Atipamezole Reverses Cardiovascular Changes Induced by High-Dose Medetomidine in Cats Undergoing Sedation for Semen Collection

This study aimed at describing the change in echocardiographic variables after high-dose medetomidine and the reversal with atipamezole in six cats undergoing sedation for semen collection. Further cardiac Troponin I (cTnI) concentration and the effect of repeated sedation were assessed. Echocardiography was performed before and 20 min after sedation with 0.1 mg/kg medetomidine intramuscularly (IM) for urethral catheterisation. Prior to epididymectomy, S-ketamine was administered intravenously. Twenty minutes after reversal with 0.5 mg/kg atipamezole IM, the third echocardiography was performed. Sedation with medetomidine and reversal with atipamezole was repeated on day 7, 14, 21 and 28. Heart rate (HR) and rhythm were monitored throughout all sedations. On day 0 and 28 cTnI concentrations were measured before and after the procedure. After normality testing, the values were compared over time. The administration of medetomidine led to a marked reduction in HR, cardiac output and ventricular systolic function and a significant increase in left ventricular dimensions. Rhythm abnormalities, such as ventricular premature complexes and idioventricular rhythm, could be observed. The administration of atipamezole completely reversed sedation and the changes in haemodynamic variables. No significant increase in cTnI concentrations could be detected, although two out of six cats showed values above the reference range

Impact of air pollution on hospital patients admitted with ST- and non-ST-segment elevation myocardial infarction in heavily polluted cities within the European Union

Background: Air pollution triggered diseases have become a leading health problem worldwide. The main adverse effects of air pollutants on human health are related to the cardiovascular system and particularly show an increasing prevalence of myocardial infarct and stroke. The aim of the study was to evaluate the influence of main air pollutants on non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI) admissions to local interventionalcardiology centers.Methods: Between 2014 and 2015, a multicenter registry of 1957 patients with acute myocardial infarction (STEMI, NSTEMI) admitted to interventional cardiology departments in three Polish cities were under investigation. The air pollution (PM2.5, PM10, NO2, SO2, O3) and weather conditions (temperature, barometric pressure, humidity) data for each city were collected as daily averages. The case-crossover design and conditional logistic regression were used to explore the association between acute myocardial infarctions and short-term air pollution exposure.Results: Occurrence of NSTEMI on the day of air pollution was triggered by PM2.5 (OR = 1.099, p = 0.01) and PM10 (OR = 1.078, p = 0.03). On the following day after the air pollution was recorded, NSTEMI was induced by: PM2.5 (OR = 1.093, p = 0.025), PM10 (OR = 1.077, p = 0.025) and SO2 (OR = 1.522, p = 0.009). For STEMI, events that occurred on the day in which air pollution was triggered by: PM2.5 (OR = 1.197, p < 0.001), PM10 (OR = 1.163, p < 0.001), SO2 (OR = 1.670, p = 0.001) and NO2 (OR = 1.287, p = 0.011). On the following day after air pollution was recorded, STEMI was induced by: PM2.5 (OR = 1.172, p < 0.001), PM10 (OR = 1.131, p = 0.001), SO2 (OR = 1.550, p = 0.005) and NO2 (OR = 1.265, p = 0.02). None of the weather conditions indicated were statistically significant for acute myocardial infarction occurrence.Conclusions: The most important pollutants triggering acute myocardial infarction occurrence in the population of southern Poland, both on the day of air pollution and the following day are particulate matters (PM2.5, PM10) and gaseous pollutants including NO2 and SO2. These pollutants should be regarded as modifiable risk factors and thus, their reduction is a priority in order to decrease total morbidity and mortality in Poland

Transmissibility of Atypical Scrapie in Ovine Transgenic Mice: Major Effects of Host Prion Protein Expression and Donor Prion Genotype

