Scores composites CHC pour la WAIS-IV : normes francophones

Les résultats des recherches contemporaines, montrant notamment l'importance du raisonnement fluide, de la mémoire de travail (IMT) et de la vitesse de traitement (IVT) dans le fonctionnement cognitif, ont conduit les concepteurs de la WAIS-IV à introduire de nouvelles épreuves pour renforcer l'évaluation de ces dimensions cognitives. L'interprétation des scores de la WAIS-IV repose maintenant sur quatre indices factoriels (ICV, IRP, IMT et IVT), ainsi que sur le QIT. Les concepteurs de la WAIS-IV indiquent que l'un des objectifs de la révision consistait à actualiser les fondements théoriques de cette échelle. Pourtant, la structure globale de la WAIS-IV ne correspond que partiellement à celle proposée dans le modèle qui fait consensus aujourd'hui, le modèle de Cattell-Horn-Carroll (CHC). Par exemple, la WAIS-IV ne propose pas d'indice de raisonnement fluide, bien que les constructeurs soulignent l'importance de cette dimension dans le fonctionnement cognitif. Dans cet article, nous proposons, pour la WAIS-IV, les normes francophones de cinq scores composites CHC, à savoir le raisonnement fluide (Gf), compréhension-connaissances (Gc), le traitement visuel (Gv), la mémoire à court terme (Gsm), et l'IVT (Gs). Ces normes ont été établies en utilisant une procédure d'approximation statistique. À l'instar des scores CHC que nous avons proposés pour le WISCIV, ces normes pour la WAIS-IV permettent aux cliniciens de basculer vers une grille d'interprétation basée sur le modèle dominant et d'utiliser les cinq scores composites CHC en complément des quatre indices standard dans le cadre d'analyses normatives et ipsatives.

Pi*-pi* bonding interactions generated by halogen oxidation of zirconium(IV) redox-active ligand complexes.

The new complex, [Zr(pda)2]n (1, pda2- = N,N'-bis(neo-pentyl)-ortho-phenylenediamide, n = 1 or 2), prepared by the reaction of 2 equiv of pdaLi2 with ZrCl4, reacts rapidly with halogen oxidants to afford the new product ZrX2(disq)2 (3, X = Cl, Br, I; disq- = N,N'-bis(neo-pentyl)-ortho-diiminosemiquinonate) in which each redox-active ligand has been oxidized by one electron. The oxidation products 3a-c have been structurally characterized and display an unusual parallel stacked arrangement of the disq- ligands in the solid state, with a separation of approximately 3 A. Density functional calculations show a bonding-type interaction between the SOMOs of the disq- ligands to form a unique HOMO while the antibonding linear combination forms a unique LUMO. This orbital configuration leads to a closed-shell-singlet ground-state electron configuration (S = 0). Temperature-dependent magnetism measurements indicate a low-lying triplet excited state at approximately 750 cm-1. In solution, 3a-c show strong disq--based absorption bands that are invariant across the halide series. Taken together these spectroscopic measurements provide experimental values for the one- and two-electron energies that characterize the pi-stacked bonding interaction between the two disq- ligands.

Dipeptidyl-peptidase-IV by cleaving neuropeptide Y induces lipid accumulation and PPAR-γ expression.

We evaluated the effects of dipeptidyl peptidase-IV (DPPIV), and its inhibitor, vildagliptin, on adipogenesis and lipolysis in a pre-adipocyte murine cell line (3T3-L1). The exogenous rDPPIV increased lipid accumulation and PPAR-γ expression, whereas an inhibitor of DPPIV, the anti-diabetic drug vildagliptin, suppresses the stimulatory role of DPPIV on adipogenesis and lipid accumulation, but had no effect on lipolysis. NPY immunoneutralization or NPY Y(2) receptor blockage inhibited DPPIV stimulatory effects on lipid accumulation, collectively, indicating that DPPIV has an adipogenic effect through NPY cleavage and subsequent NPY Y(2) activation. Vildagliptin inhibits PPAR-γ expression and lipid accumulation without changing lipolysis, suggesting that this does not impair the ability of adipose tissue to store triglycerides inside lipid droplets. These data indicate that DPPIV and NPY interact on lipid metabolism to promote adipose tissue depot.

DSM-IV and DSM-5 alcohol use disorder among young Swiss men.

BACKGROUND AND AIMS: Previous studies suggest that the new DSM-5 criteria for alcohol use disorder (AUD) will increase the apparent prevalence of AUD. This study estimates the 12-month prevalence of AUD using both DSM-IV and DSM-5 criteria and compares the characteristics of men in a high risk sample who meet both, only one and neither sets of diagnostic criteria. DESIGN, SETTING AND PARTICIPANTS: 5943 Swiss men aged 18-25 years who participated in the Cohort Study on Substance Use Risk Factors (C-SURF), a population-based cohort study recruited from three of the six military recruitment centres in Switzerland (response rate = 79.2%). MEASUREMENTS: DSM-IV and DSM-5 criteria, alcohol use patterns, and other substance use were assessed. FINDINGS: Approximately 31.7% (30.5-32.8) of individuals met DSM-5 AUD criteria [21.2% mild (20.1-22.2); 10.5% moderate/severe (9.7-11.3)], which was less than the total rate when DSM-IV criteria for alcohol abuse (AA) and alcohol dependence (AD) were combined [36.8% overall (35.5-37.9); 26.6% AA (25.4-27.7); 10.2% AD (9.4-10.9)]. Of 2479 respondents meeting criteria for either diagnoses, 1585 (63.9%) met criteria for both. For those meeting DSM-IV criteria only (n = 598, 24.1%), hazardous use was most prevalent, whereas the criteria larger/longer use than intended and tolerance to alcohol were most prevalent for respondents meeting DSM-5 criteria only (n = 296, 11.9%). Two in five DSM-IV alcohol abuse cases and one-third of DSM-5 mild AUD individuals fulfilled the diagnostic criteria due to the hazardous use criterion. The addition of the craving and excluding of legal criterion, respectively, did not affect estimated AUD prevalence. CONCLUSIONS: In a high-risk sample of young Swiss males, prevalence of alcohol use disorder as diagnosed by DSM-5 was slightly lower than prevalence of DSM-IV diagnosis of dependence plus abuse; 63.9% of those who met either criterion met criteria for both.

Promoter IV of the class II transactivator gene is essential for positive selection of CD4+ T cells.

Major histocompatibility complex class II (MHCII) expression is regulated by the transcriptional coactivator CIITA. Positive selection of CD4(+) T cells is abrogated in mice lacking one of the promoters (pIV) of the Mhc2ta gene. This is entirely due to the absence of MHCII expression in thymic epithelia, as demonstrated by bone marrow transfer experiments between wild-type and pIV(-/-) mice. Medullary thymic epithelial cells (mTECs) are also MHCII(-) in pIV(-/-) mice. Bone marrow-derived, professional antigen-presenting cells (APCs) retain normal MHCII expression in pIV(-/-) mice, including those believed to mediate negative selection in the thymic medulla. Endogenous retroviruses thus retain their ability to sustain negative selection of the residual CD4(+) thymocytes in pIV(-/-) mice. Interestingly, the passive acquisition of MHCII molecules by thymocytes is abrogated in pIV(-/-) mice. This identifies thymic epithelial cells as the source of this passive transfer. In peripheral lymphoid organs, the CD4(+) T-cell population of pIV(-/-) mice is quantitatively and qualitatively comparable to that of MHCII-deficient mice. It comprises a high proportion of CD1-restricted natural killer T cells, which results in a bias of the V beta repertoire of the residual CD4(+) T-cell population. We have also addressed the identity of the signal that sustains pIV expression in cortical epithelia. We found that the Jak/STAT pathways activated by the common gamma chain (CD132) or common beta chain (CDw131) cytokine receptors are not required for MHCII expression in thymic cortical epithelia.

Ist ein Dossier bei der IV, ist es meist bereits zu spät! Replik und Erweiterung der durch R. Conne angestossenen Diskussion über Arbeitsfähigkeit und Invalidenversicherung

Im Artikel «Arbeitsfähigkeit und Invalidenversicherung » von R. Conne [1] wird treffend das heutige Malaise der Arbeitsplatzrehabilitation beschrieben. Dies gilt aber nicht nur für die Arbeitsunfähigkeit aus psychischen Gründen, sondern ebenso für die Arbeitsunfähigkeit wegen muskuloskeletaler Schmerzen. Die Schwierigkeiten einer Arbeitsplatzrehabilitation sind aber nicht speziell auf die Invalidenversicherung zurückzuführen. Sie gründen einerseits auf strukturellen Gegebenheiten der Schweiz, wie eine wenig in den Betrieben verankerte Arbeitsmedizin, und Zugang zu Rehabilitationsmedizin, und andererseits auf dem Fehlen einer klaren Kostenträgerregelung oder -verantwortung. R. Conne beschreibt in seinem Artikel treffend das heutige Malaise in der Schweiz in bezug auf Arbeitsplatzrehabilitation oder Wiedererlangung der Arbeitsfähigkeit. Er bezieht sich dabei vor allem auf die Arbeitsunfähigkeit aus psychischen Gründen. Wir möchten als am Rande angesprochene Arbeitsmedizinerin und angesprochener Rehabilitationsmediziner die Diskussion aufgreifen und erweitern. Die Erweiterung betrifft einerseits den Einbezug von nicht psychisch begründeter Arbeitsunfähigkeit und andererseits auch die allgemeine Versicherungssituation in der Schweiz, und dies verschiebt unserer Meinung nach den Problemfokus von der Invalidenversicherung auf die allgemeine Versicherungssituation. [Autoren]

Calmodulin-dependent protein kinase IV during T-cell development.

In a primary cell culture system of fetal rat brain, the calmodulin-dependent protein-kinase IV (CaMKIV) could be induced by the thyroid hormone T3 in a time- and concentration-dependent manner, provided the tissue was excised not later than day 15 of gestation (E15) (Krebs et al., J. Biol. Chem. 271, 11055, 1996). We report here that in the fetal thymus CaMKIV could not be detected earlier than day 16 of gestation and that the expression of this enzyme was fully upregulated at day 18. In mouse fetal thymus organ culture (FTOC) of day 14 embryonic thymus, CaMKIV could not be detected, even after several days of culture if a minimal culture medium lacking fetal calf serum was used. However, after addition of fetal calf serum to the culture medium the expression of CaMKIV could be specifically induced. Furthermore, it could also be shown that during T-cell development in the adult murine thymus the expression of CaMKIV was tightly regulated. Taken together, these results demonstrate that the expression of CaMKIV, an enzyme involved in the regulation of Ca(2+)-dependent gene expression, is itself under stringent regulatory control during tissue development.

Long-lasting antidiabetic effect of a dipeptidyl peptidase IV-resistant analog of glucagon-like peptide-1.

Glucagon-like peptide-1(7-37) (GLP-1) is the most potent insulinotropic hormone characterized thus far. Because its activity is preserved in non-insulin-dependent diabetes mellitus (NIDDM) patients, it is considered a potential new drug for the treatment of this disease. One limitation in its therapeutic use is a short half-life in vivo (5 minutes), due in part to a fast degradation by the endoprotease dipeptidylpeptidase IV (DPPIV). Recently, it was reported that GLP-1 became resistant to DPPIV when the alanine residue at position 8 was replaced by a glycine (GLP-1-Gly8). We report here that this change slightly decreased the affinity of the peptide for its receptor (IC50, 0.41 +/- 0.14 and 1.39 +/- 0.61 nmol/L for GLP-1 and GLP-1-Gly8, respectively) but did not change the efficiency to stimulate accumulation of intracellular cyclic adenosine monophosphate (cAMP) (EC50, 0.25 +/- 0.05 and 0.36 +/- 0.06 nmol/L for GLP-1 and GLP-1-Gly8, respectively). Second, we demonstrate for the first time that this mutant has an improved insulinotropic activity compared with the wild-type peptide when tested in vivo in an animal model of diabetes. A single injection of 0.1 nmol GLP-1-Gly8 in diabetic mice fed a high-fat diet can correct fasting hyperglycemia and glucose intolerance for several hours, whereas the activity of 1 nmol GLP-1 vanishes a few minutes after injection. These actions were correlated with increased insulin and decreased glucagon levels. Interestingly, normoglycemia was maintained over a period that was longer than the predicted peptide half-life, suggesting a yet undescribed long-term effect of GLP-1-Gly8. GLP-1-Gly8 thus has a markedly improved therapeutic potential compared with GLP-1, since it can be used at much lower doses and with a more flexible schedule of administration.