Constitutive Overexpression of Muscarinic Receptors Leads to Vagal Hyperreactivity

BACKGROUND: Alterations in muscarinic receptor expression and acetylcholinesterase (AchE) activity have been observed in tissues from Sudden Infant Death Syndrome (SIDS). Vagal overactivity has been proposed as a possible cause of SIDS as well as of vasovagal syncopes. The aim of the present study was to seek whether muscarinic receptor overexpression may be the underlying mechanism of vagal hyperreactivity. Rabbits with marked vagal pauses following injection of phenylephrine were selected and crossed to obtain a vagal hyperreactive strain. The density of cardiac muscarinic receptors and acetylcholinesterase (AchE) gene expression were assessed. Blood markers of the observed cardiac abnormalities were also sought. METHODOLOGY/PRINCIPAL FINDINGS: Cardiac muscarinic M(2) and M(3) receptors were overexpressed in hyperreactive rabbits compared to control animals (2.3-fold and 2.5-fold, respectively) and the severity of the phenylephrine-induced bradycardia was correlated with their densities. A similar overexpression of M(2) receptors was observed in peripheral mononuclear white blood cells, suggesting that cardiac M(2) receptor expression can be inferred with high confidence from measurements in blood cells. Sequencing of the coding fragment of the M(2) receptor gene revealed a single nucleotide mutation in 83% of hyperreactive animals, possibly contributing for the transcript overexpression. Significant increases in AchE expression and activity were also assessed (AchE mRNA amplification ratio of 3.6 versus normal rabbits). This phenomenon might represent a compensatory consequence of muscarinic receptors overexpression. Alterations in M(2) receptor and AchE expression occurred between the 5th and the 7th week of age, a critical period also characterized by a higher mortality rate of hyperreactive rabbits (52% in H rabbits versus 13% in normal rabbits) and preceeded the appearance of functional disorders. CONCLUSIONS/SIGNIFICANCE: The results suggest that cardiac muscarinic receptor overexpression plays a critical role in the development of vagal hyperreactivity, whereas AchE hyperactivity appears as a compensatory consequence of it. Since similar vagal disorders were observed recently by us in SIDS, muscarinic receptor overexpression could become a marker of risk of vasovagal syncopes and SIDS

Leaders’ Impact on Public Spending Priorities: The Case of the German Laender

We examine determinants of the composition of public expenditure in the German Laender (states) over the period 1993-2008, as the Laender exhibit a high degree of institutional and political homogeneity and are endowed with extensive fiscal competences. Our prime contribution is an investigation into how political leaders' socioeconomic background influences public spending priorities. Applying sociological theory, we link preferences for the composition of public spending to social status. In contrast to approaches relying on political budget cycles or partisan theory, we find strong and theory-consistent evidence that prime ministers tend to favour fiscal policies supporting the social class in which they are socialised. Governments led by prime ministers from a poor socioeconomic background spend significantly more on social security, education, health, infrastructure, and public safety

Leave the Drama on the Stage: The Effect of Cultural Participation on Health

The aim of this study is to estimate the causal effect of cultural participation on health status. Cultural activities may directly impact upon health through palliative coping or substituting health-compromising behaviors. Cultural engagement may also facilitate the development of social networks, which can improve health via social support and the dissemination of social health norms. Previous estimates on the arts-health relationship are potentially biased due to reverse causality and unobserved heterogeneity. Using individual-level data from Germany, we employ propensity-score matching methods. The treatment group is confined to individuals that visit cultural events at least once a month. The participation equation includes a rich set of personal characteristics that cover the respondents' demographic and social background, social capital and leisure-time activities, health-related lifestyle, personality and childhood environment. We explicitly consider reverse causality by including the pre-treatment trends in health outcomes among the covariates. To deal with time-fixed unobserved heterogeneity, we combine the matching model with a difference-indifference approach. We find that frequent cultural-event visits are unrelated to health once we account for unobserved persistent differences across individuals. However, examining the dose-response relationship we find positive mental-health effects of low levels of cultural participation compared to non-attendance. Our results may thus yield important insights on the effectiveness of arts participation as a means to reduce social inequalities in health

Predicting Transitions in Low and High Levels of Risk Behavior from Early to Middle Adolescence: The TRAILS Study

The present study examined the joint development of substance use and externalizing problems in early and middle adolescence. First, it was tested whether the relevant groups found in previous studies i.e., those with an early onset, a late onset, and no onset or low levels of risk behavior could be identified, while using a developmental model of a single, underlying construct of risk behavior. Second, departing from Moffitt’s taxonomy of antisocial behavior, it was tested if early, but not late, onset risk behavior is predicted by a problematic risk profile in childhood. Data were used from TRAILS, a population based cohort study, starting at age 11 with two follow-ups at mean ages of 13.6 and 16.3 years. Latent transition analyses demonstrated that, both in early and middle adolescence, a single underlying construct of risk behavior, consisting of two classes (labeled as low and high risk behavior), adequately represented the data. Respondents could be clearly classified into four possible transition patterns from early to middle adolescence, with a transition from high to low being almost non-existent (2.5 %), low to low (39.4 %) and low to high (41.8 %) being the most prevalent, and high to high (16.2 %) substantial. As hypothesized, only the high-high group was characterized by a clear adverse predictor profile in late childhood, while the low-high group was not. This study demonstrates that the development of substance use is correlated with externalizing problems and underscores the theory that etiologies of early and later onset risk behavior are different

Проблема ада как компонент проблемы зла в христианской религиозно-философской парадигме

Целью данной работы выступает религиоведческое исследование темы получившей название проблема ада в ее философско-теологическом измерении. Соответственно цели автор ставит перед собой такие задания как: проследить становление традиционной концепции ада, выявить богословские и философские предпосылки формирования данного учения, провести религиоведческий и философский анализ альтернативных учений относительно загробного воздаяния

Political Leaders' Socioeconomic Background and Fiscal Performance in Germany

This paper investigates whether the socioeconomic status of the head of government helps explain fiscal performance. Applying sociological research that attributes differences in people's ways of thinking and acting to their relative standing within society, we test whether the social status of German prime ministers can help explain differences in fiscal performance among the German Laender. Our empirical findings show that the tenures of prime ministers from a poorer socioeconomic background are associated with higher levels of public spending and debt financing