) and was related to intrauterine fetal death (p = 0.03). Our data show that presence of C4d in murine and human placentae is strongly related to adverse fetal outcome in the setting of SLE and APS. The excessive deposition of C4d supports the concept of severe autoantibody-mediated injury at the fetal–maternal interface. We suggest C4d as a potential biomarker of autoantibody-mediated fetal loss in SLE and APS. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

ObjectivesAction control refers to the successful translation of intention into behaviour. The purpose of this study was to explore the potential usefulness of extending intention-exercise profiles with past exercise behaviour and exercise habit strength and the potential discriminative effect of action planning items and theory of planned behaviour (TPB) concepts.DesignProspective data from 330 undergraduate students (M age = 21.5; 25.5% males).MethodMeasures of exercise behaviour, exercise habit strength, TPB concepts and action plans were assessed at T1; subsequent exercise behaviour was assessed again two weeks later. Profiles were created from T1 exercise behaviour, intention, habit strength and T2 exercise behaviour. Data were analyzed using chi-square analysis, discriminant function analysis and analysis of variance and interpreted using p-values and effect sizes.ResultsThere was considerable asymmetry in the intention-exercise relationship, with successful exercise intenders reporting stronger exercise habits. However, more than 40% of strongly habitual exercise intenders were not following on these intentions. Measures of perceived behavioural control were the consistent predictor of action control, but could not discriminate differences between key target groups. Effect sizes for significant differences were mostly large. Planning items were generally unrelated to exercise action control.ConclusionThe extension of intention-exercise profiles revealed noticeable distributions to allow for better exercise target group detection. Measures of controllability of exercise behaviour should be promoted in several of these target groups, but research should explore additional predictors of key target groups in order to enhance exercise levels.

There is ample evidence to suggest that a significant part of daily eating behaviours consists of habits. In line with this, the concept of habit is increasingly incorporated into studies investigating the behavioural and psychosocial determinants of food choice, yielding evidence that habit is one of the most powerful predictors of eating behaviour. Research shows that habitual behaviour is fundamentally different from non-habitual behaviour: when behaviour is habitual, people require little information to make decisions, intentions are poor predictors of behaviour, and behaviour is triggered by situational cues. These insights have vast implications for research in the food domain that are only just beginning to be addressed. Also, theorizing on habits has important implications for behaviour change interventions, yet few interventions that are based on habit theory have been tested in a food context. The present article provides an overview of habit research and discusses possibilities to increase our knowledge of the role of habits in eating behaviour. It is shown that interventions targeting habitual behaviour can try to (i) change the situation that triggers the habitual behaviour, (ii) promote or inhibit the habitual response and (iii) change relevant contingencies. These insights can act as a starting point for future intervention research.

In the context of health campaigns, interpersonal communication can serve at least 2 functions: (a) to stimulate change through social interaction and (b) in a secondary diffusion process, to further disseminate message content. In a 3-wave prospective study of 1,079 smokers, the authors demonstrate that mass media messages (antismoking campaigns and news coverage relevant to smoking cessation) have an indirect effect on smoking cessation intention and behavior via interpersonal communication. Exposure to campaigns and news coverage prompts discussion about the campaigns, and, in turn, about smoking cessation. Interpersonal communication regarding smoking cessation then influences intention to quit smoking and attempts to quit smoking. The study finds evidence not only for the social interaction function of interpersonal communication, but also for the secondary diffusion function. A substantial number of smokers who are not directly exposed to the antismoking campaigns are nevertheless indirectly exposed via communication with people who have seen these campaigns. These results imply that encouragement of interpersonal communication can be an important campaign objective.

