Protein-loaded PLGA-PEG-PLGA microspheres: a tool for cell therapy.

International audienceA promising strategy to repair injured organs is possible by delivering a growth factor via poly-(D,L lactide-co-glycolide) (PLGA) microspheres; the latter are coated with adhesion molecules that serve as a support for cell delivery. At present, PLGA is not the optimal choice of polymer because of poor or incomplete protein release. The use of a more hydrophilic PLGA-PEG-PLGA (A-B-A) copolymer increases the degree of protein release. In this work, the impact of different combinations of (B) and (A) segments on the protein-release profile has been investigated. Continuous-release profiles, with no lag phases, were observed. The triblock ABA with a low molecular weight of PEG and a high molecular weight of PLGA showed an interesting release pattern with a small burst (<10% in 48 h) followed by sustained, protein release over 36 days. Incomplete protein release was found to be due to various causes: protein adsorption, protein aggregation and protein denaturation under acidic conditions. Interestingly, cell viability and cell adhesion on microspheres coated with fibronectin highlight the interest of these polymers for tissue engineering applications

New PLGA-P188-PLGA matrix enhances TGF-β3 release from pharmacologically active microcarriers and promotes chondrogenesis of mesenchymal stem cells

The use of injectable scaffolding materials for in vivo tissue regeneration has raised great interest in various clinical applications because it allows cell implantation through minimally invasive surgical procedures. In case of cartilage repair, a tissue engineered construct should provide a support for the cell and allow sustained in situ delivery of bioactive factors capable of inducing cell differentiation into chondrocytes. Pharmacologically active microcarriers (PAMs), made of biodegradable poly(d,l-lactide-co-glycolide acid) (PLGA), are a unique system, which combines these properties in an adaptable and simple microdevice. However, a limitation of such scaffold is low and incomplete protein release that occurs using the hydrophobic PLGA based microspheres. To circumvent this problem, we developed a novel formulation of polymeric PAMs containing a P188 poloxamer, which protects the protein from denaturation and may positively affect chondrogenesis. This poloxamer was added as a free additive for protein complexation and as a component of the scaffold covalently linked to PLGA. This procedure allows getting a more hydrophilic scaffold but also retaining the protective polymer inside the microcarriers during their degradation. The novel PLGA-P188-PLGA PAMs presenting a fibronectin-covered surface allowed enhanced MSC survival and proliferation. When engineered with TGFβ3, they allowed the sustained release of 70% of the incorporated TGF-β3 over time. Importantly, they exerted superior chondrogenic differentiation potential compared to previous FN-PAM-PLGA-TGF-β3, as shown by an increased expression of specific cartilage markers such as cartilage type II, aggrecan and COMP. Therefore, this microdevice represents an efficient easy-to-handle and injectable tool for cartilage repair

Iterative Structural and Functional Synergistic Resolution Recovery (iSFS-RR) Applied to PET-MR Images in Epilepsy

Structural Functional Synergistic Resolution Recovery (SFS-RR) is a technique that uses supplementary structural information from MR or CT to improve the spatial resolution of PET or SPECT images. This wavelet-based method may have a potential impact on the clinical decision-making of brain focal disorders such as refractory epilepsy, since it can produce images with better quantitative accuracy and enhanced detectability. In this work, a method for the iterative application of SFS-RR (iSFS-RR) was firstly developed and optimized in terms of convergence and input voxel size, and the corrected images were used for the diagnosis of 18 patients with refractory epilepsy. To this end, PET/MR images were clinically evaluated through visual inspection, atlas-based asymmetry indices (AIs) and SPM (Statistical Parametric Mapping) analysis, using uncorrected images and images corrected with SFS-RR and iSFS-RR. Our results showed that the sensitivity can be increased from 78% for uncorrected images, to 84% for SFS-RR and 94% for the proposed iSFS-RR. Thus, the proposed methodology has demonstrated the potential to improve the management of refractory epilepsy patients in the clinical routine

Impact of the COVID-19 pandemic on the care of cancer patients in Spain

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Càncer; EspanyaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cáncer; EspañaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cancer; SpainBackground Studies evaluating the effects of the COVID-19 pandemic on public healthcare systems are limited, particularly in cancer management. As no such studies have been carried out in Spain, our objective is to describe and quantify the impact of the COVID-19 pandemic on cancer patients in Spanish hospitals during the first wave of the pandemic. Materials and methods This retrospective, multicenter, nationwide study collected information from hospital departments treating oncology patients. An electronic questionnaire comparing outcomes and management of oncohematological patients for the March-June 2019 and March-June 2020 periods was used. Results Information from 78 departments (36 tertiary hospitals) was analyzed. Forty-four departments implemented adapted protocols during March 2020. Most of these (n = 38/44; 86.4%) carried out COVID-19 triage, while 26 of 44 (59.1%) carried out onsite polymerase chain reaction tests for clinically suspected cases. A shift from in-person to telephone visits was observed in 43 of 44 (97.7%) departments. Comparing the March-June 2019 and March-June 2020 periods, the number of new patients decreased by 20.8% (from 160.2 to 126.4). Decreases were also seen in the mean number of total (2858.2 versus 1686.1) and cancer (465.5 versus 367.2) biopsies, as well as the mean number of bone marrow biopsies (30.5 versus 18.6). Concerning the number of patients visiting specific cancer care departments, a decrease from 2019 to 2020 was seen for mean number of chemotherapy treatments (712.7 versus 643.8) and radiation therapy (2169.9 versus 2139.9). Finally, a reduction from 2019 to 2020 of 12.9% (from 8.6 to 7.4) in the mean number of patients included in clinical trials was noted. Conclusions This study provides the first comprehensive data concerning the impact of COVID-19 on cancer care in Spain. The pandemic caused a 20.8% decrease in newly diagnosed patients, which may impact future outcomes. Measures must be taken to ensure cancer management receives priority in times of healthcare emergencies.This work was supported by funding from the AECC, a non-profit organization, whose medical department funded the study and the medical writing (no grant number)

The entangling side of the Unruh-Hawking effect

We show that the Unruh effect can create net quantum entanglement between inertial and accelerated observers depending on the choice of the inertial state. This striking result banishes the extended belief that the Unruh effect can only destroy entanglement and furthermore provides a new and unexpected source for finding experimental evidence of the Unruh and Hawking effects.Comment: 4 pages, 4 figures. Added Journal referenc

Malignant Mesothelioma subtyping via sampling driven multiple instance prediction on tissue image and cell morphology data

Malignant Mesothelioma is a difficult to diagnose and highly lethal cancer usually associated with asbestos exposure. It can be broadly classified into three subtypes: Epithelioid, Sarcomatoid, and a hybrid Biphasic subtype in which significant components of both of the previous subtypes are present. Early diagnosis and identification of the subtype informs treatment and can help improve patient outcome. However, the subtyping of malignant mesothelioma, and specifically the recognition of transitional features from routine histology slides has a high level of inter-observer variability. In this work, we propose an end-to-end multiple instance learning (MIL) approach for malignant mesothelioma subtyping. This uses an adaptive instance-based sampling scheme for training deep convolutional neural networks on bags of image patches that allows learning on a wider range of relevant instances compared to max or top-N based MIL approaches. We also investigate augmenting the instance representation to include aggregate cellular morphology features from cell segmentation. The proposed MIL approach enables identification of malignant mesothelial subtypes of specific tissue regions. From this a continuous characterisation of a sample according to predominance of sarcomatoid vs epithelioid regions is possible, thus avoiding the arbitrary and highly subjective categorisation by currently used subtypes. Instance scoring also enables studying tumor heterogeneity and identifying patterns associated with different subtypes. We have evaluated the proposed method on a dataset of 234 tissue micro-array cores with an AUROC of 0.89±0.05 for this task. The dataset and developed methodology is available for the community at: https://github.com/measty/PINS

Evidence of the Generation of Isosaccharinic Acids and Their Subsequent Degradation by Local Microbial Consortia within Hyper-Alkaline Contaminated Soils, with Relevance to Intermediate Level Radioactive Waste Disposal

The contamination of surface environments with hydroxide rich wastes leads to the formation of high pH (>11.0) soil profiles. One such site is a legacy lime works at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to pH 12. Soil and porewater profiles around the site indicated clear evidence of the presence of the α and β stereoisomers of isosaccharinic acid (ISA) resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are of particular interest with regards to the disposal of cellulosic materials contained within the intermediate level waste (ILW) inventory of the United Kingdom, where they may influence radionuclide mobility via complexation events occurring within a geological disposal facility (GDF) concept. The mixing of uncontaminated soils with the alkaline leachate of the site resulted in ISA generation, where the rate of generation in-situ is likely to be dependent upon the prevailing temperature of the soil. Microbial consortia present in the uncontaminated soil were capable of surviving conditions imposed by the alkaline leachate and demonstrated the ability to utilise ISAs as a carbon source. Leachate-contaminated soil was sub-cultured in a cellulose degradation product driven microcosm operating at pH 11, the consortia present were capable of the degradation of ISAs and the generation of methane from the resultant H2/CO2 produced from fermentation processes. Following microbial community analysis, fermentation processes appear to be predominated by Clostridia from the genus Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and Methanomassiliicoccus sp. The study is the first to identify the generation of ISA within an anthropogenic environment and advocates the notion that microbial activity within an ILW-GDF is likely to influence the impact of ISAs upon radionuclide migration

Evidence mapping based on systematic reviews of therapeutic interventions for soft tissue sarcomas

Soft tissue sarcomas are a heterogeneous group of rare tumours of mesenchymal origin. Evidence mapping is one of the most didactic and friendly approaches to organise and summarise the range of research activity in broad topic fields. The objective of this evidence mapping is to identify, describe and organise the current available evidence about therapeutic interventions on soft tissues sarcomas. We followed the methodology of global evidence mapping. We performed a search of the PubMed, EMBASE, The Cochrane Library and Epistemonikos to identify systematic reviews (SRs) with or without meta-analyses published between 1990 and March 2016. Two independent literature reviewers assessed eligibility and extracted data. Methodological quality of the included systematic reviews was assessed using AMSTAR. We organised the results according to identified PICO questions and used tables and a bubble plot to display the results. The map is based on 24 SRs that met eligibility criteria and included 66 individual studies. Three-quarters were either observational or uncontrolled clinical trials. The quality of the included SRs was in general moderate or high. We identified 64 PICO questions from them. The corresponding results mostly favoured the intervention arm. This evidence mapping was built on the basis of SRs, which mostly included non-experimental studies and were qualified by the AMSTAR tool as of moderate quality. The evidence mapping created from PICO questions is a useful approach to describe complex and huge clinical topics through graphical media and orientate further research to fulfil the existing gaps. However, it is important to delimitate the steps of the evidence mapping in a pre-established protocol

Spectroscopic study of blue compact galaxies V. oxygen abundance and the metallicity-luminosity relation

This is the fifth paper in a series studying the stellar components, star formation histories, star formation rates and metallicities of a blue compact galaxy (BCG) sample. Based on our high-quality ground-based spectroscopic observations, we have determined the electron temperatures, electron densities, nitrogen abundances and oxygen abundances for 72 star-forming BCGs in our sample, using different oxygen abundance indicators. The oxygen abundance covers the range 7.15 < 12 + log (O/H)< 9.0, and nitrogen is found to be mostly a product of secondary nucleosynthesis for 12 + log (O/H)>8.2 and apparently a product of primary nucleosynthesis for 12 + log (O/H)< 8.2. To assess the possible systematic differences among different oxygen abundance indicators, we have compared oxygen abundances of BCGs obtained with the Te method, R23 method, P method, N2 method and O3N2 method. The oxygen abundances derived from the Te method are systematically lower by 0.1-0.25 dex than those derived from the strong line empirical abundance indicators, consistent with previous studies based on region samples. We confirm the existence of the metallicity-luminosity relation in BCGs over a large range of abundances and luminosities. Our sample of galaxies shows that the slope of the metallicity-luminosity relation for the luminous galaxies (~-0.05) is slightly shallower than that for the dwarf galaxies (~-0.17). An offset was found in the metallicity-luminosity relation of the local galaxies and that of the intermediate redshift galaxies. It shows that the metallicity-luminosity relation for the emission line galaxies at high redshift is displaced to lower abundances, higher luminosities, or both.Comment: 11 pages, 4 figure