Type I hypersensitivity and its pharmacological modulation in {\it Trichinella\/}-induced intestinal fluid secretion and rapid rejection of the parasite in immunized rats

Studies were performed to test the hypothesis that type I hypersensitivity underlies worm induced intestinal fluid secretion and the rapid rejection of Trichinella spiralis from immunized rats, and the two events may be related in a cause-effect manner.^ Two approaches were taken. One was to determine whether inhibition of anaphylaxis-mediated Cl$\sp{-}$ and fluid secretion accompanying a secondary infection impedes worm rejection from immune hosts. The other was to determine whether induction of intestinal fluid secretion in nonimmune hosts interfered with worm establishment. In both studies, fluid secretion was measured volumetrically 30 min after a challenge infection and worms were counted.^ In immunized rats indomethacin did not affect the worm-induced fluid secretion when used alone, despite inhibiting mucosal prostaglandin synthesis. Fluid secretion was reduced by treatment with diphenhydramine and further reduced by the combination of diphenhydramine and indomethacin. The paradoxical effects of indomethacin when used alone compared with its coadministration with diphenhydramine is explained by the enhancing effect of indomethacin on histamine release. Abolishing net fluid secretion in these studies had no effect on rapid worm rejection in immune hosts.^ Worm establishment was reduced in recipients of immune serum containing IgE antibodies. Net intestinal fluid secretion induced in normal rats by PGE$\sb2$, cholera toxin, or hypertonic mannitol solution had no effect on worm establishment compared with untreated controls.^ In a related experiment, worm-induced intestinal fluid secretion and worm rejection in immune rats were partially blocked by concurrent injection with 5-HT$\sb2$ and 5-HT$\sb3$ blockers (Ketanserin and MDL-72222), suggesting that 5-HT is involved. This possible involvement was supported in that treatment of nonimmune rats with 5-HT significantly inhibited worm establishment in the intestine.^ Results indicate that anaphylaxis is the basis for both worm-induced intestinal fluid secretion and rapid rejection of T. spiralis in immune rats, but these events are independent of one another. 5-HT is a possible mediator of worm rejection, however, its mechanism of action is related to something other than fluid secretion. ^

Identification of two vitamin D response elements in the rat osteopontin gene

Studies to elucidate the function of vitamin D have demonstrated an important role in regulating bone-related cells, including osteoblasts and osteoclasts. A seemingly paradoxical observation is that 1,25(OH)$\sb2$D$\sb3$, the active metabolite of vitamin D, stimulates bone resorption, yet regulates transcription of genes expressed by osteoblasts. One mechanism that could explain these actions is the upregulation of transcription of osteoblast-specific genes. These gene products could then act as effectors to influence osteoclastic activity. We hypothesized that molecular signals could be deposited directly into the mineralized matrix in the form of noncollagenous proteins, such as osteopontin (OPN). The structure, biosynthesis and localization of OPN suggest that it could function to mediate the molecular "cross talk" between osteoblasts and osteoclasts in response to 1,25(OH)$\sb2$D$\sb3$. To begin to address this hypothesis, elucidation of the molecular mechanisms of action involved in the transactivation of OPN by 1,25(OH)$\sb2$D$\sb3$ is essential.^ In the present study, the rat opn gene was isolated and characterized. Functional analysis by transient transfection of the 5$\sp\prime$ flanking sequences of the rat opn gene fused to the luciferase gene demonstrated that OPN is transcriptionally upregulated by 1,25(OH)$\sb2$D$\sb3$, mediated through two vitamin D response elements (VDRE). Both proximal and distal VDREs are structurally similar (two imperfect direct repeats separated by a 3 nucleotide spacer) and bind protein complexes that include the VDR and retinoid-X receptor (RXR). Isolated VDRE expression constructs produce functional activity of equivalent magnitude of responsiveness to 1,25(OH)$\sb2$D$\sb3$. However, expression constructs containing either VDRE and at least 200 bp of 5$\sp\prime$ and 3$\sp\prime$ flanking sequence demonstrated that the distal VDRE produces an amplitude of response significantly higher than the proximal VDRE. We conclude that the transcriptional upregulation of the opn gene by 1,25(OH)$\sb2$D$\sb3$ involves the transactivation of two VDREs, while maximal responsiveness requires interaction of the VDREs with additional cis-elements contained in the 5$\sp\prime$ sequence. ^

Well-being and learning in school

Although there are various definitions for the term “well-being,” it is agreed that well-being in school represents a set of subjective feelings and attitudes toward school. Moreover, enjoyment (some use the term “happiness”) is recognized as a core element of well-being in general as well as at school. Well-being in school is defined as an indicator of the quality of scholastic life, and contributes to students’ physical and psychological health and development. As such it is strongly connected to learning. Well-being in school consists of cognitive, emotional, and physical components, i.e., a learner’s thoughts, feelings, and bodily sensations. Consequently, it differs significantly from an individual’s cognitive appraisals like satisfaction, or from discrete positive emotions like enjoyment. Well-being in school can be described through the relationship of positive and negative aspects of school life

An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke

OBJECTIVE We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO. METHODS Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates. RESULTS Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%-26%) in those with 0 to 3 points to 73% (95% CI: 66%-79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%-28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%-4%) in the highest. CONCLUSION Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk.