Antibodies recognizing plasminogen, a key component of the fibrinolytic system, associate with venous thrombotic events in PR3-ANCA vasculitis. Here, we investigated the prevalence and function of anti-plasminogen antibodies in independent UK and Dutch cohorts of patients with ANCA-associated vasculitis (AAV). We screened Ig isolated from patients (AAV-IgG) and healthy controls by ELISA. Eighteen of 74 (24%) UK and 10/38 (26%) Dutch patients with AAV had anti-plasminogen antibodies compared with 0/50 and 1/61 (2%) of controls. We detected anti-plasminogen antibodies in both PR3-ANCA– and MPO-ANCA–positive patients. In addition, we identified anti-tissue plasminogen activator (tPA) antibodies in 13/74 (18%) patients, and these antibodies were more common among patients with anti-plasminogen antibodies (P = 0.011). Eighteen of 74 AAV-IgG (but no control IgG) retarded fibrinolysis in vitro, and this associated with anti-plasminogen and/or anti-tPA antibody positivity. Only 4/18 AAV-IgG retarded fibrinolysis without harboring these antibodies; dual-positive samples retarded fibrinolysis to the greatest extent. Patients with anti-plasminogen antibodies had significantly higher percentages of glomeruli with fibrinoid necrosis (P < 0.05) and cellular crescents (P < 0.001) and had more severely reduced renal function than patients without these antibodies. In conclusion, anti-plasminogen and anti-tPA antibodies occur in AAV and associate with functional inhibition of fibrinolysis in vitro. Seropositivity for anti-plasminogen antibodies correlates with hallmark renal histologic lesions and reduced renal function. Conceivably, therapies that enhance fibrinolysis might benefit a subset of AAV patients.

Contains fulltext : 87624.pdf (Publisher’s version ) (Closed access) OBJECTIVE: It remains unclear whether unipolar psychotic depression should be treated with an antidepressant and an antipsychotic or with an antidepressant alone. METHOD: In a multi-center RCT, 122 patients (18-65 years) with DSM-IV-TR psychotic major depression and HAM-D-17 > or = 18 were randomized to 7 weeks imipramine (plasma-levels 200-300 microg/l), venlafaxine (375 mg/day) or venlafaxine-quetiapine (375 mg/day, 600 mg/day). Primary outcome was response on HAM-D-17. Secondary outcomes were response on CGI and remission (HAM-D-17). RESULTS: Venlafaxine-quetiapine was more effective than venlafaxine with no significant differences between venlafaxine-quetiapine and imipramine, or between imipramine and venlafaxine. Secondary outcomes followed the same pattern. CONCLUSION: That unipolar psychotic depression should be treated with a combination of an antidepressant and an antipsychotic and not with an antidepressant alone, can be considered evidence based with regard to venlafaxine-quetiapine vs. venlafaxine monotherapy. Whether this is also the case for imipramine monotherapy is likely, but cannot be concluded from the data. 01 maart 2010

The purpose of this study was to explore the role of habit in predicting physical activity with the theory of planned behavior (TPB). The study extended previous research by (a) including a measure of temporal intention stability in the regression equation, and (b) unpacking the intention × behavior × habit relationship. Participants were 153 undergraduate students who completed a habit measure and measures of the TPB at Time 1 followed by measures of intention and behavior 2 weeks later. Results using regression analysis demonstrated that habit explained 7% additional variance after accounting for the TPB and temporal stability of intention and its interaction with intention. Follow-up analyses showed considerable asymmetry in the three-way relationship between intention, behavior, and habit, where high habit participants were composed primarily of intenders (i.e., intended to be active >3 times/week at 30 min) who engaged in regular physical activity (70%, n = 28) and low habit participants were inactive nonintenders (i.e., did not intend to be active >3 times/week at 30 min and were subsequently not active; 69%, n = 25). The results support the notion that some properties of physical activity may have an automatic component and that habits may be important to physical activity action control.

The additive and interactive effect of habit strength in the explanation of young adults’ fruit consumption was studied within the context of the theory of planned behaviour (TPB). Additionally, behavioural and control beliefs were modelled as predictors of profile membership based on current fruit consumption, motivation and habit strength towards fruit consumption. Cross-sectional data were available from undergraduate students (n = 538; mean age = 21.19; S.D. = 2.57) who completed measures of fruit consumption, habit strength, TPB-concepts, and behavioural and control beliefs. Data were analyzed using stepwise regression analysis, simple slope analysis, and discriminant function analysis. Results showed that, based on a significant intention × habit interaction (β = .13), the intention-fruit consumption relationship was more than twice as strong at low levels of habit strength (β = .39) than at high levels of habit strength (β = .16). Furthermore, beliefs regarding health and weight management were relatively unable to distinguish profiles created from motivation, habit strength and current fruit consumption. Rather, beliefs about controllability of fruit consumption were amongst the most consistent discriminating beliefs. Findings suggest that stronger fruit consumption habits make fruit consumption less intentional and that interventions aiming to increase fruit consumption may need to develop persuasive messages focusing on situational beliefs, rather than emphasizing health outcomes.

