A bio-sourced molecule as carbon black coupling agent in rubber compounds with low hysteresis

The prime application of rubber composites is represented by tire compounds. To achieve the desired tire performances an equilibrium between dynamic rigidity and hysteresis must be acquired. Amorphous precipitated silica is the preferred reinforcing filler to have low energy dissipations and thus low fuel consumption. Indeed, silica is characterized by nano dimensions and by the possibility of establishing chemical bonds with rubber chains allowing the achievement of high hysteresis at low temperatures, to promote wet traction, and low hysteresis at medium-high temperatures, for low fuel consumption. Carbon black (CB) is the main filler for tire compounds, but it does not have functional groups able to promote chemical bonds with the rubber matrix, though it would be highly desirable. In this work, a pyrrole compound (PyC) containing a thiol group, and which can be synthesized starting from bio-based building blocks was used to functionalize CB by the socalled “pyrrole methodology”. The thiol group was expected to react with the sulphurbased crosslinking system and/or with rubber chains, thus forming strong bonds with the rubber matrix. Results The synthesis of the PyC and the functionalization reaction were characterized by high atom efficiency. A poly(styrene-co-butadiene) copolymer from anionic solution polymerization was used as the main rubber for the compound preparation. The crosslinked composite material filled with functionalized CB revealed substantial improvements with respect to the composite with pristine CB, in particular: high rigidity and low hysteresis at high temperature. Composite properties were even comparable to those of silica-based rubber composites. The formation of the expected rubber-filler chemical bond via the thiol group of the selected PyC was confirmed studying such functionalizing agent in a squalene-based model compound. The results here reported pave the way to CB-based rubber composites with a low environmental impact

Targeted metabolomic profiles of piglet plasma reveal physiological changes over the suckling period

The suckling phase is a critical period for the piglets due to their incomplete immune system development and their rapid growth rates. In this study, we analysed the metabolomic profiles of piglets over this period. Eighteen piglets (nine males and nine females) from three different litters were included in the study. Body weight was recorded at birth (T0), 12 (T1) and 21 (T2) days after birth. Plasma samples were collected at two critical time points of the suckling phase (T1 and T2) and about 180 metabolites of five different biochemical classes (glycerophospholipids, amino acids, biogenic amines, hexoses and acylcarnitines) were analyzed using a target metabolomics approach based on Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Metabolites whose levels could discriminate the plasma profiles at T1 and T2 were identified using the sparse version of Multilevel Partial Least Squares Discriminant Analysis (sMLPLS-DA), coupled with a stability test based on a Leave One Out (LOO) procedure. The level of twenty-three metabolites differed significantly (P < 0.1; both for stability and the effect size) between the two time points. Higher levels of six acylcarnitine (C14:1, C14:1-OH, C16-OH, C4, C5 and C5-OH), serine, threonine and tyrosine, and one phosphatidylcholine (PC ae C42:3) were observed at T1, whereas one biogenic amine (creatinine), eight phosphatidylcholines including PC aa C30:2, PC ae C30:0, PC ae C32:1, PC ae C38:4, PC ae C40:4, PC ae C42:4, PC ae C42:5 and PC ae C44:6, and four sphingomyelins, including SM (OH) C22:1, SM C16:0, SM C16:1 and SM C18:0, were more abundant at T2. The Metabolite Set Enrichment Analysis and the Pathway Analysis modules suggested a perturbation of the \u201cglycine and serine metabolism\u201d and the \u201csphingolipid metabolism\u201d. Differences of these metabolites between these two time points might be related to the rapid growth and immunological maturation phases of the piglets in this period. Our results provided new information that could describe the biological changes of the piglets over the suckling period. The identified metabolites may be useful markers of the developmental processes occurring in the piglets over this critical pre-weaned phase

