Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized trial of adjuvant chemotherapy (Cx) with cisplatin plus gemcitabine (CG) versus cisplatin plus docetaxel (CD) in patients (pts) with completely resected non-small cell lung cancer (NSCLC) with quality of life (QoL) as the primary objective.

7532 Background: Adjuvant Cx with vinorelbine plus cisplatin (VC) improves survival of resected NSCLC but has an immediate negative impact on QoL (Bezjak, JCO 2008). In advanced stages NSCLC, GC and DC have comparable efficacy and might be superior to VC in QoL outcomes. This trial was designed to provide with data on other adjuvant Cx regimens for pts with resected NSCLC. METHODS Pts with stage IB to III resected (R0) NSCLC, without major postoperative complication, were eligible. Surgery has to be standardized. Cx consisted of cisplatin (75 mg/m2, D1) plus gemcitabine 1,250 mg/m2 (D1,8) or docetaxel (75 mg/m2 D1) for 3 cycles. The primary endpoint was QoL (EORTC QLQC30) and the trial was designed to detect a 10 points difference in QoL scores (α=0.05; power 80%). Relapse-free survival, overall survival (OS), safety profile and costs were the secondary endpoints. RESULTS 136 pts (median age: 57 yrs, 74% males, pTNM: 32% IB, 34% II, 34% III; histology: 55% ADC, 23% SCC) were included. 67 and 69 pts were randomized in the GC and DC arms, respectively. Surgery was a (bi)lobectomy in 85% of cases. No imbalance was found between arms regarding major pts characteristics. Overall, a Gr3/4 hematological toxicity occurs for 33.8% and 21.7% of pts (p=0.11) and a Gr3/4 non-hematological toxicity occurs for 33.8% and 26.1% of pts (p=0.33), in the GC and DC arms. Compliance to QoL assessment was good (93%). At inclusion, global health status (GHS) scores (/100) were comparable between arms (mean score, 63.5 and 62.7, in the GC and DC arms, p=0.8). At the end of treatment (3rd month), GHS scores have slightly improve (mean score, 64.5 and 65.4, in the GC and DC arms, p=0.8). At the time of analysis, 15 pts (7 GC, 8 DC) have died. At 1 year, 100 and 96.8% of the pts were alive in the GC and DC arms; At 2 years, 92.9 and 89.8% of the pts were alive in the GC and DC arms (log-rank, p=0.88). CONCLUSIONS Adjuvant GC and DC have comparable effect on post-operative QoL and equivalent efficacy among pts with resected NSCLC. The GC and DC efficacy, safety profiles and QoL outcomes favorably compare with the results reported for the VC regimen. Detailed analyses will be presented at the meeting. [Table: see text].
Synthesis of reduced graphene oxide/CeO2 nanocomposites and their photocatalytic properties

With a unique structure and extraordinary properties, graphene has attracted tremendous attention in the preparation of graphene-based composites for various applications. In this study, two different strategies, including in situ growth and a self-assembly approach, have been developed to load CeO2 nanoparticles onto reduced graphene oxide (RGO) nanosheets. The microstructure and morphology of the as-synthesized RGO/CeO2 nanocomposites were investigated by x-ray diffraction, Raman spectroscopy and transmission electron microscopy. The results reveal that CeO2 nanoparticles with well-controlled size and a uniform distribution on RGO sheets with tunable density can be achieved through the self-assembly approach. The significantly enhanced photocatalytic activity of the RGO/CeO2 nanocomposites in comparison with bare CeO2 nanoparticles was revealed by the degradation of methylene blue under simulated sunlight irradiation, which can be attributed to the improved separation of electron–hole pairs and enhanced adsorption performance due to the presence of RGO. A suitable loading content of CeO2 on RGO was found to be crucial for optimizing the photocatalytic activity of the nanocomposites. It is expected that this convenient assembly approach with high controllability can be extended to the attachment of other functional nanoparticles to RGO sheets, and the resultant RGO-supported highly dispersed nanoparticles are attractive for catalysis, sensing and power source applications.
cAMP and Extracellular Signal-Regulated Kinase Signaling in Response to d-Amphetamine and Methylphenidate in the Prefrontal Cortex in Vivo: Role of β1-Adrenoceptors

