Molecular mechanisms driving the microgels behaviour: a Raman spectroscopy and Dynamic Light Scattering study

Responsive microgels based on poly(N-isopropylacrylamide) (PNIPAM) exhibit peculiar behaviours due to the competition between the hydrophilic and hydrophobic interactions of the constituent networks. The interpenetration of poly-acrilic acid (PAAc), a pH-sensitive polymer, within the PNIPAM network, to form Interpenetrated Polymer Network (IPN) microgels, affects this delicate balance and the typical Volume-Phase Transition (VPT) leading to complex behaviours whose molecular nature is still completely unexplored. Here we investigate the molecular mechanism driving the VPT and its influence on particle aggregation for PNIPAM/PAAc IPN microgels by the joint use of Dynamic Light Scattering and Raman Spectroscopy. Our results highlight that PNIPAM hydrophobicity is enhanced by the interpenetration of PAAc promoting interparticle interactions, a crossover concentration is found above which aggregation phenomena become relevant. Moreover we find that, at variance with PNIPAM, for IPN microgels a double-step molecular mechanisms occurs upon crossing the VPT, the first involving the coil-to-globule transition typical of PNIPAM and the latter associated to PAAc steric hindrance.Comment: preprint versio

Study of network composition in interpenetrating polymer networks of poly(N isopropylacrylamide) microgels:the role of poly(acrylic acid)

Hypothesis: The peculiar swelling behaviour of poly(N-isopropylacrylamide) (PNIPAM)-based responsive microgels provides the possibility to tune both softness and volume fraction with temperature, making these systems of great interest for technological applications and theoretical implications. Their intriguing phase diagram can be even more complex if poly(acrylic acid) (PAAc) is interpenetrated within PNIPAM network to form Interpenetrating Polymer Network (IPN) microgels that exhibit an additional pH-sensitivity. The effect of the PAAc/PNIPAM polymeric ratio on both swelling capability and dynamics is still matter of investigation. Experiments: Here we investigate the role of PAAc in the behaviour of IPN microgels across the volume phase transition through dynamic light scattering (DLS), transmission electron microscopy (TEM) and electrophoretic measurements as a function of microgel concentration and pH. Findings: Our results highlight that aggregation is favored at increasing weight concentration, PAAc content and pH and that a crossover PAAc content C*_{PAAc} exists above which the ionic charges on the microgel become relevant. Moreover we show that the softness of IPN microgels can be tuned ad hoc by changing the PAAc/PNIPAM ratio. These findings provide new insights into the possibility to control experimentally aggregation properties, charge and softness of IPN microgels by varying PAAc content.Comment: preprint versio

Endoscopic findings and psychometric abnormalities: what is the relationship in upper endoscopic outpatients?

Background. Psychological disorders are often associated with diseases of the upper digestive tract. Although emotions can influence gastrointestinal function in healthy individuals, psychological setting in upper gastrointestinal patients are unclear. We evaluate the psychological alterations prevalence in outpatients submitted to upper endoscopy. Materials and Methods. A total of 130 patients (50 males and 80 females; mean age 54±17 years) submitted to upper gastrointestinal endoscopy, were enrolled over the period May 2009 - September 2010. Subjects were asked to complete questionnaires before endoscopic examination. Alexithymia, anxiety, depression and coping style were assessed using the Toronto Alexithymia Scale, Spielberger Trait Anxiety Inventory, Beck Depression Inventory and Coping Inventory for Stressful Situations, respectively. Results. Coping impairment, Alexithymia, Anxiety and Depression were found respectively in 80.3%, 25.4%, 24.6% and 17.2%, often in association. Task-oriented, emotion-oriented and avoidance-oriented alterations were found in 41.8%, 40% and 30.6%, respectively. No correlations were demonstrated between diagnosis of upper gastrointestinal disease and psychometric results. Conclusions. In our study, a high prevalence of psychometric alterations in gastrointestinal outpatients was unconnected with endoscopic findings, especially considering coping style alterations. This aspect should be taken into account in patients management and a long-term follow-up should clarify a possible role of these factors in patients prognosis and compliance

Kinetics of dried blood spot-measured anti-SARS-CoV2 Spike IgG in mRNA-vaccinated healthcare workers

Introduction: One of the major criticisms facing the research community during SARS-CoV2 pandemic was the lack of large-scale, longitudinal data on the efficacy of the SARS-CoV2 mRNA vaccines. Currently, even if COVID-19 antiviral treatments have been authorized by European Medicine Agency, prevention through approved specific vaccines is the best approach available in order to contain the ongoing pandemic. Objectives: Here, we studied the antibody kinetic over a one-year period from vaccination with the Pfizer-BioNTech (Pfizer) vaccines and subsequent boosting with either the BioNTech or Moderna (Spikevax) vaccines in a large cohort of 8,071 healthcare workers (HCW). We also described the impact of SARS-CoV2 infection on antibody kinetic over the same period. Methods: We assessed the anti SARS-CoV2 Spike IgG antibody kinetic by the high throughput dried blood spot (DBS) collection method and the GSP®/DELFIA® Anti-SARS-CoV2 IgG assay (PerkinElmer®). Results: Our data support existing models showing that SARS-CoV2 vaccination elicits strong initial antibodies responses that decline with time but are transitorily increased by administering a vaccine booster. We also showed that using heterologous vaccine/booster combinations a stronger antibody response was elicited than utilizing a booster from the same vaccine manufacturer. Furthermore, by considering the impact of SARS-CoV2 infection occurrence in proximity to the scheduled booster administration, we confirmed that booster dose did not contribute significantly to elicit higher antibody responses. Conclusion: DBS sampling in our large population of HCWs was fundamental to collect a large number of specimens and to clarify the effective mRNA vaccine-induced antibody kinetic and the role of both heterologous boosters and SARS-CoV2 infection in modulating antibody responses

Exploring chitosan-shelled nanobubbles to improve HER2 + immunotherapy via dendritic cell targeting

Immunotherapy is a valuable approach to cancer treatment as it is able to activate the immune system. However, the curative methods currently in clinical practice, including immune checkpoint inhibitors, present some limitations. Dendritic cell vaccination has been investigated as an immunotherapeutic strategy, and nanotechnology-based delivery systems have emerged as powerful tools for improving immunotherapy and vaccine development. A number of nanodelivery systems have therefore been proposed to promote cancer immunotherapy. This work aims to design a novel immunotherapy nanoplatform for the treatment of HER2 + breast cancer, and specially tailored chitosan-shelled nanobubbles (NBs) have been developed for the delivery of a DNA vaccine. The NBs have been functionalized with anti-CD1a antibodies to target dendritic cells (DCs). The NB formulations possess dimensions of approximately 300 nm and positive surface charge, and also show good physical stability up to 6 months under storage at 4 °C. In vitro characterization has confirmed that these NBs are capable of loading DNA with good encapsulation efficiency (82%). The antiCD1a-functionalized NBs are designed to target DCs, and demonstrated the ability to induce DC activation in both human and mouse cell models, and also elicited a specific immune response that was capable of slowing tumor growth in mice in vivo. These findings are the proof of concept that loading a tumor vaccine into DC-targeted chitosan nanobubbles may become an attractive nanotechnology approach for the future immunotherapeutic treatment of cancer. GRAPHICAL ABSTRACT: [Image: see text

Local structure of temperature and pH-sensitive colloidal microgels

The temperature dependence of the local intra-particle structure of colloidal microgel particles, composed of interpenetrated polymer networks, has been investigated by small-angle neutron scattering at different pH and concentrations, in the range (299÷315) K, where a volume phase transition from a swollen to a shrunken state takes place. Data are well described by a theoretical model that takes into account the presence of both interpenetrated polymer networks and cross-linkers. Two different behaviors are found across the volume phase transition. At neutral pH and T 307 K, a sharp change of the local structure from a water rich open inhomogeneous interpenetrated polymer network to a homogeneous porous solid-like structure after expelling water is observed. Differently, at acidic pH, the local structure changes almost continuously. These findings demonstrate that a fine control of the pH of the system allows to tune the sharpness of the volume-phase transition

Spain

This report is part of the project The Factbook on the Illicit Trade in Tobacco Products (hereafter ITTP). It focuses on Spain, where the illicit trade in tobacco products is an emerging issue, particularly in certain regions. After tax increases in 2009-2010, Spain became a destination market of illicit tobacco and the ITTP penetration peaked at 8.8% in 2013. Nevertheless, the ITTP level is lower than the European average. In the past, ITTP penetration had decreased from 6% to almost 1% between 1998 and 2010, due to the successful enforcement actions against contraband. Spain used to be a transit country