Characterization of diblock copolymer order-order transitions in semidilute aqueous solution using fluorescence correlation spectroscopy

The temperature and pH-dependent diffusion of poly(glycerol monomethacrylate)-block-poly(2-hydroxypropyl methacrylate) nanoparticles prepared via polymerization-induced self-assembly in water is characterized using fluorescence correlation spectroscopy (FCS). Lowering the solution temperature or raising the solution pH induces a worm-to-sphere transition and hence an increase in diffusion coefficient by a factor of between four and eight. FCS enables morphological transitions to be monitored at relatively high copolymer concentrations (10% w/w) compared to those required for dynamic light scattering (0.1% w/w). This is important because such transitions are reversible at the former concentration, whereas they are irreversible at the latter. Furthermore, the FCS data suggest that the thermal transition takes place over a very narrow temperature range (less than 2 °C). These results demonstrate the application of FCS to characterize order-order transitions, as opposed to order-disorder transitions. The temperature and pH-dependent diffusion of poly(glycerol monomethacrylate)-block-poly(2-hydroxypropylmethacrylate)- nanoparticles in water is characterized using fluorescence correlation spectroscopy. Lowering either the solution temperature or pH induces a worm-to-sphere transition and hence an increase in diffusion coefficient by a factor of between four and eight

Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer

Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC

Uso de compuestos nutracéuticos en nuevas formulaciones de piensos acuícolas

Trabajo presentado en las X Jornadas de Acuicultura en el Litoral Suratlántico: Nuevos retos y perspectivas para la sostenibilidad de la acuicultura, celebrado entre el 22 y 23 de noviembre de 2023 en Huelva.[EN] Different strategies have been followed to improve the aquaculture of main European farmed fish, such as genetic selection, refinements in culture conditions or enhanced feed formulation and management. However, more knowledge is required to exploit fish phenotypic plasticity to obtain those that better match aquaculture or market conditions. The overall objective of this mini-review is to identify the latest productive traits recently performed, mainly in commercial carnivorous species, and underlying biological processes that would be susceptible to improve the competitivity of aquaculture sector through nutritional issues. Thus, this work is framed within the concepts of Circular Economy and Blue Growth, where it is intended to point out the use of natural compounds extracted from seaweeds, microalgae and by-products of the industry for their inclusion in aquafeeds, allowing a more efficient use of more sustainable vegetable protein sources, and also to evaluate if these nutraceutical compounds counteract detrimental effects observed by nutritional interventions or environmentally challenged.[ES] La producción acuícola ha seguido diferentes estrategias para su optimización a lo largo de las últimas décadas, como el desarrollo de la selección genética, la mejora de las condiciones de cultivo, o el avance en la formulación y gestión de los piensos. Sin embargo, se requiere más conocimiento para explotar la plasticidad fenotípica de los peces para obtener aquellos que se ajusten mejor a las condiciones de la acuicultura o del mercado. El objetivo general de esta mini-revisión es identificar los últimos avances realizados recientemente, principalmente en especies carnívoras comerciales, y los procesos biológicos subyacentes que serían susceptibles de mejorar la competitividad del sector acuícola a través de intervenciones nutricionales. Así, este trabajo se enmarca dentro de los conceptos de Economía Circular y Crecimiento Azul, donde se pretende señalar el uso de compuestos naturales extraídos de algas, microalgas y subproductos de la industria para su inclusión en alimentos acuícolas, permitiendo un uso más eficiente de fuentes de proteínas vegetales más sostenibles, y también evaluar si estos compuestos nutracéuticos son capaces de contrarrestar los efectos perjudiciales observados por las formulaciones inadecuadas o desafiados por factores ambientales estresantes.This work was supported by the Projects “FEDER-UCA18-107182”, “FisioBream-II Call for Young Researchers CEI⋅MAR 2019”, “ALGAE4FISH-CEI·MAR Empresa 2018”, “VALINVA-CEI·MAR Empresa 2019”, “SeriBlue-CEI·MAR Empresa 2020”, and co-financed by the spin-off LifeBioencapsulation S.L. (Almería) and Biotechnology Biopolym S.A. (Granada)

Clinical Predictors of Hyperperfusion Syndrome Following Carotid Stenting: Results From a National Prospective Multicenter Study

[Objectives] The aim of the HISPANIAS (HyperperfusIon Syndrome Post-carotid ANgIoplasty And Stenting) study was to define CHS rates and develop a clinical predictive model for cerebral hyperperfusion syndrome (CHS) after carotid artery stenting (CAS).[Background] CHS is a severe complication following CAS. The presence of clinical manifestations is estimated on the basis of retrospective reviews and is still uncertain.[Methods] The HISPANIAS study was a national prospective multicenter study with 14 recruiting hospitals. CHS was classified as mild (headache only) and moderate-severe (seizure, impaired level of consciousness, or development of focal neurological signs).[Results] A total of 757 CAS procedures were performed. CHS occurred in 22 (2.9%) patients, in which 16 (2.1%) had moderate-severe CHS and 6 (0.8%) had mild CHS (only headache). The rate of hemorrhages was 0.7% and was associated with high mortality (20%). Pre-operative predictors of moderate-severe CHS in multivariate analysis were female sex (odds ratio [OR]: 3.24; 95% confidence interval [CI]: 1.11 to 9.47; p = 0.03), older patients (OR: 1.09; 95% CI: 1.01 to 1.17; p = 0.02), left carotid artery treated (OR: 4.13; 95% CI: 1.11 to 15.40; p = 0.03), and chronic renal failure (OR: 6.29; 95% CI: 1.75 to 22.57; p = 0.005). The area under the curve of this clinical and radiological model was 0.86 (95% CI: 0.81 to 0.92; p = 0.001).[Conclusions] The rate of CHS in the HISPANIAS study was 2.9%, with moderate-severe CHS of 2.1%. CHS was independently associated with female sex, older age, history of chronic kidney disease, and a treated left carotid artery. Although further investigations are needed, the authors propose a model to identify high-risk patients and develop strategies to decrease CHS morbidity and mortality in the future.This study was supported by a Spanish grant from the Instituto de Salud Carlos III (ISCIII-FIS IP14/00971, 2014–2017). The ITRIBIS project has the registration number REGPOT-2013-1. Cooperative Cerebrovascular Disease Research Network (INVICTUS+) (RD16/0019/0015). Dr. Mancha is supported by a Río Hortega contract (CM16/00015). Abbott and Grifols have partial financial supported the conduction of the HISPANIAS project but had no role in the design of the study, interpretation of the data, or manuscript approval.Peer reviewe

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe