Health related quality of life outcomes in HIV-Infected patients starting different combination regimens in a randomised multinational trial: the INITIO-QoL Substudy

The health-related quality of life (HRQoL) outcomes in HIV-infected, treatment-naive patients starting different HAART regimens in a 3-year, randomized, multinational trial were compared. HRQoL was measured in a subgroup of patients enrolled in the INITIO study (153/911), using a modified version of the MOS-HIV questionnaire. The regimens compared in the INITIO trial were composed by two NRTIs (didanosine + stavudine) plus either an NNRTI (efavirenz) or a PI (nelfinavir), or both (efavirenz + nelfinavir). Primary HRQoL outcomes were Physical and Mental Health Summary scores (PHS and MHS, respectively). During follow-up, an increase of PHS score was observed in all treatment arms. The MHS score remained substantially unchanged with the four-drug combination and showed with both NNRTI- and PI-based three-drug regimens a marked trend toward improvement, which became statistically significant when a multiple imputation method was used to adjust for missing data. Overall, starting all the combination regimens compared in the INITIO study was associated with a maintained or slightly improved HRQOL status, consistently with the positive immunological and virological changes observed in the main study. The observed differences in the MHS indicate a possible HRQoL benefit associated to the use of three-drug, two-class regimens and no additional benefit for the use of four-drug, three-class regimens, confirming that three-drug, two-class regimens that include two NRTIs plus either an NNRTI or a PI should be preferred as initial treatment of HIV infection

Lipid profile during pregnancy in HIV-infected women

Purpose: We investigated the evolution of serum lipid levels in HIV-infected pregnant women and the potential effect of antiretroviral treatment during pregnancy using data from a national surveillance study. Method: Fasting lipid measurements collected during routine care in pregnancy were used, analyzing longitudinal changes and differences in lipid values at each trimester by protease inhibitors (Pls) and stavudine use. Multivariate analyses were used to control for simultaneous factors potentially leading to hyperlipidemia. Study population included 248 women. Results: Lipid values increased progressively and significantly during pregnancy: mean increases between the first and third trimesters were 141.6 mg/dL for triglycerides (p <.001), 60.8 mg/dL for total cholesterol (p <.001), 13.7 mg/dL for HDL cholesterol (p <.001), and 17.8 mg/dL for LDL cholesterol (p =.001). At all trimesters, women on PIs had significantly higher triglyceride values compared to women not on Pis. The effect of Pls on cholesterol levels was less consistent. Stavudine showed a dyslipidemic effect at first trimester only. Multivariate analyses confirmed these observations and suggested a potential role of other cofactors in the development of hyperlipidemia during pregnancy. Conclusion: The changes observed point to the need to further explore the causes and the clinical correlates of hyperlipidemia during pregnancy in women with HIV

Learning about Actions and Events in Shared NeMuS

The categorization process of information from pure data or learned in unsuper- vised artificial neural networks is still manual, especially in the labeling phase. Such a process is fundamental to knowledge representation [6], especially for symbol-based systems like logic, natural language processing and textual infor- mation retrieval. Unfortunately, applying categorization theory in large volumes of data does not lead to good results mainly because there is no generic and systematic way of categorizing such data processed by artificial neural networks and joining investigated conceptual structures. Connectionist approaches are capable of extracting information from arti- ficial neural networks, but categorizing them as symbolic knowledge have been little explored. The obstacle lies on the difficulty to find logical justification from response patterns of these networks [2]. This gets worse when considering induc- tive learning from dynamic data which is very important to Cognitive Sciences that considers categorization as a mental operation of classifying objects, actions and events [1]. We shall address the discoveries of our on-going investigation on the problem of inductively learning (IL) from dynamic data by applying a novel framework for neural-symbolic representation and reasoning called share Neural Multi-Space (NeMuS) used in the Amao system[4]. Instead of woking like traditional ap- proaches for ILP, e.g. [5], Amao uses a shared NeMuS of a give background knowledge (BK) and uses inverse unification as the generalization mechanism of a set of logically connected expressions from the Herbrand Base (HB) of BK that defines positive examples

A Carleman estimate and an energy method for a first-order symmetric hyperbolic system

For a symmetric hyperbolic system of the first order, we prove a Carleman estimate under some positivity condition concerning the coefficient matrices. Next, applying the Carleman estimate, we prove an observability L2-estimate for initial values by boundary data

Raltegravir, tenofovir, and emtricitabine in an HIV-Infected patient with HCV chronic hepatitis, NNRTI intolerance and protease inhibitors-induced severe liver toxicity

<p>Abstract</p> <p>Background</p> <p>in HIV-infected patients with HCV-related chronic hepatitis, liver impairment and drug toxicity may substantially reduce the number of possible therapeutic options.</p> <p>Case Description</p> <p>we here describe the case of an HCV-HIV coinfected woman who had repeated severe episodes of drug-related liver toxicity with indinavir, saquinavir, fosamprenavir, and darunavir, with minimal further therapeutic options left in this class. Previous treatment-limiting side effects with efavirenz and nevirapine also precluded use of non-nucleoside reverse transcriptase inhibitors. Introduction of an integrase-inhibitor regimen based on raltegravir, tenofovir, and emtricitabine allowed a prompt achievement of undetectable viral load and a substantial rise of CD4 count to high levels, with no subsequent episodes of hepatic toxicity, and no other side effects.</p> <p>Conclusions</p> <p>given the relatively common prevalence of HCV-related chronic hepatitis among people with HIV, raltegravir might represent an important alternative option for a substantial number of patients who cannot be treated with protease inhibitors or NNRTI because of drug-related hepatic toxicity.</p

Load Management with Predictions of Solar Energy Production for Cloud Data Centers

Power supply of big infrastructures is today a tremendous operational cost for providers and the expected growth of Internet traffic and services will lead to a further expansion of the computing and networking infrastructures and this, in its turn, raises also concerns in terms of sustainability. In this context, renewable energy generators can help to both reduce costs and alleviate the concerns of sustainability of big infrastructures. In this paper, we consider the case of Data Centers (DCs) composed of a few sites located in different geographical positions and powered with solar energy. Due to the intermittent nature of solar energy, different time zones and price of electricity in different locations, load management strategies are fundamental. We consider predictions of the solar energy production performed through Artificial Neural Networks and we assess the impact of predictions on load management decisions and, ultimately, on the DC performance

Architecture of Ancestral Genomic Components in the Sicilian Mastiff

The Sicilian Mastiff (or Mannara dog), is an indigenous Sicilian livestock guardian dog (LGD) breed with approximately 700 registered individuals. Formal recognition as a distinct breed was conferred by the Italian Kennel Club in 2023 and efforts to attain international recognition are ongoing. Previous studies have identified the Maremma and the Abruzzes sheepdog as the closest relative of the Sicilian Mastiff, highlighting a shared history and overlapping functional characteristics typical of LGDs. Thus, investigating the genetic makeup of the Sicilian Mastiff becomes essential to safeguarding and enhancing its cultural heritage and role in Sicilian pastoralism. In this study, the genetic investigation of 12 Sicilian Mastiffs revealed significant divergence from other breeds, while also confirming a close genetic relationship with the Maremma sheepdog. Therefore, local ancestry inference analyses were performed to identify genomic regions potentially influenced by the Maremma sheepdog, in comparison with other European and Mediterranean LGD breeds. Several genomic regions exhibited strong introgression with the Maremma sheepdog. Among the genes within highly introgressed (99th percentile) regions identified in at least three of these comparisons, several were associated with traits characteristic of LGD. These traits included behavioral attributes such as aggression towards strangers, morphological features such as drop ears, and physical attributes enhancing their guarding abilities. These findings support the hypothesis that centuries of selective pressures shaped the Sicilian Mastiff, highlighting its genetic and cultural value for pastoral communities. To explore the Sicilian Mastiff’s genetic evolution and adaptability, extensive sampling is being conducted to assess changes in its genetic variability and structure over the past decade. During this period, breeders have been encouraged to adopt more stringent and informed selection practices. This longitudinal approach aims to provide valuable insights into the impact of modern management practices on the genetic profile of the breed

Differences in Nevirapine Biotransformation as a Factor for its Sex-Dependent Dimorphic Profile of Adverse Drug Reactions

OBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity