51 research outputs found
Near-field electrospinning of conjugated polymer light-emitting nanofibers
The authors report on the realization of ordered arrays of light-emitting
conjugated polymer nanofibers by near-field electrospinning. The fibers, made
by poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene], have diameters of
few hundreds of nanometers and emission peaked at 560 nm. The observed
blue-shift compared to the emission from reference films is attributed to
different polymer packing in the nanostructures. Optical confinement in the
fibers is also analyzed through self-waveguided emission. These results open
interesting perspectives for realizing complex and ordered architectures by
light-emitting nanofibers, such as photonic circuits, and for the precise
positioning and integration of conjugated polymer fibers into light-emitting
devices.Comment: 11 pages, 6 figures Nanoscale, 201
Anisotropic conjugated polymer chain conformation tailors the energy migration in nanofibers
Conjugated polymers are complex multi-chromophore systems, with emission
properties strongly dependent on the electronic energy transfer through active
sub-units. Although the packing of the conjugated chains in the solid state is
known to be a key factor to tailor the electronic energy transfer and the
resulting optical properties, most of the current solution-based processing
methods do not allow for effectively controlling the molecular order, thus
making the full unveiling of energy transfer mechanisms very complex. Here we
report on conjugated polymer fibers with tailored internal molecular order,
leading to a significant enhancement of the emission quantum yield. Steady
state and femtosecond time-resolved polarized spectroscopies evidence that
excitation is directed toward those chromophores oriented along the fiber axis,
on a typical timescale of picoseconds. These aligned and more extended
chromophores, resulting from the high stretching rate and electric field
applied during the fiber spinning process, lead to improved emission
properties. Conjugated polymer fibers are relevant to develop optoelectronic
plastic devices with enhanced and anisotropic properties.Comment: 43 pages, 15 figures, 1 table in Journal of the American Chemical
Society, (2016
Bright light emission and waveguiding in conjugated polymer nanofibers electrospun from organic-salt added solutions
Light emitting electrospun nanofibers of
poly-[(9,9-dioctylfluorenyl-2,7-diyl)-co-(N,N'-diphenyl)-N,N'-di(p-butyl-oxy-phenyl)-1,4-diaminobenzene)]
(PFO-PBAB) are produced by electrospinning under different experimental
conditions. In particular, uniform fibers with average diameter of 180 nm are
obtained by adding an organic salt to the electrospinning solution. The
spectroscopic investigation assesses that the presence of the organic salt does
not alter the optical properties of the active material, therefore providing an
alternative approach for the fabrication of highly emissive conjugated polymer
nanofibers. The produced nanofibers display self-waveguiding of light, and
polarized photoluminescence, which is especially promising for embedding active
electrospun fibers in sensing and nanophotonic devices.Comment: 31 pages, 9 figures, 1 table. Macromolecules (2013
Sub-ms dynamics of the instability onset of electrospinning
Electrospun polymer jets are imaged for the first time at an ultra-high rate
of 10,000 frames per second, investigating the process dynamics, and the
instability propagation velocity and displacement in space. The polymer
concentration, applied voltage bias and needle-collector distance are
systematically varied, and their influence on the instability propagation
velocity and on the jet angular fluctuations analyzed. This allows us to unveil
the instability formation and cycling behavior, and its exponential growth at
the onset, exhibiting radial growth rates of the order of 10^3 s^-1. Allowing
the conformation and evolution of polymeric solutions to be studied in depth,
high-speed imaging at sub-ms scale shows a significant potential for improving
the fundamental knowledge of electrified jets, leading to obtain finely
controllable bending and solution stretching in electrospinning, and
consequently better designed nanofibers morphologies and structures.Comment: 23 pages, 9 figure
Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis
The liver is a very tolerogenic organ. It is continually exposed to a multitude of antigens and is able to promote an effective immune response against pathogens and simultaneously immune tolerance against self-antigens. In spite of strong peripheral and central tolerogenic mechanisms, loss of tolerance can occur in autoimmune liver diseases, such as autoimmune hepatitis (AIH) through a combination of genetic predisposition, environmental factors, and an imbalance in immunological regulatory mechanisms. The liver hosts several types of conventional resident antigen presenting cells (APCs) such as dendritic cells, B cells and macrophages (Kupffer cells), and unconventional APCs including liver sinusoidal endothelial cells, hepatic stellate cells and hepatocytes. By standard (direct presentation and cross-presentation) and alternative mechanisms (cross-dressing and MHC class II-dressing), liver APCs presents self-antigen to naive T cells in the presence of costimulation leading to an altered immune response that results in liver injury and inflammation. Additionally, the transport of antigens and antigen:MHC complexes by trogocytosis and extracellular vesicles between different cells in the liver contributes to enhance antigen presentation and amplify autoimmune response. Here, we focus on the impact of antigen presentation on the immune response in the liver and on the functional role of the immune cells in the induction of liver inflammation. A better understanding of these key pathogenic aspects could facilitate the establishment of novel therapeutic strategies in AIH
