Metronomic chemotherapy preserves quality of life ensuring efficacy in elderly advanced non small cell lung cancer patients

Metastatic non small cell lung cancers (NSCLC) are diseases with poor prognosis and platinum-based doublet chemotherapy still remains their standard cure. Elderly patients often present comorbidities that limit the utilization of this chemotherapy; therefore these patients should have a first-line treatment with low toxicity and capable to preserve the quality of life (QoL) but, at the same time, to ensure the best possible response. Furthermore, a first-line treatment allows patients to be fit for further treatments, prolonging overall survival. At this regard, metronomic chemotherapy can be an optimal choice for elderly, able to improve QoL and to obtain an optimal palliation. We retrospectively studied a cohort of 41 elderly advanced NSCLC patients with different histotypes, treated with metronomic chemotherapy (weekly carbo-paclitaxel or vinorelbine as single agent) as first choice and we analyzed the tolerability, the impact on QoL and the efficacy of these schedules: no toxicity of 3 and 4 grade was observed, together to a clinical benefit of 43%. We administered FACT-L test to evaluate QoL at baseline and after 4 months and found a significant improvement in all FACT-L parameters: physical, social, emotional and functional, confirming a QoL improvement. At a median follow-up of 20.2 months the progression free survival was of 6 months and the overall survival was of 15 months. These results suggest that metronomic chemotherapy can be an effective choice of treatment for elderly NSCLC patients and further trials with more patients are needed to confirm this proposal

Circulating neuregulin-1 and galectin-3 can be prognostic markers in breast cancer

Background: It is important to identify novel plasmatic biomarkers that can contribute to assessing the prognosis and outcome of breast cancer patients. Neuregulin-1 (NRG1) and galectin-3 (Gal-3) are proteins that are involved in breast cancer development and patient survival; therefore, we studied whether the serum concentration of these 2 proteins can be correlated to breast cancer progression. Methods: Plasmatic NRG1 and Gal-3 were evaluated in 25 healthy controls and 50 breast cancer patients at baseline and at 3 and 6 months after treatment with anthracyclines and taxanes, with or without trastuzumab. Results: NRG1 and Gal-3 were significantly more elevated in cancer patients than in healthy controls; further- more, NRG1 and Gal-3 were significantly increased after chemotherapy and were predictive of mortality at 1 year. Conclusions: Circulating NRG1 and Gal-3 can be additional biomarkers indicative of prognosis and outcomes for breast cancer patients

Comparison between soluble ST2 and high-sensitivity troponin I in predicting short-term mortality for patients presenting to the Emergency Department with chest pain

Background: High-sensitivity cardiac troponin I (hs-cTnI) and the soluble isoform of suppression of tumorigenicity 2 (sST2) are useful prognostic biomarkers in acute coronary syndrome (ACS). The aim of this study was to test the short term prognostic value of sST2 compared with hs-cTnI in patients with chest pain. Methods: Assays for hs-cTnI and sST2 were performed in 157 patients admitted to the Emergency Department (ED) for chest pain at arrival. In-hospital and 30-day follow-up mortalities were assessed. Results: The incidence of ACS was 37%; 33 patients were diagnosed with ST elevation myocardial infarction (STEMI), and 25 were diagnosed with non-ST elevation myocardial infarction (NSTEMI). Compared with the no acute coronary syndrome (NO ACS) group, the median level of hs-cTnI was higher in ACS patients: 7.22 (5.24-14) pg/mL vs 68 (15.33-163.50) pg/mL (P35 ng/mL at ED arrival died during the 30-day follow-up. Conclusions: sST2 has a greater prognostic value for 30-day cardiac mortality after discharge in patients presenting to the ED for chest pain compared with hs-cTnI. In STEMI patients, an sST2 value > 35 ng/mL at ED arrival showed the highest predictive power for short-term mortality

The kinesin Eg5 inhibitor K858 induces apoptosis but also survivin-related chemoresistance in breast cancer cells

Inhibitors of kinesin spindle protein Eg5 are characterized by pronounced antitumor activity. Our group has recently synthesized and screened a library of 1,3,4-thiadiazoline analogues with the pharmacophoric structure of K858, an Eg5 inhibitor. We herein report the effects of K858 on four different breast cancer cell lines: MCF7 (luminal A), BT474 (luminal B), SKBR3 (HER2 like) and MDA-MB231 (basal like). We demonstrated that K858 displayed anti-proliferative activity on every analyzed breast cancer cell line by inducing apoptosis. However, at the same time, we showed that K858 up-regulated survivin, an anti-apoptotic molecule. We then performed a negative regulation of survivin expression, with the utilization of wortmannin, an AKT inhibitor, and obtained a significant increase of K858-dependent apoptosis. These data demonstrate that K858 is a potent inhibitor of replication and induces apoptosis in breast tumor cells, independently from the tumor phenotype. This anti-proliferative response of tumor cells to K858 can be limited by the contemporaneous over-expression of survivin; consequently, the reduction of survivin levels, obtained with AKT inhibitors, can sensitize tumor cells to K858-induced apoptosis

A psychological intervention based on cognitive-behavioural therapy reduces psychopathological symptoms that indirectly influence the heart rate via cortisol in hypertensive patients: Preliminary results of a pilot study

