Association therapy as a prognostic factor in deep fungal infection complicating oncohaematological diseases.

A group of 31 oncohaemopathic patients (17 male, mean age 44 +/- 6 years), diagnosed as having primary deep fungal infection involving the lungs, were retrospectively evaluated. When infection was suspected on a clinical basis the major associated risks for death were the duration of bone marrow aplasia (12 +/- 7 versus 21 +/- 6 days, P < 0.001), increase in white blood cells and, in particular, prolonged granulocytopenia (11 +/- 5 versus 24 +/- 8 days, P < 0.001) when survivors were compared with patients, who died. Our therapeutic empirical approach was based on the association of i.v. amphotericin B, 1 mg kg-1 day-1, with oral 5-fluorocytosine (5-FC) 150 mg kg-1 day-1. Only 9 subjects received combination therapy for more than 7 days. For majority of them, oral 5-FC was interrupted because of altered compliance or sustained liver damage. A chi 2 test for independent parameters showed (P = 0.0021) a concentration of deaths among patients who received amphotericin B alone (15/22); none of the patients treated with amphotericin B + 5-FC (9 cases) died. Results generally suggest that a more favourable outcome was statistically associated with empirical antifungal combination therapy in deep fungal infection, although both treatment regimens showed effectiveness in terms of survival. Nevertheless the low 5-FC compliance and the small sample do not indicate the safe use of this drug in a large population

Visualisation of Avogadro’s Number

Con motivo de la redefinición de la constante de Avogadro, se presenta una breve historia y algunas reflexiones didácticas sobre su magnitud. Se revisan algunas analogías y se sugieren otras para ayudar a visualizar el alcance de su magnitud y se evalúa su utilidad. Estas analogías se enmarcan en el contexto docente de los cursos primero y segundo de las titulaciones en diversas disciplinas científicas y técnicas. Su efectividad se discute por primera vez sobre la base de un cuestionario realizado por los estudiantes correspondientes. Los resultados sugieren que los modelos más útiles, siguiendo la opinión de los estudiantes, son aquellos relacionados con ítems más sustanciales, por ejemplo, neuronas, individuos, planetas, por encima de analogías sobre construcciones geométricas. Podemos concluir, en contraste el pensamiento actual, que las descripciones visuales no siempre son las más ventajosas.On the occasion of the redefinition of the Avogadro constant, a brief history and some didactic reflections on its magnitude are presented. Some analogies are reviewed and others are suggested to help visualize the extent of its magnitude, and their usefulness is assessed. These analogies are set in the teaching context of the first and second courses of the degrees in several scientific and technic disciplines. Their effectiveness is discussed for the first time on the basis of a questionnaire filled by the corresponding students. The suggestions for educating and learning are that the most helpful models, following the opinion of the students, are those related to more substantial items, for example, neurons, individuals, planets, above analogies on geometric constructions. Challenging current thought, pictorial descriptions are not all the times so advantageousCiencias Experimentale

Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study

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Automated Large-Scale Production of Paclitaxel Loaded Mesenchymal Stromal Cells for Cell Therapy Applications

Mesenchymal stromal cells (MSCs) prepared as advanced therapies medicinal products (ATMPs) have been widely used for the treatment of different diseases. The latest developments concern the possibility to use MSCs as carrier of molecules, including chemotherapeutic drugs. Taking advantage of their intrinsic homing feature, MSCs may improve drugs localization in the disease area. However, for cell therapy applications, a significant number of MSCs loaded with the drug is required. We here investigate the possibility to produce a large amount of Good Manufacturing Practice (GMP)-compliant MSCs loaded with the chemotherapeutic drug Paclitaxel (MSCs-PTX), using a closed bioreactor system. Cells were obtained starting from 13 adipose tissue lipoaspirates. All samples were characterized in terms of number/viability, morphology, growth kinetics, and immunophenotype. The ability of MSCs to internalize PTX as well as the antiproliferative activity of the MSCs-PTX in vitro was also assessed. The results demonstrate that our approach allows a large scale expansion of cells within a week; the MSCs-PTX, despite a different morphology from MSCs, displayed the typical features of MSCs in terms of viability, adhesion capacity, and phenotype. In addition, MSCs showed the ability to internalize PTX and finally to kill cancer cells, inhibiting the proliferation of tumor lines in vitro. In summary our results demonstrate for the first time that it is possible to obtain, in a short time, large amounts of MSCs loaded with PTX to be used in clinical trials for the treatment of patients with oncological diseases

Acute kidney injury in a preterm infant homozygous for the C3435T polymorphism in the ABCB1 gene given oral morphine

A 34-week infant born from a mother with a history of drug abuse developed neonatal abstinence syndrome (NAS) in the first hours of life. Urine drug screening was positive for cocaine and heroin. The infant developed acute kidney injury and bilateral hydronephrosis while receiving oral morphine for control of NAS. Cessation of morphine therapy and urinary catheterization resulted in a rapid and complete resolution of the symptoms. Our patient was homozygous for the C3435T polymorphism in the ABCB1 gene, a polymorphism previously associated with impaired P-glycoprotein activity. We hypothesize that acute renal toxicity was related to accumulation of morphine within urothelial cells due to genetically determined impaired P-glycoprotein activity

Pharmacokinetics and pharmacogenetics of SSRIs during pregnancy : An observational study

Background: An involvement of selective serotonin reuptake inhibitors (SSRIs) in increasing the risk of malformations, neonatal withdrawal syndrome, has been suggested recently. Here, we aimed to investigate the contribution of individual pharmacogenetics of SSRI on infants' outcome. We also estimated the umbilical/maternal plasma SSRI concentration ratio in the pregnant women still on SSRI therapy at the time of delivery. Methods: Thirty-four pregnant women, referred to our hospital from January 2011 to July 2015, who were given SSRIs in the third trimester, and related children, were considered. The umbilical/maternal plasma SSRI concentration ratio was estimated in 15 mothers still on SSRI therapy at the time of delivery. For patients with pharmacokinetic analyses, blood samples were collected for pharmacogenetic analyses. Results: Nineteen newborns presented clinical signs possibly related to drug toxicity. A high umbilical/maternal plasma ratio of SSRI was observed in 10 of the 15 evaluated newborns. Five mothers were intermediate metabolizers and 1 a poor metabolizer for the major CYP enzyme involved in pharmacokinetic pathway. Conclusions: Individualized psychopharmacologic treatment that takes into account the mother's exposure to SSRI concentrations and eventually her genetic background may become the standard of care to maximize drug benefit and minimize risks to the newborn

The future of Cybersecurity in Italy: Strategic focus area

This volume has been created as a continuation of the previous one, with the aim of outlining a set of focus areas and actions that the Italian Nation research community considers essential. The book touches many aspects of cyber security, ranging from the definition of the infrastructure and controls needed to organize cyberdefence to the actions and technologies to be developed to be better protected, from the identification of the main technologies to be defended to the proposal of a set of horizontal actions for training, awareness raising, and risk management