Neuroimaging findings in cryptogenic stroke patients with and without patent foramen ovale

BACKGROUND AND PURPOSE Patent foramen ovale (PFO) and cryptogenic stroke are commonly associated but some PFOs are incidental. Specific radiological findings associated with PFO may be more likely to indicate a PFO-related cause. We examined whether specific radiological findings are associated with PFO among subjects with cryptogenic stroke and known PFO status. METHODS We analyzed the Risk of Paradoxical Embolism(RoPE) Study database of subjects with cryptogenic stroke and known PFO status, for associations between PFO and: (1) index stroke seen on imaging, (2) index stroke size, (3) index stroke location, (4) multiple index strokes, and (5) prior stroke on baseline imaging. We also compared imaging with purported high-risk echocardiographic features. RESULTS Subjects (N=2680) were significantly more likely to have a PFO if their index stroke was large (odds ratio [OR], 1.36; P=0.0025), seen on index imaging (OR, 1.53; P=0.003), and superficially located (OR, 1.54; P<0.0001). A prior stroke on baseline imaging was associated with not having a PFO (OR, 0.66; P<0.0001). Finding multiple index strokes was unrelated to PFO status (OR, 1.21; P=0.161). No echocardiographic variables were related to PFO status. CONCLUSIONS This is the largest study to report the radiological characteristics of patients with cryptogenic stroke and known PFO status. Strokes that were large, radiologically apparent, superficially located, or unassociated with prior radiological infarcts were more likely to be PFO-associated than were unapparent, smaller, or deep strokes, and those accompanied by chronic infarcts. There was no association between PFO and multiple acute strokes nor between specific echocardiographic PFO features with neuroimaging findings.

Recurrent stroke predictors differ in medically treated patients with pathogenic vs other PFOs

OBJECTIVE: To examine predictors of stroke recurrence in patients with a high vs a low likelihood of having an incidental patent foramen ovale (PFO) as defined by the Risk of Paradoxical Embolism (RoPE) score.METHODS: Patients in the RoPE database with cryptogenic stroke (CS) and PFO were classified as having a probable PFO-related stroke (RoPE score of >6, n = 647) and others (RoPE score of

From emotion perception to emotion experience: Emotions evoked by pictures and classical music.

Most previous neurophysiological studies evoked emotions by presenting visual stimuli. Models of the emotion circuits in the brain have for the most part ignored emotions arising from musical stimuli. To our knowledge, this is the first emotion brain study which examined the influence of visual and musical stimuli on brain processing. Highly arousing pictures of the International Affective Picture System and classical musical excerpts were chosen to evoke the three basic emotions of happiness, sadness and fear. The emotional stimuli modalities were presented for 70 s either alone or combined (congruent) in a counterbalanced and random order. Electroencephalogram (EEG) Alpha-Power-Density, which is inversely related to neural electrical activity, in 30 scalp electrodes from 24 right-handed healthy female subjects, was recorded. In addition, heart rate (HR), skin conductance responses (SCR), respiration, temperature and psychometrical ratings were collected. Results showed that the experienced quality of the presented emotions was most accurate in the combined conditions, intermediate in the picture conditions and lowest in the sound conditions. Furthermore, both the psychometrical ratings and the physiological involvement measurements (SCR, HR, Respiration) were significantly increased in the combined and sound conditions compared to the picture conditions. Finally, repeated measures ANOVA revealed the largest Alpha-Power-Density for the sound conditions, intermediate for the picture conditions, and lowest for the combined conditions, indicating the strongest activation in the combined conditions in a distributed emotion and arousal network comprising frontal, temporal, parietal and occipital neural structures. Summing up, these findings demonstrate that music can markedly enhance the emotional experience evoked by affective pictures.

