The new European Parliament: Workable but impaired? CEPS Commentary, 27 June 2014

The ongoing selection of the next President of the European Commission has underscored the growing importance of the European Parliament in EU decisionmaking and in promoting democratic legitimacy at EU level. Strikingly, the new Parliament will be more Eurosceptical, radical and fragmented than ever before, which, among other things, will constrain the building of majorities to pass legislation and adopt decisions. The close relationship between the outcome of the EP elections and the governability of the EP should prompt a serious debate on the matter.

Impaired renal endothelial nitric oxide synthase and reticulocyte production as modulators of hypertension induced by recombinant human erythropoietin in the rat

INTRODUCTION AND AIMS: Hypertension is a common side effect of recombinant human erythropoietin (rHuEPO) therapy; however, the exact pathways remain to be elucidated. The discovery of non-hematopoietic actions of rHuEPO increased the number of patients that could putatively benefit from this therapy; however, to achieve those effects higher doses are usually needed, which increase the risk and incidence of adverse events. Our aim was to study the effect of a broad range of rHuEPO doses on hematological and biochemical parameters, blood pressure and renal function and damage in the rat, focusing on endothelial nitric oxide synthase (eNOS) and hypoxia-inducible factors (HIFs). METHODS: Male Wistar rats were divided in 5 groups receiving different doses of rHuEPO (100, 200, 400 and 600 IU/kg body weight (BW)/week) and saline solution (control), during 3 weeks. Blood and 24h urine were collected to perform hematological and biochemical analysis. Blood pressure (BP) was measured by the tail-cuff method. The kidney tissue was collected to mRNA and protein expression assays and to characterize renal lesions. RESULTS: A dose-dependent increase in red blood cells count, hematocrit and hemoglobin levels was found with rHuEPO therapy, in rHuEPO200, rHuEPO400 and rHuEPO600 groups. Increased reticulocyte count was found in the rHuEPO400 and rHuEPO600 groups. BP raised in all groups receiving rHuEPO. The rHuEPO200 and rHuEPO600 groups presented increased kidney protein levels of HIF2α and a reduction in kidney protein levels of eNOS, along with the highest grade of vascular and tubular renal lesions. CONCLUSIONS: Our study showed that rHuEPO-induced hypertension might involve indirect (hematological) and direct (renal) effects which varies according to the dose used. Thus, rHuEPO therapy should be performed rationally and under adequate surveillance, as hypertension develops even with lower doses. Especial caution with higher doses should be taken, as rHuEPO-induced hypertension leads to early renal damage without alterations in traditional markers of renal function, thus masking the serious adverse effects and risks.

Immune recovery in HIV-infected patients after candida esophagitis is impaired despite long-term antiretroviral therapy.

OBJECTIVE Candida esophagitis belongs to the most common AIDS-defining diseases, however, a comprehensive immune pathogenic concept is lacking. DESIGN We investigated the immune status of 37 HIV-1-infected patients from the Swiss HIV cohort study at diagnosis of Candida esophagitis, 1 year before, 1 year later and after 2 years of suppressed HIV RNA. We compared these patients to 3 groups: 37 HIV-1-infected patients without Candida esophagitis but similar CD4 counts as the patients at diagnosis (advanced HIV group), 15 HIV-1-infected patients with CD4 counts >500 cells/μl, CD4 nadir >350 cells/μl and suppressed HIV RNA under combination antiretroviral therapy (cART) (early cART group), and 20 healthy individuals. METHODS We investigated phenotype, cytokine production and proliferative capacity of different immune cells by flow cytometry and ELISpot. RESULTS We found that patients with Candida esophagitis had nearly abolished CD4 proliferation in response to C. albicans, significantly increased percentages of dysfunctional CD4 cells, significantly decreased cytotoxic NK-cell counts and peripheral innate lymphoid cells and significantly reduced IFN-γ and IL-17 production compared to the early cART group and healthy individuals. Most of these defects remained for more than 2 years despite viral suppression. The advanced HIV group without opportunistic infection showed partly improved immune recovery. CONCLUSIONS Our data indicate that Candida esophagitis in HIV-1-infected patients is caused by an accumulation of multiple, partly Candida-specific immunological defects. Long-term immune recovery is impaired, illustrating that specific immunological gaps persist despite cART. These data also support the rationale for early cART initiation to prevent irreversible immune defects.

Higher self-control capacity predicts lower anxiety-impaired cognition during math examinations

We assumed that self-control capacity, self-efficacy, and self-esteem would enable students to keep attentional control during tests. Therefore, we hypothesized that the three personality traits would be negatively related to anxiety-impaired cognition during math examinations. Secondary school students (N = 158) completed measures of self-control capacity, self-efficacy, and self-esteem at the beginning of the school year. Five months later, anxiety-impaired cognition during math examinations was assessed. Higher self-control capacity, but neither self-efficacy nor self-esteem, predicted lower anxiety-impaired cognition 5 months later, over and above baseline anxiety-impaired cognition. Moreover, self-control capacity was indirectly related to math grades via anxiety-impaired cognition. The findings suggest that improving self-control capacity may enable students to deal with anxiety-related problems during school tests.

Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions

Substance P (SP) play a central role in nociceptive transmission and it is an agonist of the Neurokinin-1 receptor located in the lamina I of the spinal cord. SP is a major proteolytic product of the protachykinin-1 primarily synthesized in neurons. Proprotein convertases (PCs) are extensively expressed in the central nervous system (CNS) and specifically cleave at C-terminal of either a pair of basic amino acids, or a single basic residue. The proteolysis control of endogenous protachykinins has a profound impact on pain perception and the role of PCs remain unclear. The objective of this study was to decipher the role of PC1 and PC2 in the proteolysis surrogate protachykinins (i.e. Tachykinin 20-68 and Tachykinin 58-78) using cellular fractions of spinal cords from wild type (WT), PC1-/+ and PC2-/+ animals and mass spectrometry. Full-length Tachykinin 20-68 and Tachykinin 58-78 was incubated for 30 minutes in WT, PC1-/+ and PC2-/+ mouse spinal cord S9 fractions and specific C-terminal peptide fragments were identified and quantified by mass spectrometry. The results clearly demonstrate that both PC1 and PC2 mediate the formation of SP and Tachykinin 58-71, an important SP precursor, with over 50% reduction of the rate of formation in mutant PC 1 and PC2 mouse S9 spinal cord fractions. The results obtained revealed that PC1 and PC2 are involved in the C-terminal processing of protachykinin peptides and suggest a major role in the maturation of the protachykinin-1 protein.

Youth driving without impairment: report on the youth impaired driving public hearings - a community challenge.

Mode of access: Internet.

Modeling and participation: elements in education to reduce alcohol impaired driving. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Together we can help prevent alcohol-impaired driving.

National Institute on Alcohol Abuse and Alcoholism, Rockville, Md.

Treatment for the impaired driver. Volume II: case studies. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Treatment for the impaired driver. Volume I: approaches. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Saturation patrols targeting impaired driving - guidelines for community-based alcohol enforcement programs.

Mode of access: Internet.

Enforcement of underage impaired-driving laws - issues, problems, recommended solutions.

Mode of access: Internet.

Attitudinal and behavioral changes of alcohol impaired drivers and analytical study of the alcohol education program of the Boston Alcohol Safety Action Project. Analytical studies 5 and 6.

National Highway Traffic Safety Administration, Washington, D.C.

How do I do this when I can't see what I'm doing? : information processing for the visually disabled /

Includes bibliographical references and index.

Reading, writing, and other communication aids for visually and physically handicapped persons.

Mode of access: Internet.