High precision astrometry mission for the detection and characterization of nearby habitable planetary systems with the Nearby Earth Astrometric Telescope (NEAT)

A complete census of planetary systems around a volume-limited sample of solar-type stars (FGK dwarfs) in the Solar neighborhood (d a parts per thousand currency signaEuro parts per thousand 15 pc) with uniform sensitivity down to Earth-mass planets within their Habitable Zones out to several AUs would be a major milestone in extrasolar planets astrophysics. This fundamental goal can be achieved with a mission concept such as NEAT-the Nearby Earth Astrometric Telescope. NEAT is designed to carry out space-borne extremely-high-precision astrometric measurements at the 0.05 mu as (1 sigma) accuracy level, sufficient to detect dynamical effects due to orbiting planets of mass even lower than Earth's around the nearest stars. Such a survey mission would provide the actual planetary masses and the full orbital geometry for all the components of the detected planetary systems down to the Earth-mass limit. The NEAT performance limits can be achieved by carrying out differential astrometry between the targets and a set of suitable reference stars in the field. The NEAT instrument design consists of an off-axis parabola single-mirror telescope (D = 1 m), a detector with a large field of view located 40 m away from the telescope and made of 8 small movable CCDs located around a fixed central CCD, and an interferometric calibration system monitoring dynamical Young's fringes originating from metrology fibers located at the primary mirror. The mission profile is driven by the fact that the two main modules of the payload, the telescope and the focal plane, must be located 40 m away leading to the choice of a formation flying option as the reference mission, and of a deployable boom option as an alternative choice. The proposed mission architecture relies on the use of two satellites, of about 700 kg each, operating at L2 for 5 years, flying in formation and offering a capability of more than 20,000 reconfigurations. The two satellites will be launched in a stacked configuration using a Soyuz ST launch vehicle. The NEAT primary science program will encompass an astrometric survey of our 200 closest F-, G- and K-type stellar neighbors, with an average of 50 visits each distributed over the nominal mission duration. The main survey operation will use approximately 70% of the mission lifetime. The remaining 30% of NEAT observing time might be allocated, for example, to improve the characterization of the architecture of selected planetary systems around nearby targets of specific interest (low-mass stars, young stars, etc.) discovered by Gaia, ground-based high-precision radial-velocity surveys, and other programs. With its exquisite, surgical astrometric precision, NEAT holds the promise to provide the first thorough census for Earth-mass planets around stars in the immediate vicinity of our Sun.

Association of polymorphisms of endothelial nitric oxide synthase (eNOS) gene with the risk of primary open angle glaucoma in a Brazilian population

The present study aimed to investigate the association of endothelial nitric oxide synthase (eNOS) gene polymorphisms with primary open angle glaucoma (POAG). We conducted a case-control study that included 90 patients with POAG and 127 healthy controls whose blood samples were genotyped for the functional polymorphisms T-786C and Glu298Asp of the eNOS gene by Taqman fluorescent allelic discrimination assay. The T-786C polymorphism was significantly associated as a risk factor for POAG among women (OR: 228; 95% CI: 1.11 to 4.70, p = 0.024) and marginally associated to the risk of POAG in the patients >= 52 years of age at diagnosis (OR: 2.11; 95% CI: 0.98 to 4.55, p = 0,055). However, these results was not confirmed after adjustments for gender, age, self-declared skin color, tobacco smoking and eNOS genotypes by multivariate logistic regression model (OR: 2.08; 95% CI: 0.87 to 5.01, p = 0.101 and OR: 2.20; 95% CI: 0.95 to 5.12, p = 0.067, respectively). The haplotype CG of T-786C and Glu298Asp showed a borderline association with risk of POAG in the overall analysis (OR: 1.76; 95% CI: 0.98 to 3.14, p = 0.055) and among women (OR: 2.02; 95% CI: 0.98 to 4.16, p = 0.052). Furthermore, the CG haplotype was significantly associated with the development of POAG for the age at diagnosis group >= 52 years (OR: 3.48; 95% CI: 1.54 to 7.84, p = 0.002). We suggested that haplotypes of the polymorphisms T-786C and Glu298Asp of eNOS may interact with gender and age in modulating the risk of POAG. (C) 2012 Elsevier B.V. All rights reserved.

