T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites.

T-type Ca2+ channels (T channels) underlie rhythmic burst discharges during neuronal oscillations that are typical during sleep. However, the Ca2+-dependent effectors that are selectively regulated by T currents remain unknown. We found that, in dendrites of nucleus reticularis thalami (nRt), intracellular Ca2+ concentration increases were dominated by Ca2+ influx through T channels and shaped rhythmic bursting via competition between Ca2+-dependent small-conductance (SK)-type K+ channels and Ca2+ uptake pumps. Oscillatory bursting was initiated via selective activation of dendritically located SK2 channels, whereas Ca2+ sequestration by sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) and cumulative T channel inactivation dampened oscillations. Sk2-/- (also known as Kcnn2) mice lacked cellular oscillations, showed a greater than threefold reduction in low-frequency rhythms in the electroencephalogram of non-rapid-eye-movement sleep and had disrupted sleep. Thus, the interplay of T channels, SK2 channels and SERCAs in nRt dendrites comprises a specialized Ca2+ signaling triad to regulate oscillatory dynamics related to sleep.

A follow-up study on the quality of alcohol dependence-related information on the web.

ABSTRACT: In order to evaluate the one-year evolution of web-based information on alcohol dependence, we re-assessed alcohol-related sites in July 2007 with the same evaluating tool that had been used to assess these sites in June 2006. Websites were assessed with a standardized form designed to rate sites on the basis of accountability, presentation, interactivity, readability, and content quality. The DISCERN scale was also used, which aimed to assist persons without content expertise in assessing the quality of written health publications. Scores were highly stable for all components of the form one year later (r = .77 to .95, p < .01). Analysis of variance for repeated measures showed no time effect, no interaction between time and scale, no interaction between time and group (affiliation categories), and no interaction between time, group, and scale. The study highlights lack of change of alcohol-dependence-related web pages across one year.

CD14 expression on monocytes and TNF alpha production in patients with septic shock, cardiogenic shock or bacterial pneumonia.

OBJECTIVES: In patients with septic shock, circulating monocytes become refractory to stimulation with microbial products. Whether this hyporesponsive state is induced by infection or is related to shock is unknown. To address this question, we measured TNF alpha production by monocytes or by whole blood obtained from healthy volunteers (controls), from patients with septic shock, from patients with severe infection (bacterial pneumonia) without shock, and from patients with cardiogenic shock without infection. MEASUREMENTS: The numbers of circulating monocytes, of CD14+ monocytes, and the expression of monocyte CD14 and the LPS receptor, were assessed by flow cytometry. Monocytes or whole blood were stimulated with lipopolysaccharide endotoxin (LPS), heat-killed Escherichia coli or Staphylococcus aureus, and TNF alpha production was measured by bioassay. RESULTS: The number of circulating monocytes, of CD14+ monocytes, and the monocyte CD14 expression were significantly lower in patients with septic shock than in controls, in patients with bacterial pneumonia or in those with cardiogenic shock (p < 0.001). Monocytes or whole blood of patients with septic shock exhibited a profound deficiency of TNF alpha production in response to all stimuli (p < 0.05 compared to controls). Whole blood of patients with cardiogenic shock also exhibited this defect (p < 0.05 compared to controls), although to a lesser extent, despite normal monocyte counts and normal CD14 expression. CONCLUSIONS: Unlike patients with bacterial pneumonia, patients with septic or cardiogenic shock display profoundly defective TNF alpha production in response to a broad range of infectious stimuli. Thus, down-regulation of cytokine production appears to occur in patients with systemic, but not localised, albeit severe, infections and also in patients with non-infectious circulatory failure. Whilst depletion of monocytes and reduced monocyte CD14 expression are likely to be critical components of the hyporesponsiveness observed in patients with septic shock, other as yet unidentified factors are at work in this group and in patients with cardiogenic shock.

