Modelling the distribution of health related quality of life of advancedmelanoma patients in a longitudinal multi-centre clinical trial using M-quantile random effects regression

Health-related quality of life assessment is important in the clinical evaluation of patients with metastatic disease that may offer useful information in understanding the clinical effectiveness of a treatment. To assess if a set of explicative variables impacts on the health-related quality of life, regression models are routinely adopted. However, the interest of researchers may be focussed on modelling other parts (e.g. quantiles) of this conditional distribution. In this paper, we present an approach based on quantile and M-quantile regression to achieve this goal. We applied the methodologies to a prospective, randomized, multi-centre clinical trial. In order to take into account the hierarchical nature of the data we extended the M-quantile regression model to a three-level random effects specification and estimated it by maximum likelihood

Impact of monotherapy on HIV-1 reservoir, immune activation, and co-infection with Epstein-Barr virus

Abstract Objectives Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear. Methods This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study. Markers of HIV-1 reservoir (HIV-1 DNA and intracellular HIV-1 RNA) were quantified by real-time PCR. Markers of T-(CD3(+)CD8(+)CD38(+)) and B-(CD19(+)CD80/86(+) and CD19(+)CD10-CD21(low)CD27(+)) cell activation were evaluated by flow cytometry. Plasma levels of microbial translocation markers were quantified by real-time PCR (16S ribosomal DNA and mitochondrial [mt] DNA) or by ELISA (LPS and sCD14). EBV was typed and quantified by multiplex real-time PCR. Results At baseline, no differences were found between mART and cART groups. Three (10%) mART-treated patients had a virological failure vs none in the cART group. Levels of HIV-1 DNA, intracellular HIV-1 RNA and EBV-DNA remained stable in the mART group, while decreased significantly in the cART group. Percentages of T-and B-activated cells significantly increased in the mART-treated patients, while remained at low levels in the cART-treated ones (p = 0.014 and p<0.001, respectively). Notably, levels of mtDNA remained stable in the cART group, but significantly rose in the mART one (p<0.001). Conclusions Long-term mART is associated with higher levels of T-and B-cell activation and, conversely to cART, does not reduce the size of HIV-1 reservoir and EBV co-infection

Self-efficacy for coping. Utility of the Cancer behavior inventory (Italian) for use in palliative care

Background: Newer models of palliative and supportive cancer care view the person as an active agent in managing physical and psychosocial challenges. Therefore, personal efficacy is an integral part of this model. Due to the lack of instruments in Italian to assess coping self-efficacy, the present study included the translation and validation of the Italian version of the Cancer Behavior Inventory-Brief (CBI-B/I) and an initial analysis of the utility of self-efficacy for coping in an Italian sample of palliative care patients. Methods: 216 advanced cancer patients who attended palliative care clinics were enrolled. The CBI-B/I was administered along with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the Mini Mental Adjustment to Cancer Scale (Mini-MAC), the Cancer Concerns Checklist (CCL), and the Hospital Anxiety and Depression Scale (HADS). The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ratings of functional capacity were completed by physicians. Results: Factor analysis confirmed that the structure of the CBI-B/I was consistent with the English version. Internal consistency reliability and significant correlations with the EORTC QLQ-C30, Mini-MAC, and HADS supported the concurrent validity of the CBI-B/I. Differences in CBI-B/I scores for high versus low levels of the CCL and ECOG-PS supported the clinical utility of the CBI-B/I. Conclusions: The CBI-B/I has strong psychometric properties and represents an important addition to newer model of palliative and supportive care. In order to improve clinical practice, the CBI-B/I could be useful in identifying specific self-efficacy goals for coping in structured psychosocial intervention

The EMAS Registration of the Livenza Furniture District in the Province of Pordenone (Italy)

Abstract: One of the most important manufacturing areas of the Friuli Venezia Giulia region is the territory close to Pordenone, the Livenza furniture district. This industrial district, consisting of industries of wood, wood and cork products, furniture, straw articles, and weave materials, located in 11 municipalities of that area, was the \ufb01rst Italian district to obtain the Eco-Management and Audit Scheme (EMAS) Registration in 2006. Data and information from a questionnaire compiled by more than 100 \ufb01rms and 11 municipalities of the district were used to draw up the territorial environmental analysis (TEA). For the EMAS registration renewal, obtained in 2016, the TEA was updated by reviewing the methodology of the environmental impact evaluation: the ecological footprint(EF)wascomparedwiththecarryingcapacity(CC)ofthatarea. Theresultsputinlightthat theEFwasgreaterthantheCC.Severalactionsforreducingtheenvironmentalimpactsofthedistrict activities were highlighted

The EMAS Recognition of the Livenza Furniture District in the Province of Pordenone (Italy)

The EC Regulation No 761/2001, known as EMAS II, provided the possibility of obtaining the EMAS recognition also by industrial districts. As a consequence, the Livenza furniture district obtained the EMAS recognition in 2006 as the first industrial district in Italy. The Livenza district includes several manufacturing enterprises which carry out their activity in 11 municipalities of the province of Pordenone, Italy. Industries of wood, wood and cork products, straw articles, weave materials and furniture take part in the district. A Territorial Environmental Analysis was drawn up to obtain the recognition, by collecting data and information from questionnaires compiled by more than 100 firms and by the 11 municipalities of the district. For the EMAS registration renewal, obtained by the district in 2016, the Territorial Environmental Analysis was updated by revising in particular the methodology of evaluation of environmental impacts. More specifically, Ecological Footprint (EF) (that is, the quantitative evaluation of consumption of raw materials and energy and of waste production) was compared with Carrying Capacity (CC) (that is, the quantitative evaluation of the area able to assure the availability of the resources required and to absorb waste produced). In this way, it was possible to put in light that the EF of the district is much greater than the corresponding CC. The main actions which might be chosen to reduce EF have been pinpointed, with the aim of warranting a better sustainability of the district activities

Premature aging and immune senescence in HIV-infected children

Objective: Several pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV. Design: Seventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0\u20135 years, were studied for biological aging and immune senescence. Methods: Telomere length and T-cell receptor rearrangement excision circle levels were quantified in peripheral blood cells by real-time PCR. CD4+ and CD8+ cells were analysed for differentiation, senescence, and activation/exhaustion markers by flow cytometry. Results: Telomere lengths were significantly shorter in HIV+ than in HEU and HUU children (overall, P < 0.001 adjusted for age); HIV+ ART-naive (42%) children had shorter telomere length compared with children on ART (P = 0.003 adjusted for age). T-cell receptor rearrangement excision circle levels and CD8+ recent thymic emigrant cells (CD45RA+CD31+) were significantly lower in the HIV+ than in control groups (overall, P = 0.025 and P = 0.005, respectively). Percentages of senescent (CD28-CD57+), activated (CD38+HLA-DR+), and exhausted (PD1+) CD8+ cells were significantly higher in HIV+ than in HEU and HUU children (P = 0.004, P < 0.001, and P < 0.001, respectively). Within the CD4+ cell subset, the percentage of senescent cells did not differ between HIV+ and controls, but programmed cell death receptor-1 expression was upregulated in the former. Conclusions: HIV-infected children exhibit premature biological aging with accelerated immune senescence, which particularly affects the CD8+ cell subset. HIV infection per se seems to influence the aging process, rather than exposure to ART for prophylaxis or treatmen

Effects of Microencapsulated Ferulic Acid or Its Prodrug Methyl Ferulate on Neuroinflammation Induced by Muramyl Dipeptide

Ferulic acid (Fer) is known for its antioxidant and anti-inflammatory activities, which are possibly useful against neurodegenerative diseases. Despite the ability of Fer to permeate the brain, its fast elimination from the body does not allow its therapeutic use to be optimized. The present study proposes the preparation and characterization of tristearin- or stearic acid-based solid lipid microparticles (SLMs) as sustained delivery and targeting systems for Fer. The microparticles were produced by conventional hot emulsion techniques. The synthesis of the methyl ester of Fer (Fer-Me) allowed its encapsulation in the SLMs to increase. Fer-Me was hydrolyzed to Fer in rat whole blood and liver homogenate, evidencing its prodrug behavior. Furthermore, Fer-Me displayed antioxidant and anti-inflammatory properties. The amount of encapsulated Fer-Me was 0.719 +/- 0.005% or 1.507 +/- 0.014% in tristearin or stearic acid SLMs, respectively. The tristearin SLMs were able to control the prodrug release, while the stearic acid SLMs induced a significant increase of its dissolution rate in water. Jointly, the present results suggest that the tristearin SLMs loaded with Fer-Me could be a potential formulation against peripheral neuropathic pain; conversely, the stearic acid SLMs could be useful for Fer-Me uptake in the brain after nasal administration of the formulation

Immune senescence and immune activation in elderly colorectal cancer patients

In our previous study, we found that low thymic output and short telomere length were associated with a higher risk of tumor in elderly cancer patients. Here, we aimed to examine in depth the impact of immunological and biological senescence and immune activation on disease outcome in elderly patients with colorectal cancer (CRC).Peripheral blood samples from 81 CRC patients were studied for immune activation, immune senescence and recent thymic emigrant (RTE) CD4 and CD8 cells by flow cytometry. T-cell receptor rearrangement excision circle (TREC) levels and telomere lengths were measured by real-time PCR. Plasma levels of microbial translocation markers, LPS and sCD14, were quantified by ELISA. While TREC levels and telomere length were not prognostic of disease outcome, high percentages of immune senescent and immune activated CD8 cells were associated with a higher risk of a negative event (relapse, progression, or death) in all studied patients and disease relapse in I-Ill staged patients. Levels of sCD14 and LPS were higher in patients who will experience a negative event than in patients who will not. In conclusion, in elderly CRC patients higher immunological senescence and immune activation negatively impact the disease outcome; how these characteristics influence the antineoplastic treatments remains to be investigated

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

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