Is ALT control really necessary for routine ART monitoring in resource poor settings?

2006 AIDS Conference in Toront

Loss of correlation between HIV viral load and CD4+ T-cell counts in HIV/HTLV-1 co-infection in treatment naive Mozambican patients

Seven hundred and four HIV-1/2-positive, antiretroviral therapy (ART) naïve patients were screened for HTLV-1 infection. Antibodies to HTLV-1 were found in 32/704 (4.5%) of the patients. Each co-infected individual was matched with two HIV mono-infected patients according to World Health Organization clinical stage, age +/-5 years and gender. Key clinical and laboratory characteristics were compared between the two groups. Mono-infected and co-infected patients displayed similar clinical characteristics. However, co-infected patients had higher absolute CD4+ T-cell counts (P = 0.001), higher percentage CD4+ T-cell counts (P < 0.001) and higher CD4/CD8 ratios (P < 0.001). Although HIV plasma RNA viral loads were inversely correlated with CD4+ T-cell-counts in mono-infected patients (P < 0.0001), a correlation was not found in co-infected individuals (P = 0.11). Patients with untreated HIV and HTLV-1 co-infection show a dissociation between immunological and HIV virological markers. Current recommendations for initiating ART and chemoprophylaxis against opportunistic infections in resource-poor settings rely on more readily available CD4+ T-cell counts without viral load parameters. These guidelines are not appropriate for co-infected individuals in whom high CD4+ T-cell counts persist despite high HIV viral load states. Thus, for co-infected patients, even in resource-poor settings, HIV viral loads are likely to contribute information crucial for the appropriate timing of ART introduction

Anomalous cooling of the massive white dwarf in U Geminorum following a narrow dwarf nova outburst

We obtained Hubble GHRS medium resolution (G160M grating) phase-resolved spectroscopic observations of the prototype dwarf nova U Geminorum during dwarf nova quiescence, 13 days and 61 days following the end of a narrow outburst. The spectral wavelength ranges were centered upon three different line regions: N V (1238\AA, 1242\AA), Si III (1300\AA) and He II (1640\AA). All of the quiescent spectra at both epochs are dominated by absorption lines and show no emission features. The Si III and He II absorption line velocities versus orbital phase trace the orbital motion of the white dwarf but the N~V absorption velocities appear to deviate from the white dwarf motion. We confirm our previously reported low white dwarf rotational velocity, V sin i= 100 km/s. We obtain a white dwarf orbital velocity semi-amplitude K1=107 km/s. Using the gamma-velocity of Wade (1981) we obtain an Einstein redshift of 80.4 km/s and hence a carbon core white dwarf mass of ~1.1 Msun. We report the first subsolar chemical abundances of C and Si for U Gem with C down by 0.05 with respect to the Sun, almost certainly a result of C depletion due to thermonuclear processing. This C-depletion is discussed within the framework of a weak TNR, contamination of the secondary during the common envelope phase, and mixing of C-depleted white dwarf gas with C-depleted matter deposited during a dwarf nova event. Remarkably the Teff of the white dwarf 13 days after outburst is only 32,000K, anomalously cooler than previous early post-outburst measurements. Extensive cooling during an extraordinarily long (210 days) quiescence followed by accretion onto an out-of-equilibrium cooled degenerate could explain the lower Teff.Comment: 16 pages AAS-Latex, 4 Figures, accepted for publication in Ap

Differential effects on membrane permeability and viability of human keratinocyte cells undergoing very low intensity megasonic fields

Among different therapeutic applications of Ultrasound (US), transient membrane sonoporation (SP) - a temporary, non-lethal porosity, mechanically induced in cell membranes through US exposure - represents a compelling opportunity towards an efficient and safe drug delivery. Nevertheless, progresses in this field have been limited by an insufficient understanding of the potential cytotoxic effects of US related to the failure of the cellular repair and to the possible activation of inflammatory pathway. In this framework we studied the in vitro effects of very low-intensity US on a human keratinocyte cell line, which represents an ideal model system of skin protective barrier cells which are the first to be involved during medical US treatments. Bioeffects linked to US application at 1 MHz varying the exposure parameters were investigated by fluorescence microscopy and fluorescence activated cell sorting. Our results indicate that keratinocytes undergoing low US doses can uptake drug model molecules with size and efficiency which depend on exposure parameters. According to sub-cavitation SP models, we have identified the range of doses triggering transient membrane SP, actually with negligible biological damage. By increasing US doses we observed a reduced cells viability and an inflammatory gene overexpression enlightening novel healthy relevant strategies

