Molecular determination of epidermal growth factor receptor in normal and neoplastic colorectal mucosa

The epidermal growth factor receptor (EGFr) is considered a major target for treatment of colorectal cancer (CRC). We found a mean EGFr content significantly lower but more activated in colonic neoplastic tissue than in paired normal mucosa. Phosphorylated (pY1068) EGFr detection in CRC may be a better tool than EGFr detection to select patients for targeted therapies

Irinotecan toxicity: genes or intestinal microflora?

No abstract availabl

Analytic estimates and topological properties of the weak stability boundary

The weak stability boundary (WSB) is the transition region of the phase space where the change from gravitational escape to ballistic capture occurs. Studies on this complicated region of chaotic motion aim to investigate its unique, fuel saving properties to enlarge the frontiers of low energy transfers. This “fuzzy stability” region is characterized by highly sensitive motion, and any analysis of it has been carried out almost exclusively using numerical methods. On the contrary this paper presents, for the planar circular restricted 3 body problem (PCR3BP), 1) an analytic definition of the WSB which is coherent with the known algorithmic definitions; 2) a precise description of the topology of the WSB; 3) analytic estimates on the “stable region” (nearby the smaller primary) whose boundary is, by definition, the WSB

Successful selective arterial embolizations for bone metastases in renal cell carcinoma integrated with systemic therapies: A case report

the initial cytoreductive nephrectomy to 3 successive lines of medical treatment (sunitinib, everolimus, and sorafenib) and multiple locoregional treatments (spinal surgery, radiation therapy, and selective arterial embolization), resulting in a surprisingly long survival of over 75 months. In the era of target therapy, integration strategies, including additional locoregional treatment to medical therapy, are essential to optimize the clinical benefit, to maximize treatment duration overcoming focal progressive disease, and to improve the quality of life. In this context, we would highlight that selective transcatheter embolization of bone metastases from renal cell carcinoma should be considered as an effective and safe option in the palliative setting for patients with bone metastasis, especially for pain relief

A method for the analysis of cyclist shorts with different pads for perineal area protection: comparison between drum and road tests

AbstractAim of the present study was to develop an integrated protocol consisting on drum indoor tests and road outdoor tests to quantify the compression of the cyclist perineal zone. During indoor tests 5 cyclists performed 3 trials with different shorts on a cycling drum simulator: the pressure distribution between the saddle and the bottom of the cyclist, and the 3D pelvic motion were synchronously recorded. In the outdoor tests three of the five cyclists performed 5 trials for each shorts at the same speed and cadence of the indoor tests on a flat tarmac road including three potholes in each trial. Finally the pads were mechanically tested with a cyclic fatigue test. Results allowed to have more precise information about the pressure distribution acting on the perineal area in different conditions and to define significant loading cycles for the fatigue testing of the shorts padding material

Specialisation in Palliative Medicine for Physicians in Europe 2014 - A supplement of the EAPC Atlas of Palliative Care in Europe

This booklet describes the existing programmes on specialisation in palliative medicine within the WHO European region

Comparative analysis of specialization in palliative medicine processes within the World Health Organization European region

Abstract, Context Palliative medicine (PM), still in the development phase, is a new, growing specialty aimed at caring for both oncology and non-oncology patients. There is still confusion about the training offered in the various European PM certification programs. Objectives To provide a detailed, comparative update and analysis of the PM certification process in Europe, including the different training approaches and their main features. Methods Experts from each country completed an online survey addressing historical background, program name, training requirements, length of time in training, characteristic and content, official certifying institution, effectiveness of accreditation, and 2013 workforce capacity. We prepared a comparative analysis of the data provided. Results In 2014, 18 of 53 European countries had official programs on specialization in PM (POSPM): Czech Republic, Denmark, Finland, France, Georgia, Germany, Hungary, Ireland, Israel, Italy, Latvia, Malta, Norway, Poland, Portugal, Romania, Slovakia, and the U.K. Ten of these programs were begun in the last five years. The PM is recognized as a “specialty,” “subspecialty,” or “special area of competence,” with no substantial differences between the last two designations. The certification contains the term “palliative medicine” in most countries. Clinical training varies, with one to two years being the most frequent duration. There is a clear trend toward establishing the POSPM as a mandatory condition for obtaining a clinical PM position in countries' respective health systems. Conclusion PM is growing as a specialization field in Europe. Processes leading to certification are generally long and require substantial clinical training. The POSPM education plans are heterogeneous. The European Association for Palliative Care should commit to establishing common learning standards, leading to additional European-based recognition of expertise in PM

Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: The L-carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial

Objectives. This study was performed to evaluate the effects of l-carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. Background. Carnitine is a physiologic compound that performs an essential role in myocardial energy production at the mitochondrial level. Myocardial carnitine deprivation occurs during ischemia, acute myocardial infarction and cardiac failure. Experimental studies have suggested that exogenous carnitine administration during these events has a beneficial effect on function. Methods. The l-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial was a randomized, double-blind, placebo-controlled, multicenter trial in which 472 patients with a first acute myocardial infarction and high quality two-dimensional echocardiograms received either placebo (239 patients) or l-carnitine (233 patients) within 24 h of onset of chest pain. Placebo or l-carnitine was given at a dose of 9 g/day intravenously for the first 5 days and then 6 g/day orally for the next 12 months. Left ventricular volumes and ejection fraction were evaluated on admission, at discharge from hospital and at 3, 6 and 12 months after acute myocardial infarction. Results. A significant attenuation of left ventricular dilation in the first year after acute myocardial infarction was observed in patients treated with l-carnitine compared with those receiving placebo. The percent increase in both end-diastolic and endsystolic volumes from admission to 3-, 6- and 12-mouth evaluation was significantly reduced in the l-carnitine group. No significant differences were observed in left ventricular ejection fraction changes over time in the two groups. Although not designed to demonstrate differences in clinical end points, the combined incidence of death and congestive heart failure after discharge was 14 (6%) in the l-carnitine treatment group versus 23 (9.6%) in the placebo group (p = NS). Incidence of ischemic events during follow-up was similar in the two groups of patients. Conclusions. l-Carnitine treatment initiated early after acute myocardial infarction and continued for 12 months can attenuate left ventricular dilation during the first year after an acute myocardial infarction, resulting in smaller left ventricular volumes at 3, 6 and 12 months after the emergent event

Integrated Molecular Characterization of Gastrointestinal Stromal Tumors (GIST) Harboring the Rare D842V Mutation in PDGFRA Gene.

Gastrointestinal stromal tumors (GIST) carrying the D842V activating mutation in the platelet-derived growth factor receptor alpha (PDGFRA) gene are a very rare subgroup of GIST (about 10%) known to be resistant to conventional tyrosine kinase inhibitors (TKIs) and to show an indolent behavior. In this study, we performed an integrated molecular characterization of D842V mutant GIST by whole-transcriptome and whole-exome sequencing coupled with protein-ligand interaction modelling to identify the molecular signature and any additional recurrent genomic event related to their clinical course. We found a very specific gene expression profile of D842V mutant tumors showing the activation of G-protein-coupled receptor (GPCR) signaling and a relative downregulation of cell cycle processes. Beyond D842V, no recurrently mutated genes were found in our cohort. Nevertheless, many private, clinically relevant alterations were found in each tumor (TP53, IDH1, FBXW7, SDH-complex). Molecular modeling of PDGFRA D842V suggests that the mutant protein binds imatinib with lower affinity with respect to wild-type structure, showing higher stability during the interaction with other type I TKIs (like crenolanib). D842V mutant GIST do not show any actionable recurrent molecular events of therapeutic significance, therefore this study supports the rationale of novel TKIs development that are currently being evaluated in clinical studies for the treatment of D842V mutant GIST

Generic perturbations of linear integrable Hamiltonian systems

In this paper, we investigate perturbations of linear integrable Hamiltonian systems, with the aim of establishing results in the spirit of the KAM theorem (preservation of invariant tori), the Nekhoroshev theorem (stability of the action variables for a finite but long interval of time) and Arnold diffusion (instability of the action variables). Whether the frequency of the integrable system is resonant or not, it is known that the KAM theorem does not hold true for all perturbations; when the frequency is resonant, it is the Nekhoroshev theorem which does not hold true for all perturbations. Our first result deals with the resonant case: we prove a result of instability for a generic perturbation, which implies that the KAM and the Nekhoroshev theorem do not hold true even for a generic perturbation. The case where the frequency is non-resonant is more subtle. Our second result shows that for a generic perturbation, the KAM theorem holds true. Concerning the Nekhrosohev theorem, it is known that one has stability over an exponentially long interval of time, and that this cannot be improved for all perturbations. Our third result shows that for a generic perturbation, one has stability for a doubly exponentially long interval of time. The only question left unanswered is whether one has instability for a generic perturbation (necessarily after this very long interval of time)