New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions

Chronic graft-versus-host disease (cGvHD) is a severe complication of allogeneic hematopoietic stem cell transplantation that affects various organs leading to a reduced quality of life. The condition often requires enduring immunosuppressive therapy, which can also lead to the development of severe side effects. Several approaches including small molecule inhibitors, antibodies, cytokines, and cellular therapies are now being developed for the treatment of cGvHD, and some of these therapies have been or are currently tested in clinical trials. In this review, we discuss these emerging therapies with particular emphasis on tyrosine kinase inhibitors (TKIs). TKIs are a class of compounds that inhibits tyrosine kinases, thereby preventing the dissemination of growth signals and activation of key cellular proteins that are involved in cell growth and division. Because they have been shown to inhibit key kinases in both B cells and T cells that are involved in the pathophysiology of cGvHD, TKIs present new promising therapeutic approaches. Ibrutinib, a Bruton tyrosine kinase (Btk) inhibitor, has recently been approved by the Food and Drug Administration (FDA) in the United States for the treatment of adult patients with cGvHD after failure of first-line of systemic therapy. Also, Janus Associated Kinases (JAK1 and JAK2) inhibitors, such as itacitinib (JAK1) and ruxolitinib (JAK1 and 2), are promising in the treatment of cGvHD. Herein, we present the current status and future directions of the use of these new drugs with particular spotlight on their targeting of specific intracellular signal transduction cascades important for cGvHD, in order to shed some light on their possible mode of actions

Donor-transmitted Triple-Hit Lymphoma in a Renal Allograft Recipient

simultaneous appearance of DLBCL in the donor and recipient after renal transplantatio

IART® (Intra-Operative Avidination for Radionuclide Therapy) for accelerated radiotherapy in breast cancer patients. Technical aspects and preliminary results of a phase II study with 90Y-labelled biotin

Background: Breast conserving surgery (BCS) plus external beam radiotherapy (EBRT) is considered the standard treatment for early breast cancer. We have investigated the possibility of irradiating the residual gland, using an innovative nuclear medicine approach named IART® (Intra-operative Avidination for Radionuclide Therapy). Aim: The objective of this study was to determine the optimal dose of avidin with a fixed activity (3.7 GBq) of 90Y-biotin, in order to provide a boost of 20 Gy, followed by EBRT to the whole breast (WB) at the reduced dose of 40 Gy. Local and systemic toxicity, patient's quality of life, including the cosmetic results after the combined treatment with IART® and EBRT, were assessed. Methods: After tumour excision, the surgeon injected native avidin diluted in 30 ml of saline solution into and around the tumour bed (see video). Patients received one of three avidin dose levels: 50 mg (10 pts), 100 mg (15 pts) and 150 mg (10 pts). Between 12 to 24 h after surgery, 3.7 GBq 90Y-biotin spiked with 185 MBq 111In-biotin was administered intravenously (i.v.). Whole body scans and SPECT images were performed up to 30 h post-injection for dosimetric purposes. WB-EBRT was administered four weeks after the IART® boost. Local toxicity and quality of life were evaluated. Results: Thirty-five patients were evaluated. No side effects were observed after avidin administration and 90Y-biotin infusion. An avidin dose level of 100 mg resulted the most appropriate in order to deliver the required radiation dose (19.5 + 4.0 Gy) to the surgical bed. At the end of IART®, no local toxicity occurred and the overall cosmetic result was good. The tolerance to the reduced EBRT was also good. The highest grade of transient local toxicity was G3, which occurred in 3/32 pts following the completion of WB-EBRT. The combination of IART® +EBRT was well accepted by the patients, without any changes to their quality of life. Conclusions: These preliminary results support the hypothesis that IART® may represent a valid approach to accelerated WB irradiation after BCS. We hope that this nuclear medicine technique will contribute to a better management of breast cancer patients. © the authors; licensee ecancermedicalscience

Meta-analysis of tumour burden in pre-operative axillary ultrasound positive and negative breast cancer patients