Diagnostic et traitement des infections d'implants orthopédiques [Update on implant related infections in orthopaedic surgery. Diagnosis and treatment]

Infections associated with implants are increasingly important in modem medicine. Biofilms are the cause that these infections are more difficult to diagnose and to cure. Particularly low-grade infections are difficult to distinguish from aseptic failure, because they often present with early loosening and persisting pain. For an accurate diagnosis, clinical signs and symptoms, laboratory markers of infection, microbiology, histology and imaging examinations are needed. The treatment goal is eradication of infection and an optimal functional result. Successful treatment requires adequate surgical procedure combined with long-term antimicrobial therapy, ideally with an agent acting on biofilms.

Trypanosoma cruzi: identification of specific epimastigote antigens by human immune sera

Soluble antigens from epimastigotes of Trypanosoma cruzi were analyzed by western blot in terms of their reactivity with sera from patients with Chagas' disease. In addition, sera from patients with visceral (AVL) and tegumentar leishmaniasis (ATL) were also tested in order to identify cross-reactivities with Trypanosoma cruzy antigens. Twenty eight polypeptides with molecular weights ranging from 14 kDa to 113 kDa were identified with sera from Chagas' disease patients. An extensive cross-reactivity was observed when sera from human visceral leishmaniasis were used, while only a slight cross-reaction was observed with sera from tegumentar leishmaniasis. On the other hand, 10 polypeptidesspecifically reacting with sera from Chagas' disease patients were identified. Among them, the antigens with molecular weights of 46 kDa and 25 kDa reacted with all sera teste and may be good candidates for specific immunodiagnosis of Chagas' disease.

Longitudinal analysis of income-related health inequality

This paper considers the characterisation and measurement of income-related health inequality using longitudinal data. The paper elucidates the nature of the Jones and Lopez Nicholas (2004) index of “health-related income mobility” and explains the negative values of the index that have been reported in all the empirical applications to date. The paper further questions the value of their index to health policymakers and proposes an alternative index of “income-related health mobility” that measures whether the pattern of health changes is biased in favour of those with initially high or low incomes. We illustrate our work by investigating mobility in the General Health Questionnaire measure of psychological well-being over the first nine waves of the British Household Panel Survey from 1991 to 1999.

MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo.

PURPOSE: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or "wet" Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice. METHODS: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with "wet" AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8(+/-) mice expressing ß-galactosidase. Aged Mfge8(+/-) and Mfge8(-/-) mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV. RESULTS: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8(-/-) mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8(-/-) mice as compared to controls. CONCLUSIONS: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8(-/-) mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD.

Simulations of parasitic and intrinsic capacitances related to Multiple-Gate-Field-Effect Transistor architectures

Report for the scientific sojourn carried out at the Université Catholique de Louvain, Belgium, from March until June 2007. In the first part, the impact of important geometrical parameters such as source and drain thickness, fin spacing, spacer width, etc. on the parasitic fringing capacitance component of multiple-gate field-effect transistors (MuGFET) is deeply analyzed using finite element simulations. Several architectures such as single gate, FinFETs (double gate), triple-gate represented by Pi-gate MOSFETs are simulated and compared in terms of channel and fringing capacitances for the same occupied die area. Simulations highlight the great impact of diminishing the spacing between fins for MuGFETs and the trade-off between the reduction of parasitic source and drain resistances and the increase of fringing capacitances when Selective Epitaxial Growth (SEG) technology is introduced. The impact of these technological solutions on the transistor cut-off frequencies is also discussed. The second part deals with the study of the effect of the volume inversion (VI) on the capacitances of undoped Double-Gate (DG) MOSFETs. For that purpose, we present simulation results for the capacitances of undoped DG MOSFETs using an explicit and analytical compact model. It monstrates that the transition from volume inversion regime to dual gate behaviour is well simulated. The model shows an accurate dependence on the silicon layer thickness,consistent withtwo dimensional numerical simulations, for both thin and thick silicon films. Whereas the current drive and transconductance are enhanced in volume inversion regime, our results show thatintrinsic capacitances present higher values as well, which may limit the high speed (delay time) behaviour of DG MOSFETs under volume inversion regime.