Antibiotics or No Antibiotics, That Is the Question: An Update on Efficient and Effective Use of Antibiotics in Dental Practice
The antimicrobial resistance (AMR) phenomenon is an emerging global problem and is induced by overuse and misuse of antibiotics in medical practice. In total, 10% of antibiotic prescriptions are from dentists, usually to manage oro-dental pains and avoid postsurgical complications. Recent research and clinical evaluations highlight new therapeutical approaches with a reduction in dosages and number of antibiotic prescriptions and recommend focusing on an accurate diagnosis and improvement of oral health before dental treatments and in patients' daily lives. In this article, the most common clinical and operative situations in dental practice, such as endodontics, management of acute alveolar abscesses, extractive oral surgery, parodontology and implantology, are recognized and summarized, suggesting possible guidelines to reduce antibiotic prescription and consumption, maintaining high success rates and low complications rates. Additionally, the categories of patients requiring antibiotic administration for pre-existing conditions are recapitulated. To reduce AMR threat, it is important to establish protocols for treatment with antibiotics, to be used only in specific situations. Recent reviews demonstrate that, in dentistry, it is possible to minimize the use of antibiotics, thoroughly assessing patient's conditions and type of intervention, thus improving their efficacy and reducing the adverse effects and enhancing the modern concept of personalized medicine
The Evolving Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma Treatment
Hepatocellular carcinoma (HCC) is one of most common cancers and the fourth leading cause of death worldwide. Commonly, HCC development occurs in a liver that is severely compromised by chronic injury or inflammation. Liver transplantation, hepatic resection, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), and targeted therapies based on tyrosine protein kinase inhibitors are the most common treatments. The latter group have been used as the primary choice for a decade. However, tumor microenvironment in HCC is strongly immunosuppressive; thus, new treatment approaches for HCC remain necessary. The great expression of immune checkpoint molecules, such as programmed death-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activating gene 3 protein (LAG-3), and mucin domain molecule 3 (TIM-3), on tumor and immune cells and the high levels of immunosuppressive cytokines induce T cell inhibition and represent one of the major mechanisms of HCC immune escape. Recently, immunotherapy based on the use of immune checkpoint inhibitors (ICIs), as single agents or in combination with kinase inhibitors, anti-angiogenic drugs, chemotherapeutic agents, and locoregional therapies, offers great promise in the treatment of HCC. This review summarizes the recent clinical studies, as well as ongoing and upcoming trials
Actors on the Scene: Immune Cells in the Myeloma Niche
Two mechanisms are involved in the immune escape of cancer cells: the immunoediting of tumor cells and the suppression of the immune system. Both processes have been revealed in multiple myeloma (MM). Complex interactions between tumor plasma cells and the bone marrow (BM) microenvironment contribute to generate an immunosuppressive milieu characterized by high concentration of immunosuppressive factors, loss of effective antigen presentation, effector cell dysfunction, and expansion of immunosuppressive cell populations, such as myeloid-derived suppressor cells, regulatory T cells and T cells expressing checkpoint molecules such as programmed cell death 1. Considering the great immunosuppressive impact of BM myeloma microenvironment, many strategies to overcome it and restore myeloma immunosurveillance have been elaborated. The most successful ones are combined approaches such as checkpoint inhibitors in combination with immunomodulatory drugs, anti-monoclonal antibodies, and proteasome inhibitors as well as chimeric antigen receptor (CAR) T cell therapy. How best to combine anti-MM therapies and what is the optimal timing to treat the patient are important questions to be addressed in future trials. Moreover, intratumor MM heterogeneity suggests the crucial importance of tailored therapies to identify patients who might benefit the most from immunotherapy, reaching deeper and more durable responses
Second-line treatments for Advanced Hepatocellular Carcinoma: A Systematic Review and Bayesian Network Meta-analysis
Background & Aims
A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line treatments for HCC has been performed to better tailor their use based on improved patient stratification and to identify the best available option.