The present study explored the influence of the Big Five dimensions extroversion and conscientiousness on action control regarding both moderate and vigorous physical activity within the framework of the theory of planned behavior (TPB). Prospective data were available from 186 respondents, who completed measures of intention, cognitive and affective attitude, subjective norm, perceived behavioral control, extroversion, conscientiousness, and physical activity at T1. Four weeks later, physical activity was assessed again. Respondents were grouped into four profiles: nonintenders, successful nonintenders, unsuccessful intenders, and successful intenders. Logistic regression analyses revealed that successful enactment in moderate physical activity was associated with extroversion, subjective norm, and affective attitude, whereas successful enactment in vigorous physical activity was associated with conscientiousness. Findings illustrate the differential role played by personality dimensions and TPB concepts in the explanation of moderate and vigorous physical activity action control.

We investigated the frequency of the 5/5 homozygous CNDP1 (carnosinase) genotype, which was found to be associated with a reduced risk of developing diabetic nephropathy, in three ethnic groups in The Netherlands. Particularly interesting were the South Asian Surinamese, who have a high prevalence of diabetic nephropathy. Furthermore, we investigated the association between this gene and carnosinase activity in South Asian Surinamese and whether carnosinase was expressed in the kidney. We genotyped 290 South Asian Surinamese, 532 African Surinamese, and 472 White Dutch in a cross-sectional population study. Furthermore, an independent cohort of South Asian Surinamese was genotyped. In this population, carnosinase activity was measured in serum. Immunostaining and in situ hybridization for CNDP1 were performed on kidney tissue. Both South Asian populations had lower frequencies of the 5/5 homozygous genotype than African Surinamese and White Dutch (23.0%, 27.2%, 38.2%, and 41.3%, respectively; chi-square, p

Clustering refers to the co-occurrence of behaviour and may be particularly relevant in light of the present obesity epidemic. Since evidence regarding clustering of motivational and habitual constructs within the framework of the Theory of Planned Behaviour (TPB) is limited, clustering effects of TPB cognitions and habit strength regarding soft drink consumption and television viewing were studied in a sample of Dutch adolescents (n = 312; mean age = 14.62; SD = 1.62) using cross-sectional data. Results showed that not only soft drink consumption and television viewing cluster (r = .42), but also their intentional (r = .36) and habitual (r = .37) constructs. Furthermore, unmediated effects were found between habit strength and its respective behaviour, whereas habit strength was associated with its clustered behaviour through decreased perceptions of controllability. Our findings suggest that interventions that aim to change habitual soft drink consumption and television viewing may need to incorporate an environmental component, as well as explore the potential usefulness of synergistic effects of incorporating multiple clustered behaviours, as well as their corresponding beliefs and habits in health behaviour change interventions.

Background: Depression can occur in patients with or without trait anxiety. Although it is assumed that assessment of defenses can be useful in planning biological treatment, no studies have confirmed this hypothesis. In this study we focus on the relation between trait anxiety and defensive functioning, and on the combined influence of these personality characteristics on response to antidepressants among inpatients with a major depressive episode. Methods: Major depressive episode was diagnosed using the Schedule for Affective Disorders and Schizophrenia (SADS) and the severity of the depression was measured with the Hamilton Rating Scale for Depression (HAM-D). The level of trait anxiety was assessed using a questionnaire with 34 questions pertaining to trait anxiety. The Defense Style Questionnaire (DSQ 88) was used to assess defensive functioning followed by a weighted overall defensive functioning score (ODF). Partial correlations and multiple regression analyses were used to analyze the data. Results: The final sample included 85 patients. A significant negative effect of trait anxiety by ODF (p: 0.000) was found on the outcome score, i.e. the combination of a high score on trait anxiety and a low score on the ODF resulted in a significantly higher final score on the HAM-D. Conclusions: The most important finding in this study is that the combination of a high level of trait anxiety and immature defensive functioning evidently had a negative effect on antidepressant treatment outcome.

