Abatacept in the treatment of rheumatoid arthritis

T-cell biology has regained importance in the pathogenesis of rheumatoid arthritis. Despite the significant improvements associated with the introduction of tumor necrosis factor-α blockade, reasonable proportions of failures and suboptimal responses have been reported, necessitating a search for alternative targeted therapies. This has included drug therapy designed to interrupt T-cell activation via the co-stimulation pathway. Abatacept is a recombinant fusion protein that blocks the co-stimulatory signal mediated by the CD28-CD80/86 pathway, which is required for T-cell activation. Several clinical trials have confirmed the safety and efficacy of this drug in the treatment of rheumatoid arthritis. This review summarizes the clinical data supporting this line of treatment and considers the safety and efficacy data from phase II and III trials

O ensino tradicional na disciplina Percepção Musical: principais aspectos em destaque por autores da área nos últimos anos

Este artigo tem a finalidade de expor os principais aspectos problematizados nos últimos anos sobre a diretriz pedagógica dominante na disciplina Percepção Musical, ou seja, a da escola tradicional. Professores e pesquisadores da matéria tem argumentado questões importantes para uma nova perspectiva no campo, contrapondo-se ao ensino musical fragmentado, o forte direcionamento aos ditados, à pouca flexibilidade de repertório, entre outros. A partir do estudo de sete dissertações e teses defendidas entre 1999 e 2011, e artigos publicados nos anais da Associação Brasileira de Educação Musical - ABEM, de 2001 a 2011, são expostos neste texto cinco principais tópicos que se destacam durante as argumentações e reflexões sobre a disciplina. Tais documentos foram tratados sob a ótica da Análise de Conteúdo e propiciam um diálogo significativo sobre a relação ensino e aprendizagem na disciplina no âmbito do ensino superior de Música

Effects of food provisioning on the daily ration and dive site use of great hammerhead sharks, Sphyrna mokarran

Wildlife provisioning is popular, economically valuable, and a rapidly growing part of marine tourism, with great potential to benefit conservation. However, it remains controversial due to limited understanding of its implications on the behavior and ecology of target species. In this study, we modeled how various abiotic and biotic factors influenced great hammerhead sharks' (Sphyrna mokarran) use of a recreational dive site in Bimini, the Bahamas, where shark-feeding has been conducted since 2012. Further, we calculated bioenergetic models to estimate their daily ration and examined if individual sharks fulfilled their daily energetic requirements from food uptake during dives. Between December 2016 and May 2017, we collected data during 104 provisioning dives in collaboration with a local dive operator. Twenty-eight individual great hammerhead sharks were observed, 11 were philopatric (i.e., identified at the dive site in previous years), and 17 were new (i.e., identified at the dive site for the first time during this study) individuals. On average, four sharks were observed daily, occasionally up to nine individuals, with some individuals spending more than 2 h attending each dive, consuming up to 4.75 kg of provisioned food per dive and returning repeatedly throughout the study period. When we grouped sharks based on their previous experience of the dive site (i.e., philopatric vs. new sharks), we found significantly higher attendance indices, i.e., the number of attended dives divided by the total number dives, and longer presence times during dives in philopatric sharks and different responses toward the number of boats and conspecifics between the two groups. Overall, great hammerhead sharks increased their bait uptake during longer dives and when more boats were present at the dive site. Finally, nine of 12 provisioned great hammerhead sharks were regularly able to fuel their daily energetic requirements from provisioned food alone, with two sharks doing so on 77.8% of all dives. Our study provides insights into how largebodied marine predators react toward wildlife tourism associated provisioning and allows further discussion about daily energy uptake during provisioning dives, its potential impacts on the ecological role of the target species and associated management measures

Amplified and Homozygously Deleted Genes in Glioblastoma: Impact on Gene Expression Levels

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Glioblastoma multiforme (GBM) displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown. [Methodology]: Single-nucleotide polymorphism (SNP)-arrays were used to determine the frequency of recurrent amplicons and homozygous deletions in GBM (n = 46), and to evaluate the impact of copy number alterations (CNA) on mRNA levels of the genes involved. [Principal Findings]: Recurrent amplicons were detected for chromosomes 7 (50%), 12 (22%), 1 (11%), 4 (9%), 11 (4%), and 17 (4%), whereas homozygous deletions involved chromosomes 9p21 (52%) and 10q (22%). Most genes that displayed a high correlation between DNA CNA and mRNA levels were coded in the amplified chromosomes. For some amplicons the impact of DNA CNA on mRNA expression was restricted to a single gene (e.g., EGFR at 7p11.2), while for others it involved multiple genes (e.g., 11 and 5 genes at 12q14.1-q15 and 4q12, respectively). Despite homozygous del(9p21) and del(10q23.31) included multiple genes, association between these DNA CNA and RNA expression was restricted to the MTAP gene. [Conclusions]: Overall, our results showed a high frequency of amplicons and homozygous deletions in GBM with variable impact on the expression of the genes involved, and they contributed to the identification of other potentially relevant genes.This work was partially supported by Fundação para a Ciência e a Tecnologia, Portugal [FCT PIC/IC/83108/2007]; PhD fellowships from Fundação para a Ciência e a Tecnologia, Portugal [SFRH/BD/23086/2005, SFRH/BD/11820/2003]; Fundación Mutua Madrileña, Madrid, Spain [AP87692011]; and Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain [RTICC RD06/0020/0035].Peer Reviewe

