A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

<p>Abstract</p> <p>Background</p> <p>HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed.</p> <p>Methods</p> <p>We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90^thday after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure.</p> <p>Results</p> <p>The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards.</p> <p>Conclusions</p> <p>GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.</p

Nutritional Therapy

Nutritional status is a major player in the complex management of patients affected by Covid-19 requiring intensive care unit (ICU) treatment. These represent the 20% of the hospitalized population infected by SARS-CoV2 [1]

Fluxes of radiocaesium in selected rural study sites in Russia and Ukraine

Food production and food harvesting systems common in the areas contaminated by the Chernobyl accident in Russia and Ukraine can be grouped into three major categories: collective farm produce, private farming produce and foods collected from natural ecosystems. The contribution of each of these sources to radiocaesium intake by people living in rural settlements in the mid 1990s has been estimated at two major studysites, one in each country. The collective farm system provided the smallest contribution (7–14%) to the intake of radiocaesium at both sites. Natural food was the major contributor to intake at the Russian site (83%). Whereas private farm produce was the major contributor (68%) at the Ukrainian studysite. The difference between the two sites was mainly because private milk production was stopped at the Russian site due to the contamination in 1986. A retrospective assessment of the situation 1 year after the accident shows that collective farming could have been a minor contributor to radiocaesium intake (8%), whilst private farming would have been the major contributor wherever private milk production and consumption continued. The extent to which inhabitants consume natural foods from forests has a considerable effect on their radiocaesium intake. The comparative importance of food products from natural ecosystems increases with time due to the long effective ecological half-lives of radiocaesium in unimproved pastures and forests. Estimation of the fluxes of radiocaesium from the different production and harvesting systems showed that the contribution from private farming and food harvesting from natural ecosystems may be significant, contributing 14–30% to the total fluxes of radiocaesium from an area even if the quantity of food produced in these systems is small. However, the major contributor to the flux exported from an area was the collective farming system, accounting for about 70–86% of the total

Environmental mobility of radiocaesium in the Pripyat catchment, Ukraine/Belarus

Evidence from research in the Pripyat catchment, reviewed here, indicates that under the ecological conditions prevalent in this area, radiocaesium (137Cs) is highly mobile in both river water and poorly drained organic soils. Data collected at three different spatial and temporal scales demonstrate the effects of hydrological events on 137Cs mobility. During the period 1988–1994, 137Cs contamination in some poorly drained organic soils in the Pripyat catchment and in the milk from cows grazing on these soils are generally declining much faster than the radioactive half life. However, sharp increases in levels of 137Cs in both floodplain soils and milk to 2–3 times that observed immediately after the initial deposition have been measured immediately after summer floods. The processes causing these observed changes have not yet been fully explained but the sites where enhanced 137Cs mobility has been detected are clearly associated with the spatial patterns of organic soils and river flooding

The seroconversion study of the natural history of HIV infection

Vengono descritte le caratteristiche epidemiologiche dei pazienti afferenti alla coorte dei sieroconveriti per infezione da HIV in Iatli

Tumor necrosis factor-alpha inhibition of skeletal muscle regeneration is mediated by a caspase-dependent stem cell response

Skeletal muscle is susceptible to injury following trauma, neurological dysfunction, and genetic diseases. Skeletal muscle homeostasis is maintained by a pronounced regenerative capacity, which includes the recruitment of stem cells. Chronic exposure to tumor necrosis factor-alpha (TNF) triggers a muscle wasting reminiscent of cachexia. To better understand the effects of TNF upon muscle homeostasis and stem cells, we exposed injured muscle to TNF at specific time points during regeneration. TNF exposure delayed the appearance of regenerating fibers, without exacerbating fiber death following the initial trauma. We observed modest cellular caspase activation during regeneration, which was markedly increased in response to TNF exposure concomitant with an inhibition in regeneration. Caspase activation did not lead to apoptosis and did not involve caspase-3. Inhibition of caspase activity improved muscle regeneration in either the absence or the presence of TNF, revealing a nonapoptotic role for this pathway in the myogenic program. Caspase activity was localized to the interstitial cells, which also express Sca-1, CD34, and PW1. Perturbation of PW1 activity blocked caspase activation and improved regeneration. The restricted localization of Sca-1+, CD34+, PW1+ cells to a subset of interstitial cells with caspase activity reveals a critical regulatory role for this population during myogenesis, which may directly contribute to resident muscle stem cells or indirectly regulate stem cells through cell-cell interaction