PAP1 [poly(A) polymerase 1] homozygosity and hyperadenylation are major determinants of increased mRNA stability of CDR1 in azole-resistant clinical isolates of Candida albicans.

Using genetically matched azole-susceptible (AS) and azole-resistant (AR) clinical isolates of Candida albicans, we recently demonstrated that CDR1 overexpression in AR isolates is due to its enhanced transcriptional activation and mRNA stability. This study examines the molecular mechanisms underlying enhanced CDR1 mRNA stability in AR isolates. Mapping of the 3' untranslated region (3' UTR) of CDR1 revealed that it was rich in adenylate/uridylate (AU) elements, possessed heterogeneous polyadenylation sites, and had putative consensus sequences for RNA-binding proteins. Swapping of heterologous and chimeric lacZ-CDR1 3' UTR transcriptional reporter fusion constructs did not alter the reporter activity in AS and AR isolates, indicating that cis-acting sequences within the CDR1 3' UTR itself are not sufficient to confer the observed differential mRNA decay. Interestingly, the poly(A) tail of the CDR1 mRNA of AR isolates was approximately 35-50 % hyperadenylated as compared with AS isolates. C. albicans poly(A) polymerase (PAP1), responsible for mRNA adenylation, resides on chromosome 5 in close proximity to the mating type-like (MTL) locus. Two different PAP1 alleles, PAP1-a/PAP1-alpha, were recovered from AS (MTL-a/MTL-alpha), while a single type of PAP1 allele (PAP1-alpha) was recovered from AR isolates (MTL-alpha/MTL-alpha). Among the heterozygous deletions of PAP1-a (Deltapap1-a/PAP1-alpha) and PAP1-alpha (PAP1-a/Deltapap1-alpha), only the former led to relatively enhanced drug resistance, to polyadenylation and to transcript stability of CDR1 in the AS isolate. This suggests a dominant negative role of PAP1-a in CDR1 transcript polyadenylation and stability. Taken together, our study provides the first evidence, to our knowledge, that loss of heterozygosity at the PAP1 locus is linked to hyperadenylation and subsequent increased stability of CDR1 transcripts, thus contributing to enhanced drug resistance.

A noninvasive diagnostic tool to differentiate myocarditis from myocardial infarction: late gadolinium enhanced cardiac magnetic resonance.

Studies in adults have shown that late gadolinium enhanced cardiac magnetic resonance is a safe and noninvasive diagnostic tool which allows one to differentiate myocardial infarction from myocarditis. We believe that it may also be highly useful in the paediatric population for the same purpose.

Enhanced Proinflammatory Cytokine Response to Bacterial Lipopolysaccharide in the Adult Male Rat after either Neonatal or Prepubertal Ablation of Biological Testosterone Activity.

A sex steroid-dependent modulation of the immune function in mammals is accepted, and evidence suggests that while estrogens enhance, androgens inhibit the immune response. The aim of this study was to explore in the adult male rat the effect of either neonatal flutamide (FTM) treatment or prepubertal orchidectomy (ODX) on endocrine markers in the basal condition and peripheral tumor necrosis factor alpha (TNFα) levels during inflammatory stress. For these purposes, (1) 5-day-old male rats were subcutaneously injected with either sterile vehicle alone or containing 1.75 mg FTM, and (2) 25-day-old male rats were sham operated or had ODX. Rats were sacrificed (at 100 days of age) in the basal condition for determination of peripheral metabolite levels. Additional rats were intravenously injected with bacterial lipopolysaccharide (LPS; 25 μg/kg body weight, i.v.) and bled for up to 4 h. Data indicate that (1) ODX increased peripheral glucocorticoid levels and reduced those of testosterone, whereas FTM-treated rats displayed low circulating leptin concentrations, and (2) LPS-induced TNFα secretion in plasma was significantly enhanced in the FTM and ODX groups. Our study supports that neonatal FTM treatment affected adiposity function, and adds data maintaining that androgens have a suppressive role in proinflammatory cytokine release in plasma during inflammation.