Advances in primary immunodeficiency diseases in Latin America: epidemiology, research, and perspectives

Primary immunodeficiencies (PIDs) are genetic disorders of the immune system comprising many different phenotypes. Although previously considered rare, recent advances in their clinical, epidemiological, and molecular definitions are revealing how much we still need to learn about them. For example, geographical and ethnic variations as well as the impact of certain practices influence their frequency and presentation, making it necessary to consider their study in terms of regions. The Latin American Society for Immunodeficiencies was established as an organization dedicated to provide scientific support for basic and clinical research and to develop tools and educational resources to promote awareness in the medical community. Initiatives such as these are positively influencing the way PIDs are tackled in these countries, as shown by recent reports and publications. This paper provides a historical compilation and a current view of the many issues faced by scientists studying these diseases in these countries, highlighting the diverse scientific contributions and offering a promising perspective for the further developments in this field in Latin America.

Potential Drug-Drug Interactions in Prescriptions to Patients over 45 Years of Age in Primary Care, Southern Brazil

Background: Few cross-sectional studies involving adults and elderly patients with major DDIs have been conducted in the primary care setting. The study aimed to investigate the prevalence of potential drug-drug interactions (DDIs) in patients treated in primary care. Methodology/Principal Findings: A cross-sectional study involving patients aged 45 years or older was conducted at 25 Basic Health Units in the city of Maringa (southern Brazil) from May to December 2010. The data were collected from prescriptions at the pharmacy of the health unit at the time of the delivery of medication to the patient. After delivery, the researcher checked the electronic medical records of the patient. A total of 827 patients were investigated (mean age: 64.1; mean number of medications: 4.4). DDIs were identified in the Micromedex (R) database. The prevalence of potential DDIs and major DDIs was 63.0% and 12.1%, respectively. In both the univariate and multivariate analyses, the number of drugs prescribed was significantly associated with potential DDIs, with an increasing risk from three to five drugs (OR = 4.74; 95% CI: 2.90-7.73) to six or more drugs (OR = 23.03; 95% CI: 10.42-50.91). Forty drugs accounted for 122 pairs of major DDIs, the most frequent of which involved simvastatin (23.8%), captopril/enalapril (16.4%) and fluoxetine (16.4%). Conclusions/Significance: This is the first large-scale study on primary care carried out in Latin America. Based on the findings, the estimated prevalence of potential DDIs was high, whereas clinically significant DDIs occurred in a smaller proportion. Exposing patients to a greater number of prescription drugs, especially three or more, proved to be a significant predictor of DDIs. Prescribers should be more aware of potential DDIs. Future studies should assess potential DDIs in primary care over a longer period of time.

RAND-like Appropriateness Methodology Consensus for Primary Open-Angle Glaucoma in Latin America

PURPOSE: To report the results of a Latin American consensus panel regarding the diagnosis and management of primary open-angle glaucoma and to compare these results with those from a similar panel in the United States. DESIGN: A RAND-like (Research and Development) appropriateness methodology was used to assess glaucoma practice in Latin America. METHODS: The 148 polling statements created for the RAND-like analysis in the United States and 10 additional statements specific to glaucoma care in Latin America were presented to a panel of Latin American glaucoma experts. Panelists were polled in private using the RAND-like methodology before and after the panel meeting. RESULTS: Consensus agreement or disagreement among Latin American experts was reached for 51.3% of statements before the meeting and increased to 66.5% in the private, anonymous meeting after polling (79.0% agreement, 21.0% disagreement). Although there was a high degree of concordance (111 of 148 statements; 75%) between the results of this Latin American panel and the United States panel, there were some notable exceptions relating to diagnostic and therapeutic decision making. CONCLUSIONS: This RAND-like consensus methodology provides a perspective of how Latin American glaucoma practitioners view many aspects of glaucoma and compares these results with those obtained using a similar methodology from practitioners in the United States. These findings may be helpful to ophthalmologists providing glaucoma care in Latin America and in other regions of the world. (Am J Ophthalmol 2012;154: 460-465. (C) 2012 by Elsevier Inc. All rights reserved.)

