The Vineland-II in Preschool Children with Autism Spectrum Disorders: An Item Content Category Analysis

We investigated which item subsets of the Vineland-II can discriminate low-functioning preschoolers with ASD from matched peers with other neurodevelopmental disorders, using a regression analysis derived from a normative sample to account for cognitive and linguistic competencies. At variance with the typical profile, a pattern with Communication more impaired than Socialization was observed. The source of the frequently reported Socialization delay in ASD appears to be in Playing and Imitating skills only, not in other social adaptive behavior skills. The combination of item subsets Playing, Following instructions, Beginning to talk, and Speech skills provided the best discrimination between the two clinical groups. Evaluation of the Vineland-II score on item content categories is a useful procedure for a more efficient clinical description

Pain coping strategies in paediatric patients newly diagnosed with leukaemia compared with healthy peers

Objective: Children with leukaemia experience special difficulties adapting to stressful medical procedures and to the adverse effects of chemotherapy, though they can implement their coping strategies. The aims of the study were to assess whether the coping-with-pain strategies could be influenced by a child's personal and illness factors and to render possible comparisons between children with leukaemia and healthy peers. Another aim was to compare parents' and children's reports on coping strategies. Methods: A total of 125 patients (average age = 6.79 years; SD = 3.40) with acute leukaemia (lymphocytic leukaemia 90.4% and myeloid leukaemia 9.6%) and agematched healthy children with their parents were enrolled in the study. A sociodemographic questionnaire and the Waldon–Varni Pediatric Pain Coping Inventory, parent and self-report versions, were administered 1 month after diagnosis. Data regarding the therapy's side effects were recorded. Results: The comparison between proxy-reports of the two groups of parents found significant differences in terms of social support, self-cognitive instructions and catastrophising strategies. Children aged 6–10 years relied more heavily on distraction than children of other ages, using more problem-solving and self-cognitive instructions. The results indicated moderate parent–child agreement. Conclusion: Health professionals could help paediatric leukaemic patients in adopting more efficiently pain coping strategies applicable for different ages

Pain Coping Strategies in Pediatric Patients with Acute Leukemias in the First Month of Therapy: Effects of Treatments and Implications on Procedural Analgesia

Children with leukemia experience difficulties adapting to medical procedures and to the chemotherapy’s adverse effects. Study’s objectives were to identify which coping strategies could be associated with the treatments’ factors and with the dosage of sedation analgesic drugs during bone marrow aspirates. A total of 125 patients (mean = 6.79 years; standard deviation = 3.40), majority with acute lymphoblastic leukemia (90.4%) and their parents received, one month after diagnosis, the Pediatric Pain Coping Inventory. Data on the severe treatment effects and on the dosage of drugs in sedation-analgesia were also collected. An ANCOVA model (R2 = 0.25) showed that, weighing the age factor (F = 3.47; df = 3; p = 0.02), the number of episodes of fever (F = 4.78; df = 1; p = 0.03), nausea (F = 4.71; df = 1; p = 0.03) and mucositis (F = 5.81; df = 1; p = 0.02) influenced the use of distraction. Cognitive self-instructions (R2 = 0.22) were influenced by the number of hospitalizations (F = 5.14; df = 1; p = 0.03) and mucositis (F = 8.48; df = 3; p = 0.004) and by child’s age (F = 3.76; df = 3; p = 0.01). Children who sought parental support more frequently (F = 9.7; df = 2; p = 0.0001) and who tended not to succumb to a catastrophic attitude (F = 13.33; df = 2; p = 0.001) during the induction treatment phase required lower drug dosages, especially propofol. The clinical application of these results could be to encourage the use of cognitive self-instructions and search for social support

Pain Coping Strategies in Pediatric Patients with Acute Leukemias in the First Month of Therapy: Effects of Treatments and Implications on Procedural Analgesia