Management of the axilla in breast cancer is becoming increasingly conservative. Patients identified with a low axillary nodal burden (two or fewer involved nodes) at sentinel node biopsy (SNB) can avoid completion axillary node clearance (cANC). 'Fast track' to ANC in patients with involved nodes on pre-operative ultrasound may be over-treating a subgroup of these patients with low nodal burden, which would have precluded their need for ANC. This systematic review assesses the proportion of patients with involved nodes on pre-operative axillary ultrasound, which would fit low axillary burden criteria. Meta-analysis of studies comparing axillary burden of breast cancer patients identified as pre-operative ultrasound negative versus positive was performed. The primary outcome measure was the number of patients with two or fewer involved nodes (macrometastases only). Pooled odds ratio (OR), 95% confidence intervals (CIs), means and probabilities of identifying two or fewer involved nodes versus greater than two were calculated. Six studies reported the axillary burden in 4271 patients who were either directed straight to ANC or cANC after SNB. There was a significantly greater axillary burden in the ultrasound positive versus negative groups (OR 5.95, 95% CI 5.80-6.11) with mean nodal retrieval values of 2.9 [standard error (SE) 0.2] and 1.6 (SE 0.2) nodes, respectively. Cumulative probabilities identified 78.9% of ultrasound negative and 43.2% of ultrasound positive patients possessed low axillary burden. Pre-operative ultrasound positive patients have significantly higher axillary burden. However, nearly half do fit the criteria of low axillary burden and could be considered for omission of ANC

The assessment of minimal residual disease versus that of somatic mutations for predicting the outcome of acute myeloid leukemia patients

Background: In addition to morphological and cytogenetic features, acute myeloid leukemias are characterized by mutations that can be used for target-therapy; also the minimal/measurable residual disease (MRD) could be an important prognostic factor. The purpose of this retrospective study was to investigate if somatic mutations could represent an additional prognostic value in respect of MRD alone. Method: At baseline, 98 patients were tested for NPM1, FLT3, and for WT1 expression; 31 for ASXL1, TET2, IDH1, IDH2, N-RAS, WT1, c-KIT, RUNX1, and DNMT3A. The same genes have been also tested after induction and consolidation. Results: Overall, 60.2% of our patients resulted mutated: 24.5% carried mutations of FLT3-ITD, 38.7% of NPM1, 48.4% of c-KIT, 25.8% of N-RAS and 19.3% of IDH2. The probability of achieving a complete response (CR) was higher for younger patients, with low ELN risk score, NPM1-mutated, with low WT1 levels, and without FLT3. The presence of additional mutations represented a poor predictive factor: only 19% of these cases achieved CR in comparison to 43% of subjects without any of it. Concerning survival, it was conditioned by a lower ELN risk score, younger age, reduction > 1 log of the NPM1 mutational burden, disappearance of FLT3 mutations and lower WT1 expression. Regarding the role of the additional mutations, they impaired the outcome of 20% of the already MRD-negative patients. Concerning the possibility of predicting relapse, we observed an increase of the NPM1 mutational burden at the time-point immediately preceding the relapse (about 2 months earlier) in 50% of subjects. Similarly concerning WT1, an increase of its expression anticipated disease recurrence in 64% of cases. Conclusions: We demonstrated that additional somatic mutations are able to impair outcome of the already MRD-negative subjects. About MRD, we suggest a prognostic role also for the WT1 expression. Finally, we considered as relevant the assessment of NPM1 quantity clearance instead of the presence/absence of mutations alone. Still remains in doubt the utility in terms of long-term prognosis of a baseline more complex mutational screening; we could hypothesize that it would be useful for those patients where other markers are not available or who reached the MRD negativity

The PLASMONX Project for advanced beam physics experiments

The Project PLASMONX is well progressing into its design phase and has entered as well its second phase of procurements for main components. The project foresees the installation at LNF of a Ti:Sa laser system (peak power > 170 TW), synchronized to the high brightness electron beam produced by the SPARC photo-injector. The advancement of the procurement of such a laser system is reported, as well as the construction plans of a new building at LNF to host a dedicated laboratory for high intensity photon beam experiments (High Intensity Laser Laboratory). Several experiments are foreseen using this complex facility, mainly in the high gradient plasma acceleration field and in the field of mono- chromatic ultra-fast X-ray pulse generation via Thomson back-scattering. Detailed numerical simulations have been carried out to study the generation of tightly focused electron bunches to collide with laser pulses in the Thomson source: results on the emitted spectra of X-rays are presented