Inhibition of cPLA(2) and sPLA(2) Activities in Primary Cultures of Rat Cortical Neurons by Centella asiatica Water Extract

Leaf extract of Centella asiatica has been used as an alternative medicine for memory improvement in the Indian Ayurvedic system of medicine for a long time. Although several studies have revealed its effect in ameliorating the cognitive impairment in rat models of Alzheimer's disease, the molecular mechanism of C. asiatica on neuroprotection still remains unexplained. In this study, we investigated the effects of C. asiatica water extract on activity of subtypes of phospholipase A(2) (PLA(2)) in primary cultures of rat cortical neurons and quantified by HPLC a possible molecule responsible for the activity. The cPLA(2) and sPLA(2) activities were inhibited in vitro by asiaticoside present in the water extract of C. asiatica. This extract may be a candidate for the treatment of neurodegenerative processes because of its pharmacological activity in the brain and its low toxicity, as attested by its long popular use as a natural product.

HPV16 Oncoproteins Induce MMPs/RECK-TIMP-2 Imbalance in Primary Keratinocytes: Possible Implications in Cervical Carcinogenesis

Cervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors beyond viral infection are necessary for tumor establishment and progression. Tumor progression is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs) produced by either the tumor cells themselves or tumor-associated fibroblasts or macrophages. Increased MMPs expression, including MMP-2, MMP-9 and MT1-MMP, has been observed during cervical carcinoma progression. These proteins have been associated with degradation of ECM components, tumor invasion, metastasis and recurrence. However, few studies have evaluated the interplay between HPV infection and the expression and activity of MMPs and their regulators in cervical cancer. We analyzed the effect of HPV16 oncoproteins on the expression and activity of MMP-2, MMP-9, MT1-MMP, and their inhibitors TIMP-2 and RECK in cultures of human keratinocytes. We observed that E7 expression is associated with increased pro-MMP-9 activity in the epithelial component of organotypic cultures, while E6 and E7 oncoproteins co-expression down-regulates RECK and TIMP-2 levels in organotypic and monolayers cultures. Finally, a study conducted in human cervical tissues showed a decrease in RECK expression levels in precancer and cancer lesions. Our results indicate that HPV oncoproteins promote MMPs/ RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome.

GeoHealth: A Georeferenced System for Health Data Analysis in Primary Care

The Primary Care Information System (SIAB) concentrates basic healthcare information from all different regions of Brazil. The information is collected by primary care teams on a paper-based procedure that degrades the quality of information provided to the healthcare authorities and slows down the process of decision making. To overcome these problems we propose a new data gathering application that uses a mobile device connected to a 3G network and a GPS to be used by the primary care teams for collecting the families' data. A prototype was developed in which a digital version of one SIAB form is made available at the mobile device. The prototype was tested in a basic healthcare unit located in a suburb of Sao Paulo. The results obtained so far have shown that the proposed process is a better alternative for data collecting at primary care, both in terms of data quality and lower deployment time to health care authorities.

Temperature rise during Er:YAG cavity preparation of primary enamel

This study aimed to assess in vitro thermal alterations taking place during the Er:YAG laser cavity preparation of primary tooth enamel at different energies and pulse repetition rates. Forty healthy human primary molars were bisected in a mesio-distal direction, thus providing 80 fragments. Two small orifices were made on the dentin surface to which type K thermocouples were attached. The fragments were individually fixed with wax in a cylindrical PlexiglassA (R) abutment and randomly assigned to eight groups, according to the laser parameters (n = 10): G1 -aEuro parts per thousand 250 mJ/ 3 Hz, G2 -aEuro parts per thousand 250 mJ/ 4 Hz, G3 -aEuro parts per thousand 250 mJ/ 6 Hz, G4 -aEuro parts per thousand 250 mJ/10 Hz, G5 -aEuro parts per thousand 250 mJ/ 15 Hz, G6 -aEuro parts per thousand 300 mJ/ 3 Hz, G7 -aEuro parts per thousand 300 mJ/ 4 Hz and G8 -aEuro parts per thousand 300 mJ/ 6 Hz. An area of 4 mm(2) was delimited. Cavities were done (2 mm long x 2 mm wide x 1 mm thick) using non-contact (12 mm) and focused mode. Temperature values were registered from the start of laser irradiation until the end of cavity preparation. Data were analyzed by one-way ANOVA and Tukey test (p a parts per thousand currency signaEuro parts per thousand 0.05). Groups G1, G2, G6, and G7 were statistically similar and furnished the lowest mean values of temperature rise. The set 250 mJ/10 and 15 Hz yielded the highest temperature values. The sets 250 and 300 mJ and 6 Hz provided temperatures with mean values below the acceptable critical value, suggesting that these parameters ablate the primary tooth enamel. Moreover, the temperature elevation was directly related to the increase in the employed pulse repetition rates. In addition, there was no direct correlation between temperature rise and energy density. Therefore, it is important to use a lower pulse frequency, such as 300 mJ and 6 Hz, during cavity preparation in pediatric patients.

