Orexin/hypocretin (Orx/Hcrt) transmission and drug-seeking behavior: is the paraventricular nucleus of the thalamus (PVT) part of the drug seeking circuitry?

The orexin/hypocretin (Orx/Hcrt) system has long been considered to regulate a wide range of physiological processes, including feeding, energy metabolism, and arousal. More recently, concordant observations have demonstrated an important role for these peptides in the reinforcing properties of most drugs of abuse. Orx/Hcrt neurons arise in the lateral hypothalamus (LH) and project to all brain structures implicated in the regulation of arousal, stress, and reward. Although Orx/Hcrt neurons have been shown to massively project to the paraventricular nucleus of the thalamus (PVT), only recent evidence suggested that the PVT may be a key relay of Orx/Hcrt-coded reward-related communication between the LH and both the ventral and dorsal striatum. While this thalamic region was not thought to be part of the "drug addiction circuitry," an increasing amount of evidence demonstrated that the PVT-particularly PVT Orx/Hcrt transmission-was implicated in the modulation of reward function in general and several aspects of drug-directed behaviors in particular. The present review discusses recent findings that suggest that maladaptive recruitment of PVT Orx/Hcrt signaling by drugs of abuse may promote persistent compulsive drug-seeking behavior following a period of protracted abstinence and as such may represent a relevant target for understanding the long-term vulnerability to drug relapse after withdrawal.

Pulmonary biomarkers in COPD exacerbations: a systematic review.

Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems. Innovative sampling techniques have led to the identification of several pulmonary biomarkers. Although some molecules are promising, their usefulness in clinical practice is not yet established. Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD. We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method. Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further. Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease's clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment. According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels. Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis. Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited. In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes. However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use. Clinical trials that incorporate biomarkers in decisional algorithms are required.

Real-time recording of circadian liver gene expression in freely moving mice reveals the phase-setting behavior of hepatocyte clocks.

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) in the hypothalamus, which is thought to set the phase of slave oscillators in virtually all body cells. However, due to the lack of appropriate in vivo recording technologies, it has been difficult to study how the SCN synchronizes oscillators in peripheral tissues. Here we describe the real-time recording of bioluminescence emitted by hepatocytes expressing circadian luciferase reporter genes in freely moving mice. The technology employs a device dubbed RT-Biolumicorder, which consists of a cylindrical cage with reflecting conical walls that channel photons toward a photomultiplier tube. The monitoring of circadian liver gene expression revealed that hepatocyte oscillators of SCN-lesioned mice synchronized more rapidly to feeding cycles than hepatocyte clocks of intact mice. Hence, the SCN uses signaling pathways that counteract those of feeding rhythms when their phase is in conflict with its own phase.

Theory of mind and cognitive processes in aging and Alzheimer type dementia: a systematic review.

OBJECTIVES: Theory of mind (ToM) performance in aging and dementia of the Alzheimer type (DAT) has been a growing interest of researchers and recently, theoretical trends in ToM development have led to a focus on determining the cognitive skills involved in ToM performance. The aim of the present review is to answer three main questions: How is ToM assessed in aging and DAT? How does ToM performance evolve in aging and DAT? Do cognitive processes influence ToM performance in aging and DAT? METHOD: A systematic review was conducted to provide a targeted overview of recent studies relating ToM performance with cognitive processes in aging and DAT. RESULTS: RESULTS suggest a decrease in ToM performance, more pronounced in complex ToM tasks. Moreover, the review points up the strong involvement of executive functions, especially inhibition, and reasoning skills in ToM task achievement. CONCLUSION: Current data suggest that the structure of ToM tasks itself could lead to poor performance, especially in populations with reduced cognitive abilities.

From Leadership to Citizenship Behavior in Public Organizations: When Values Matter

After decades of management reforms in the public sector, questions on the impact of leader-ship behavior in public organizations have been attracting increasing attention. This paper investigates the relationship between transformational leadership behavior and organizational citizenship behavior as one major extra-role outcome of transformational leadership. Refer-ring to a growing body of research that shows the importance of public service values and employee identification in public administration research, we include public service motiva-tion and organizational goal clarification as mediating variables in our analysis. Structural equation modeling is applied as the method of analysis for a sample of 569 public managers at the local level of Switzerland. The findings of our study support the assumed indirect relation-ship between leadership and employee behavior and emphasize the relevance of public ser-vice values when analyzing leadership behavior in public sector organizations.

Music and felt emotions: how systematic pitch level variations affect the experience of pleasantness and arousal

Pitch is a fundamental musical factor; however, findings about its contribution to the elicitation of emotions are contradictory. The purpose of this work was to assess the effect of systematic pitch variations on self-reports of felt valence and arousal. In a within-subject design, 49 subjects listened to four 1-minute classical piano excerpts, each presented at three different pitch levels (one octave lower than the original version, the original version and one octave higher than the original version). Compared to excerpts both without octave modification and in the +1 octave variant, pleasantness of excerpts in the -1 octave variant was significantly lower. This main effect was stronger for women than men and, importantly, was modulated by the specific characteristics of the stimuli. There was also a significant, yet smaller, negative relationship between pitch level and arousal, moderated by gender: Compared to higher pitch, lower pitch was associated with higher arousal in men only. Regarding the complex outcomes of this study, future studies should investigate to which extent our findings can be generalized to other musical works. The ultimate goal might be to demonstrate how pitch level interacts with other musical features and listeners' characteristics in eliciting diverse affective experiences.