ObjectiveThis study aimed at assessing the effectiveness of cognitive-behavioural therapy (CBT) integrated with psychoeducation in a group of hypertensive patients with clinically significant psychopathological symptoms.MethodsOne hundred hypertensive patients completed the Symptom Checklist-90-Revised. Of them, 17 scored above the clinical range (cut-off = 0.75) on the Global Severity Index and were included in the study. Psychological distress was assessed again after the intervention (T1) and 6 months after the end of treatment (T2). In addition, the cortisol dosage and the heart rate (HR) measurement were collected at both T0 and T2. Then, mediation analyses were carried out to calculate whether psychopathological distress might predict HR through elevated serum cortisol levels, at both T0 and T2.ResultsThe psychological intervention (CBT integrated with psychoeducation) reduced most of the psychopathological symptoms (anxiety, depression, somatisations, obsessions and compulsions, hostility, interpersonal sensitivity and paranoid ideation) but not cortisol dosage and HR measurement. However, psychological distress indirectly predicted HR via cortisol at T0 but not at T2.ConclusionThese results suggest and encourage the replicability of data in larger sample sizes and the comparison with a control group. Nevertheless, these results highlight a need for a multidimensional assessment of disorders affecting the mental and physical spheres of patients to support their overall well-being

Human Hand Motion Analysis and Synthesis of Optimal Power Grasps for a Robotic Hand

Biologically inspired robotic systems can find important applications in biomedical robotics, since studying and replicating human behaviour can provide new insights into motor recovery, functional substitution and human-robot interaction. The analysis of human hand motion is essential for collecting information about human hand movements useful for generalizing reaching and grasping actions on a robotic system. This paper focuses on the definition and extraction of quantitative indicators for describing optimal hand grasping postures and replicating them on an anthropomorphic robotic hand. A motion analysis has been carried out on six healthy human subjects performing a transverse volar grasp. The extracted indicators point to invariant grasping behaviours between the involved subjects, thus providing some constraints for identifying the optimal grasping configuration. Hence, an optimization algorithm based on the Nelder-Mead simplex method has been developed for determining the optimal grasp configuration of a robotic hand, grounded on the aforementioned constraints. It is characterized by a reduced computational cost. The grasp stability has been tested by introducing a quality index that satisfies the form-closure property. The grasping strategy has been validated by means of simulation tests and experimental trials on an arm-hand robotic system. The obtained results have shown the effectiveness of the extracted indicators to reduce the non-linear optimization problem complexity and lead to the synthesis of a grasping posture able to replicate the human behaviour while ensuring grasp stability. The experimental results have also highlighted the limitations of the adopted robotic platform (mainly due to the mechanical structure) to achieve the optimal grasp configuration

Radiotherapy in indolent primary cutaneous B-cell lymphoma

not applicabl

Enhanced expression of a cloned and sequenced Ciona intestinalis TNFa-like (CiTNFa) gene during the LPS-induced inflammatory response.

A tumor necrosis factor-alpha (TNFα)-like gene from Ciona intestinalis (CiTNFα-like) body wall challengedprepared in the presence of detergents. Both soluble and hemocyte-bound CiTNFα-like protein therefore appeared to be modulated by the LPS challenge with bacterial lipopolysaccharide (LPS) was cloned and sequenced 4 h after LPS inoculation. An open reading frame of 936 bp encoding a propeptide of 312 amino acids (35.4 kDa) displaying a transmembrane domain from positions 7 to 29, a TACE cleavage site, and a mature peptide domain of 185 amino acids (20.9 kDa), was determined with a predicted isoelectric point of 9.4. The phylogenetic tree based on deduced amino acid sequences of invertebrate TNF-like protein and vertebrate TNFs supported the divergence between the ascidian and vertebrate TNF families, whereas D. melanogaster Eiger A and B TNF-like sequences were distinctly separated from the chordate TNFs. Thus, the ascidian TNFα-like cytokine was upregulated by in vivo LPS challenge supporting its proinflammatory role. In the pharynx, increased expression levels were found following analysis by real-time polymerase chain reaction, whereas in situ hybridization assay showed positive hemocytes both in the tissue and in circulating hemocytes. Finally, Western blot with monoclonal antibodies disclosed human TNFα epitopes in a 15-kDa protein component of the hemolymph serum and in a 43- kDa protein contained in the hemocyte lysate supernatan

Status of Charcoal Canker on Oak Trees at a Site of Community Importance: Case Study of the Relict Castelfidardo Forest (SIC Area IT520008, Castelfidardo, AN, Italy)

Oaks are dominant and key tree species in Mediterranean forest ecosystems. However, in recent decades, oak forests have been heavily impacted by oak decline, a worldwide phenomenon exacerbated by climate change. The charcoal disease agent Biscogniauxia mediterranea is involved in the decline of Mediterranean oak formations in a variety of contexts. Here, we investigated the impact and role of B. mediterranea in the decline of oaks in Castelfidardo Forest, a relict wood of the late Holocene and a Site of Community Importance. We established five plots within which we recorded tree positions, any symptoms and signs of decline, association of B. mediterranea to declining trees, and deadwood and associated mycota. Of 471 oaks inspected, 7.0% showed brownish exudates on the stems, 46.9% showed epicormic shoots along the main trunk, and 24.4% showed black carbonaceous stromata on diseased branches and trunks. The decline was most severe for Quercus cerris, which comprised plots #4 and #5, at 50.0% (81/162 trees) and 29.0% (33/114), respectively; then for Quercus robur for plot #3, at 40.0% (38/95); and finally for Quercus pubescens for plots #1 and #2, at 13.7% (7/51) and 12.3% (6/49), respectively. Bark tissues were collected from trees with charcoal cankers and taken to the laboratory for microscopic examination and identification by mycological and molecular methods. This investigation revealed a close association between oaks with pronounced reduction of vitality and incidence of B. mediterranea. Deadwood was equally distributed among the five plots, and was heavily colonized by Basidiomycota. The high incidence of the charcoal canker pathogen B. mediterranea appeared to be related to environmental stresses. However, the absence of silvicultural management, high competition among physiologically mature trees, and the geographic isolation of this residual forest may have predisposed oaks to decline