d-Amphetamine and methylphenidate are widely used in the treatment of attention-deficit/hyperactivity disorder. Both drugs increase extracellular norepinephrine and dopamine in the prefrontal cortex, where they are believed to exert their therapeutic effects. However, the molecular mechanisms underlying their action are poorly understood. To investigate the intracellular signaling pathways activated by d-amphetamine and methylphenidate in the prefrontal cortex in vivo in mice, we measured the cAMP-dependent Ser845 phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluR1 subunit and the active form of extracellular signal-regulated kinase (ERK). Administration of d-amphetamine (5–10 mg/kg) or methylphenidate (10–20 mg/kg) increased phosphorylation of GluR1. Basal and d-amphetamine–induced GluR1 phosphorylation was reduced by propranolol, a general β-adrenoceptor antagonist, and betaxolol, a β1-antagonist, but not by (±)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol (ICI-118,515), a β2-antagonist. The effect of methylphenidate was also blocked by propranolol and betaxolol. The d-amphetamine effect was slightly potentiated by prazosin, an α1-adrenoceptor antagonist, and mimicked by yohimbine, an α2 antagonist. Blockade of dopamine or N-methyl-d-aspartate (NMDA) receptors or serotonin depletion had no effect on d-amphetamine–induced GluR1 phosphorylation. d-amphetamine but not methylphenidate increased ERK phosphorylation. This effect required multiple signaling pathways because it was blocked by β1- and α1-adrenoceptor antagonists, by dizocilpine maleate (MK801), an NMDA antagonist, and by serotonin depletion. In contrast, blockade of dopamine receptors had no effect on d-amphetamine–induced ERK phosphorylation. Propranolol and betaxolol increased the hyperlocomotion produced by d-amphetamine and methylphenidate. Thus, both d-amphetamine and methylphenidate potently activate the cAMP pathway in the prefrontal cortex through β1-adrenergic receptors. This activation could have behavioral consequences and contribute to the treatment of attention-deficit/hyperactivity disorder.
Mesalazine in childhood inflammatory bowel disease

A study was undertaken in paediatric patients suffering from ulcerative, Crohn's or indeterminate colitis. This aimed to compare the occurrence and tolerance of side‐effects arising during treatment with position‐release mesalazine (Asacol) with those occurring during previous treatment with sulphasalazine (Salazopyrin). The drugs were used to maintain remission from colitis. The occurrence of adverse reactions was also monitored.
Predictive, interactive multiple memory systems

Most lesion studies in animals, and neuropsychological and functional neuroimaging studies in humans, have focused on finding dissociations between the functions of different brain regions, for example in relation to different types of memory. While some of these dissociations can be questioned, particularly in the case of neuroimaging data, we start by assuming a “modal model” in which at least three different memory systems are distinguished: an episodic system (which stores associations between items and spatial/temporal contexts, and which is supported primarily by the hippocampus); a semantic system (which extracts combinations of perceptual features that define items, and which is supported primarily by anterior temporal cortex); and modality‐specific perceptual systems (which represent the sensory features extracted from a stimulus, and which are supported by higher sensory cortices). In most situations however, behavior is determined by interactions between these systems. These interactions reflect the flow of information in both “forward” and “backward” directions between memory systems, where backward connections transmit predictions about the current item/features based on the current context/item. Importantly, it is the resulting “prediction error”—the difference between these predictions and the forward transmission of sensory evidence—that drives memory encoding and retrieval. We describe how this “predictive interactive multiple memory systems” (PIMMS) framework can be applied to human neuroimaging data acquired during encoding or retrieval phases of the recognition memory paradigm. Our novel emphasis is thus on associations rather than dissociations between activity measured in key brain regions; in particular, we propose that measuring the functional coupling between brain regions will help understand how these memory systems interact to guide behavior. © 2010 Wiley‐Liss, Inc.
Anticonvulsant and Sedative Activities of Extracts of Erythrophleum Ivorense Stem Bark in Mice