Objective: To examine the effect of two types of self-identity on attempts to quit smoking: self-identity in terms of smoking and self-identity in terms of quitting. Design: A prospective survey among an initial sample of 3,411 smokers. Smoking history variables and psychosocial variables from the theory of planned behavior are also measured. Main Outcome Measures: Intention to quit smoking and smoking cessation attempts 4 months later. Results: Both smoking identity and quitting identity matter, but they appear to play different roles in explaining intention to quit and in predicting actual attempts to quit. Quitting identity is particularly important for intention to quit, whereas both quitting identity and smoking identity are important for actually trying to quit. Recent attempts to quit slightly attenuate the negative effect of smoking identity on attempts to quit. Conclusion: A broader interpretation of self-identity in terms of both current and aspired behavior offers a better understanding of when people might change health-relevant behavior.

Five pathologic variants of FSGS were recently defined ("Columbia classification"), but the stability of these phenotypes in renal allografts remains unknown. We hypothesized that if the variants represent distinct diseases, then the pattern of recurrent FSGS in renal allografts will mimic the original disease in the native kidney. This multicenter study included 21 cases of recurrent FSGS from 19 patients who had both native and transplant biopsy samples available for analysis. These results support the Columbia classification, because 81% recurred in the same pattern as the original disease, but three variants manifested plasticity from native to allograft kidneys or in the pattern of recurrence (four FSGS, not otherwise specified [NOS] to collapsing variant, two collapsing variant to FSGS NOS, and one cellular variant to FSGS NOS). No transitions between the cellular and the collapsing variants were observed, supporting the view that these are separate entities. Three categories of recurrence were observed: Type I, recurrence of the same variant of FSGS; type II, recurrence of the same FSGS variant, preceded by a minimal change-like lesion; and type III, recurrence of a different FSGS variant in the allograft. Thus, potential evolution of the pathologic phenotype should be considered in pathologic interpretation and clinical trials.

Treatment of patients with IgA nephropathy (IgAN) depends on a reliable assessment of disease progression based on measurements of glomerular filtration rate (GFR), proteinuria, hypertension, and tubulointerstitial changes. We sought to determine whether progression could be predicted from analysis of glomerular and tubulointerstitial inflammation in biopsies taken at an early stage of IgAN. We retrospectively analyzed biopsies from 50 patients, relating the subsequent clinical course to infiltration with B- and T-lymphocytes, granule membrane protein of 17 kDa (GMP-17) positive cytotoxic T cells, macrophages, fibroblasts, and tubulointerstitial expression of human leukocyte antigen-D related (HLA-DR). At biopsy, 19 patients had decreased GFR while 13 of 31 patients with normal GFR and progressive IgAN differed significantly from 18 non-progressors in the level of proteinuria and in the severity of scores for mesangial proliferation, tubular atrophy, interstitial fibrosis, and interstitial infiltrates. On multivariate regression analysis these differences disappeared; however, associations with GMP-17-positive cytotoxic T-lymphocytes in intact renal tubules and of B-lymphocytes in the interstitium remained significant. Our study may have identified a marker of disease progression in early stages of IgAN.

The purpose of the present study is to compare the efficacy of imipramine in the treatment of psychotic versus nonpsychotic depression. Previous studies report varying results of monotherapy with antidepressants in psychotic depression. Because psychotic depression is seriously underinvestigated, performing a post hoc analysis of randomized clinical trials consisting of both psychotic and nonpsychotic depressed patients may contribute to the discussion on the optimal treatment of depressed patients with mood-congruent psychotic features. A total of 112 patients diagnosed with major depression (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) (40 with psychotic depression and 82 without psychotic features) received treatment with imipramine for 6 weeks after a washout period of 7 days. Imipramine doses were adjusted to attain a predefined fixed plasma level. Treatment response was assessed with the Hamilton Rating Scale for Depression (HAM-D). A logistic regression analysis showed a significantly larger reduction in HAM-D score in the sample with psychotic features compared with the nonpsychotic sample (regression coefficient, -3.47; SE, 1.7; P = 0.04). According to the primary outcome criterion, that is, the change in HAM-D score, imipramine was significantly more effective in the sample with psychotic depression compared with the nonpsychotic depressed patients. The contradiction between our results and those of several previous studies may be due to the fixed plasma level dosing of imipramine refraining from concurrent psychotropic medication or limiting our patient sample to patients with mood-congruent psychotic features.