Percutaneous closure of patent foramen ovale in patients with cryptogenic embolism: a network meta-analysis

BACKGROUND Up to 40% of ischaemic strokes are cryptogenic. A strong association between cryptogenic stroke and the prevalence of patent foramen ovale (PFO) suggests paradoxical embolism via PFO as a potential cause. Randomized trials failed to demonstrate superiority of PFO closure over medical therapy. METHODS AND RESULTS Randomized trials comparing percutaneous PFO closure against medical therapy or devices head-to-head published or presented by March 2013 were identified through a systematic search. We performed a network meta-analysis to determine the effectiveness and safety of PFO closure with different devices when compared with medical therapy. We included four randomized trials (2963 patients with 9309 patient-years). Investigated devices were Amplatzer (AMP), STARFlex (STF), and HELEX (HLX). Patients allocated to PFO closure with AMP were less likely to experience a stroke than patients allocated to medical therapy [rate ratio (RR) 0.39; 95% CI: 0.17-0.84]. No significant differences were found for STF (RR 1.01; 95% CI: 0.44-2.41), and HLX (RR, 0.71; 95% CI: 0.17-2.78) when compared with medical therapy. The probability to be best in preventing strokes was 77.1% for AMP, 20.9% for HLX, 1.7% for STF, and 0.4% for medical therapy. No significant differences were found for transient ischaemic attack and death. The risk of new-onset atrial fibrillation was more pronounced for STF (RR 7.67; 95% CI: 3.25-19.63), than AMP (RR 2.14; 95% CI: 1.00-4.62) and HLX (RR 1.33; 95%-CI 0.33-4.50), when compared with medical therapy. CONCLUSIONS The effectiveness of PFO closure depends on the device used. PFO closure with AMP appears superior to medical therapy in preventing strokes in patients with cryptogenic embolism.

A propensity score-matched comparison between Cardia and Amplatzer PFO closure devices - insights from the SOLUTION registry (Swiss percutaneOus patent foramen ovale cLosUre in recurrent clinical events prevenTION)

Aims: To compare clinical outcome of Amplatzer PFO (APFO) to Cardia PFO (CPFO) occluder. Percutaneous patent foramen ovale (PFO) closure prevents stroke recurrence in stroke due to paradoxical embolism. Methods and results: The primary endpoint was a composite of stroke, TIA, or peripheral embolism at follow-up. The secondary endpoint was residual shunt. Outcome was compared among 934 (APFO: 712; CPFO: 222) patients, and in 297 propensity score-matched patients. The primary endpoint occurred in 29 patients (0.71/100 patient-years): four (2%) with the CPFO (0.31/100 patient-years), and 25 (4%) with the APFO (0.89/100 patient-years) (p=0.20). Residual shunt at six months was more frequent with the CPFO (31% versus 9%, p<0.001). No differences in residual shunts were seen at the last available echocardiographic follow-up (9±18 months): APFO 11%, CPFO 14%, p=0.22. Conclusions: This study suggests that PFO closure with APFO or CPFO is equally effective for the prevention of recurrent events. Residual shunt was more frequent at six months with CPFO, but was similar to APFO at later follow-up.

The Territoriality of Fiscal Solidarity: Comparing Swiss Equalisation with European Union Structural Funding

This article theorises the territorial solidarity and fiscal federalism and compares Switzerland with the European Union. While inter-territorial solidarity is a prerequisite for legitimate fiscal equalisation, such equalisation in turn also contributes to the legitimacy of and solidarity within federal political systems. By cutting across territorial and ethno-national communities, fiscal transfers often contribute to both a “civic” sense of belonging and a “cosmopolitan” identity. After placing types and degrees of (inter-)territorial solidarity at the heart of our conceptual perspective, we discuss the effects of such solidarity through an analysis of two different forms of “federal” equalisation. Comparing the recently reformed Swiss fiscal equalisation system with the EU structural funds allows us to infer if, and how, the fiscal dimension of federalism matters for feelings of solidarity, reciprocity, unity and, ultimately, for the legitimacy of the very (nation-state or Union) structures that are to contribute to the ever-growing prosperity and happiness of their people(s). In Switzerland, a civic understanding of nationhood and cross-cutting cleavages were necessary conditions for extensive, effective and legitimate fiscal equalisation. We infer that, for the EU, this means that strengthening the equalisation component of the structural funds would contribute to an ever closer Union in a political sense: because fiscal equalisation and inter-territorial solidarity are interdependent, reinforcing the one also means cementing the other. Future studies of the EU and federal-type arrangements are advised to pay more explicit attention to the solidarity-element of territoriality – or the territoriality of (fiscal) solidarity.

Hope as a resource for self-directed career management: Investigatiing mediating effects on proactive career behaviors, life and job satisfaction

ABSTRACT Hope is increasingly recognized as an important psychological resource for career development, yet the empirical research on its functioning in this domain is sparse. This paper describes an investigation of how dispositional hope is related to career decidedness, career planning, and career self-efficacy beliefs and whether these more proximal career attitudes mediate the effects of hope on proactive career behaviors, life satisfaction, and job satisfaction. This investigation was conducted using two independent samples of university students (N = 1,334) and working professionals (N = 233). The results showed that in both samples, hope was significantly related but empirically distinct from career variables. In both samples, hope had a direct effect on proactive career behaviors, partially mediated by more career planning. Hope had significant direct and indirect effects on life satisfaction among students, mediated by the three career development attitudes. Although hope was significantly correlated with job satisfaction among employees, no direct effect of hope was found in the mediation model, but an indirect effect through career decidedness was found. The results suggest that hope is an important resource for proactive career development at different career stages and that the positive relation of hope to life and job satisfaction can partially be attributed to the positive relation between hope and favorable career development attitudes.

Determinants of antithrombotic choice for patent foramen ovale in cryptogenic stroke

Objective: We examined the influence of clinical, radiologic, and echocardiographic characteristics on antithrombotic choice in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), hypothesizing that features suggestive of paradoxical embolism might lead to greater use of anticoagulation. Methods: The Risk of Paradoxical Embolism Study combined 12 databases to create the largest dataset of patients with CS and known PFO status. We used generalized linear mixed models with a random effect of component study to explore whether anticoagulation was preferentially selected based on the following: (1) younger age and absence of vascular risk factors, (2) “high-risk” echocardiographic features, and (3) neuroradiologic findings. Results: A total of 1,132 patients with CS and PFO treated with anticoagulation or antiplatelets were included. Overall, 438 participants (39%) were treated with anticoagulation with a range (by database) of 22% to 54%. Treatment choice was not influenced by age or vascular risk factors. However, neuroradiologic findings (superficial or multiple infarcts) and high-risk echocardiographic features (large shunts, shunt at rest, and septal hypermobility) were predictors of anticoagulation use. Conclusion: Both antithrombotic regimens are widely used for secondary stroke prevention in patients with CS and PFO. Radiologic and echocardiographic features were strongly associated with treatment choice, whereas conventional vascular risk factors were not. Prior observational studies are likely to be biased by confounding by indication.

Patent foramen ovale and closure technique with the amplatzer occluder.

Proof that percutaneous closure of the patent foramen ovale (PFO) is superior to medical treatment is still incomplete. Paradoxical embolism is a rare event occurring over decades rather than years. None of the 4 randomized trials published carried enough patients or was followed up for long enough to reach superiority endpoints. All data, however, point to a benefit of PFO closure. Free wall erosion (exceedingly rare) and triggering of atrial fibrillation (in about 1% of patients) are the only noteworthy complications. They are outweighed by the supposedly prevented events of paradoxical embolisms, such as stroke, transient ischemic attacks, myocardial infarctions, or other systemic embolisms. Medical treatment with perhaps the exception of lifelong oral anticoagulation provides less protection. During a 10-year follow-up of a comparative study the annual mortality was significantly lower in the patients with PFO closure (0.4%) than in those with medical treatment (1.1%, P < 0.03). PFO closure can be accomplished in less than 1 hour with immediate resumption of physical activity. It represents thus a kind of mechanical vaccination.

Marital split-up and widowhood in old age: Differential impact on psychological and social well-being

Marital split-up and spousal loss are among the most stressful critical life events. Numerous studies have documented their detrimental effects on well-being, yet the large individual differences in psychological adaptation are still not well understood. Whereas in old age bereavement is normative and can be anticipated, divorce is an “off-time” transition for this age group. In contrast to bereavement which has been amply studied, research on later life divorce is still missing despite the increasing relevance of the topic due to the significant increase of divorces in older age. Based on a modified and extended view of Amato’s divorce-stress-adjustment model (2000), the aim of this contribution is to explore the differential impact of marital split-up and widowhood in older age on psychological (life satisfaction) and social well-being (social loneliness), and the adaptation to these critical life events. Our analyses are based on data gathered in a questionnaire study, which is part of the Swiss National Centre of Competence in Research LIVES. In a first step we compared three groups of individuals aged 60 to 75 years: a sample of 251 persons with a marital split-up (127 women; 123 men), a sample of 270 widowed persons (170 women; 100 men), and a group of 221 continuously married people (110 women; 111 men), which served as control group. In a second step, we investigated the role of socio-demographic variables, intrapersonal and interpersonal resources and variables of the context of loss as predictors for the psychological adaptation to a marital break-up and loss in old age. First results by ANCOVA indicate significant differences with regard to life satisfaction among the three groups, with divorced persons with the lowest scores, followed by the bereaved ones, and the married controls with the highest. Regarding social loneliness, divorced individuals report higher social loneliness than the bereaved group and the married controls (no significant difference between widowed and the married). In both loss groups, financial and intrapersonal resources, as well as the emotional valence of the loss are the most important predictors for the psychological and social adaptation. However, happiness in the past relationship is an important resource regarding the indicators for adaptation for the widowers, but not for individuals with a marital dissolution.