Validation of the Italian version of the Non-Communicating Children's Pain Checklist-Postoperative Version

BACKGROUND: This study evaluated the validity and reliability of the Italian version of the Non-Communicating Children's Pain Checklist-Postoperative version (I-NCCPC-PV). METHODS: The original NCCPC-PV version was translated into Italian following the guidelines for "the translation, adaptation, and validation of instruments or scales for cross-cultural healthcare research". We tested the Italian NCCPC-PV version (I-NCCPC-PV) in 40 children (3-18 years of age) with severe to profound Intellectual Disability and no verbal communication. Each child's behavior was observed by a parent or caregiver and by an external observer in a quiet situation and a painful one. They independently assessed the child's level of pain using the translated Italian version of the NCCPCPV (I-NCCPC-PV). RESULTS: The results from 80 assessments showed that children's behavioral signs differed significantly between painful and calm situations (p < 0.001). The inter-rater reliability was poor in a quiet condition (ICC 0.62) and fair in a painful situation (ICC 0.77). The inter-rater agreement was good in both calm and painful conditions (72.50% and 77.50% respectively). CONCLUSION: The Italian version of the NCCPC-PV (I-NCCPC-PV) can be used for pain assessment in children with Intellectual Disability who lack verbal communication

Circulating TRAIL Shows a Significant Post-Partum Decline Associated to Stressful Conditions

Background: Since circulating levels of TNF-related apoptosis inducing ligand (TRAIL) may be important in the physiopathology of pregnancy, we tested the hypothesis that TRAIL levels change at delivery in response to stressful conditions. Methods/Principal Findings: We conducted a longitudinal study in a cohort of 73 women examined at week 12, week 16, delivery and in the corresponding cord blood (CB). Serum TRAIL was assessed in relationship with maternal characteristics and to biochemical parameters. TRAIL did not vary between 12 (67.6627.6 pg/ml, means6SD) and 16 (64.0616.2 pg/ml) weeks ’ gestation, while displaying a significant decline after partum (49.3626.4 pg/ml). Using a cut-off decline.20 pg/ml between week 12 and delivery, the subset of women with the higher decline of circulating TRAIL (41.7%) showed the following characteristics: i) nullipara, ii) higher age, iii) operational vaginal delivery or urgent CS, iv) did not receive analgesia during labor, v) induced labor. CB TRAIL was significantly higher (131.6652 pg/ml) with respect to the corresponding maternal TRAIL, and the variables significantly associated with the first quartile of CB TRAIL (,90 pg/ml) were higher prepregnancy BMI, induction of labor and fetal distress. With respect to the biochemical parameters, maternal TRAIL at delivery showed an inverse correlation with C-reactive protein (CRP), total cortisol, glycemia and insulin at bivariate analysis, but only with CRP at multivariate analysis

TRAIL-based therapeutic approaches for the treatment of pediatric malignancies

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a pro-apoptotic ligand that has shown the exquisite ability to trigger extrinsic apoptosis in various types of cancer cells without significant toxicity toward normal cells, when compared to other pro-apoptotic ligands such as tumor necrosis factor (TNF)α or Fas ligand. Consequently, TRAIL-based therapies aim to trigger apoptosis in cancer cells by providing the soluble TRAIL or monoclonal antibodies targeting the death receptors TRAIL-R1 or TRAIL-R2. In this review, we start by highlighting the relevance of the tumor microenvironment in tumor development and elimination. We then address conventional and targeted therapeutic approaches for cancer treatment, highlighting the mechanisms involved or targeted. We describe the extrinsic and intrinsic pro-apoptotic pathways of TRAIL, together with the evidences for its pro-survival signaling, and with the relevance of these pathways in therapy. Possible mechanisms of resistance to TRAIL-induced apoptosis are highlighted (i.e. c-FLIP, Bcl-2, IAPs, p53, NF-κ B) and the rationale for the combined administration of TRAIL with drugs targeting these mechanisms is provided. Preclinical data are reported and show encouraging evidences for TRAIL consideration in pediatric malignancies (i.e., leukemia, lymphomas, neuroblastoma, osteosarcoma, medulloblastoma). Clinical trials of TRAIL-based therapies on the overall population are in phase I or II, and we put particular focus on the pediatric population, on which only few trials have been conducted or are ongoing. Finally, we consider emerging cellular therapies based on TRAIL, such as TRAIL-engineered mesenchymal stem cells or ‘inflammatory’ dendritic cells

The early determination of circulating TRAIL levels does not predict the development of pre-eclampsia.

TRAIL is a pleiotropic cytokine, showing important regulatory activities in the immune and cardiovascular systems. Among different tissues, TRAIL is expressed by placenta and can upregulated in trophoblast cells after cytokine stimulation. Since previous studies from our and other groups have demonstratedthat the serum levels of TRAIL are significantly decreased in patients affected by cardiovascular disease, we have carried out a case-control study aimed at evaluating the potential predictive role of first trimester TRAIL (12 weeks of gestational age) as a risk factor for hypertensive pregnancy disorders (HD: gestational hypertension or pre-eclampsia) and diabetes (gestational or IDDM). For each case of HD and diabetes, three controls were randomly selected matched to cases for age parity (primiparous; multiparous) and pregestational BMI We found no significant differences between both groups of cases and controls in terms of circulating TRAIL values (pg/ml) (non-parametric Mann–Whitney U test as TRAIL values did not distribute normally: for HD p ¼ 0.76, for diabetes p ¼ 0.59). Finally, none of the correlations between TRAIL values and mean pulsatility index, mean resistance index, bilateral notch at 12 weeks gestation, 20 and 30 weeks gestation was significant. Thus, although TRAIL has different functions at the placenta level, including a placental protective role, we did not find any statistically significant difference in the levels of circulating TRAIL at 12 gestational weeks between HD or diabetic and control women, indicating that TRAIL may not be a good candidate as a biomarker to evaluate early-stage lesions associated to pre-eclampsia

The circulating levels of TRAIL are extremely low after delivery but rapidly recover in both mothers and newborns

TNF-related apoptosis inducing ligand (TRAIL) plasma levels was measured in plasma samples obtained 1h (time 1) and 2-3days (time 2) after delivery in a group of healthy women (n=17) who underwent cesarean delivery, and showed a significantly increase from time 1 (39.3pg/ml median; 41.2±15.9 mean±SD) to time 2 (71.6pg/ml median; 73.8±27.8 mean±SD). Similarly, circulating TRAIL levels were extremely low in the plasma of newborns (n=41) within the first 24h after partum (time 1; 27.5pg/ml, median; 31.5±15.8 means±SD), showing a significant increase 2-3days after partum (time 2; 68.4pg/ml, median; 75.1±36.7 mean±SD). It is also noteworthy that the highest levels of plasma TRAIL were observed in newborns with the following characteristics: (i) born at later gestational age, (ii) Apgar score >9, (iii) higher birth weight, (iv) born through vaginal partum. In conclusion, we have demonstrated for the first time that the levels of circulating TRAIL are markedly low in both mothers and children after delivery, rapidly rising thereafter. Moreover, the highest levels of TRAIL are observed in newborns with the best clinical parameters

Serum TRAIL levels increase shortly after insulin therapy and metabolic stabilization in children with type 1 diabetes mellitus

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily, which plays an important role in regulating cell death and inflammation. Beyond its anti-tumor activity, increasing evidence in animal studies suggests that TRAIL plays a role in the control of autoimmune diseases, and in particular in type 1 diabetes mellitus (T1DM) . In this context, in a previous study carried out in a retrospective cohort of T1DM pediatric patients, we found significant lower levels of circulating TRAIL in T1DM patients with respect to healthy age-matched controls . However, a limitation of our previous study was as follows: (1) the lack of serial serum samples harvested from the same patients at different time post onset and (2) the lack of information about concurrent metabolic status at time of blood sampling. On these bases, the aim of the present study was to analyze the evolution of circulating TRAIL levels in a pilot group of pediatric patients admitted at Emergency Department for T1DM, from the time of hospital admission throughout the re-establishment of a normal metabolic balance and up to 18 months of clinical follow-up. Moreover, the serum levels of TRAIL in T1DM patients were analyzed in relation to the metabolic status determined at the same times

Human papillomavirus infection is associated with decreased levels of GM-CSF in cervico-vaginal fluid of infected women

Background Although human papillomavirus (HPV) is the most common sexually transmitted infection, there are very scant data about the influence of this virus on the in vitro fertilization outcome. Objectives To assess the presence of HPV in the cervico-vaginal fluid in relationship to the in vitro fertilization (IVF) outcome and to the concentration of selected cytokines, known to affect embryo implantation and gestation: granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF). Study design Cervico-vaginal samples were collected on the day of oocyte pick-up from 82 women. Vaginas were flushed with 50 mL of sterile water and 3 mL of fluid was collected. Results Twelve women (15%) were positive for HPV. Interestingly, among HPV+ women live birth rate was about half of the rate in HPV− women, although the differences were not statistically significant due to the low number of cases. Cervico-vaginal samples of a sub-group of 29 (8 HPV+ and 21 HPV−) women were analyzed for GM-CSF and G-CSF by ELISA. GM-CSF but not G-CSF was significantly lower in the cervico-vaginal fluid of HPV+ than in HPV− women. Conclusions Since GM-CSF plays an important role during pregnancy, the reduced levels of GM-CSF in the cervico-vaginal fluid of HPV+ women might contribute to explain the reduced live birth rate observed in HPV+ women