Risk Factors and Survival Impact of Primary Graft Dysfunction After Lung Transplantation in a Single Institution

Background. Lung transplantation has become a standard procedure for some end-stage lung diseases, but primary graft dysfunction (PGD) is an inherent problem that impacts early and late outcomes. The aim of this study was to define the incidence, risk factors, and impact of mechanical ventilation time on mortality rates among a retrospective cohort of lung transplantations performed in a single institution. Methods. We performed a retrospective study of 118 lung transplantations performed between January 2003 and July 2010. The most severe form of PGD (grade III) as defined at 48 and 72 hours was examined for risk factors by multivariable logistic regression models using donor, recipient, and transplant variables. Results. The overall incidence of PGD at 48 hours was 19.8%, and 15.4% at 72 hours. According multivariate analysis, risk factors associated with PGD were donor smoking history for 48 hours (adjusted odds ratio [OR], 4.83; 95% confidence interval [CI], 1.236-18.896; P = .022) and older donors for 72 hours (adjusted OR, 1.046; 95% CI, 0.997-1.098; P = .022). The operative mortality was 52.9% among patients with PGD versus 20.3% at 48 hours (P = .012). At 72 hours, the mortality rate was 58.3% versus 21.2% (P = .013). The 90-days mortality was also higher among patients with PGD. The mechanical ventilation time was longer in patients with PGD III at 48 hours namely, a mean time of 72 versus 24 hours (P = .001). When PGD was defined at 72 hours, the mean ventilation time was even longer, namely 151 versus 24 hours (P < .001). The mean overall survival for patients who developed PGD at 48 hours was 490.9 versus 1665.5 days for subjects without PGD (P = .001). Considering PGD only at 72 hours, the mean survival was 177.7 days for the PGD group and 1628.9 days for the other patients (P < .001). Conclusion. PGD showed an important impacts on operative and 90-day mortality rates, mechanical ventilation time, and overall survival among lung transplant patients. PGD at 72 hours was a better predictor of lung transplant outcomes than at 48 hours. The use of donors with a smoking history or of advanced age were risk factors for the development of PGD.

Influence of moisture and plaque on the performance of a laser fluorescence device in detecting caries lesions in primary teeth

The aim of this study was to evaluate the influence of dental plaque and moisture on performance of a laser fluorescence device in detecting occlusal and proximal caries lesions in primary teeth. Fifty-five occlusal and 58 proximal sites on primary molars were evaluated using a DIAGNOdent pen (LFpen) device. For the drying time study, the evaluations were performed in: (I) moist teeth; (II) teeth dried for 3 s, or (III) dried for 15 s. For the plaque study, the evaluations were done in sites: (I) without plaque; (II) with plaque, and (III) after cleaning. Evaluation of the teeth sections in stereomicroscope was the reference standard method. LF pen values, sensitivity, specificity, and accuracy were compared. The values obtained after 15 s of drying were higher than those obtained with moist teeth or dried for 3 s at both occlusal and proximal surfaces. However, there was no change in the performance in detecting caries lesions. With regard to the presence of plaque, there was no significant change in the readings of the device, but specificity was decreased in occlusal surfaces with plaque. At proximal surfaces, however, no significant differences were observed. In conclusion, the moisture conditions do not influence significantly the performance of the LFpen, but the presence of plaque can affect its performance in detecting occlusal caries lesions in primary teeth.

Transverse sphericity of primary charged particles in minimum bias proton-proton collisions at root s=0.9, 2.76 and 7 TeV

Measurements of the sphericity of primary charged particles in minimum bias proton-proton collisions at root s = 0.9, 2.76 and 7 TeV with the ALICE detector at the LHC are presented. The observable is measured in the plane perpendicular to the beam direction using primary charged tracks with p(T) > 0.5 GeV/c in vertical bar eta vertical bar < 0.8. The mean sphericity as a function of the charged particle multiplicity at mid-rapidity (N-ch) is reported for events with different p(T) scales ("soft" and "hard") defined by the transverse momentum of the leading particle. In addition, the mean charged particle transverse momentum versus multiplicity is presented for the different event classes, and the sphericity distributions in bins of multiplicity are presented. The data are compared with calculations of standard Monte Carlo event generators. The transverse sphericity is found to grow with multiplicity at all collision energies, with a steeper rise at low N-ch, whereas the event generators show an opposite tendency. The combined study of the sphericity and the mean p(T) with multiplicity indicates that most of the tested event generators produce events with higher multiplicity by generating more back-to-back jets resulting in decreased sphericity (and isotropy). The PYTHIA6 generator with tune PERUGIA-2011 exhibits a noticeable improvement in describing the data, compared to the other tested generators.

Cwc24p Is a General Saccharomyces cerevisiae Splicing Factor Required for the Stable U2 snRNP Binding to Primary Transcripts

Splicing of primary transcripts is an essential process for the control of gene expression. Specific conserved sequences in premature transcripts are important to recruit the spliceosome machinery. The Saccharomyces cerevisiae catalytic spliceosome is composed of about 60 proteins and 5 snRNAs (U1, U2, U4/U6 and U5). Among these proteins, there are core components and regulatory factors, which might stabilize or facilitate splicing of specific substrates. Assembly of a catalytic complex depends on the dynamics of interactions between these proteins and RNAs. Cwc24p is an essential S. cerevisiae protein, originally identified as a component of the NTC complex, and later shown to affect splicing in vivo. In this work, we show that Cwc24p also affects splicing in vitro. We show that Cwc24p is important for the U2 snRNP binding to primary transcripts, co-migrates with spliceosomes, and that it interacts with Brr2p. Additionally, we show that Cwc24p is important for the stable binding of Prp19p to the spliceosome. We propose a model in which Cwc24p is required for stabilizing the U2 association with primary transcripts, and therefore, especially important for splicing of RNAs containing non- consensus branchpoint sequences.

UVB-induced cell death signaling is associated with G1-S progression and transcription inhibition in primary human fibroblasts

DNA damage induced by ultraviolet (UV) radiation can be removed by nucleotide excision repair through two sub-pathways, one general (GGR) and the other specific for transcribed DNA (TCR), and the processing of unrepaired lesions trigger signals that may lead to cell death. These signals involve the tumor suppressor p53 protein, a central regulator of cell responses to DNA damage, and the E3 ubiquitin ligase Mdm2, that forms a feedback regulatory loop with p53. The involvement of cell cycle and transcription on the signaling to apoptosis was investigated in UVB-irradiated synchronized, DNA repair proficient, CS-B (TCR-deficient) and XP-C (GGR-deficient) primary human fibroblasts. Cells were irradiated in the G1 phase of the cell cycle, with two doses with equivalent levels of apoptosis (low and high), defined for each cell line. In the three cell lines, the low doses of UVB caused only a transient delay in progression to the S phase, whereas the high doses induced permanent cell cycle arrest. However, while accumulation of Mdm2 correlated well with the recovery from transcription inhibition at the low doses for normal and CS-B fibroblasts, for XP-C cells this protein was shown to be accumulated even at UVB doses that induced high levels of apoptosis. Thus, UVB-induced accumulation of Mdm2 is critical for counteracting p53 activation and apoptosis avoidance, but its effect is limited due to transcription inhibition. However, in the case of XP-C cells, an excess of unrepaired DNA damage would be sufficient to block S phase progression, which would signal to apoptosis, independent of Mdm2 accumulation. The data clearly discriminate DNA damage signals that lead to cell death, depending on the presence of UVB-induced DNA damage in replicating or transcribing regions.