Atypical scrapie or Nor98 has been identified as a transmissible spongiform encephalopathy (TSE) that is clearly distinguishable from classical scrapie and BSE, notably regarding the biochemical features of the protease-resistant prion protein PrPres and the genetic factors involved in susceptibility to the disease. In this study we transmitted the disease from a series of 12 French atypical scrapie isolates in a transgenic mouse model (TgOvPrP4) overexpressing in the brain ∼0.25, 1.5 or 6× the levels of the PrPARQ ovine prion protein under the control of the neuron-specific enolase promoter. We used an approach based on serum PrPc measurements that appeared to reflect the different PrPc expression levels in the central nervous system. We found that transmission of atypical scrapie, much more than in classical scrapie or BSE, was strongly influenced by the PrPc expression levels of TgOvPrP4 inoculated mice. Whereas TgOvPrP4 mice overexpressing ∼6× the normal PrPc level died after a survival periods of 400 days, those with ∼1.5× the normal PrPc level died at around 700 days. The transmission of atypical scrapie in TgOvPrP4 mouse line was also strongly influenced by the prnp genotypes of the animal source of atypical scrapie. Isolates carrying the AF141RQ or AHQ alleles, associated with increased disease susceptibility in the natural host, showed a higher transmissibility in TgOvPrP4 mice. The biochemical analysis of PrPres in TgOvPrP4 mouse brains showed a fully conserved pattern, compared to that in the natural host, with three distinct PrPres products. Our results throw light on the transmission features of atypical scrapie and suggest that the risk of transmission is intrinsically lower than that of classical scrapie or BSE, especially in relation to the expression level of the prion protein

Mental Health of Parents and Life Satisfaction of Children: A Within-Family Analysis of Intergenerational Transmission of Well-Being

This paper addresses the extent to which there is an intergenerational transmission of mental health and subjective well-being within families. Specifically it asks whether parents’ own mental distress influences their child’s life satisfaction, and vice versa. Whilst the evidence on daily contagion of stress and strain between members of the same family is substantial, the evidence on the transmission between parental distress and children’s well-being over a longer period of time is sparse. We tested this idea by examining the within-family transmission of mental distress from parent to child’s life satisfaction, and vice versa, using rich longitudinal data on 1,175 British youths. Results show that parental distress at year t-1 is an important determinant of child’s life satisfaction in the current year. This is true for boys and girls, although boys do not appear to be affected by maternal distress levels. The results also indicated that the child’s own life satisfaction is related with their father’s distress levels in the following year, regardless of the gender of the child. Finally, we examined whether the underlying transmission correlation is due to shared social environment, empathic reactions, or transmission via parent-child interaction

Hypopituitarism is associated with lower oxytocin concentrations and reduced empathic ability

Purpose Central diabetes insipidus is characterised by arginine vasopressin deficiency. Oxytocin is structurally related to vasopressin and is synthesised in the same hypothalamic nuclei, thus we hypothesised that patients with acquired central diabetes insipidus and anterior hypopituitarism would display an oxytocin deficiency. Moreover, psychological research has demonstrated that oxytocin influences social and emotional behaviours, particularly empathic behaviour. We therefore further hypothesised that central diabetes insipidus patients would perform worse on empathy-related tasks, compared to age-matched and gender-matched clinical control (clinical control-isolated anterior hypopituitarism) and healthy control groups. Method Fifty-six participants (age 46.54 ± 16.30 yrs; central diabetes insipidus: n = 20, 8 males; clinical control: n = 15, 6 males; healthy control: n = 20, 7 males) provided two saliva samples which were analysed for oxytocin and completed two empathy tasks. Results Hypopituitary patients (both central diabetes insipidus and clinical control groups) had significantly lower oxytocin concentrations compared to healthy control participants. Hypopituitary patients also performed significantly worse on both the reading the mind in the eyes task and the facial expression recognition task compared to healthy control participants. Regression analyses further revealed that central diabetes insipidus patients’ oxytocin concentrations significantly predicted their performance on easy items of the reading the mind in the eyes task. Conclusions Hypopituitarism may therefore be associated with reduced oxytocin concentrations and impaired empathic ability. While further studies are needed to replicate these findings, our data suggest that oxytocin replacement may offer a therapeutic approach to improve psychological well-being in patients with hypopituitarism

Are skin disorders related to work strain in hospital workers? A cross-sectional study

To evaluate whether occupational stress factors (high demands, low control, low social support, strain, and iso-strain) are associated with skin disorders in hospital workers and whether psychological problems, such as anxiety and depression, act as potential mechanisms through which occupational stress factors are associated with skin disorders

Cluster analysis of angiotensin biomarkers to identify antihypertensive drug treatment in population studies

Background: The recent progress in molecular biology generates an increasing interest in investigating molecular biomarkers as markers of response to treatments. The present work is motivated by a study, where the objective was to explore the potential of the molecular biomarkers of renin-angiotensin-aldosterone system (RAAS) to identify the undertaken antihypertensive treatments in the general population. Population-based studies offer an opportunity to assess the effectiveness of treatments in real-world scenarios. However, lack of quality documentation, especially when electronic health record linkage is unavailable, leads to inaccurate reporting and classification bias. Method: We present a machine learning clustering technique to determine the potential of measured RAAS biomarkers for the identification of undertaken treatments in the general population. The biomarkers were simultaneously determined through a novel mass-spectrometry analysis in 800 participants of the Cooperative Health Research In South Tyrol (CHRIS) study with documented antihypertensive treatments. We assessed the agreement, sensitivity and specificity of the resulting clusters against known treatment types. Through the lasso penalized regression, we identified clinical characteristics associated with the biomarkers, accounting for the effects of cluster and treatment classifications. Results: We identified three well-separated clusters: cluster 1 (n = 444) preferentially including individuals not receiving RAAS-targeting drugs; cluster 2 (n = 235) identifying angiotensin type 1 receptor blockers (ARB) users (weighted kappa κw = 74%; sensitivity = 73%; specificity = 83%); and cluster 3 (n = 121) well discriminating angiotensin-converting enzyme inhibitors (ACEi) users (κw = 81%; sensitivity = 55%; specificity = 90%). Individuals in clusters 2 and 3 had higher frequency of diabetes as well as higher fasting glucose and BMI levels. Age, sex and kidney function were strong predictors of the RAAS biomarkers independently of the cluster structure. Conclusions: Unsupervised clustering of angiotensin-based biomarkers is a viable technique to identify individuals on specific antihypertensive treatments, pointing to a potential application of the biomarkers as useful clinical diagnostic tools even outside of a controlled clinical setting

Functional features of gene expression profiles differentiating gastrointestinal stromal tumours according to KIT mutations and expression

<p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumours (GISTs) represent a heterogeneous group of tumours of mesenchymal origin characterized by gain-of-function mutations in <it>KIT </it>or <it>PDGFRA </it>of the type III receptor tyrosine kinase family. Although mutations in either receptor are thought to drive an early oncogenic event through similar pathways, two previous studies reported the mutation-specific gene expression profiles. However, their further conclusions were rather discordant. To clarify the molecular characteristics of differentially expressed genes according to GIST receptor mutations, we combined microarray-based analysis with detailed functional annotations.</p> <p>Methods</p> <p>Total RNA was isolated from 29 frozen gastric GISTs and processed for hybridization on GENECHIP^®HG-U133 Plus 2.0 microarrays (Affymetrix). <it>KIT </it>and <it>PDGFRA </it>were analyzed by sequencing, while related mRNA levels were analyzed by quantitative RT-PCR.</p> <p>Results</p> <p>Fifteen and eleven tumours possessed mutations in <it>KIT </it>and <it>PDGFRA</it>, respectively; no mutation was found in three tumours. Gene expression analysis identified no discriminative profiles associated with clinical or pathological parameters, even though expression of hundreds of genes differentiated tumour receptor mutation and expression status. Functional features of genes differentially expressed between the two groups of GISTs suggested alterations in angiogenesis and G-protein-related and calcium signalling.</p> <p>Conclusion</p> <p>Our study has identified novel molecular elements likely to be involved in receptor-dependent GIST development and allowed confirmation of previously published results. These elements may be potential therapeutic targets and novel markers of <it>KIT </it>mutation status.</p

Validation of the Tetracycline Regulatable Gene Expression System for the Study of the Pathogenesis of Infectious Disease

Understanding the pathogenesis of infectious disease requires the examination and successful integration of parameters related to both microbial virulence and host responses. As a practical and powerful method to control microbial gene expression, including in vivo, the tetracycline-regulatable system has recently gained the favor of many investigative groups. However, some immunomodulatory effects of the tetracyclines, including doxycycline, could potentially limit its use to evaluate host responses during infection. Here we have used a well-established murine model of disseminated candidiasis, which is highly dependent on both the virulence displayed by the fungal cells and on the host immune status, to validate the use of this system. We demonstrate that the pathogenesis of the wild type C. albicans CAF2-1 strain, which does not contain any tet-regulatable element, is not affected by the presence of doxycycline. Moreover levels of key cytokines, chemokines and many other biomarkers, as determined by multi-analyte profiling, remain essentially unaltered by the presence of the antibiotic during infection. Our results indicate that the levels of doxycycline needed to control the tetracycline regulatable promoter gene expression system have no detectable effect on global host responses during candidiasis. Because tet-regulatable systems are now being increasingly used in a variety of pathogenic microorganisms, these observations have wide implications in the field of infectious diseases