PipX, the coactivator of NtcA, is a global regulator in cyanobacteria

To modulate the expression of genes involved in nitrogen assimilation, the cyanobacterial PII-interacting protein X (PipX) interacts with the global transcriptional regulator NtcA and the signal transduction protein PII, a protein found in all three domains of life as an integrator of signals of the nitrogen and carbon balance. PipX can form alternate complexes with NtcA and PII, and these interactions are stimulated and inhibited, respectively, by 2-oxoglutarate, providing a mechanistic link between PII signaling and NtcA-regulated gene expression. Here, we demonstrate that PipX is involved in a much wider interaction network. The effect of pipX alleles on transcript levels was studied by RNA sequencing of S. elongatus strains grown in the presence of either nitrate or ammonium, followed by multivariate analyses of relevant mutant/control comparisons. As a result of this process, 222 genes were classified into six coherent groups of differentially regulated genes, two of which, containing either NtcA-activated or NtcA-repressed genes, provided further insights into the function of NtcA–PipX complexes. The remaining four groups suggest the involvement of PipX in at least three NtcA-independent regulatory pathways. Our results pave the way to uncover new regulatory interactions and mechanisms in the control of gene expression in cyanobacteria.This work was supported by the Spanish Ministry of Economy and Competitivity (Grants BFU2009-07371, BFU2012-33364, and BFU2011-26608) and the European Seventh Framework Program (Grants 289326/FP7-KBBE-2011-5 and 282004/FP7-HEALTH-2011-2.3.1-2)

O conceito de willingness to pay em questão

São revisadas as limitações do uso do conceito de willingness to pay (disposição a pagar) nas avaliações econômicas que se realizam no campo da saúde. Há na literatura econômica muitos investigadores que assinalam os múltiplos problemas metodológicos inerentes às estimações de willingness to pay. Por outro lado, o debate teórico-conceitual acerca da agregação das preferências individuais dentro de uma demanda agregada não está totalmente resolvido. Contudo, durante os últimos 20 anos, a estimação da disposição a pagar calculada pelos estudos tem aumentado de forma significativa, sendo em muitos casos um dos principais fatores de tomada de decisão em políticas de saúde. São apresentadas algumas das limitações desta técnica, assim como o possível efeito de distorção que poderia ter sobre as avaliações econômicas em saúde.The adequacy of the concept of willingness to pay within health economics evaluations is reviewed. A considerable number of researchers in the literature have pointed out multiple methodological issues involving willingness-to-pay estimates. On the other hand, the theoretical discussion about the aggregation of individual preferences within an aggregate demand remains open. However, over the last 20 years, willingness-to-pay estimates alongside health economics research significantly increased and in many cases they are one of the key factors for decision making on issues of health policies. The article describes some limitations of this approach as well as the potential distorting effect that it might have on health economics evaluations.La idoneidad del concepto de willingness to pay (disponibilidad a pagar) es revisado en las evaluaciones económicas que se realizan en el campo de la salud. Por un lado, existe dentro de la literatura económica un número importante de investigadores que señalan los múltiples problemas metodológicos que entrañan las estimaciones de willingness to pay. Por otro lado, aún el debate teórico-conceptual acerca de la agregación de las preferencias individuales dentro de una demanda agregada no ésta del todo resuelto. Sin embargo, durante los últimos 20 años la estimación de la disponibilidad a pagar dentro de las investigaciones económicas ha aumentado de forma significativa, siendo en muchos casos uno de los principales factores de la toma de decisión en políticas de salud. Plantease alguna de las limitaciones de esta técnica, así como el posible efecto distorsionador que podría tener sobre las evaluaciones económicas que se realizan en el área de la economía de la salud

Cost-effectiveness analysis for joint pain treatment in patients with osteoarthritis treated at the Instituto Mexicano del Seguro Social (IMSS): Comparison of nonsteroidal anti-inflammatory drugs (NSAIDs) vs. cyclooxygenase-2 selective inhibitors

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is one of the main causes of disability worldwide, especially in persons >55 years of age. Currently, controversy remains about the best therapeutic alternative for this disease when evaluated from a cost-effectiveness viewpoint. For Social Security Institutions in developing countries, it is very important to assess what drugs may decrease the subsequent use of medical care resources, considering their adverse events that are known to have a significant increase in medical care costs of patients with OA. Three treatment alternatives were compared: celecoxib (200 mg twice daily), non-selective NSAIDs (naproxen, 500 mg twice daily; diclofenac, 100 mg twice daily; and piroxicam, 20 mg/day) and acetaminophen, 1000 mg twice daily. The aim of this study was to identify the most cost-effective first-choice pharmacological treatment for the control of joint pain secondary to OA in patients treated at the Instituto Mexicano del Seguro Social (IMSS).</p> <p>Methods</p> <p>A cost-effectiveness assessment was carried out. A systematic review of the literature was performed to obtain transition probabilities. In order to evaluate analysis robustness, one-way and probabilistic sensitivity analyses were conducted. Estimations were done for a 6-month period.</p> <p>Results</p> <p>Treatment demonstrating the best cost-effectiveness results [lowest cost-effectiveness ratio $17.5 pesos/patient ($1.75 USD)] was celecoxib. According to the one-way sensitivity analysis, celecoxib would need to markedly decrease its effectiveness in order for it to not be the optimal treatment option. In the probabilistic analysis, both in the construction of the acceptability curves and in the estimation of net economic benefits, the most cost-effective option was celecoxib.</p> <p>Conclusion</p> <p>From a Mexican institutional perspective and probably in other Social Security Institutions in similar developing countries, the most cost-effective option for treatment of knee and/or hip OA would be celecoxib.</p

Sex-differences in the oxygenation levels of intercostales and vastus lateralis muscles during incremental exercise

This study aimed to examine sex differences in oxygen saturation in respiratory (SmO2-m.intercostales) and locomotor muscles (SmO2-m.vastus lateralis) while performing physical exercise. Twenty-five (12 women) healthy and physically active participants were evaluated during an incremental test with a cycle ergometer, while ventilatory variables (lung ventilation [V ̇E], tidal volume [Vt], and respiratory rate [RR]) were acquired through the breath-by-breath method. SmO2 was acquired using the MOXY devices on the m.intercostales and m.vastus lateralis. A two-way ANOVA (sex × time) indicated that women showed a greater significant decrease of SmO2-m.intercostales, and men showed a greater significant decrease of SmO2-m.vastus lateralis. Additionally, women reached a higher level of ΔSmO2-m.intercostales normalized to V ̇E (L·min-1) (p<0.001), whereas men had a higher level of ΔSmO2-m.vastus lateralis normalized to peak workload-to-weight (watts·kg-1, PtW) (p=0.049), as confirmed by Student's t-test. During an incremental physical exercise, women experienced a greater cost of breathing, reflected by greater deoxygenation of the respiratory muscles, whereas men had a higher peripheral load, indicated by greater deoxygenation of the locomotor muscles

Determination of the respiratory compensation point by detecting changes in intercostal muscles oxygenation by using near-infrared spectroscopy

This study aimed to evaluate if the changes in oxygen saturation levels at intercostal muscles (SmO2-m.intercostales) assessed by near-infrared spectroscopy (NIRS) using a wearable device could determine the respiratory compensation point (RCP) during exercise. Fifteen healthy competitive triathletes (8 male; 29±6 years; height 167.6±25.6 cm; weight 69.2±9.4 kg; V ̇O2-máx 58.4±8.1 mL·kg-1·min-1) were evaluated in a cycle ergometer during the maximal oxygen-uptake test (V ̇O2-máx), while lung ventilation (V ̇E), power output (watts, W) and SmO2-m.intercostales were measured. RCP was determined by visual method (RCPvisual: changes at ventilatory equivalents (V ̇E·V ̇CO2-1, V ̇E·V ̇O2-1) and end-tidal respiratory pressure (PetO2, PetCO2) and NIRS method (RCPNIRS: breakpoint of fall in SmO2-m.intercostales). During exercise, SmO2-m.intercostales decreased continuously showing a higher decrease when V ̇E increased abruptly. A good agreement between methods used to determine RCP was found (visual vs NIRS) at %V ̇O2-máx, V ̇O2, V ̇E, and W (Bland-Altman test). Correlations were found to each parameters analyzed (r=0.854; r=0.865; r=0.981; and r=0,968; respectively. p<0.001 in all variables, Pearson test), with no differences (p<0.001 in all variables, t-student test) between methods used (RCPvisual and RCPNIRS). We concluded that changes at SmO2-m.intercostales measured by NIRS could adequately determine RCP in triathletes

Excess Higgs Production in Neutralino Decays

The ATLAS and CMS experiments have recently claimed discovery of a Higgs boson-like particle at ~5 sigma confidence and are beginning to test the Standard Model predictions for its production and decay. In a variety of supersymmetric models, a neutralino NLSP can decay dominantly to the Higgs and the LSP. In natural SUSY models, a light third generation squark decaying through this chain can lead to large excess Higgs production while evading existing BSM searches. Such models can be observed at the 8 TeV LHC in channels exploiting the rare diphoton decays of the Higgs produced in the cascade decay. Identifying a diphoton resonance in association with missing energy, a lepton, or b-tagged jets is a promising search strategy for discovery of these models, and would immediately signal new physics involving production of a Higgs boson. We also discuss the possibility that excess Higgs production in these SUSY decays can be responsible for enhancements of up to 50% over the SM prediction for the observed rate in the existing inclusive diphoton searches, a scenario which would likely by the end of the 8 TeV run be accompanied by excesses in the diphoton + lepton/MET and SUSY multi-lepton/b searches and a potential discovery in a diphoton + 2b search.Comment: 42 pages, 19 figure