Chimerism indicates the presence of cells from one individual in another individual, and has been associated with several autoimmune diseases. Although this finding may point towards a role for chimerism in the induction of SLE, it could also indicate that chimerism is the result of repair mechanisms after injury.To perform a post-mortem investigation for the presence of chimerism in 48 organs from seven women with SLE and establish whether there was a relationship between chimerism and injury.Chimeric male cells in female tissue specimens were identified by in situ hybridisation of the Y-chromosome. Organs were categorised into four different groups according to injury experienced.were compared with those for unaffected control organs. Results: Chimerism was found in all seven patients with SLE. Y-chromosome-positive cells were present in 24 of 48 organs from women with SLE, which was significantly more than in control organs (p0.001). Chimerism occurred more often in organs from patients with SLE who had experienced injury than in normal control organs, irrespective of whether the injury experienced was SLE-related, non-SLE-related or both.This is the first report of the distribution of chimerism in a large number of organs from women with SLE. It shows that the occurrence of chimerism is related to injury. The data support the hypothesis that tissue chimerism is the result of a repair process.

In patients who have anti-neutrophil cytoplasm autoantibody (ANCA)-associated glomerulonephritis and are on dialysis at time of diagnosis, renal function is sometimes insufficiently restored by immunosuppressive treatment, which often coincides with potentially lethal adverse effects. This study investigated the clinical and histologic variables that determine the chances of dialysis independence, dialysis dependence, or death after 12 mo in these patients. Sixty-nine patients who had ANCA-associated glomerulonephritis and were dialysis dependent at diagnosis received uniform, standard immunosuppressive therapy plus either intravenous methylprednisolone or plasma exchange. Eleven clinical and histologic variables were assessed. Univariate and binary logistic regression analyses were performed. Predictive parameters were entered into a two-step binary logistic regression analysis to differentiate among the outcomes of dialysis independence, dialysis dependence, or death. The point at which the chance of therapy-related death exceeded the chance of dialysis independence was determined. The chance of recovery exceeded the chance of dying in most cases. Intravenous methylprednisolone as adjunctive therapy plus

In this review we want to summarize the results of the placebo-controlled randomized clinical trials with beta- blocking adrenergic agents during electroconvulsive therapy (ECT), and review the effect on seizure duration and cardio- vascular variables. We searched for studies in the electronic databases Medline. Keywords combined in the search were: "beta-adrenergic blocking agents" and "electroconvulsive therapy". The only limitation specified in the search was that the publications should include only randomized controlled trials. Esmolol and other beta-blocking adrenergic agents can have a significant effect on seizure duration during ECT, it short- ens seizure duration, and this effect is probably dose dependent. Therefore routine administration is not recommended. Since the relation between seizure duration and efficacy of ECT is dependent on electrode placement it seems advisable to use bilateral electrode placement with patients with cardiovascular risk factors and an indication for use of esmolol during every session before seizure induction. In the absence of cardiovascular risk factors but with prolonging hypertension or tachycardia during ECT sessions, es- molol also is again preferred. Labetalol is an alternative although, especially in high dose, the longer half-life can be con- sidered as a disadvantage. Experiences with landiolol are limited.

Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glomerulonephritis anti-Thy-1 nephritis in Lewis rat substrains. Glomerular lesions in Lewis/Møllegard rats resolve spontaneously, whereas Lewis/Maastricht (Lew/Maa) rats develop progressive glomerulosclerosis. This predisposition for progressive glomerulosclerosis is governed by unknown genes that are expressed by renal cells. Here, differential gene expression analysis using a rat complementary DNA micro array revealed neuronal activity-regulated pentraxin (Narp) as a candidate gene involved in the remodeling or progression of damaged glomeruli. Glomerular Narp mRNA expression was monitored during disease in both Lewis sub strains. Immunohistochemistry revealed that Narp protein is exclusively expressed in Lew/Maa glomeruli 7 and 14 days after induction of anti-Thy-1 nephritis. Double-immunofluorescent staining showed that proliferating mesangial cells and parietal epithelial cells (PECs) at sites of adhesion to podocytes are partially Narp-positive, whereas podocytes fail to express Narp. Immunohistochemistry in nephritic Wistar, unilaterally nephrectomized Wistar and Sprague-Dawley rats showed that Narp protein is present only in strains that develop progressive glomerulosclerosis but never in strains that show remodeling. We conclude that Narp is a predictor for anti-Thy-1 nephritis-induced glomerulosclerosis and its expression by PECs may be involved in the progression to glomerulosclerosis.