Miracle-dz/UniFAR-FTUs huggingface dataset:
Mouse fibroblast interferon modifies Salmonella typhimurium infection in infant mice

The effect of mouse fibroblast interferon on Salmonella typhimurium infection in infant mice was examined. The lethality to mice that had been given S. typhimurium intragastrically was significantly reduced in a dose-dependent manner when the mice were pretreated with fibroblast interferon. Lower doses of interferon delayed the development of disease. Interferon neutralized with anti-interferon globulin did not influence the lethality of S. typhimurium to mice. In mice treated with interferon there was also a reduced invasiveness of S. typhimurium in intestinal epithelial cells in vivo. It was further demonstrated in an in vitro system that interferon pretreatment of mouse L-929 cells inhibited the invasiveness of the bacteria in a dose-dependent manner. The in vitro inhibition was neutralized with anti-interferon globulin. The results indicate that interferon inhibits Salmonella bacteria from invading cells and establishing an intracellular state of infection. This may represent an important factor in the pathogenesis of disease.
Region-Specific Overexpression of P-glycoprotein at the Blood-Brain Barrier Affects Brain Uptake of Phenytoin in Epileptic Rats

Recent studies have suggested that overexpression of the multidrug transporter P-glycoprotein (P-gp) in the hippocampal region leads to decreased levels of antiepileptic drugs and contributes to pharmacoresistance that occurs in a subset of epileptic patients. Whether P-gp expression and function is affected in other brain regions and in organs that are involved in drug metabolism is less studied. Therefore, we investigated P-gp expression in different brain regions and liver of chronic epileptic rats, several months after electrically induced status epilepticus (SE), using Western blot analysis. P-gp function was determined by measuring phenytoin (PHT) levels in these brain regions using high-performance liquid chromatography, in the absence and presence of a P-gp-specific inhibitor, tariquidar (TQD). In addition, the pharmacokinetic profile of PHT was determined. PHT concentration was reduced by 20 to 30% in brain regions that had P-gp overexpression (temporal hippocampus and parahippocampal cortex) and not in brain regions in which P-gp expression was not changed after SE. Inhibition of P-gp by TQD significantly increased the PHT concentration, specifically in regions that showed P-gp overexpression. Despite increased P-gp expression in the liver of epileptic rats, pharmacokinetic analysis showed no significant change of PHT clearance in control versus epileptic rats. These findings show that overexpression of P-gp at the blood-brain barrier of specific limbic brain regions causes a decrease of local PHT levels in the rat brain.
La diversification alimentaire : évaluer l'intérêt d'une fiche-conseil à partir du ressenti du médecin généraliste

Introduction : la diversification alimentaire est une etape clef de l’alimentation du nourrisson. Les parents souhaiteraient etre plus guides et recevoir des fiches. L’objectif de notre etude est d’explorer la gestion de la diversification par le medecin generaliste et recueillir son avis sur l’utilisation d’une fiche-conseil. Materiel et methode : une etude qualitative a ete realisee, basee sur 15 entretiens semi-diriges de generalistes installes en region PACA. Nous avons releve les difficultes rencontrees avec la diversification, les solutions proposees et leur avis sur une fiche. Nous sommes alles jusqu’a "saturation des donnees". Les donnees ont ete etudiees par analyse de contenu thematique a l’aide du logiciel NVivo. Resultats : dans la diversification alimentaire, les medecins estiment qu’ils doivent surtout surveiller la croissance, rassurer les parents et donner des conseils personnalises mais generaux. Les difficultes rencontrees concernent la diversite des recommandations, la gestion de l’angoisse parentale et le manque de temps. Ils proposent de publier des recommandations claires, de renforcer l’education a la sante et de s’appuyer sur un support ecrit. La fiche-conseil leur apparait comme une source pertinente d’informations, de reassurance, permettant d’eviter les oublis, et d’optimiser le temps des consultations. Cependant leur benefice reste limite sans accompagnement. Discussion : la gestion de la diversification varie selon les medecins. Les attentes parentales et leur perception par le generaliste se rejoignent sur les grandes lignes mais s’opposent sur certains points. Les nombreuses variations des recommandations ces dernieres annees compliquent parfois leur application. Conclusion : le generaliste met la relation de confiance et la surveillance de la croissance de l’enfant au cœur de la gestion de la diversification. Sa prise en charge consiste a articuler la norme des recommandations avec la singularite du couple parents/enfant. La fiche-conseil comme outil d’aide au dialogue apparait comme un intermediaire adapte pour atteindre cet objectif.
The metabolism of lipoprotein (a): an ever-evolving story