Vascular depression. An age-related mood disorder

Neuropathological and radiological evidences implicating cerebrovascular disease in the pathogenesis of certain types of geriatric depression have led to the relatively recent description of vascular depression, an age-related mood disorder. Its clinical and radiological presentation, the frequent coexistence of cognitive disorders including impairment in executive function and resistance to antidepressant therapy distinguish it from other types of depression. This article presents an overview of the existing literature on the epidemiology, pathophysiology, clinical features and therapeutic particularities of vascular depression. (C) 2010 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.

Longitudinal analysis of income-related health inequality: welfare foundations and alternative measures

This paper elaborates the approach to the longitudinal analysis of income-related health inequalities first proposed in Allanson, Gerdtham and Petrie (2010). In particular, the paper establishes the normative basis of their mobility indices by embedding their decomposition of the change in the health concentration index within a broader analysis of the change in “health achievement” or wellbeing. The paper further shows that their decomposition procedure can also be used to analyse the change in a range of other commonly-used incomerelated health inequality measures, including the generalised concentration index and the relative inequality index. We illustrate our work by extending their investigation of mobility in the General Health Questionnaire measure of psychological well-being over the first nine waves of the British Household Panel Survey from 1991 to 1999.

MARCKS-related protein (MRP) is a substrate for the Leishmania major surface protease leishmanolysin (gp63).

Myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP; MacMARCKS) are protein kinase C substrates in diverse cell types. Activation of murine macrophages by cytokines increases MRP expression, but infection with Leishmania promastigotes during activation results in MRP depletion. We therefore examined the effect of Leishmania major LV39 on recombinant MRP. Both live promastigotes and a soluble fraction of LV39 lysates degraded MRP to yield lower molecular weight fragments. Degradation was independent of MRP myristoylation and was inhibited by protein kinase C-dependent phosphorylation of MRP. MRP was similarly degraded by purified leishmanolysin (gp63), a Leishmania surface metalloprotease. Degradation was evident at low enzyme/substrate ratios, over a broad pH range, and was inhibited by 1,10-phenanthroline and by a hydroxamate dipeptide inhibitor of leishmanolysin. Using mass spectrometric analysis, cleavage was shown to occur within the effector domain of MRP between Ser(92) and Phe(93), in accordance with the substrate specificity of leishmanolysin. Moreover, an MRP construct in which the effector domain had been deleted was resistant to cleavage. Thus, Leishmania infection may result in leishmanolysin-dependent hydrolysis of MRP, a major protein kinase C substrate in macrophages.

Accounting for the dead in the longitudinal analysis of income-related health inequalities

This paper develops an accounting framework to consider the effect of deaths on the longitudinal analysis of income-related health inequalities. Ignoring deaths or using inverse probability weights (IPWs) to re-weight the sample for mortality-related attrition can produce misleading results, since to do so would be to disregard the most extreme of all health outcomes. Incorporating deaths into the longitudinal analysis of income-related health inequalities provides a more complete picture in terms of the evaluation of health changes in respect to socioeconomic status. We illustrate our work by investigating health mobility in Quality Adjusted Life Years (QALYs) as measured by the SF6D from 1999 till 2004 using the British Household Panel Survey (BHPS). We show that for Scottish males explicitly accounting for the dead, rather than using IPWs to account for mortality-related attrition, changes the direction of the relationship between relative health changes and initial income position, while for other population groups it increases the strength of this relationship by up to 14 times. When deaths are explicitly incorporated into the analysis it is found that over this five year period for both Scotland and England & Wales the relative health changes were significantly regressive such that the poor experienced a larger share of the health losses relative to their initial share of health and a large amount of this was related to mortality.