Macroeconomia e estratégias de desenvolvimento.

bitstream/item/144234/1/2009CL-25.pd

PfHPRT: a new biomarker candidate of acute Plasmodium falciparum infection.

Plasmodium falciparum is a protozoan parasite that causes human malaria. This parasitic infection accounts for approximately 655,000 deaths each year worldwide. Most deaths could be prevented by diagnosing and treating malaria promptly. To date, few parasite proteins have been developed into rapid diagnostic tools. We have combined a shotgun and a targeted proteomic strategy to characterize the plasma proteome of Gambian children with severe malaria (SM), mild malaria, and convalescent controls in search of new candidate biomarkers. Here we report four P. falciparum proteins with a high level of confidence in SM patients, namely, PF10_0121 (hypoxanthine phosphoribosyltransferase, pHPRT), PF11_0208 (phosphoglycerate mutase, pPGM), PF13_0141 (lactate dehydrogenase, pLDH), and PF14_0425 (fructose bisphosphate aldolase, pFBPA). We have optimized selected reaction monitoring (SRM) assays to quantify these proteins in individual patients. All P. falciparum proteins were higher in SM compared with mild cases or control subjects. SRM-based measurements correlated markedly with clinical anemia (low blood hemoglobin concentration), and pLDH and pFBPA were significantly correlated with higher P. falciparum parasitemia. These findings suggest that pHPRT is a promising biomarker to diagnose P. falciparum malaria infection. The diagnostic performance of this marker should be validated prospectively

Tenofovir disoproxil fumarate induces peripheral neuropathy and alters inflammation and mitochondrial biogenesis in the brains of mice.

Mounting evidence suggests that antiretroviral therapy (ART) drugs may contribute to the prevalence of HIV-associated neurological dysfunction. The HIV envelope glycoprotein (gp120) is neurotoxic and has been linked to alterations in mitochondrial function and increased inflammatory gene expression, which are common neuropathological findings in HIV+ cases on ART with neurological disorders. Tenofovir disproxil fumarate (TDF) has been shown to affect neurogenesis in brains of mice and mitochondria in neurons. In this study, we hypothesized that TDF contributes to neurotoxicity by modulating mitochondrial biogenesis and inflammatory pathways. TDF administered to wild-type (wt) and GFAP-gp120 transgenic (tg) mice caused peripheral neuropathy, as indicated by nerve conduction slowing and thermal hyperalgesia. Conversely TDF protected gp120-tg mice from cognitive dysfunction. In the brains of wt and gp120-tg mice, TDF decreased expression of mitochondrial transcription factor A (TFAM). However, double immunolabelling revealed that TFAM was reduced in neurons and increased in astroglia in the hippocampi of TDF-treated wt and gp120-tg mice. TDF also increased expression of GFAP and decreased expression of IBA1 in the wt and gp120-tg mice. TDF increased tumor necrosis factor (TNF) α in wt mice. However, TDF reduced interleukin (IL) 1β and TNFα mRNA in gp120-tg mouse brains. Primary human astroglia were exposed to increasing doses of TDF for 24 hours and then analyzed for mitochondrial alterations and inflammatory gene expression. In astroglia, TDF caused a dose-dependent increase in oxygen consumption rate, extracellular acidification rate and spare respiratory capacity, changes consistent with increased metabolism. TDF also reduced IL-1β-mediated increases in IL-1β and TNFα mRNA. These data demonstrate that TDF causes peripheral neuropathy in mice and alterations in inflammatory signaling and mitochondrial activity in the brain

Constant-time solution to the Global Optimization Problem using Bruschweiler's ensemble search algorithm

A constant-time solution of the continuous Global Optimization Problem (GOP) is obtained by using an ensemble algorithm. We show that under certain assumptions, the solution can be guaranteed by mapping the GOP onto a discrete unsorted search problem, whereupon Bruschweiler's ensemble search algorithm is applied. For adequate sensitivities of the measurement technique, the query complexity of the ensemble search algorithm depends linearly on the size of the function's domain. Advantages and limitations of an eventual NMR implementation are discussed.Comment: 14 pages, 0 figure

Exact results on spin dynamics and multiple quantum dynamics in alternating spin-1/2 chains with XY-Hamiltonian at high temperatures

We extend the picture of a transfer of nuclear spin-1/2 polarization along a homogeneous one-dimensional chain with the XY-Hamiltonian to the inhomogeneous chain with alternating nearest neighbour couplings and alternating Larmor frequencies. To this end, we calculate exactly the spectrum of the spin-1/2 XY-Hamiltonian of the alternating chain with an odd number of sites. The exact spectrum of the XY-Hamiltonian is also applied to study the multiple quantum (MQ) NMR dynamics of the alternating spin-1/2 chain. MQ NMR spectra are shown to have the MQ coherences of zero and $\pm$ second orders just as in the case of a homogeneous chain. The intensities of the MQ coherences are calculated.Comment: 10 pages, 4 figure