Lipoprotein (a) [Lp(a)] is characterized by apolipoprotein (a) [apo(a)] covalently bound to apolipoprotein B 100. It was described in human plasma by Berg et al. in 1963 and the gene encoding apo(a) (LPA) was cloned in 1987 by Lawn and colleagues. Epidemiologic and genetic studies demonstrate that increases in Lp(a) plasma levels increase the risk of atherosclerotic cardiovascular disease. Novel Lp(a) lowering treatments highlight the need to understand the regulation of plasma levels of this atherogenic lipoprotein. Despite years of research, significant uncertainty remains about the assembly, secretion, and clearance of Lp(a). Specifically, there is ongoing controversy about where apo(a) and apoB-100 bind to form Lp(a); which apoB-100 lipoproteins bind to apo(a) to create Lp(a); whether binding of apo(a) is reversible, allowing apo(a) to bind to more than one apoB-100 lipoprotein during its lifespan in the circulation; and how Lp(a) or apo(a) leave the circulation. In this review, we highlight past and recent data from stable isotope studies of Lp(a) metabolism, highlighting the critical metabolic uncertainties that exist. We present kinetic models to describe results of published studies using stable isotopes and suggest what future studies are required to improve our understanding of Lp(a) metabolism.
Context Effects in Subjective Mental Workload Ratings

The impact of performance context on subjective mental workload ratings was assessed with the Subjective Workload Assessment Technique (SWAT) and the NASA Task Load Index (TLX). In Experiment 1, a strong context effect was demonstrated. A low range of task difficulty produced considerably higher ratings on a common set of difficulty levels than did a high range of task difficulty. In Experiment 2, increasing the participants′ range of experiences during practice eliminated the context effect. We recommend that methods for standardizing context, such as providing experience with the complete difficulty range, be developed for subjective mental workload evaluations. Actual or potential applications of this research include providing methodologies for controlling context effects in practical assessments of mental workload to increase the validity of subjective measures.
Is the excessive reliance on the board monitoring justified in the context of corporate governance framework

This paper attempts to extend the concept of 'bundle of governance mechanisms' and analyses the dynamics of various governance mechanisms in relation to each other. Further, this paper seeks to answer if it is justified to exercise a huge reliance on board monitoring alone while designing or analysing the governance structure of a firm. This paper uses the total interpretive structural modelling (TISM) approach to analyse the various hierarchical relationships based on the relative driving power and dependence of various monitoring mechanisms. The findings suggest that a huge reliance on board monitoring is justified to an extent as it has the driving power to strengthen other governance mechanisms. However, the relationship between board monitoring and firm performance is moderated by other governance mechanisms like product market competition and ownership concentration. Thus, board monitoring alone should not be considered as a benchmark to assess the quality of the governance structure of a firm.
Complementation of a capsule deficient Cryptococcus neoformans with CAP64 restores virulence in a murine lung infection.

Cryptococcosis is a systemic infection in humans caused by the opportunistic fungal pathogen, Cryptococcus neoformans. The infection usually presents as chronic meningoencephalitis, but infects via the respiratory tract. A polysaccharide capsule is a major virulence factor, which allows the yeast to resist host defenses. However, the essential role of the capsule in allowing it to resist host defenses during the initial lung infection has not been clearly shown. A mutant acapsular C. neoformans strain 602 was complemented with the CAP64 gene to obtain an encapsulated strain, TYCC38-602. TYCC38-602 persisted in the lungs of C.B-17 mice after intratracheal inoculation and disseminated to the brain, whereas the mutant acapsular 602 and the plasmid control transformant CIP3-602 strains grew less readily in the lung and were infrequently detected in the brain. T cell-mediated immunity, developed to the encapsulated organism, was required to control growth within the lungs and had a significant impact on numbers of yeasts detected in the brain. The parent acapsular strain, but not the transformant control, also required T cells for optimal inhibition of growth within the lung, but not for maintaining control of the colony-forming units (cfu) in the brain. In summary, the cryptococcal capsule plays an important role in lung virulence and dissemination to the brain, and intact immunity is required to control lung growth of the encapsulated yeast.
Justification for Use of a Single Trichrome Stain as the Sole Means for Routine Detection of Intestinal Parasites in Concentrated Stool Specimens

ABSTRACT Of 12,321 stool samples analyzed over a 6-year interval, 870 (7.1%) were positive for a total of 1,019 parasites, of which 1,011 (99.2%) were found in trichrome-stained smears of unconcentrated specimens while only 479 (47.0%) were detected in iodine-stained smears of concentrated samples. Stool specimens were next analyzed by trichrome staining of both unconcentrated and concentrated specimens preserved in either mercury-polyvinyl alcohol (PVA) or cupric PVA. Of 2,198 specimens, 171 (7.8%) were positive for a total of 208 parasites, 192 (92.3%) and 204 (98.1%) of which were found in the unconcentrated and concentrated specimens, respectively (P < 0.05). In our patient population, examination of a single trichrome-stained smear of a concentrated stool specimen is a cost-effective alternative to routinely analyzing both concentrated and unconcentrated specimens for parasites.
Transpiration, and nitrogen uptake and flow in two maize (Zea mays L.) inbred lines as affected by nitrogen supply.

BACKGROUND AND AIMS The influence of two nitrogen (N) levels on growth, water relations, and N uptake and flow was investigated in two different inbred lines of maize (N-efficient Zi330 and N-inefficient Chen94-11) to analyse the differences in N uptake and cycling within a plant. METHODS Xylem sap from different leaves of the inbred lines cultured in quartz sand was collected by application of pressure to the root system. Plant transpiration was measured on a daily basis by weighing five pots of each of the treatments. KEY RESULTS N-efficient Zi330 had a higher relative growth rate and water-use efficiency at both high (4 mm) and low (0.08 mm) N levels. At a high N level, the amount of N taken up was similar for the two inbred lines; the amount of N transported in the xylem and retranslocated in the phloem was slight greater in Chen94-11 than in Zi330. At a low N level, however, the total amount of N taken up, transported in the xylem and retranslocated in the phloem of Zi330 was 2.2, 2.7 and 2.7 times more, respectively, than that of Chen94-11. Independent of inbred line and N level, the amounts of N transported in the xylem and cycled in the phloem were far more than that taken up by roots at the same time. Low N supply shifted NO(3)(-1) reduction towards the roots. The major nitrogenous compound in the xylem sap was NO(3)(-1), when plants grew at the high N level, while amino acid-N was predominant when plants grew at the low N level. CONCLUSIONS The N-efficient maize inbred line Zi330 had a higher ability to take up N and cycle N within the plant than N-inefficient Chen94-11 when grown under N-deficiency.
The evolutionary origin of the vertebrate basal ganglia and its role in action selection

Abstract The group of nuclei within the basal ganglia of the forebrain is central to the control of movement. We present data showing that the structure and function of the basal ganglia have been conserved throughout vertebrate evolution over some 560 million years. The interaction between the different nuclei within the basal ganglia is conserved as well as the cellular and synaptic properties and transmitters. We consider the role of the conserved basal ganglia circuitry for basic patterns of motor behaviour controlled via brainstem circuits. The output of the basal ganglia consists of tonically active GABAergic neurones, which target brainstem motor centres responsible for different patterns of behaviour, such as eye and locomotor movements, posture, and feeding. A prerequisite for activating or releasing a motor programme is that this GABAergic inhibition is temporarily reduced. This can be achieved through activation of GABAergic projection neurons from striatum, the input level of the basal ganglia, given an appropriate synaptic drive from cortex, thalamus and the dopamine system. The tonic inhibition of the motor centres at rest most likely serves to prevent the different motor programmes from becoming active when not intended. Striatal projection neurones are subdivided into one group with dopamine 1 receptors that provides increased excitability of the direct pathway that can initiate movements, while inhibitory dopamine 2 receptors are expressed on neurones that instead inhibit movements and are part of the ‘indirect loop’ in mammals as well as lamprey. We review the evidence showing that all basic features of the basal ganglia have been conserved throughout vertebrate phylogeny, and discuss these findings in relation to the role of the basal ganglia in selection of behaviour.
Differential effects of daily snack food intake on the reinforcing value of food in obese and nonobese women.

BACKGROUND Food reinforcement, ie, motivation to obtain food, is associated with energy intake and obesity. Finding ways to decrease the reinforcing value of unhealthy foods may help with adherence to diets and maintenance of weight loss. Our previous study in nonobese adults showed that daily consumption of the same snack food (food consumed apart from meals) for 14 d significantly decreased its reinforcing value. OBJECTIVES The aims of this study were to replicate and extend these findings to obese individuals and to examine the effects of different portion sizes of snack foods on food reinforcement. DESIGN Food reinforcement and liking were tested in 31 obese and 27 nonobese women at baseline and after 2 wk of daily consumption of 0, 100, or 300 kcal/d of the same snack food. RESULTS We found a significant interaction of phase, portion size, and body mass index on the pattern of operant responding for food. Obese women had a significant increase in food reinforcement after consuming the 300-kcal portion of food for 2 wk, whereas nonobese women had the opposite response. No significant differences were found on the reinforcing value with the 0- and 100-kcal portion-size conditions. Women in the 300-kcal group (obese and nonobese) reported a significant decrease in snack food liking from baseline to after daily intake. CONCLUSIONS These findings suggest that obese and nonobese women respond differently to the daily intake of a snack food and that this may not be a viable mechanism for reducing food reinforcement in obese women. This trial was registered at www.clinicaltrials. gov as NCT00837694.
[Effect of the administration of rectal indomethacin on amylase serum levels after endoscopic retrograde cholangiopancreatography, and its impact on the development of secondary pancreatitis episodes].

BACKGROUND Hyperamylasemia and acute pancreatitis represent the most frequent major complication after endoscopic retrograde cholangiopancreatography (ERCP), developing in 1-30% of cases. OBJECTIVE To determine the incidence of hyperamylasemia and acute pancreatitis after ERCP, and to assess the utility of rectal indomethacin to prevent these events. MATERIAL AND METHODS A randomized clinical trial. During a 12-month period 150 patients were included. They were divided up into a study group (n = 75), where 100 mg of rectal indomethacin were administered 2 hours prior to the procedure, and a control group (n = 75), which received rectal glycerin. Two hours after ERCP serum amylase levels were measured and classified as follows: 0<or=150 IU/L, 1 = 151-599 IU/L, 2>or=600 IU/L. Clinical pancreatitis episodes were quantified and classified according to Ranson's criteria. RESULTS Gender distribution: 100 women and 50 men. Mean age: 55.37 +/- 18.0 for the study group, and 51.1 +/- 17.0 for the control group. A diagnosis of benign pathology was present in 56 (74.7%) cases in the study group, and 59 (78.7%) controls. After ERCP 13 (17.3%) patients in the study group and 28 (37.3%) in the control group developed hyperamylasemia (p (2) 0.05). Hyperamylasemia > 600 IU/L was found in 3 patients in the study group, and in 10 in the control group (p = 0.001). Mild pancreatitis was detected in 4 (5.3%) patients in the study group, and in 12 (16%) patients in the control group (p = 0.034). There were no deaths or adverse drug reactions. CONCLUSIONS Rectal indomethacin before ERCP decreases the risk of hyperamylasemia and pancreatitis. Indomethacine is a feasible, low-cost drug with minimal or nil side effects.
Synthesis and Photophysical Property Studies of the 2,6,8-Triaryl-4-(phenylethynyl)quinazolines

The 2-aryl-6,8-dibromo-4-chloroquinazolines derived from the 2-aryl-6,8-dibromoquinazolin-4(3H)-ones were subjected to the Sonogashira cross-coupling with terminal acetylenes at room temperature to afford novel 2-aryl-6,8-dibromo-4-(alkynyl)quinazoline derivatives. Further transformation of the 2-aryl-6,8-dibromo-4-(phenylethynyl)quinazolines via Suzuki-Miyaura cross-coupling with arylboronic acids occurred without selectivity to afford the corresponding 2,6,8-triaryl-4-(phenylethynyl)quinazolines. The absorption and emission properties of these polysubstituted quinazolines were also determined.
p38 MAPK inhibitors suppress biomarkers of hypertension end-organ damage, osteopontin and plasminogen activator inhibitor-1

Abstract The assessment of target organ damage is important in defining the optimal treatment of hypertension and blood pressure-related cardiovascular disease. The aims of the present study were (1) to investigate candidate biomarkers of target organ damage, osteopontin (OPN) and plasminogen activator inhibitor-1 (PAI-1), in models of malignant hypertension with well characterized end-organ pathology; and (2) to evaluate the effects of chronic treatment with a p38 MAPK inhibitor. Gene expression, plasma concentrations, and renal immunohistochemical localization of OPN and PAI-1 were measured in stroke-prone spontaneously hypertensive rats on a salt–fat diet (SFD SHR-SP) and in spontaneously hypertensive rats receiving Nω-nitro-L-arginine methyl ester (L-NAME SHR). Plasma concentrations of OPN and PAI-1 increased significantly in SFD SHR-SP and L-NAME SHR as compared with controls, (2.5–4.5-fold for OPN and 2.0–9.0-fold for PAI-1). The plasma levels of OPN and PAI-1 were significantly correlated with the urinary excretion of albumin (p<0.0001). Elevations in urinary albumin, plasma OPN and PAI-1 were abolished by chronic treatment (4–8 weeks) with a specific p38 MAPK inhibitor, SB-239063AN. OPN immunoreactivity was localized predominantly in the apical portion of tubule epithelium, while PAI-1 immunoreactivity was robust in glomeruli, tubules and renal artery endothelium. Treatment with the p38 MAPK inhibitor significantly reduced OPN and PAI-1 protein expression in target organs. Kidney gene expression was increased for OPN (4.9- and 7.9-fold) and PAI-1 (2.8- and 11.5-fold) in SFD SHR-SP and L-NAME SHR, respectively. In-silico pathway analysis revealed that activation of p38 MAPK was linked to OPN and PAI-1 via SP1, c-fos and c-jun; suggesting that these pathways may play an important role in p38 MAPK-dependent hypertensive renal dysfunction. The results suggest that enhanced OPN and PAI-1 expression reflects end-organ damage in hypertension and that suppression correlates with end-organ protection regardless of overt antihypertensive action.
Differential Effects of Ethanol on Permissive versus Nonpermissive Macrophages Infected with Legionella pneumophila

Abstract The effect of ethanol treatment was studied in terms of effect on permissive versus nonpermissive macrophages for growth of Legionella pneumophila, which is an intracellular bacterium causing pneumonia in immunocompromised patients. It was found that ethanol treatment of permissive macrophages from <L. pneumophila-susceptible A/J mice evinced a decrease in replication of the bacteria compared with nontreated infected macrophages. Whereas there was more than a 100-fold increase in Legionella growth over a 48-hr culture period in infected A/J mouse macrophages, treatment of the macrophages with 0.5% ethanol depressed the ability of the macrophages to be infected by Legionella approximately 45%. A lower concentration of ethanol had a lesser effect but still resulted in inhibition of the ability of the cells to replicate Legionella. In contrast to ethanol-induced inhibition of the A/J mouse macrophages to replicate Legionella, macrophages from Legionella-resistant BALB/c mice, which only minimally replicated Legionella (i.e., only a 2-fold increase or less over a 48-hr period), treatment with ethanol resulted in their greater replication of the Legionella. This effect was most marked with the 1.0% concentration of ethanol after 7 days of pretreatment, while the 0.5% and 0.1% concentrations of alcohol caused less enhancement of bacterial growth in the cells, but these concentrations still had a significant enhancement effect. Thus, ethanol had differing effects on growth of the opportunistic intracellular bacterium Legionella in macrophages from permissive versus nonpermissive mice. Studies on the mechanisms involved are in progress.