Combined simulation and mutagenesis analyses reveal the involvement of key residues for peroxisome proliferator-activated receptor alpha helix 12 dynamic behavior.

The dynamic properties of helix 12 in the ligand binding domain of nuclear receptors are a major determinant of AF-2 domain activity. We investigated the molecular and structural basis of helix 12 mobility, as well as the involvement of individual residues with regard to peroxisome proliferator-activated receptor alpha (PPARalpha) constitutive and ligand-dependent transcriptional activity. Functional assays of the activity of PPARalpha helix 12 mutants were combined with free energy molecular dynamics simulations. The agreement between the results from these approaches allows us to make robust claims concerning the mechanisms that govern helix 12 functions. Our data support a model in which PPARalpha helix 12 transiently adopts a relatively stable active conformation even in the absence of a ligand. This conformation provides the interface for the recruitment of a coactivator and results in constitutive activity. The receptor agonists stabilize this conformation and increase PPARalpha transcription activation potential. Finally, we disclose important functions of residues in PPARalpha AF-2, which determine the positioning of helix 12 in the active conformation in the absence of a ligand. Substitution of these residues suppresses PPARalpha constitutive activity, without changing PPARalpha ligand-dependent activation potential.

Histological behavior of glutaraldehyde cross-linked bovine collagen injected into the human bladder for the treatment of vesicoureteral reflux

Endoscopic subureteral collagen injection has become an accepted means for the treatment of vesicoureteral reflux in children. The aim of this study was to evaluate the histological behavior of glutaraldehyde cross-linked bovine collagen implants. The specimens were harvested from 29 patients who underwent reimplant surgery 2 to 30 months (mean 9.5) after unsuccessful subureteral injection therapy. In addition to routine hematoxylin and eosin staining, a new staining method (solophenyl red 3BL) able to demonstrate selectively neoformation of types I and III human collagen, was applied. Invasion of host fibroblasts into the bovine implant and the formation of endogenous types I and III collagen were demonstrated in all 29 cases. Adverse histological reactions were rare and, if present, they were predominantly of an inflammatory nature.

Increased condom use without other major changes in sexual behavior among the general population in Switzerland.

The expression of DNA topoisomerase II alpha and beta genes was studied in murine normal tissues. Northern blot analysis using probes specific for the two genes showed that the patterns of expression were different among 22 tissues of adult mice. Expression levels of topoisomerase II alpha gene were high in proliferating tissues, such as bone marrow and spleen, and undetectable or low in 17 other tissues. In contrast, high or intermediate expression of topoisomerase II beta gene was found in a variety of tissues (15) of adult mice, including those with no proliferating cells. Topoisomerase II gene expression was also studied during murine development. In whole embryos both genes were expressed at higher levels in early than late stages of embryogenesis. Heart, brain and liver of embryos two days before delivery, and these same tissues plus lung and thymus of newborn (1-day-old) mice expressed appreciable levels of the two genes. Interestingly, a post-natal induction of the beta gene expression was observed in the brain but not in the liver; conversely, the expression of the alpha gene was increased 1 day after birth in the liver but not in the brain. However, gene expression of a proliferation-associated enzyme, thymidylate synthase, was similar in these tissues between embryos and newborns. Thus, the two genes were differentially regulated in the post-natal period, and a tissue-specific role may be suggested for the two isoenzymes in the development of differentiated tissues such as the brain and liver. Based on the differential patterns of expression of the two isoforms, this analysis indicates that topoisomerase II alpha may be a specific marker of cell proliferation, whereas topoisomerase II beta may be implicated in functions of DNA metabolism other than replication.

Assessment of youth-friendly health care: a systematic review of indicators drawn from young people's perspectives.

PURPOSE: To review the literature on young people's perspectives on health care with a view to defining domains and indicators of youth-friendly care. METHODS: Three bibliographic databases were searched to identify studies that purportedly measured young people's perspectives on health care. Each study was assessed to identify the constructs, domains, and indicators of adolescent-friendly health care. RESULTS: Twenty-two studies were identified: 15 used quantitative methods, six used qualitative methods and one used mixed methodology. Eight domains stood out as central to young people's positive experience of care. These were: accessibility of health care; staff attitude; communication; medical competency; guideline-driven care; age appropriate environments; youth involvement in health care; and health outcomes. Staff attitudes, which included notions of respect and friendliness, appeared universally applicable, whereas other domains, such as an appropriate environment including cleanliness, were more specific to particular contexts. CONCLUSION: These eight domains provide a practical framework for assessing how well services are engaging young people. Measures of youth-friendly health care should address universally applicable indicators of youth-friendly care and may benefit from additional questions that are specific to the local health setting.