Variability in spatial distribution of mineral phases in the Lower Bowland Shale, UK, from the mm- to μm-scale: quantitative characterization and modelling

The microstructure of a highly laminated Lower Bowland Shale sample is characterized at the micron-to millimeter scale, to investigate how such characterization can be utilized for microstructure-based modelling of the shale's geomechanical behavior. A mosaic of scanning electron microscope (SEM) back-scattered electron (BSE) images was studied. Mineral and organic content and their anisotropy vary between laminae, with a high variability in fracturing and multi-micrometer aggregates of feldspars, carbonates, quartz and organics. The different microstructural interface types and heterogeneities were located and quantified, demonstrating the microstructural complexity of the Bowland Shale, and defining possible pathways for fracture propagation. A combination of counting-box, dispersion, covariance and 2D mapping approaches were used to determine that the total surface of each lamina is 3 to 11 times larger than the scale of heterogeneities relative to mineral proportion and size. The dispersion approach seems to be the preferential technique for determining the representative elementary area (REA) of phase area fraction for these highly heterogeneous large samples, supported by 2D quantitative mapping of the same parameter. Representative microstructural models were developed using Voronoï tessellation using these characteristic scales. These models encapsulate the microstructural features required to simulate fluid flow through these porous Bowland Shales at the mesoscale

Engaging adolescents in using online patient portals

IMPORTANCE: Many health care systems offer adolescents access to health information through online patient portals, but few studies have explored how to engage adolescents in using and benefiting from online portals. OBJECTIVE: To determine how US children\u27s hospitals have attempted to encourage adolescent portal use, barriers to engaging adolescents, and ideal future goals for engagement. DESIGN, SETTING, AND PARTICIPANTS: This qualitative study performed structured qualitative interviews with informatics administrators from children\u27s hospitals across the US between February and July 2022. Informatics administrators were employed by US health care systems that managed a children\u27s hospital with at least 50 dedicated pediatrics beds. Data analysis was performed from November 2022 to January 2023. MAIN OUTCOMES AND MEASURES: This study used thematic analysis of (1) current steps that health care systems had taken to engage adolescents in using their online patient portals and (2) barriers to engaging adolescents and ideal future goals and outcomes of engagement. RESULTS: Among 58 total interviews with 65 informatics administrators who represented 63 hospitals across 58 health care systems, 6 themes of approaches to engaging adolescents in portal use were identified: (1) promoting and educating adolescents about portal enrollment, (2) establishing workflows to support enrollment, (3) seeking and incorporating feedback, (4) creating a culture or environment supporting engagement, (5) increasing portal utility, and (6) limited efforts. Barriers to engaging adolescents in portal use related to either (1) stakeholder investment, interest, and capabilities or (2) intersecting technical, ethical, and legal factors. Participants identified 4 ideal future efforts to engage adolescents: (1) develop adaptable private means of communication with adolescents, (2) use adolescent-centric user design, (3) enhance promotion and education about portal use, and (4) simplify and adapt workflows to encourage enrollment. Participants described 3 ideal outcomes of this future engagement: (1) provide education about current health, (2) prepare for transition to adulthood, and (3) improve digital health education of adolescents. CONCLUSIONS AND RELEVANCE: In this qualitative study of informatics administrators, children\u27s hospitals across the US were found to have varying degrees of efforts to engage adolescents in using their portals. Most of these efforts focused on supporting adolescent enrollment, but fewer efforts focused on making the portal useful and interesting to adolescents

Morning versus Afternoon Body Mass in Free-Living or Controlled Euhydration

The standard protocol to assess hydration status is by measuring body mass in the early morning without controlling fluid intake. However, obtaining first-morning body mass is not necessarily feasible for many situations, for example, most physical activities take place in the afternoon. Thus, first-morning body mass might not be practical to assess hydration status. PURPOSE: To investigate first-morning body mass versus afternoon body mass in free- living and controlled euhydration. METHODS: 9 males (age: 21 ± 2; mass: 79.7 ± 17.8 kg) and 5 females (age: 22 ± 2; mass: 60.5 ± 13.6 kg) visited the laboratory in the morning (7:00-9:00am) and afternoon (2:00-4:00pm) for six days to measure their nude body mass and urine specific gravity (USG). Participants were in the free-living (FL) condition for the first three consecutive days, and then in a euhydrated (EUH) state (USGRESULTS: There were no interactions between FL and EUH with morning and afternoon in USG (Morning-FL, 1.017±0.005; Afternoon-FL, 1.012±0.006; Morning-EUH, 1.011±0.004; Afternoon-EUH, 1.007±0.004; p=0.390). No statistically significant differences were found between morning and afternoon in both FL and EUH controlled (Morning-FL, 72.7±18.3 kg; Afternoon-FL, 72.0±18.1 kg; Morning-EUH, 72.9±18.1 kg; Afternoon-EUH, 73.1±18.1 kg, p=0.661). CONCLUSION: There is no difference between morning and afternoon body mass, regardless of the hydration status. This means that first morning body mass is no more, or less, accurate than afternoon