Intratumoral patterns of clonal evolution in gliomas

Few studies have explored the patterns of clonal evolution in gliomas. Here, we investigate the cytogenetic patterns of intratumoral clonal evolution of gliomas and their impact on tumor histopathology and patient survival. Cytogenetic analysis of 90 gliomas was performed in individual tumor cells (>200 cells/tumor) using multicolor (N = 16 probes) interphase-FISH. Overall, chromosome gains were more frequent than chromosome losses. Gains of chromosome 7 and/or EGFR amplification were detected in 91% of the cases, whereas del(9p21) (77%) and del(10q23) (78%) were the most frequent chromosome losses. Virtually, all cases (99%) showed >/=2 tumor cell clones, with higher numbers among high- versus low-grade gliomas (p = 0.001). Nine different cytogenetic patterns were found in the ancestral tumor clones. In most gliomas, ancestral clones showed abnormalities of chromosome 7, 9p, and/or 10q and cytogenetic evolution consisted of acquisition of additional abnormalities followed by tetraploidization. Conversely, early tetraploidization was associated with low-grade astrocytomas-2/3 pilocytic and 3/6 grade II diffuse astrocytomas-and combined loss of 1p36/19q13 with oligodendrogliomas, respectively; both aberrations were associated with a better patient outcome (p = 0.03). Overall, our results support the existence of different pathways of intratumoral evolution in gliomas

A new classification system for degenerative spondylolisthesis of the lumbar spine

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.PURPOSE: There is no consensus for a comprehensive analysis of degenerative spondylolisthesis of the lumbar spine (DSLS). A new classification system for DSLS based on sagittal alignment was proposed. Its clinical relevance was explored. METHODS: Health-related quality-of-life scales (HRQOLs) and clinical parameters were collected: SF-12, ODI, and low back and leg pain visual analog scales (BP-VAS, LP-VAS). Radiographic analysis included Meyerding grading and sagittal parameters: segmental lordosis (SL), L1-S1 lumbar lordosis (LL), T1-T12 thoracic kyphosis (TK), pelvic incidence (PI), pelvic tilt (PT), and sagittal vertical axis (SVA). Patients were classified according to three main types-1A: preserved LL and SL; 1B: preserved LL and reduced SL (≤5°); 2A: PI-LL ≥10° without pelvic compensation (PT < 25°); 2B: PI-LL ≥10° with pelvic compensation (PT ≥ 25°); type 3: global sagittal malalignment (SVA ≥40 mm). RESULTS: 166 patients (119 F: 47 M) suffering from DSLS were included. Mean age was 67.1 ± 11 years. DSLS demographics were, respectively: type 1A: 73 patients, type 1B: 3, type 2A: 8, type 2B: 22, and type 3: 60. Meyerding grading was: grade 1 (n = 124); grade 2 (n = 24). Affected levels were: L4-L5 (n = 121), L3-L4 (n = 34), L2-L3 (n = 6), and L5-S1 (n = 5). Mean sagittal parameter values were: PI: 59.3° ± 11.9°; PT: 24.3° ± 7.6°; SVA: 29.1 ± 42.2 mm; SL: 18.2° ± 8.1°. DSLS types were correlated with age, ODI and SF-12 PCS (ρ = 0.34, p < 0.05; ρ = 0.33, p < 0.05; ρ = -0.20, and p = 0.01, respectively). CONCLUSION: This classification was consistent with age and HRQOLs and could be a preoperative assessment tool. Its therapeutic impact has yet to be validated. LEVEL OF EVIDENCE: 4.No funds were received in support of this work. No benefits in any forms have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript

Determinants of crop-livestock integration by small farmers in Benin

Despite the numerous work conducted on integrated crop-livestock systems, very little is known about factors determining farmers’ trend to integrate. Our study aimed at a socioeconomic characterization of endogenous crop-livestock integration in Benin and identification of determinants of farmers’ decision to use these practices. Two hundred and forty farmers were surveyed in three agro- ecological regions randomly selected. A semi-structured questionnaire was used to collect information on farmer’s characteristics, production factors and agriculture and breeding by-products valorization practices. On the basis of main links between both productions, three integration levels (no integration, NI: 36%; partial integration, PI: 55%; total integration, TI: 9%) were identified and characterized according to socioeconomic characteristics of farmers. Then the multinomial logistic regression technique was used to predict the integration level of a given farmer in function of its socioeconomic characteristics. The three integration levels differ significantly (p&lt;0.001) according to variables such as membership in farmers’ association, educational level, weight of agricultural experience, farming equipment and size of herds. The decision by a farmer to choose the total integration type significantly depends (p &lt;0.001) on the size of his cattle herd, his membership in farmers’ association, the weight of his agricultural experience and his equipment value. Thus, integration is a practice used by small farmers with good experience in agriculture. Strategies for improving integration of cropping and breeding are to motivated farmers for cattle keeping and membership in an association.© 2015 International Formulae Group. All rights reserved.Keywords: Animal feeding, integrated soil fertility management, resilience, sustainabilit