Pathogen burden, inflammation, proliferation and apoptosis in human in-stent restenosis - Tissue characteristics compared to primary atherosclerosis

Pathogenic events leading to in-stent restenosis (ISR) are still incompletely understood. Among others, inflammation, immune reactions, deregulated cell death and growth have been suggested. Therefore, atherectomy probes from 21 patients with symptomatic ISR were analyzed by immunohistochemistry for pathogen burden and compared to primary target lesions from 20 stable angina patients. While cytomegalovirus, herpes simplex virus, Epstein-Barr virus and Helicobacter pylori were not found in ISR, acute and/or persistent chlamydial infection were present in 6/21 of these lesions (29%). Expression of human heat shock protein 60 was found in 8/21 of probes (38%). Indicated by distinct signals of CD68, CD40 and CRP, inflammation was present in 5/21 (24%), 3/21 (14%) and 2/21 (10%) of ISR cases. Cell density of ISR was significantly higher than that of primary lesions ( 977 +/- 315 vs. 431 +/- 148 cells/mm(2); p < 0.001). There was no replicating cell as shown by Ki67 or PCNA. TUNEL+ cells indicating apoptosis were seen in 6/21 of ISR specimens (29%). Quantitative analysis revealed lower expression levels for each intimal determinant in ISR compared to primary atheroma (all p < 0.05). In summary, human ISR at the time of clinical presentation is characterized by low frequency of pathogen burden and inflammation, but pronounced hypercellularity, low apoptosis and absence of proliferation. Copyright (C) 2004 S. Karger AG, Basel

Black Stork Down: Military Discourses in Bird Conservation in Malta

Tensions between Maltese hunters and bird conservation NGOs have intensified over the past decade. Conservation NGOs have become frustrated with the Maltese State for conceding to the hunter lobby and negotiating derogations from the European Union’s Bird Directive. Some NGOs have recently started to organize complex field-operations where volunteers are trained to patrol the landscape, operate drones and other surveillance technologies, detect illegalities, and lead police teams to arrest poachers. We describe the sophisticated military metaphors which conservation NGOs have developed to describe, guide and legitimize their efforts to the Maltese public and their fee-paying members. We also discuss why such groups might be inclined to adopt these metaphors. Finally, we suggest that anthropological studies of discourse could help understand delicate contexts such as this where conservation NGOs, hunting associations and the State have ended in political deadlock

A contingent valuation study to estimate the parental willingness-to-pay for childhood diarrhoea and gender bias among rural households in India

We used contingent valuation technique to estimate the parental willingness to pay for an episode of diarrhoea among 324 children of both sexes aged between five and seven years in two rural villages of Chennai in India. The aim was to examine if there was any gender bias in the parental willingness to treat children for a diarrhoeal episode, and if so to what extent. The willingness to pay was specified as a hedonic function of the duration and severity of an episode, and of parents' socioeconomic characteristics. The findings suggest that parents were willing to pay more to protect their male child compared to the female child suffering from a diarrhoeal episode. The median willingness to pay to avoid an episode for male and female children were calculated at Rs. 33.7 (approx. US$0.72) and Rs. 25.2 (approx. US$ 0.54) respectively – a difference of around 34%. After adjusting for the greater duration and severity of the illness, it was found that the difference between the two medians increased to 51%

Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using primary motor neuron cultures or motor neuron cell lines we demonstrated that expression of DAOR199W, promoted the formation of ubiquitinated protein aggregates, activated autophagy and increased apoptosis. The aim of this study was to characterise the effects of DAOR199W in vivo, using transgenic mice overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were evident in mice expressing DAOR199W, which were associated with a significant loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When separated by gender, this effect was greater in females (26%; p< 0.0132). In addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse model of ALS to determine whether the effects of SOD1G93A were potentiated in the double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not affected, onset of neurological signs was significantly earlier in female double transgenic animals than their female SOD1G93A littermates (125 days vs 131 days, P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor neuron function (i.e. kyphosis and loss of motor neurons) were detected which were most marked in females and could contribute to the earlier onset of neurological signs in double transgenic females compared to SOD1G93A littermates, highlighting the importance of recognizing gender effects present in animal models of ALS

Interpersonal and affective dimensions of psychopathic traits in adolescents : development and validation of a self-report instrument