Children with leukemia experience difficulties adapting to medical procedures and to the chemotherapy’s adverse effects. Study’s objectives were to identify which coping strategies could be associated with the treatments’ factors and with the dosage of sedation analgesic drugs during bone marrow aspirates. A total of 125 patients (mean = 6.79 years; standard deviation = 3.40), majority with acute lymphoblastic leukemia (90.4%) and their parents received, one month after diagnosis, the Pediatric Pain Coping Inventory. Data on the severe treatment effects and on the dosage of drugs in sedation-analgesia were also collected. An ANCOVA model (R2 = 0.25) showed that, weighing the age factor (F = 3.47; df = 3; p = 0.02), the number of episodes of fever (F = 4.78; df = 1; p = 0.03), nausea (F = 4.71; df = 1; p = 0.03) and mucositis (F = 5.81; df = 1; p = 0.02) influenced the use of distraction. Cognitive self-instructions (R2 = 0.22) were influenced by the number of hospitalizations (F = 5.14; df = 1; p = 0.03) and mucositis (F = 8.48; df = 3; p = 0.004) and by child’s age (F = 3.76; df = 3; p = 0.01). Children who sought parental support more frequently (F = 9.7; df = 2; p = 0.0001) and who tended not to succumb to a catastrophic attitude (F = 13.33; df = 2; p = 0.001) during the induction treatment phase required lower drug dosages, especially propofol. The clinical application of these results could be to encourage the use of cognitive self-instructions and search for social suppor

Antiproliferative activity of 8-methoxypsoralen on DU145 prostate cancer cells under UVA and blue light

The use of photoactivatable 8-methoxypsoralen (8-MOP) as potential focal treatment towards prostate cancer cells is proposed here. Our results, obtained on isolated DNA and DU145 cells, indicate that blue light, besides UVA, is able to activate 8-MOP. When compared to UVA, blue light irradiation led to a modulation of the extent and the types of 8-MOP-DNA damage, specially cross-links, coupled to a still valuable antiproliferative effect. Our data suggest that the proapototic activity of 8-MOP is related not only to DNA damage and reactive oxygen species generation but also to the modulation of cell signalling pathways. In particular, a different activation of p38 and p44/42 mitogen-activated protein kinases was detected depending on the light wavelengths

Evolving morphology of the large-scale relativistic jets from XTE J1550−564

International audienceWe present an in-depth study of the large scale, western jet of the microquasar XTE J1550−564, based on X-ray and radio observations performed in 2002–2003. The jet is spatially resolved in both observing windows. The X-ray jet is expanding in time along the axis of the jet's propagation: we observe the formation of a tail (∼2.25 arcsec), which appears to extend backwards with an apparent velocity ∼−0.10c. The origin of this feature is discussed in the framework of scenarios of energy dissipation. A single power law adequately describes the broad-band spectra, supporting a synchrotron origin of the X-ray emission. However, a spectral break at ≈10^15 Hz is necessary in coincidence with a re-flare at 8.64 GHz in 2002 September. This finding may be indicative of emission from newly accelerated low-energy particles. The first detection of the jet is in 2001 February (F_8.64 GHz = 0.25 ± 0.09 mJy) in the flux rising phase. A phase of stable emission is followed by a rapid decay (t_decay = 167 ± 5 d). The decay at radio frequencies is significantly shorter than in X-rays (t_decay = 338 ± 14 d). We detected a high fraction (up to ∼9 per cent) of linearly polarized radiation at 4.8 and 8.6 GHz. The orientation of the electric vector is consistent with the picture of a shock-compressed magnetic field, and there are hints of variations on month-time-scales, possibly connected with the evolution of the jet structure

Wild-type wine Saccharomyces cerevisiae as a tool to evaluate the effects on eukaryotic life of locally used herbicides

Nowadays, agricultural pesticides are frequently used to avoid attacks by weeds, moulds, bacteria, insects and mice that can damage cultivars. They belong to the heterogeneous class of xenobiotics. The toxicity of these compounds on mammals is often unknown. Thanks to the high degree in the evolutionary context of generic stress responses, understanding how yeast cells respond to pesticides can contribute in elucidating toxicity mechanisms in more complex and less accessible eukaryotes. In this work, we aimed to investigate how three herbicides belonging to different classes, never tested before on eukaryotes, can affect the biological activity of enological Saccharomyces cerevisiae strains, with particular attention to cell growth, viability and ethanol production. We also evaluated the global metabolic profile of yeast cells by testing several different carbon sources and how metabolic patterns could be affected by xenobiotics. Differing from all the previously reported works, we used commercial grade herbicides, authorized for use in the central regions of Italy, in order to reproduce as far as possible the same conditions applied in the fields. At the same time, we chose, instead of a commercial strain, a wild-type S. cerevisiae strain adopted for enological applications, existing on vineyards of the same geographical areas where herbicides are used, in order to get important information also on the safety of locally produced wines

Long-term effectiveness and drug survival of golimumab in patients affected by psoriatic arthritis with cutaneous involvement

Objectives To determine the effectiveness of golimumab (GLM) in improving joint, periarticular structures and cutaneous manifestations in patients with moderate to severe psoriatic arthritis (PsA) with cutaneous psoriasis in different real-life clinical settings and 48-month drug survival.Methods Clinical and laboratory records were collected from PsA patients treated with GLM at baseline (TO) and after 6, 12, 24, 36, and 48 months of treatment. Comparisons were performed using a paired t-test or Wilcoxon test. Drug survival rates were analyzed using Kaplan-Meier estimates. p value< 0.05 was considered statistically significant.Results Data from 105 patients were collected. PsO occurred in 80% of patients and enthesitis in 78%, peripheral and axial arthritis in 63.8% and 35.3%, respectively, while erosions in 36.2%. The main comorbidities were cardiovascular diseases (31.4%) and metabolic syndrome (MetS) (19%). A statistically significant improvement in articular and cutaneous psoriasis was registered at T48 of GLM-therapy in clinical (DAPSA p <0.0001; PASI p < 0.01; BASDAI p < 0.0001) and laboratory (CRP< 0.05) indexes. Gender (p= 0.652), BMI (p = 0.655), smoking habit (p = 0.466), and line of treatment (p = 0.208) did not affect treatment efficacy nor persistence. At T48, 42% of patients discontinued GLM: the most frequent reason was an insufficient response or loss of efficacy (28.6%).Conclusion A 48-month GLM high drug persistence of PsA patients was observed in real-life, in patients presenting high disease activity, elevated prevalence of comorbidities, and more than one line of treatment at baseline. Patients' characteristics as gender, smoke, BMI, different lines of treatment, and concomitant methotrexate treatment affected treatment persistence, making GLM effective and safe in moderate-severe PsA in a long-term real-life setting

Prognostic Role of Soluble and Extracellular Vesicle-Associated PD-L1, B7-H3 and B7-H4 in Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors

The treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the advent of immune checkpoint inhibitors (ICIs). Despite encouraging results, their efficacy remains limited to a subgroup of patients. Circulating immune checkpoints in soluble (s) form and associated with extracellular vesicles (EVs) represent promising markers, especially in ICI-based therapeutic settings. We evaluated the prognostic role of PD-L1 and of two B7 family members (B7-H3, B7-H4), both soluble and EV-associated, in a cohort of advanced NSCLC patients treated with first- (n = 56) or second-line (n = 126) ICIs. In treatment-naïve patients, high baseline concentrations of sPD-L1 (>24.2 pg/mL) were linked to worse survival, whereas high levels of sB7-H3 (>0.5 ng/mL) and sB7-H4 (>63.9 pg/mL) were associated with better outcomes. EV characterization confirmed the presence of EVs positive for PD-L1 and B7-H3, while only a small portion of EVs expressed B7-H4. The comparison between biomarker levels at the baseline and in the first radiological assessment under ICI-based treatment showed a significant decrease in EV-PD-L1 and an increase in EV-B7H3 in patients in the disease response to ICIs. Our study shows that sPD-L1, sB7-H3 and sB7-H4 levels are emerging prognostic markers in patients with advanced NSCLC treated with ICIs and suggests potential EV involvement in the disease response to ICIs

Targeting PIK3CA Actionable Mutations in the Circulome: A Proof of Concept in Metastatic Breast Cancer

The study of circulating cancer-derived components (circulome) is considered the new frontier of liquid biopsy. Despite the recognized role of circulome biomarkers, their comparative molecular profiling is not yet routine. In advanced breast cancer (BC), approximately 40% of hormone-receptor-positive, HER2-negative BC cases harbor druggable PIK3CA mutations suitable for combined alpelisib/fulvestrant treatment. This pilot study investigates PIK3CA mutations in circulating tumor DNA (ctDNA), tumor cells (CTCs), and extracellular vesicles (EVs) with the aim of determining which information on molecular targetable profiling could be recollected in each of them. The in-depth molecular analysis of four BC patients demonstrated, as a proof-of-concept study, that it is possible to retrieve mutational information in the three components. Patient-specific PIK3CA mutations were found in both tissue and ctDNA and in 3/4 cases, as well as in CTCs, in the classical population (large-sized CD45−/EpCAM+/− cells), and/or in the “non-conventional” sub-population (smaller-sized CD44+/EpCAM−/CD45− cells). Consistent mutational profiles of EVs with CTCs suggest that they may have been released by CTCs. This preliminary evidence on the molecular content of the different circulating biomaterials suggests their possible function as a mirror of the intrinsic heterogeneity of BC. Moreover, this study demonstrates, through mutational assessment, the tumor origin of the different CTC sub-populations sustaining the translational value of the circulome for a more comprehensive picture of the disease