Erythrophleum ivorense is used traditionally for many ailments such as convulsion, swellings, pain and emesis. Therefore, this study aimed to investigate the anticonvulsant and sedative activities of extracts of Erythrophleum ivorense stem bark in mice. Anticonvulsant effect of the extracts was assessed using picrotoxin, pentylenetetrazole and strychnine-induced convulsion and sedative effect was evaluated using pentobarbitone-induced hypnotic method. The results of this study showed that, crude methanolic extract and ethyl acetate extract significantly (p < 0.05) delayed the onset, shortened the duration and offered protection against pentylenetetrazole-induced convulsion. The extracts also antagonized picrotoxin-induced convulsion profoundly but did not antagonize strychnine-induced convulsion. Crude methanolic extract and ethyl acetate extract significantly (p < 0.05) prolonged the time of sodium pentobarbital-induced hypnosis. The median lethal dose (LD50) of the crude methanolic extract was found to be 87 mg/kg. In conclusion, crude methanolic extract and ethyl acetate extract of Erythrophleum ivorense possessed anticonvulsant and CNS depressant properties.
Apoptosis in Rat Placenta Is Zone-Dependent and Stimulated by Glucocorticoids1

Abstract Apoptosis, or physiological cell death, is elevated in the placenta of human pregnancies complicated by fetal growth retardation, suggesting that placental apoptosis may be a key factor in the overall control of feto-placental growth. The present study used DNA internucleosomal fragmentation analysis to characterize apoptosis in the two morphologically and functionally distinct regions of the rat placenta, the basal and labyrinth zones, during the last week of pregnancy (Days 16, 22, and 23). In addition, because glucocorticoids are potent inhibitors of feto-placental growth and can stimulate apoptosis in other tissues, we examined whether dexamethasone treatment in vivo induces placental apoptosis. DNA fragmentation was clearly evident in both placental zones at each stage of pregnancy, with higher levels evident in the basal zone compared with the labyrinth zone on Days 22 and 23. TUNEL analysis, which identifies dying cells in situ, demonstrated positive staining of cells in the basal zone, particularly giant trophoblast cells. Dexamethasone treatment increased DNA fragmentation in the basal zone but not the labyrinth zone. Similarly, maternal treatment with carbenoxolone, which can enhance local concentrations of endogenous glucocorticoid by inhibition of 11β-hydroxysteroid dehydrogenase, also increased DNA fragmentation in the basal zone but not in the labyrinth zone. These effects of dexamethasone and carbenoxolone on placental apoptosis were associated with reduced placental and fetal weights. In conclusion, this study shows that apoptosis occurs in both zones of the rat placenta, particularly in the basal zone near term, and is elevated after increased glucocorticoid exposure in vivo. These data support the hypothesis that placental apoptosis is an important player in the regulation of feto-placental growth, and establish the rat as a useful model to study the endocrine control of placental apoptosis.
Effect of the Factor V Leiden mutation on the severity of meningococcal disease.

BACKGROUND One of the most serious complications of meningococcal disease is the syndrome of purpura fulminans, which is characterized by intravascular thrombosis and hemorrhagic infarction of skin, limbs and digits. The reasons why some patients with meningococcal disease develop purpura fulminans while others have minimal thrombotic and skin involvement despite having profound septic shock are not yet understood. The Factor V Leiden mutation (FV(L)) is associated with thrombotic events, and we hypothesized that children carrying FV(L) who develop meningococcal disease may be at increased risk of purpura fulminans. METHODS We determined the FV(L) genotype by PCR and restriction enzyme digestion (Mnl1) in 259 children with meningococcal disease and 80 healthy controls. In addition 79 parents of children with fatal meningococcal disease were studied. RESULTS There was no significant increase in the frequency of FV(L) in patients with meningococcal disease (10%) as compared with healthy controls (9%) or with the parents of children who died of meningococcal disease (12%). Although the mortality was not increased in patients heterozygous for FV(L), they had increased complications of purpura fulminans, as assessed by requirement for skin grafting, referral to plastic surgeon and/or amputation. Among survivors 5 of 24 (21%) of those heterozygous for FV(L) had complications, compared with 14 of 233 (7%) who were wild type [P < 0.03; relative risk, 3.1 (95% confidence intervals, 1.2 to 7.9)]. CONCLUSIONS FV(L) exacerbates purpura fulminans in meningococcal disease but does not have a significant effect on mortality.
Defining the Involvement of p38α MAPK in the Production of Anti- and Proinflammatory Cytokines Using an SB 203580-resistant Form of the Kinase*