We report the development and psychometric evaluations of a self-report instrument designed to screen for psychopathic traits among mainstream community adolescents. Tests of item functioning were initially conducted with 26 adolescents. In a second study the new instrument was administered to 150 high school adolescents, 73 of who had school records of suspension for antisocial behavior. Exploratory factor analysis yielded a 4-factor structure (Impulsivity α = .73, Self-Centredness α = .70, Callous-Unemotional α = .69, and Manipulativeness α = .83). In a third study involving 328 high school adolescents, 130 with records of suspension for antisocial behaviour, competing measurement models were evaluated using confirmatory factor analysis. The superiority of a first-order model represented by four correlated factors that was invariant across gender and age was confirmed. The findings provide researchers and clinicians with a psychometrically strong, self-report instrument and a greater understanding of psychopathic traits in mainstream adolescents

Dietary availability patterns of the brazilian macro-regions

<p>Abstract</p> <p>Introduction</p> <p>Epidemiological studies have raised concerns about the role of dietary patterns on the risk of chronic diseases and also in the formulation of better informed nutrition policies.</p> <p>Objective</p> <p>The development of a dietary availability patterns according to geographic regions in Brazil.</p> <p>Methodology</p> <p>The 2002-2003 Brazilian Household Budget Survey was conducted in 48,470 households. Dietary availability patterns were identified by Principal Component Analysis using as a unit of analysis the survey's Primary Sampling Units (PSUs) and purchased amounts for 21 food groups. Each of the extracted dietary availability patterns was regressed on socioeconomics categories.</p> <p>Results</p> <p>There were no differences in dietary availability patterns between urban and rural areas. In all regions, a rice and beans pattern was identified. This pattern explained 15% to 28% of the variance dependent on the region of the country. In South, Southeast and Midwest regions, a mixed pattern including at least 10 food groups explaining 8% to 16% of the variance. In the North region (Amazon forest included) the first pattern was based on fish and nuts and then it was designed as regional pattern. In multiple linear regression the rice and beans pattern was associated with the presence of adolescents in the households, except for North region, whereas the presence of adolescents was associated with the Regional pattern. A mixed patterns were associated with a higher income and education (p < 0.05), except in the South region.</p> <p>Conclusion</p> <p>The rice and beans and regional dietary availability patterns, both considered healthy eating patterns are still important in the country. Brazil has taken many actions to improve nutrition as part of their public health policies, the data of the Household Budget Survey could help to recognize the different food choices in the large regions of the country.</p

Intolerance of uncertainty predicts fear extinction in amygdala-ventromedial prefrontal cortical circuitry

Background: Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmPFC) is important for fear-extinction learning. Aberrant recruitment of this circuitry is associated with anxiety disorders. Here, we sought to determine if individual differences in future threat uncertainty sensitivity, a potential risk factor for anxiety disorders, underly compromised recruitment of fear extinction circuitry. Twenty-two healthy subjects completed a cued fear conditioning task with acquisition and extinction phases. During the task, pupil dilation, skin conductance response, and functional magnetic resonance imaging were acquired. We assessed the temporality of fear extinction learning by splitting the extinction phase into early and late extinction. Threat uncertainty sensitivity was measured using self-reported intolerance of uncertainty (IU). Results: During early extinction learning, we found low IU scores to be associated with larger skin conductance responses and right amygdala activity to learned threat vs. safety cues, whereas high IU scores were associated with no skin conductance discrimination and greater activity within the right amygdala to previously learned safety cues. In late extinction learning, low IU scores were associated with successful inhibition of previously learned threat, reflected in comparable skin conductance response and right amgydala activity to learned threat vs. safety cues, whilst high IU scores were associated with continued fear expression to learned threat, indexed by larger skin conductance and amygdala activity to threat vs. safety cues. In addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction. Similar patterns of IU and extinction learning were found for pupil dilation. The results were specific for IU and did not generalize to self-reported trait anxiety. Conclusions: Overall, the neural and psychophysiological patterns observed here suggest high IU individuals to disproportionately generalize threat during times of uncertainty, which subsequently compromises fear extinction learning. More broadly, these findings highlight the potential of intolerance of uncertainty-based mechanisms to help understand pathological fear in anxiety disorders and inform potential treatment targets

Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation:a multidisciplinary expert advisory board

The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5mg, 5mg, 15mg and 20mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise