A projected cost-utility analysis of avacopan for the treatment of antineutrophil cytoplasmic antibody-associated vasculitis in Spain.

Background: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are rare autoimmune diseases characterized by inflammation of blood vessels. This study aimed to assess the cost-utility of avacopan in combination with rituximab (RTX) or cyclophosphamide (CYC) compared with glucocorticoids (GC) for the treatment of severe, active AAV in Spain.

Methods: A 9-state Markov model was designed to reflect the induction of remission and sustained remission of AAV over a lifetime horizon.

Factors Underpinning the Shift to Eveningness during Early Adolescence: Pubertal Development and Family Conflicts.

Biological and psychosocial factors have been related to the shift to eveningness during early adolescence but it is necessary to study them from a longitudinal perspective. This longitudinal study examined the contribution of these factors to the onset of a shift towards eveningness in early adolescence. A sample of 440 (49.

Circadian preference and relationship satisfaction among three types of couples.

Mate selection is part of a growing interest in the study of processes by which couples are established, consolidated and/or separated. Similarity in psychological traits has been related to the well-being of couples, but given the possible effect of temporal convergence, it is necessary to control for the relationship length and whether or not both members of the couple live together. The aim of this study was to analyse the association between Morningness/Eveningness (M/E) similarity and relationship satisfaction in young-dating-non-cohabiting, young-married-cohabiting and old-married-cohabiting couples.

Social jetlag, academic achievement and cognitive performance: Understanding gender/sex differences.

Adolescents in high school suffer from circadian misalignment, undersleeping on weekdays and oversleeping on weekends. Since high schools usually impose early schedules, adolescents suffer from permanent social jetlag (SJL) and thus are a suitable population to study the effects of SJL on both academic and cognitive performance. In this study, 796 adolescents aged 12-16 years reported information about their sleep habits, morningness-eveningness (M-E), cognitive abilities and grade point average (GPA).

Chronotype and time-of-day effects on mood during school day.

Existing evidence suggests an association between mood, time-of-day and morningness-eveningness (M-E). Since few studies have been carried out among adolescents, in this study daily mood fluctuations were analyzed in the naturalistic school context during 2 d in order to test how chronotype and time-of-day are related to mood during the school schedule period and check if sleep length is involved in the above relation. A sample of 655 adolescents (12-16 years) reported mood levels (current level of pleasantness) three times during school day (8:10-8:30 h, 10:20-11:40 h, 13:50-14:10 h).

Evening adolescents: the role of family relationships and pubertal development.

Accumulating evidence suggests that evening-type adolescents are exposed to a number of determinants that might have a negative impact on their health condition. Despite the fact that biological and psychosocial factors are interrelated, their impacts on the shift toward eveningness during puberty have been considered only separately. In this study, the effects of frequency of conflicts and functional autonomy on the relationship between pubertal development and Morningness-Eveningness (M-E) were tested together.

Daily fluctuations in attention at school considering starting time and chronotype: an exploratory study.

Interest to investigate daily fluctuations in cognitive tasks, so-called "school-rhythms", lies in exploring the most favourable time-of-day for learning considering the analysis of variations in performance taking into account individual differences. The aim of this study was to describe daily fluctuations in attention at three different times of the school day, two different days, considering chronotype and three different school start times (08:00, 08:15 and 08:30 h). Participants were 669 adolescents aged 12-16.

Circadian preference and thinking styles: implications for school achievement.

Research has shown that thinking styles could have an influence on academic achievement. Previous studies have described that evening types are usually right-thinkers who tend to be creative and intuitive, whereas morning types tend to be left-thinkers who prefer verbal and analytic strategies in processing information. However, these studies have been realized among undergraduates, who have more freedom to choose their time schedules according to their circadian preference than adolescents or adult workers.

mTORC2 targets AGC kinases through Sin1-dependent recruitment.

The protein kinase TOR (target of rapamycin) is a key regulator of cell growth and metabolism with significant clinical relevance. In mammals, TOR signals through two distinct multi-protein complexes, mTORC1 and mTORC2 (mammalian TOR complex 1 and 2 respectively), the subunits of which appear to define the operational pathways. Rapamycin selectively targets mTORC1 function, and the emergence of specific ATP-competitive kinase inhibitors has enabled assessment of dual mTORC1 and mTORC2 blockade.

CD69 modulates sphingosine-1-phosphate-induced migration of skin dendritic cells.

In this study, we have investigated the role of CD69, an early inducible leukocyte activation receptor, in murine dendritic cell (DC) differentiation, maturation, and migration. Skin DCs and DC subsets present in mouse lymphoid organs express CD69 in response to maturation stimuli. Using a contact sensitization model, we show that skin DCs migrated more efficiently to draining lymph nodes (LNs) in the absence of CD69.

Polysialylated neuropilin-2 enhances human dendritic cell migration through the basic C-terminal region of CCL21.

Dendritic cell (DC) migration to secondary lymphoid organs is a critical step to properly exert its role in immunity and predominantly depends on the interaction of the chemokine receptor CCR7 with its ligands CCL21 and CCL19. Polysialic acid (PSA) has been recently reported to control CCL21-directed migration of mature DCs. Here, we first demonstrate that PSA present on human mature monocyte-derived dendritic cells did not enhance chemotactic responses to CCL19.

CCR7-dependent stimulation of survival in dendritic cells involves inhibition of GSK3beta.

Chemokine receptor CCR7 regulates chemotaxis and survival in mature dendritic cells (DCs). We studied the role of glycogen synthase kinase-3beta (GSK3beta) in the regulation of CCR7-dependent survival. We show that GSK3beta behaves as a proapoptotic regulator in cultured monocyte-derived human DCs and murine splenic DCs in vitro, and in lymph node DCs in vivo.

PKC maturation is promoted by nucleotide pocket occupation independently of intrinsic kinase activity.

The protein kinase C (PKC) Ser/Thr kinases account for approximately 2% of the human kinome and regulate diverse cellular behaviors. PKC catalytic activity requires priming phosphorylations at three conserved sites within the kinase domain. Here we demonstrate that priming of PKC is dependent on the conformation of the nucleotide binding pocket but not on its intrinsic kinase activity.

Calcium-induced decrease of the thermal stability and chaperone activity of alpha-crystallin.

Alpha-crystallin, one of the major proteins in the vertebrate eye lens, acts as a molecular chaperone, like the small heat-shock proteins, by protecting other proteins from denaturing under stress or high temperature conditions. alpha-Crystallin aggregation is involved in lens opacification, and high [Ca(2+)] has been associated with cataract formation, suggesting a role for this cation in the pathological process. We have investigated the effect of Ca(2+) on the thermal stability of alpha-crystallin by UV and Fourier-transform infrared (FTIR) spectroscopies.