Type 2 diabetes in children and adolescents: literature review

OBJECTIVE: the objective of this manuscript was to perform a critical review of epidemiology, pathophysiology, diagnosis e treatment of T2DM in youth. SOURCES OF DATA: this review is based on the relevant literature published. The sources available for the authors were integrated with sources identified through Medline database. The key words used for searching were Type 2 Diabetes in the Youth in the last ten years. SUMMARY OF THE FINDINGS: the pathophysiology (altered beta-cell function and insulin resistance) of T2DM in youth is similar to adult's pathophysiology. Familiar Type 2 diabetes history, presence of obesity, acanthosis nigricans, high fasting plasma C-peptide levels and absence of islet-cell auto-antibodies are important clues to diagnostic the T2DM in youth. Five to 25% of these patients can present ketosis at diagnosis. Insulin therapy can be discontinued during the evolution. Compliance to diet and an exercise program essential aspects of the treatment of adolescents. CONCLUSION: as obesity in the young is currently increasing in several developed or developing countries, T2DM in the youth can be consider an emergent problem also in our population.OBJETIVO: análise crítica dos estudos sobre a epidemiologia, fisiopatologia, diagnóstico e tratamento do DM2 no jovem. MÉTODOS: revisão da literatura nos últimos 10 anos, através de pesquisa no banco de dados Medline, utilizando os termos diabetes do tipo 2 no jovem. RESULTADOS: a fisiopatologia do DM2 no jovem é semelhante à do adulto, e compreende tanto a resistência à ação da insulina como uma alteração na função da célula beta-pancreática. O antecedente familiar para DM2, a presença de obesidade, a acanthosis nigricans, o peptídeo C de jejum superior a 0,6 ng/ml, a ausência de auto-anticorpos antiilhotas pancreáticas, em combinações variáveis, são pontos importantes para o diagnóstico desse tipo de DM. Cinco a 25% dos jovens com esse tipo de DM podem apresentar cetoacidose no diagnóstico. Nesses pacientes, o tratamento inicial com insulina é possível de ser descontinuado durante a evolução. A aderência à dieta e ao exercício físico são os elementos mais importantes do tratamento destes adolescentes. CONCLUSÃO: como a obesidade nos jovens tem aumentado, tanto em países industrializados como nos países em industrialização, o DM2 no jovem pode ser considerado um problema emergente também na nossa população.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Centro de DiabetesUNIFESP, EPM, Centro de DiabetesSciEL

Endothelial cells, endoplasmic reticulum stress and oxysterols

Oxysterols are bioactive lipids that act as regulators of lipid metabolism, inflammation, cell viability and are involved in several diseases, including atherosclerosis. Mounting evidence linked the atherosclerosis to endothelium dysfunction; in fact, the endothelium regulates the vascular system with roles in processes such as hemostasis, cell cholesterol, hormone trafficking, signal transduction and inflammation. Several papers shed light the ability of oxysterols to induce apoptosis in different cell lines including endothelial cells. Apoptotic endothelial cell and endothelial denudation may constitute a critical step in the transition to plaque erosion and vessel thrombosis, so preventing the endothelial damaged has garnered considerable attention as a novel means of treating atherosclerosis. Endoplasmic reticulum (ER) is the site where the proteins are synthetized and folded and is necessary for most cellular activity; perturbations of ER homeostasis leads to a condition known as endoplasmic reticulum stress. This condition evokes the unfolded protein response (UPR) an adaptive pathway that aims to restore ER homeostasis. Mounting evidence suggests that chronic activation of UPR leads to cell dysfunction and death and recently has been implicated in pathogenesis of endothelial dysfunction. Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation, maintaining basal levels of autophagic activity it is critical for cell survival. Several evidence suggests that persistent ER stress often results in stimulation of autophagic activities, likely as a compensatory mechanism to relieve ER stress and consequently cell death. In this review, we summarize evidence for the effect of oxysterols on endothelial cells, especially focusing on oxysterols-mediated induction of endoplasmic reticulum stress

A Statistical Analysis of Supersymmetric Dark Matter in the MSSM after WMAP

We study supersymmetric dark matter in the general flavor diagonal MSSM by means of an extensive random scan of its parameter space. We find that, in contrast with the standard mSUGRA lore, the large majority of viable models features either a higgsino or a wino-like lightest neutralino, and yields a relic abundance well below the WMAP bound. Among the models with neutralino relic density within the WMAP range, higgsino-like neutralinos are still dominant, though a sizeable fraction of binos is also present. In this latter case, relic density suppression mechanisms are shown to be essential in order to obtain the correct neutralino abundance. We then carry out a statistical analysis and a general discussion of neutralino dark matter direct detection and of indirect neutralino detection at neutrino telescopes and at antimatter search experiments. We point out that current data exclude only a marginal portion of the viable parameter space, and that models whose thermal relic abundance lies in the WMAP range will be significantly probed only at future direct detection experiments. Finally, we emphasize the importance of relic density enhancement mechanisms for indirect detection perspectives, in particular at future antimatter search experiments.Comment: 39 pages, 25 figure

