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141.
142.
Umberto Raucci Rossella Rossi Roberto Da Cas Concita Rafaniello Nadia Mores Giulia Bersani Antonino Reale Nicola Pirozzi Francesca Menniti-Ippolito Giuseppe Traversa Italian Multicenter Study Group for Vaccine Safety in Drug Children 《PloS one》2013,8(7)
Objective
Stevens-Johnson Syndrome (SJS) is one of the most severe muco-cutaneous diseases and its occurrence is often attributed to drug use. The aim of the present study is to quantify the risk of SJS in association with drug and vaccine use in children.Methods
A multicenter surveillance of children hospitalized through the emergency departments for acute conditions of interest is currently ongoing in Italy. Cases with a diagnosis of SJS were retrieved from all admissions. Parents were interviewed on child’s use of drugs and vaccines preceding the onset of symptoms that led to the hospitalization. We compared the use of drugs and vaccines in cases with the corresponding use in a control group of children hospitalized for acute neurological conditions.Results
Twenty-nine children with a diagnosis of SJS and 1,362 with neurological disorders were hospitalized between 1st November 1999 and 31st October 2012. Cases were more frequently exposed to drugs (79% vs 58% in the control group; adjusted OR 2.4; 95% CI 1.0–6.1). Anticonvulsants presented the highest adjusted OR: 26.8 (95% CI 8.4–86.0). Significantly elevated risks were also estimated for antibiotics use (adjusted OR 3.3; 95% CI 1.5–7.2), corticosteroids (adjusted OR 4.2; 95% CI 1.8–9.9) and paracetamol (adjusted OR 3.2; 95% CI 1.5–6.9). No increased risk was estimated for vaccines (adjusted OR: 0.9; 95% CI 0.3–2.8).Discussion
Our study provides additional evidence on the etiologic role of drugs and vaccines in the occurrence of SJS in children. 相似文献143.
Yulia Kundel Nicola J. Nasser Ofer Purim Rinat Yerushalmi Eyal Fenig Raphael M. Pfeffer Salomon M. Stemmer Shulamith Rizel Zvi Symon Bella Kaufman Aaron Sulkes Baruch Brenner 《PloS one》2013,8(7)
Background
Pain from bone metastases of breast cancer origin is treated with localized radiation. Modulating doses and schedules has shown little efficacy in improving results. Given the synergistic therapeutic effect reported for combined systemic chemotherapy with local radiation in anal, rectal, and head and neck malignancies, we sought to evaluate the tolerability and efficacy of combined capecitabine and radiation for palliation of pain due to bone metastases from breast cancer.Methodology/Principal Findings
Twenty-nine women with painful bone metastases from breast cancer were treated with external beam radiation in 10 fractions of 3 Gy, 5 fractions a week for 2 consecutive weeks. Oral capecitabine 700 mg/m2 twice daily was administered throughout radiation therapy. Rates of complete response, defined as a score of 0 on a 10-point pain scale and no increase in analgesic consumption, were 14% at 1 week, 38% at 2 weeks, 52% at 4 weeks, 52% at 8 weeks, and 48% at 12 weeks. Corresponding rates of partial response, defined as a reduction of at least 2 points in pain score without an increase in analgesics consumption, were 31%, 38%, 28%, 34% and 38%. The overall response rate (complete and partial) at 12 weeks was 86%. Side effects were of mild intensity (grade I or II) and included nausea (38% of patients), weakness (24%), diarrhea (24%), mucositis (10%), and hand and foot syndrome (7%).Conclusions/Significance
External beam radiation with concurrent capecitabine is safe and tolerable for the treatment of pain from bone metastases of breast cancer origin. The overall and complete response rates in our study are unusually high compared to those reported for radiation alone. Further evaluation of this approach, in a randomized study, is warranted.Trial Registration
ClinicalTrials.gov NCT01784393 NCT01784393相似文献144.
145.
Edmond M. Linossi Indu R. Chandrashekaran Tatiana B. Kolesnik James M. Murphy Andrew I. Webb Tracy A. Willson Lukasz Kedzierski Alex N. Bullock Jeffrey J. Babon Raymond S. Norton Nicos A. Nicola Sandra E. Nicholson 《PloS one》2013,8(8)
Suppressor of Cytokine Signaling (SOCS)5 is thought to act as a tumour suppressor through negative regulation of JAK/STAT and epidermal growth factor (EGF) signaling. However, the mechanism/s by which SOCS5 acts on these two distinct pathways is unclear. We show for the first time that SOCS5 can interact directly with JAK via a unique, conserved region in its N-terminus, which we have termed the JAK interaction region (JIR). Co-expression of SOCS5 was able to specifically reduce JAK1 and JAK2 (but not JAK3 or TYK2) autophosphorylation and this function required both the conserved JIR and additional sequences within the long SOCS5 N-terminal region. We further demonstrate that SOCS5 can directly inhibit JAK1 kinase activity, although its mechanism of action appears distinct from that of SOCS1 and SOCS3. In addition, we identify phosphoTyr317 in Shc-1 as a high-affinity substrate for the SOCS5-SH2 domain and suggest that SOCS5 may negatively regulate EGF and growth factor-driven Shc-1 signaling by binding to this site. These findings suggest that different domains in SOCS5 contribute to two distinct mechanisms for regulation of cytokine and growth factor signaling. 相似文献
146.
Blanda Di Luccia Nicola Manzo Loredana Baccigalupi Viola Calabrò Elvira Crescenzi Ezio Ricca Alessandra Pollice 《PloS one》2013,8(7)
It is now commonly accepted that the intestinal microbiota plays a crucial role in the gut physiology and homeostasis, and that both qualitative and quantitative alterations in the compositions of the gut flora exert profound effects on the host’s intestinal cells. In spite of this, the details of the interaction between commensal bacteria and intestinal cells are still largely unknown and only in few cases the molecular mechanisms have been elucidated. Here we analyze the effects of molecules produced and secreted by Lactobacillus gasseri SF1183 on human intestinal HCT116 cells. L. gasseri is a well known species of lactic acid bacteria, commonly associated to the human intestine and SF1183 is a human strain previously isolated from an ileal biopsy of an healthy volunteer. SF1183 produces and secretes, in a growth phase-dependent way, molecule(s) able to drastically interfere with HCT116 cell proliferation. Although several attempts to purify and identify the bioactive molecule(s) have been so far unsuccessful, a partial characterization has indicated that it is smaller than 3 kDa, thermostable and of proteinaceous nature. L. gasseri molecule(s) stimulate a G1-phase arrest of the cell cycle by up-regulation of p21WAF1 rendering cells protected from intrinsic and extrinsic apoptosis. A L. gasseri-mediated reduction of apoptosis and of cell proliferation could be relevant in protecting epithelial barrier integrity and helping in reconstituting tissutal homeostasis. 相似文献
147.
Martin Neumann Ebru Coskun Lars Fransecky Liliana H. Mochmann Isabelle Bartram Nasrin Farhadi Sartangi Sandra Heesch Nicola G?kbuget Stefan Schwartz Christian Brandts Cornelia Schlee Rainer Haas Ulrich Dührsen Martin Griesshammer Hartmut D?hner Gerhard Ehninger Thomas Burmeister Olga Blau Eckhard Thiel Dieter Hoelzer Wolf-Karsten Hofmann Claudia D. Baldus 《PloS one》2013,8(1)
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup. 相似文献
148.
Ronan A. Lyons Denise Kendrick Elizabeth M. L. Towner Carol Coupland Mike Hayes Nicola Christie Judith Sleney Sarah Jones Richard Kimberlee Sarah E. Rodgers Samantha Turner Mariana Brussoni Yana Vinogradova Tinnu Sarvotham Steven Macey 《PloS one》2013,8(4)
Objective
To determine whether advocacy targeted at local politicians leads to action to reduce the risk of pedestrian injury in deprived areas.Design
Cluster randomised controlled trial.Setting
239 electoral wards in 57 local authorities in England and Wales.Participants
617 elected local politicians.Interventions
Intervention group politicians were provided with tailored information packs, including maps of casualty sites, numbers injured and a synopsis of effective interventions.Main outcome measures
25–30 months post intervention, primary outcomes included: electoral ward level: percentage of road traffic calmed; proportion with new interventions; school level: percentage with 20 mph zones, Safe Routes to School, pedestrian training or road safety education; politician level: percentage lobbying for safety measures. Secondary outcomes included politicians’ interest and involvement in injury prevention, and facilitators and barriers to implementation.Results
Primary outcomes did not significantly differ: % difference in traffic calming (0.07, 95%CI: −0.07 to 0.20); proportion of schools with 20 mph zones (RR 1.47, 95%CI: 0.93 to 2.32), Safe Routes to School (RR 1.34, 95%CI: 0.83 to 2.17), pedestrian training (RR 1.23, 95%CI: 0.95 to 1.61) or other safety education (RR 1.16, 95%CI: 0.97 to 1.39). Intervention group politicians reported greater interest in child injury prevention (RR 1.09, 95%CI 1.03 to 1.16), belief in potential to help prevent injuries (RR 1.36, 95%CI 1.16 to 1.61), particularly pedestrian safety (RR 1.55, 95%CI 1.19 to 2.03). 63% of intervention politicians reported supporting new pedestrian safety schemes. The majority found the advocacy information surprising, interesting, effectively presented, and could identify suitable local interventions.Conclusions
This study demonstrates the feasibility of an innovative approach to translational public health by targeting local politicians in a randomised controlled trial. The intervention package was positively viewed and raised interest but changes in interventions were not statistically significance. Longer term supported advocacy may be needed.Trial Registration
Current Controlled Trials ISRCTN91381117 相似文献149.
While nitrate acquisition has been extensively studied, less information is available on transport systems of urea. Furthermore, the reciprocal influence of the two sources has not been clarified, so far. In this review, we will discuss recent developments on plant response to urea and nitrate nutrition. Experimental evidence suggests that, when urea and nitrate are available in the external solution, the induction of the uptake systems of each nitrogen (N) source is limited, while plant growth and N utilization is promoted. This physiological behavior might reflect cooperation among acquisition processes, where the activation of different N assimilatory pathways (cytosolic and plastidic pathways), allow a better control on the nutrient uptake. Based on physiological and molecular evidence, plants might increase (N) metabolism promoting a more efficient assimilation of taken-up nitrogen. The beneficial effect of urea and nitrate nutrition might contribute to develop new agronomical approaches to increase the (N) use efficiency in crops. 相似文献
150.