How Low Can We Go in Contrast-Enhanced CT Imaging of the Chest?: A Dose-Finding Cadaver Study Using the Model-based Iterative Image Reconstruction Approach.

RATIONALE AND OBJECTIVES: Dose reduction may compromise patients because of a decrease of image quality. Therefore, the amount of dose savings in new dose-reduction techniques needs to be thoroughly assessed. To avoid repeated studies in one patient, chest computed tomography (CT) scans with different dose levels were performed in corpses comparing model-based iterative reconstruction (MBIR) as a tool to enhance image quality with current standard full-dose imaging. MATERIALS AND METHODS: Twenty-five human cadavers were scanned (CT HD750) after contrast medium injection at different, decreasing dose levels D0-D5 and respectively reconstructed with MBIR. The data at full-dose level, D0, have been additionally reconstructed with standard adaptive statistical iterative reconstruction (ASIR), which represented the full-dose baseline reference (FDBR). Two radiologists independently compared image quality (IQ) in 3-mm multiplanar reformations for soft-tissue evaluation of D0-D5 to FDBR (-2, diagnostically inferior; -1, inferior; 0, equal; +1, superior; and +2, diagnostically superior). For statistical analysis, the intraclass correlation coefficient (ICC) and the Wilcoxon test were used. RESULTS: Mean CT dose index values (mGy) were as follows: D0/FDBR = 10.1 ± 1.7, D1 = 6.2 ± 2.8, D2 = 5.7 ± 2.7, D3 = 3.5 ± 1.9, D4 = 1.8 ± 1.0, and D5 = 0.9 ± 0.5. Mean IQ ratings were as follows: D0 = +1.8 ± 0.2, D1 = +1.5 ± 0.3, D2 = +1.1 ± 0.3, D3 = +0.7 ± 0.5, D4 = +0.1 ± 0.5, and D5 = -1.2 ± 0.5. All values demonstrated a significant difference to baseline (P < .05), except mean IQ for D4 (P = .61). ICC was 0.91. CONCLUSIONS: Compared to ASIR, MBIR allowed for a significant dose reduction of 82% without impairment of IQ. This resulted in a calculated mean effective dose below 1 mSv.

Real-time dual-wavelength digital holographic microscopy for extended measurement range with enhanced axial resolution

We report on advanced dual-wavelength digital holographic microscopy (DHM) methods, enabling single-acquisition real-time micron-range measurements while maintaining single-wavelength interferometric resolution in the nanometer regime. In top of the unique real-time capability of our technique, it is shown that axial resolution can be further increased compared to single-wavelength operation thanks to the uncorrelated nature of both recorded wavefronts. It is experimentally demonstrated that DHM topographic investigation within 3 decades measurement range can be achieved with our arrangement, opening new applications possibilities for this interferometric technique. ©2008 COPYRIGHT SPIE

Role of enhanced detoxication in a deltamethrin-resistant population of Triatoma infestans (Hemiptera, Reduviidae) from Argentina

Deltamethrin and other pyrethroids have been extensively used in Argentina since 1980, for the chemical control of Triatoma infestans Klug (Hemiptera: Reduviidae). Recently, resistance to deltamethrin was detected in field populations by the survival of bugs exposed by topical application to the diagnostic dose estimated on the CIPEIN susceptible strain. Results of the current study showed low resistant ratios (RRs) to deltamethrin for the resistant populations (RR ranged from 2.0 for San Luis colony to 7.9 for Salta colony). Biochemical studies were made on the most resistant colony (Salta) and the susceptible strain (CIPEIN), in order to establish the importance of degradative mechanisms as a cause of the detected resistance. Esterase activity was measured on 3 days old first instars through phenylthioacetate and a-naphtyl acetate activities. The results showed a significant difference in no cholinesterase esterase activity from susceptible (7.6 ± 0,7 µM S./i.min.) and Salta resistant colony (9.5 ± 0.8 µM S./i.min.). Cytochrome P450 mono-oxygenase (P450) activity was measured on individual insects through ethoxycoumarine deethylase (ECOD) activity using a fluorescence micro plate reader. The dependence of ECOD activity on age and body region of the nymphs, and pH and time of incubation were studied in order to optimize the measurement. As a result, comparative studies were performed on abdomens of 2 days old first instars at pH 7.2 and 4 h incubation time. ECOD activity of first nymphs was significantly lower in the susceptible colony (61.3 ± 9.08 pg ECOD/ insect) than in the resistant one (108.1± 5.7 pg ECOD/ insect). These results suggest that degradative esterases (no-cholinesterase) and mono-oxygenases cytochrome P450, play an important role in the resistance to deltamethrin in Salta colony from Argentina.

Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment

Physical activity is beneficial for healthy ageing. It may also help maintain good cognitive function in older age. Aerobic activity improves cardiovascular fitness, but it is not known whether this sort of fitness is necessary for improved cognitive function.��Eleven studies of aerobic physical activity programmes for healthy people over the age of 55 years have been included in this review. Eight of these 11 studies reported that aerobic exercise interventions resulted in increased fitness of the trained group and an improvement in at least one aspect of cognitive function. The largest effects were on cognitive speed, auditory and visual attention. However, the cognitive functions which improved were not the same in each study and the majority of comparisons yielded no significant results.��The data are insufficient to show that the improvements in cognitive function which can be attributed to physical exercise are due to improvements in cardiovascular fitness.

Athletic injuries of the extensor carpi ulnaris subsheath: MRI findings and utility of gadolinium-enhanced fat-saturated T1-weighted sequences with wrist pronation and supination

Purpose: To report the magnetic resonance imaging (MRI) findings in athletic injuries of the extensor carpi ulnaris (ECU) subsheath, assessing the utility of gadolinium-enhanced (Gd) fat-saturated (FS) T1-weighted sequences with wrist pronation and supination. Methods and Materials: Sixteen patients (13 males, 3 females; mean age 30.3 years) with athletic injuries of the ECU subsheath sustained between January 2003 and June 2009 were included in this retrospective study. Initial and follow‑up 1.5-T wrist MRIs were performed with transverse T1-weighted and STIR sequences in pronation, and Gd FS T1-weighted sequences with wrist pronation and supination. Two radiologists assessed the type of injury (A to C), ECU tendon stability, associated lesions and rated pulse sequences using a three-point scale: 1 = poor, 2 = good and 3 = excellent. Results: Gd-enhanced FS T1-weighted transverse sequences in supination (2.63) and pronation (2.56) were most valuable, compared with STIR (2.19) and T1 weighted (1.94). Nine type A, one type B and six type C injuries were found. There were trends towards diminution in size, signal intensity and enhancement of associated pouches on follow‑up MRI and tendon stabilisation within the ulnar groove. Conclusion: Gd-enhanced FS T1-weighted sequences with wrist pronation and supination are most valuable in assessing and follow‑up athletic injuries of the ECU subsheath on 1.5-T MRI.

OER as a Model for Enhanced Teaching and Learning

This article presents preliminary findings from a research study conducted by the Institute for the Study of Knowledge Management in Education on the role of open educational resources (OER) in transforming pedagogy. Based on a study of art and humanities teachers participating in an OER training network, the study reveals how exposure to OER resources and tools support collaboration among teachers, as well as new conversations about teaching practices. These findings have implications for engaging teachers in adopting new OER use practices, and for how OER can be integrated as a model for innovation in teaching and in resource development.