The Role of Antimatter Searches in the Hunt for Supersymmetric Dark Matter

We analyze the antimatter yield of supersymmetric (SUSY) models with large neutralino annihilation cross sections. We introduce three benchmark scenarios, respectively featuring bino, wino and higgsino-like lightest neutralinos, and we study in detail the resulting antimatter spectral features. We carry out a systematic and transparent comparison between current and future prospects for direct detection, neutrino telescopes and antimatter searches. We demonstrate that often, in the models we consider, antimatter searches are the only detection channel which already constrains the SUSY parameter space. Particularly large antiprotons fluxes are expected for wino-like lightest neutralinos, while significant antideuteron fluxes result from resonantly annihilating binos. We introduce a simple and general recipe which allows to assess the visibility of a given SUSY model at future antimatter search facilities. We provide evidence that upcoming space-based experiments, like PAMELA or AMS, are going to be, in many cases, the unique open road towards dark matter discovery.Comment: 34 pages, 18 figures; V2: misprints in the labels of fig. 2,3 and 5 correcte

Status of the VERITAS Observatory

VERITAS, an Imaging Atmospheric Cherenkov Telescope (IACT) system for gammma-ray astronomy in the GeV-TeV range, has recently completed its first season of observations with a full array of four telescopes. A number of astrophysical gamma-ray sources have been detected, both galactic and extragalactic, including sources previously unknown at TeV energies. We describe the status of the array and some highlight results, and assess the technical performance, sensitivity and shower reconstruction capabilities.Comment: Submitted to Proceedings of "4th Heidelberg International Symposium on High Energy Gamma-Ray Astronomy 2008

The LISA pathfinder mission

ISA Pathfinder (LPF), the second of the European Space Agency's Small Missions for Advanced Research in Technology (SMART), is a dedicated technology validation mission for future spaceborne gravitational wave detectors, such as the proposed eLISA mission. LISA Pathfinder, and its scientific payload - the LISA Technology Package - will test, in flight, the critical technologies required for low frequency gravitational wave detection: it will put two test masses in a near-perfect gravitational free-fall and control and measure their motion with unprecedented accuracy. This is achieved through technology comprising inertial sensors, high precision laser metrology, drag-free control and an ultra-precise micro-Newton propulsion system. LISA Pathfinder is due to be launched in mid-2015, with first results on the performance of the system being available 6 months thereafter. The paper introduces the LISA Pathfinder mission, followed by an explanation of the physical principles of measurement concept and associated hardware. We then provide a detailed discussion of the LISA Technology Package, including both the inertial sensor and interferometric readout. As we approach the launch of the LISA Pathfinder, the focus of the development is shifting towards the science operations and data analysis - this is described in the final section of the paper

Sub-femto-g free fall for space-based gravitational wave observatories: LISA pathfinder results

We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2 ± 0.1 fm s−2/√Hz or (0.54 ± 0.01) × 10−15 g/√Hz, with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8 ± 0.3) fm/√Hz, about 2 orders of magnitude better than requirements. At f ≤ 0.5 mHz we observe a low-frequency tail that stays below 12 fm s−2/√Hz down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA

VERITAS Observations of the gamma-Ray Binary LS I +61 303

LS I +61 303 is one of only a few high-mass X-ray binaries currently detected at high significance in very high energy gamma-rays. The system was observed over several orbital cycles (between September 2006 and February 2007) with the VERITAS array of imaging air-Cherenkov telescopes. A signal of gamma-rays with energies above 300 GeV is found with a statistical significance of 8.4 standard deviations. The detected flux is measured to be strongly variable; the maximum flux is found during most orbital cycles at apastron. The energy spectrum for the period of maximum emission can be characterized by a power law with a photon index of Gamma=2.40+-0.16_stat+-0.2_sys and a flux above 300 GeV corresponding to 15-20% of the flux from the Crab Nebula.Comment: accepted for publication in The Astrophysical Journa

VERITAS Observations of the BL Lac Object 1ES 1218+304

The VERITAS collaboration reports the detection of very-high-energy (VHE) gamma-ray emission from the high-frequency-peaked BL Lac object 1ES 1218+304 located at a redshift of z=0.182. A gamma-ray signal was detected with high statistical significance for the observations taken during several months in the 2006-2007 observing season. The photon spectrum between ~160 GeV and ~1.8 TeV is well described by a power law with an index of Gamma = 3.08 +/- 0.34(stat) +/- 0.2(sys). The integral flux above 200 GeV corresponds to ~6% of that of the Crab Nebula. The light curve does not show any evidence for VHE flux variability. Using lower limits on the density of the extragalactic background light (EBL) in the near-IR to mid-IR we are able to limit the range of intrinsic energy spectra for 1ES 1218+304. We show that the intrinsic photon spectrum is harder than a power law with an index of Gamma = 2.32 +/- 0.37. When including constraints from the spectra of 1ES 1101-232 and 1ES 0229+200, the spectrum of 1ES 1218+304 is likely to be harder than Gamma = 1.86 +/- 0.37.Comment: Submitted to Proceedings of "4th Heidelberg International Symposium on High Energy Gamma-Ray Astronomy 2008

Beyond the required LISA free-fall performance: new LISA pathfinder results down to 20 μHz

In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20  μHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05)  fm s^{-2}/sqrt[Hz] above 2 mHz and (6±1)×10  fm s^{-2}/sqrt[Hz] at 20  μHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency