Second-line chemotherapy for advanced pancreatic cancer: Which is the best option?

Despite recent biological insight and therapeutic advances, the prognosis of advanced pancreatic cancer still remains poor. For more than 15 years, gemcitabine monotherapy has been the cornerstone of first-line treatment. Recently, prospective randomized trials have shown that novel upfront combination regimens tested in prospective randomized trials have resulted in improved patients' outcome increasing the proportion of putative candidate to second-line therapy.

Nonpegylated liposomal doxorubicin combination regimen in patients with diffuse large B-cell lymphoma and cardiac comorbidity. Results of the HEART01 phase II trial conducted by the Fondazione Italiana Linfomi.

The purpose of this phase 2, multicenter study was to determine the activity and safety of nonpegylated liposomal doxorubicin as part of "R-COMP" combination in patients with diffuse large B-cell lymphoma and coexisting cardiac disorders. The study was conducted using a Bayesian continuing assessment method using complete remission rate and rate of cardiac events as study endpoints. Between November 2009 and October 2011, 50 evaluable patients were enrolled (median age, 76 years).

Sublethal effects in Perinereis gualpensis (Polychaeta: Nereididae) exposed to mercury-pyrene sediment mixture observed in a multipolluted estuary.

Sediment-living organisms can be subjected to a multi-pollution condition due to an increase in the diversity of contaminants. Sediment mixtures of Mercury (Hg) and some polycyclic aromatics hydrocarbons like Pyrene (Pyr) are common in heavily industrialized coastal zones. In the present study, greater than (>) and less than (<) probable effect concentration levels (PELs) of Hg and Pyr were assessed using spiked sediments in order to determine combined (Hg + Pyr) effects in uptake, metabolization and oxidative balance in the polychaete Perinereis gualpensis at short and medium-term exposure.

Pesticide impact study in the peri-urban horticultural area of Gran La Plata, Argentina.

Vegetable production systems are characterized by intense pesticide use, yet the effects on the surrounding environment are largely unknown and need to be studied. Given this knowledge gap, the objective of this work is to determine the impact of horticulture on a representative watercourse by conducting an integrated study of the occurrence and concentration of pesticides in bottom sediments and their relation to lethal and sublethal effects on benthic fauna. Two sampling campaigns were conducted during seasons of low and high pesticide application in five sites along the Carnaval creek, located in the peri-urban area of La Plata City (Buenos Aires, Argentina).

Morphovolumetric changes after EMDR treatment in drug-naïve PTSD patients.

Introduction: Few studies have investigated the effects of efficacious psychotherapy on structural alterations of discrete brain regions associated with posttraumatic stress disorder (PTSD). We therefore proposed to evaluate the neurobiological effects of eye movement desensitization and reprocessing (EMDR) on 19 patients with drug-naïve PTSD without comorbidity, matched with 19 untreated healthy controls.

Methods: We administered the Clinician Administered PTSD Scale (CAPS) and conducted brain MRI measurements (with Optimized Voxel-Based Morphometry).

Chemosensory adaptations of the mountain fly Drosophila nigrosparsa (Insecta: Diptera) through genomics' and structural biology's lenses.

Chemoreception is essential for survival. Some chemicals signal the presence of nutrients or toxins, others the proximity of mating partners, competitors, or predators. Chemical signal transduction has therefore been studied in multiple organisms.

Occurrence and fate of pesticides in the Argentine stretch of the Paraguay-Paraná basin.

The Argentine stretch of the del Plata basin crosses regions devoted to extensive and intensive agriculture mostly with chemical pest control. The utilization of pesticides in the region has increased 900% in the last two decades associated with the introduction of biotech crops and direct-seeding techniques. Our objective was to study the occurrence, concentration, and fate of pesticides in surface water and bottom sediments of the principal tributaries and main watercourse of the Paraguay-Paraná River.

Factors affecting the mechanical behavior of collagen hydrogels for skin tissue engineering.

The effect of the production factors yielding a functional dermal substitute was investigated by means of monotonic and cyclic uniaxial tensile tests, as well as electron microscopy visualizations. The role of (i) plastic compression, (ii) product incubation, and (iii) cell permanence in the collagenous matrix in order to achieve a skin-like behavior were characterized in terms of material and structural stiffness, in-plane kinematics, and cyclic response, as well as pore size and network density. The plastic compression resulted in a denser and stiffer material, while no corresponding change was observed in the behavior of the entire structure.

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer.

Background: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression.

Methods: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines.

Tissue-specific bioconcentration and biotransformation of cypermethrin and chlorpyrifos in a native fish (Jenynsia multidentata) exposed to these insecticides singly and in mixtures.

The aim of the present study was to evaluate the accumulation of cypermethrin and chlorpyrifos when the fish Jenynsia multidentata was exposed to these pesticides singly and in technical and commercial mixtures. Adult female fish were exposed over 96 h to 0.04 μg/L of cypermethrin; 0.

About ATMPs, SOPs and GMP: The Hurdles to Produce Novel Skin Grafts for Clinical Use.

Background: The treatment of severe full-thickness skin defects represents a significant and common clinical problem worldwide. A bio-engineered autologous skin substitute would significantly reduce the problems observed with today's gold standard.

Methods: Within 15 years of research, the Tissue Biology Research Unit of the University Children's Hospital Zurich has developed autologous tissue-engineered skin grafts based on collagen type I hydrogels.

Differential effects of contractile potentiators on action potential-induced Ca transients of frog and mouse skeletal muscle fibres.

Muscle fibres, isolated from frog tibialis anterior and mouse flexor digitorum brevis (FDB) were loaded with the fast dye MagFluo-4 to study the effects of potentiators caffeine, nitrate, Zn and perchlorate on Ca transients elicited by single action potentials. Overall, the potentiators doubled the transients amplitude and prolonged by about 1.5-fold their decay time.

Fully Endoscopic Freehand Evacuation of Spontaneous Supratentorial Intraparenchymal Hemorrhage.

Objective: A modification of other reported endoscopic techniques for intracerebral clot evacuation is described and illustrated.

Methods: From January 2014 to December 2014, we operated on 6 patients harboring a spontaneous supratentorial intracerebral hemorrhage using a fully endoscopic freehand technique. Clinical chart and surgical videos were analyzed.

Water quality of the main tributaries of the Paraná Basin: glyphosate and AMPA in surface water and bottom sediments.

The Paraná River, the sixth largest in the world, is the receptor of pollution loads from tributaries traversing urban and industrialized areas plus agricultural expanses, particularly so in the river's middle and lower reaches along the Argentine sector. In the present study, we analyzed and discussed the main water quality parameters, sediment compositions, and content of the herbicide glyphosate plus its metabolite aminomethylphosphonic acid (AMPA) in water and sediments. Samples were obtained from distal positions in the principal tributaries of the Paraná and the main watercourse during surveys conducted in 2011 and 2012 to monitor the basin.

Traumatic Presentation of a Periorbital Dermoid Cyst: A Case Report.

Dermoid cysts are largely considered benign, developmental neoplasms that frequently present during childhood. Orbitofacial dermoids represent a unique group of embryologically derived soft tissue masses that often present as localized, well-circumscribed swellings along the embryonal suture lines. Clinical presentation is variable, but in rare instances, may be preceded by local trauma, possibly suggesting an inciting event as the initial stimulus to cyst enlargement.

3D-Printing of Arteriovenous Malformations for Radiosurgical Treatment: Pushing Anatomy Understanding to Real Boundaries.

Radiosurgery of arteriovenous malformations (AVMs) is a challenging procedure. Accuracy of target volume contouring is one major issue to achieve AVM obliteration while avoiding disastrous complications due to suboptimal treatment. We describe a technique to improve the understanding of the complex AVM angioarchitecture by 3D prototyping of individual lesions.

Brain phosphorylation of MeCP2 at serine 164 is developmentally regulated and globally alters its chromatin association.

MeCP2 is a transcriptional regulator whose functional alterations are responsible for several autism spectrum and mental disorders. Post-translational modifications (PTMs), and particularly differential phosphorylation, modulate MeCP2 function in response to diverse stimuli. Understanding the detailed role of MeCP2 phosphorylation is thus instrumental to ascertain how MeCP2 integrates the environmental signals and directs its adaptive transcriptional responses.

APOBEC4 Enhances the Replication of HIV-1.

APOBEC4 (A4) is a member of the AID/APOBEC family of cytidine deaminases. In this study we found a high mRNA expression of A4 in human testis. In contrast, there were only low levels of A4 mRNA detectable in 293T, HeLa, Jurkat or A3.

First-Ever Stroke and Transient Ischemic Attack Incidence and 30-Day Case-Fatality Rates in a Population-Based Study in Argentina.

Background And Purpose: Epidemiological data about stroke are scarce in low- and middle-income Latin-American countries. We investigated annual incidence of first-ever stroke and transient ischemic attack (TIA) and 30-day case-fatality rates in a population-based setting in Tandil, Argentina.

Methods: We prospectively identified all first-ever stroke and TIA cases from overlapping sources between January 5, 2013, and April 30, 2015, in Tandil, Argentina.

Fungistatic activity of all-trans retinoic acid against Aspergillus fumigatus and Candida albicans.

Purpose: Fungal infections are a major complication in hematologic and neoplastic patients causing severe morbidity and mortality. Aspergillus fumigatus and Candida albicans are among the most invasive opportunistic pathogens in immunocompromised patients, and classic antifungal drugs are frequently unsuccessful in these patients. Recent reports hypothesize that the antifungal efficacy of all-trans retinoic acid (ATRA) is mainly related to its strong capacity to stimulate monocyte-mediated immunity, but no consideration was given to its potential direct fungistatic activity.

The Immune Revolution in Gastrointestinal Tumours: Leading the Way or Just Following?

The encouraging results in immunotherapy for melanoma also led the way for translational and clinical research about immune-related mechanisms possibly relevant for gastrointestinal tumours. It is in fact now evident that the immune checkpoint modulation and in particular cell-mediated immune-response through programmed cell death-1 (PD-1) and the cytotoxic T-lymphocyte antigen-4 (CTLA4) receptors along with the regulatory T cells activity all have a relevant role in gastrointestinal cancers as well. This review aims to explore the state of the art of immunotherapy for gastrointestinal tumours, deepening recent scientific evidence regarding anti PD-1/PDL-1 and anti CTLA4 monoclonal antibodies, peptide based vaccine, DNA based vaccine, and pulsed dendritic cells, either alone or in combination with other antineoplastic medical therapy and locoregional treatments.

Quantitative proteomics reveals the importance of nitrogen source to control glucosinolate metabolism in Arabidopsis thaliana and Brassica oleracea.

Accessing different nitrogen (N) sources involves a profound adaptation of plant metabolism. In this study, a quantitative proteomic approach was used to further understand how the model plant Arabidopsis thaliana adjusts to different N sources when grown exclusively under nitrate or ammonium nutrition. Proteome data evidenced that glucosinolate metabolism was differentially regulated by the N source and that both TGG1 and TGG2 myrosinases were more abundant under ammonium nutrition, which is generally considered to be a stressful situation.

Health facilities humanisation: design guidelines supported by statistical evidence.

Background: Healthcare building humanisation is currently a widely debated issue and the development of patient centered and evidence based design is growing worldwide. Many international health organizations and researchers understand the importance of Patient Centred Design and leading architects incorporate it into the design process. In Italy this design approach is still at an early stage.