Enhanced multi-layer protection in multi-service GMPLS networks

This paper focuses on QoS routing with protection in an MPLS network over an optical layer. In this multi-layer scenario each layer deploys its own fault management methods. A partially protected optical layer is proposed and the rest of the network is protected at the MPLS layer. New protection schemes that avoid protection duplications are proposed. Moreover, this paper also introduces a new traffic classification based on the level of reliability. The failure impact is evaluated in terms of recovery time depending on the traffic class. The proposed schemes also include a novel variation of minimum interference routing and shared segment backup computation. A complete set of experiments proves that the proposed schemes are more efficient as compared to the previous ones, in terms of resources used to protect the network, failure impact and the request rejection ratio

Enhanced production of indole-3-acetic acid by a genetically modified strain of Pseudomonas fluorescens CHA0 affects root growth of cucumber but does not improve protection of the plant against Pythium root rot

The biocontrol strain CHA0 of Pseudomonas fluorescens produces small amounts of indole-3-acetic acid via the tryptophan side chain oxidase and the tryptophan transaminase pathways. A recombinant plasmid (pME3468) expressing the tryptophan monooxygenase pathway was introduced into strain CHA0; this resulted in elevated synthesis of indole-3-acetic acid in vitro, especially after addition of -tryptophan. In natural soil, strain CHA0/pME3468 increased fresh root weight of cucumber by 17-36%, compared to the effect of strain CHA0; root colonization was about 106 cells per g of root. However, both strains gave similar protection of cucumber against Pythium ultimum. In autoclaved soil, at 6×107 cells per g of root, strain CHA0 stimulated growth of roots and shoots, whereas strain CHA0/pME3468 caused root stunting and strong reduction of plant weight. These results are in agreement with the known effects of exogenous indole-3-acetic acid on plant roots and suggest that in the system examined, indole-3-acetic acid does not contribute to the biocontrol properties of strain CHA0.

Enhanced diastolic reflections on arterial pressure pulse during exercise recovery.

During recovery from a maximal or submaximal aerobic exercise, augmentation of central (aortic) systolic pressure by reflected pressure waves is blunted in healthy humans. However, the extent to which reflected pressure waves modify the central pulse in diastole in these conditions remains unknown. We evaluated systolic and diastolic central reflected waves in 11 endurance-trained athletes on recovery from a maximal running test on a treadmill (treadmill-max) and a 4000 m run in field conditions. On both occasions in each subject, the radial pulse was recorded with applanation tonometry in the resting preexercise state and then 5, 15, 25, 35, and 45 min after exercise termination. From the central waveform, as reconstructed by application of a generalized transfer function, we computed a systolic (AIx) and a diastolic index (AId) of pressure augmentation by reflections. At 5 min, both indices were below preexercise. At further time-points, AIx remained low, while AId progressively increased, to overshoot above preexercise at 45 min. The same behavior was observed with both exercise types. Beyond the first few minutes of recovery following either maximal or submaximal aerobic exercise, reflected waves selectively augment the central pressure pulse in diastole, at least in endurance-trained athletes.

Cost-effectiveness of the implementation of an enhanced recovery protocol for colorectal surgery.

BACKGROUND: Enhanced recovery protocols may reduce postoperative complications and length of hospital stay. However, the implementation of these protocols requires time and financial investment. This study evaluated the cost-effectiveness of enhanced recovery implementation. METHODS: The first 50 consecutive patients treated during implementation of an enhanced recovery programme were compared with 50 consecutive patients treated in the year before its introduction. The enhanced recovery protocol principally implemented preoperative counselling, reduced preoperative fasting, preoperative carbohydrate loading, avoidance of premedication, optimized fluid balance, standardized postoperative analgesia, use of a no-drain policy, as well as early nutrition and mobilization. Length of stay, readmissions and complications within 30 days were compared. A cost-minimization analysis was performed. RESULTS: Hospital stay was significantly shorter in the enhanced recovery group: median 7 (interquartile range 5-12) versus 10 (7-18) days (P = 0·003); two patients were readmitted in each group. The rate of severe complications was lower in the enhanced recovery group (12 versus 20 per cent), but there was no difference in overall morbidity. The mean saving per patient in the enhanced recovery group was euro1651. CONCLUSION: Enhanced recovery is cost-effective, with savings evident even in the initial implementation period.