Despite its lack of specificity, the inhibitor SB 203580 has been widely used to implicate p38 mitogen-activated protein kinase (MAPK) in the synthesis of many cytokines. Here we show unequivocally that the production of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor α (TNFα) requires p38 MAPK activity by demonstrating that the inhibitory effects of SB 203580 were reversed by expression of an SB 203580-resistant form of p38α (SBR-p38α) that fails to bind to SB 203580. This strategy established the requirement for p38 activity for the lipopolysaccharide-stimulated production of IL-10, IL-1β, and IL-6 by the monocytic cell WEHI 274 and the production of IL-6 and TNFα stimulated by ligation of the Fc-γ receptor of the mast cell MC/9. Expression of SBR-p38α in primary macrophages abrogated the ability of SB 203580 to inhibit the lipopolysaccharide-stimulated production of TNFα but not of IL-10. Expression of SBR-p38α in primary T lymphocytes abrogated the ability of SB 203580 to inhibit the production of interferon-γ induced by co-ligation of CD3 and CD28 but not the production of interferon-γ or IL-10 induced by IL-12. These results suggest that the levels of p38 MAPK activity required for maximal cytokine production vary with different cytokines and stimuli.
Constructive Criticism

New updated! The latest book from a very famous author finally comes out. Book of constructive criticism, as an amazing reference becomes what you need to get. What's for is this book? Are you still thinking for what the book is? Well, this is what you probably will get. You should have made proper choices for your better life. Book, as a source that may involve the facts, opinion, literature, religion, and many others are the great friends to join with.
Empowerment Education: Freire's Ideas Adapted to Health Education

Empowerment Education is proposed as an effective health education and preven tion model that promotes health in all personal and social arenas. The model suggests that participation of people in group action and dialogue efforts directed at commun ity targets enhances control and beliefs in ability to change people's own lives. The article is divided into three parts: a literature review demonstrating that powerlessness is linked to disease, and conversely, empowerment linked to health; an exposition of Brazilian educator Paulo Freire's empowering education theory with a comparison to traditional health education; and a case study of an empowering education substance abuse prevention project. The Alcohol and Substance Abuse Prevention (ASAP) Program is a University of New Mexico School of Medicine, Emergency Center, and community and school-based prevention project for adolescents. The case study will present ASAP's theoretical underpinnings and social practice, evaluation results, preliminary understandings of the stages for an empowering process, and future questions for practitioners interested in this approach. Empowerment education with its emphasis on organizing is recom mended to be integrated into other prevention strategies of health promotion, disease prevention, and health policy.
The inviscid limit for density-dependent incompressible fluids

Cet article est consacre a l'etude des fluides incompressibles a densite variable dans R N ou T N . On cherche a generaliser plusieurs resultats classiques pour les equations d'Euler et de Navier-Stokes incompressibles. On etablit un resultat d'existence et d'unicite sur un intervalle de temps independant de la viscosite μdu fluide ainsi qu'un critere d'explosion faisant intervenir la norme du tourbillon dans L 1 (0,T;L∞). On montre en outre que si les equations d'Euler ont une solution reguliere sur un intervalle de temps [0, T 0 ) donne alors les equations de Navier-Stokes avec memes donnees et petite viscosite ont une solution reguliere sur le meme intervalle de temps. De plus la solution visqueuse tend vers la solution d'Euler quand la viscosite tend vers 0. Le taux de convergence dans L 2 est de l'ordre de μ. En appendice, on demontre des estimations a priori de type elliptique dans des espaces de Sobolev a indice positif ou negatif.
Temperature-Dependent Function of the Glutamine Phosphoribosylpyrophosphate Amidotransferase Ammonia Channel and Coupling with Glycinamide Ribonucleotide Synthetase in a Hyperthermophile

ABSTRACT Genes encoding glutamine phosphoribosylpyrophosphate amidotransferase (GPAT) and glycinamide ribonucleotide synthetase (GARS) from Aquifex aeolicus were expressed inEscherichia coli, and the enzymes were purified to near homogeneity. Both enzymes were maximally active at a temperature of at least 90°C, with half-lives of 65 min for GPAT and 60 h for GARS at 80°C. GPAT activity is known to depend upon channeling of NH3 from a site in an N-terminal glutaminase domain to a distal phosphoribosylpyrophosphate site in a C-terminal domain where synthesis of phosphoribosylamine (PRA) takes place. The efficiency of channeling of NH3 for synthesis of PRA was found to increase from 34% at 37°C to a maximum of 84% at 80°C. The mechanism for transfer of PRA to GARS is not established, but diffusion between enzymes as a free intermediate appears unlikely based on a calculated PRA half-life of approximately 0.6 s at 90°C. Evidence was obtained for coupling between GPAT and GARS for PRA transfer. The coupling was temperature dependent, exhibiting a transition between 37 and 50°C, and remained relatively constant up to 90°C. The calculated PRA chemical half-life, however, decreased by a factor of 20 over this temperature range. These results provide evidence that coupling involves direct PRA transfer through GPAT-GARS interaction rather than free diffusion.
Topical Drug Formulations for Prolonged Corneal Anesthesia

Purpose: Ocular local anesthetics currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect of the site 1 sodium channel blocker tetrodotoxin (TTX) on the duration of corneal anesthesia, applied with either proparacaine (PPC) or the chemical permeation enhancer octyl-trimethyl ammonium bromide (OTAB). The effect of test solutions on corneal healing was also studied. Methods: Solutions of TTX, PPC, and OTAB, singly or in combination, were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet–Bonnet esthesiometer, and the duration of corneal anesthesia was calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo after corneal debridement. Results: Combination of TTX and PPC resulted in corneal anesthesia that was 8 to 10 times longer in duration than that from either drug administered alone, whereas OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed after coadministration of TTX and PPC. Conclusions: Coadministration of TTX and PPC significantly prolonged corneal anesthesia, but in view of delayed corneal reepithelialization, caution is suggested in the use of the drug combination.
Analogues of deltorphin I containing conformationally restricted amino acids in position 2: structure and opioid activity

New analogues of deltorphin I (DT I, Tyr‐d‐Ala‐Phe‐Asp‐Val‐Val‐Gly‐NH2), with the d‐Ala residue in position 2 replaced by α‐methyl‐β‐azido(amino, 1‐pyrrolidinyl, 1‐piperidinyl or 4‐morpholinyl)alanine, were synthesized by a combination of solid‐phase and solution methods. All ten new analogues were tested for receptor affinity and selectivity to μ‐ and δ‐opioid receptors. The affinity of analogues containing (R) or (S)‐α‐methyl‐β‐azidoalanine in position 2 to δ‐receptors strongly depended on the chirality of the α,α‐disubstituted residue. Peptide II, containing (S)‐α‐methyl‐β‐azidoalanine in position 2, displayed excellent δ‐receptor selectivity with its δ‐receptor affinity being only three times lower than that of DT I. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
"Mistakes happen": somatic mutation and disease.

An intriguing quality of many genetic diseases in humans is the significant intrafamilial variability observed in their clinical presentation. It seems to be likely that definition of the factors responsible for such differences will provide important clues to the normal function of the genes and to the pathobiology of their associated diseases. For some diseases, such as fragile X syndrome and Huntington disease, it has been shown that genetically related individuals do not necessarily have identical germ-line mutations, and instability at the mutant loci may account for much of the observed clinical variation.
Male and Female Drosophila Germline Stem Cells: Two Versions of Immortality

Drosophila male and female germline stem cells (GSCs) are sustained by niches and regulatory pathways whose common principles serve as models for understanding mammalian stem cells. Despite striking cellular and genetic similarities that suggest a common evolutionary origin, however, male and female GSCs also display important differences. Comparing these two stem cells and their niches in detail is likely to reveal how a common heritage has been adapted to the differing requirements of male and female gamete production.