Methods
Pubmed, Scopus, Web of Science, and ClinicalTrials.gov were searched for randomized controlled trials evaluating second-line treatment for advanced HCC in patients already treated with sorafenib. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and drug withdrawal due to adverse events. Network meta-analyses were performed considering placebo as the basis for comparison in efficacy and safety analyses. Subgroup stratification considered gender, age, sorafenib-responsiveness and drug tolerability, viral infection, macrovascular invasion, HCC extrahepatic spread, performance status, and alpha-fetoprotein levels.
Results
Fourteen phase II or III randomized controlled trials, involving 5,488 patients and 12 regimens, were included in the analysis. Regorafenib (hazard ratio (HR) = 0.63, 95% confidence interval (CI) = 0.50–0.79), cabozantinib (HR = 0.76, 95% CI = 0.63–0.92), and ramucirumab (HR = 0.82, 95% CI = 0.70–0.76) significantly prolonged OS compared with placebo. Cabozantinib (HR = 0.44, 95% CI = 0.36–0.52), regorafenib (HR = 0.46, 95% CI = 0.37–0.56), ramucirumab (HR = 0.54, 95% CI = 0.43–0.68), brivanib (HR = 0.56, 95% CI = 0.42–0.76), S-1 (HR = 0.60, 95% CI = 0.46–0.77), axitinib (HR = 0.62, 95% CI = 0.44–0.87), and pembrolizumab (HR = 0.72, 95% CI = 0.57–0.90) significantly improved PFS compared with placebo. None of the compared drugs deemed undoubtedly superior after having performed a patients’ stratification.
Conclusions
The results of this network meta-analysis suggest the use of regorafenib and cabozantinib as second-line treatments in HCC
HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years
BACKGROUND & AIMS:
In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM long-term safety profile were also evaluated.
METHODS:
One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5years were included. Biochemical and virological tests were assessed every 3months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequenced in virological breakthrough patients.
RESULTS:
One hundred and ninety-one patients (148 males, median age 53years, 72 with compensated cirrhosis) responding to 60-month LAM monotherapy continued to receive LAM monotherapy beyond the initial 5years and were followed for an additional 36-month median period (range 1-108). Virological response was maintained in 128/191 patients (67%) and HBsAg clearance was observed in 15/128 (11.7%) after a 32-month median period (range 1-65). The 63 remaining patients (33%) showed virological breakthrough after a 15-month median treatment (range 1-78). RT region analysis was performed in 38/63 breakthrough patients and LAM resistant mutations were found in 37/38. No significant side effects were observed.
CONCLUSIONS:
In long-term responder patients, continuation of LAM monotherapy resulted in persistent viral suppression in most cases with undetectable HBV DNA by real-time PCR; moreover, 11.7% of these patients cleared HBsAg. Selection of LAM resistance, however, can still occur even after successful long-term therapy, thus emphasising the importance of a careful virological monitorin
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