Chandra High Resolution X-ray Spectroscopy of AM Her

We present the results of high resolution spectroscopy of the prototype polar AM Herculis observed with Chandra High Energy Transmission Grating. The X-ray spectrum contains hydrogen-like and helium-like lines of Fe, S, Si, Mg, Ne and O with several Fe L-shell emission lines. The forbidden lines in the spectrum are generally weak whereas the hydrogen-like lines are stronger suggesting that emission from a multi-temperature, collisionally ionized plasma dominates. The helium-like line flux ratios yield a plasma temperature of 2 MK and a plasma density 1 - 9 x10^12 cm^-3, whereas the line flux ratio of Fe XXVI to Fe XXV gives an ionization temperature of 12.4 +1.1 -1.4 keV. We present the differential emission measure distribution of AM Her whose shape is consistent with the volume emission measure obtained by multi-temperature APEC model. The multi-temperature plasma model fit to the average X-ray spectrum indicates the mass of the white dwarf to be ~1.15 M_sun. From phase resolved spectroscopy, we find the line centers of Mg XII, S XVI, resonance line of Fe XXV, and Fe XXVI emission modulated by a few hundred to 1000 km/s from the theoretically expected values indicating bulk motion of ionized matter in the accretion column of AM Her. The observed velocities of Fe XXVI ions are close to the expected shock velocity for a 0.6 M_sun white dwarf. The observed velocity modulation is consistent with that expected from a single pole accreting binary system.Comment: 6 figures, AASTEX style, accepted for publication in Ap

Free boundary problem for the role of planktonic cells in biofilm formation and development

The dynamics of biofilm lifecycle are deeply influenced by the surrounding environment and the interactions between sessile and planktonic phenotypes. Bacterial biofilms typically develop in three distinct stages: attachment of cells to a surface, growth of cells into colonies, and detachment of cells from the colony into the surrounding medium. The attachment of planktonic cells plays a prominent role in the initial phase of biofilm lifecycle as it initiates the colony formation. During the maturation stage, biofilms harbor numerous microenvironments which lead to metabolic heterogeneity. Such microniches provide conditions suitable for the growth of new species, which are present in the bulk liquid as planktonic cells and can penetrate the porous biofilm matrix. We present a 1D continuum model on the interaction of sessile and planktonic phenotypes in biofilm lifestyle which considers both the initial attachment and colonization phenomena. The model is formulated as a hyperbolic-elliptic free boundary value problem with vanishing initial value. Hyperbolic equations reproduce the transport and growth of sessile species, while elliptic equations model the diffusion and conversion of planktonic cells and dissolved substrates. The attachment is modelled as a continuous, deterministic process which depends on the concentrations of the attaching species. The growth of new species is modelled through a reaction term in the hyperbolic equations which depends on the concentration of planktonic species within the biofilm. Existence and uniqueness of solutions are discussed and proved for the attachment regime. Finally, some numerical examples show that the proposed model correctly reproduces the growth of new species within the biofilm and overcomes the ecological restrictions characterizing the Wanner-Gujer type models.Comment: 17 pages, 9 figures, preprint versio

Continuum and discrete approach in modeling biofilm development and structure: a review

The scientific community has recognized that almost 99% of the microbial life on earth is represented by biofilms. Considering the impacts of their sessile lifestyle on both natural and human activities, extensive experimental activity has been carried out to understand how biofilms grow and interact with the environment. Many mathematical models have also been developed to simulate and elucidate the main processes characterizing the biofilm growth. Two main mathematical approaches for biomass representation can be distinguished: continuum and discrete. This review is aimed at exploring the main characteristics of each approach. Continuum models can simulate the biofilm processes in a quantitative and deterministic way. However, they require a multidimensional formulation to take into account the biofilm spatial heterogeneity, which makes the models quite complicated, requiring significant computational effort. Discrete models are more recent and can represent the typical multidimensional structural heterogeneity of biofilm reflecting the experimental expectations, but they generate computational results including elements of randomness and introduce stochastic effects into the solutions