Sfrp3 modulates stromal-epithelial crosstalk during mammary gland development by regulating Wnt levels

Mammary stroma is essential for epithelial morphogenesis and development. Indeed, postnatal mammary gland (MG) development is controlled locally by the repetitive and bi-directional cross-talk between the epithelial and the stromal compartment. However, the signalling pathways involved in stromal–epithelial communication are not entirely understood. Here, we identify Sfrp3 as a mediator of the stromal–epithelial communication that is required for normal mouse MG development. Using Drosophila wing imaginal disc, we demonstrate that Sfrp3 functions as an extracellular transporter of Wnts that facilitates their diffusion, and thus, their levels in the boundaries of different compartments. Indeed, loss of Sfrp3 in mice leads to an increase of ductal invasion and branching mirroring an early pregnancy state. Finally, we observe that loss of Sfrp3 predisposes for invasive breast cancer. Altogether, our study shows that Sfrp3 controls MG morphogenesis by modulating the stromal-epithelial cross-talk during pubertal development

The knee prosthesis constraint dilemma: Biomechanical comparison between varus-valgus constrained implants and rotating hinge prosthesis. A cadaver study

The real degree of constriction of rotating hinge knee (RHK) and condylar constrained prostheses (CCK) is a matter of discussion in revision knee arthroplasty. The objectives of this study are to compare the tibial rotation of both implants and validate the use of inertial sensors with optical tracking system as movement measurement tools. A total of 16 cadaver knees were used. Eight knees were replaced using a RHK (Endomodel LINK), and the remaining eight received a CCK prosthesis (LCCK, Zimmer). Tibial rotation range of motion was measured in full extension and at 30°, 60°, and 90° of flexion, with four continuous waveforms for each measurement. Measurements were made using two inertial sensors with specific software and compared with measurements obtained using the gold standard technique - the motion capture camera. The comparison of the accuracy of both measurement methods showed no statistically significant differences between inertial sensors and motion capture cameras, with p > .1; the mean error for tibial rotation was 0.21°. Tibial rotation in the RHK was significantly greater than in the CCK (5.25° vs. 2.28°, respectively), p < .05. We have shown that RHK permit greater tibial rotation, being closer to physiological values than CCKs. Inertial sensors have been validated as an effective and accurate method of measuring knee movement. The clinical significance: RHK appears to represent a lower constriction degree than CCK systems.This study wassupported by Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III and European Regional Development Fund "Una manera de hacer Europa" (grant number PI18/01625

Analysis of Li-ion battery degradation using self-organizing maps

This paper proposes a new methodology to identify the different degradation processes of Li-Ion battery cells. The goal of this study is to determine if different degradation factors can be separated by waveform analysis from aged cells with similar remaining capacity. In contrast to other works, the proposed method identifies the past operating conditions in the cell, regardless of the actual State of Health. The methodology is based on a data-driven approach by using a SOM (Self-organizing map), an unsupervised neural network. To verify the hypothesis a SOM has been trained with laboratory data from whole data cycles, to classify cells concerning their degradation path and according to their discharge voltage patterns. Additionally, this new methodology based on the SOM allows discriminating groups of cells with different cycling conditions (based on depth of discharge, ambient temperature and discharge current). This research line is very promising for classification of used cells, not only depending on their current static parameters (capacity, impedance), but also the battery use in their past life. This will allow making predictions of the Remaining Useful Life (RUL) of a battery with greater precision

Digitalization and real-time control to mitigate environmental impacts along rivers: Focus on artificial barriers, hydropower systems and European priorities

Hydropower globally represents the main source of renewable energy, and provides several benefits, e.g., water storage and flexibility; on the other hand, it may cause significant impacts on the environment. Hence sustainable hydropower needs to achieve a balance between electricity generation, impacts on ecosystems and benefits on society, supporting the achievement of the Green Deal targets. The implementation of digital, information, communication and control (DICC) technologies is emerging as an effective strategy to support such a trade-off, especially in the European Union (EU), fostering both the green and the digital transitions. In this study, we show how DICC can foster the environmental integration of hydropower into the Earth spheres, with focus on the hydrosphere (e.g., on water quality and quantity, hydropeaking mitigation, environmental flow control), biosphere (e.g., improvement of riparian vegetation, fish habitat and migration), atmosphere (reduction of methane emissions and evaporation from reservoirs), lithosphere (better sediment management, reduction of seepages), and on the anthroposphere (e.g., reduction of pollution associated to combined sewer overflows, chemicals, plastics and microplastics). With reference to the abovementioned Earth spheres, the main DICC applications, case studies, challenges, Technology Readiness Level (TRL), benefits and limitations, and transversal benefits for energy generation and predictive Operation and Maintenance (O&M), are discussed. The priorities for the European Union are highlighted. Although the paper focuses primarly on hydropower, analogous considerations are valid for any artificial barrier, water reservoir and civil structure which interferes with freshwater systems.Digitalization and real-time control to mitigate environmental impacts along rivers: Focus on artificial barriers, hydropower systems and European prioritiespublishedVersio

Epigenetics modifications and Subclinical Atherosclerosis in Obstructive Sleep Apnea: The EPIOSA study.

Background Obstructive sleep apnea (OSA) is associated with increased risk for cardiovascular morbidity and mortality. Epidemiological and animal models studies generate hypotheses for innovative strategies in OSA management by interferig intermediates mechanisms associated with cardiovascular complications. We have thus initiated the Epigenetics modification in Obstructive Sleep Apnea (EPIOSA) study (ClinicalTrials.gov identifier: NCT02131610). Methods/design EPIOSA is a prospective cohort study aiming to recruit 350 participants of caucasian ethnicity and free of other chronic or inflammatory diseases: 300 patients with prevalent OSA and 50 non-OSA subjects. All of them will be follow-up for at least 5 years. Recruitment and study visits are performed in single University-based sleep clinic using standard operating procedures. At baseline and at each one year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized questionnaire and physical examination to determine incident comorbidities and health resources utilization, with a primary focus on cardiovascular events. Confirmatory outcomes information is requested from patient records and the regional Department of Health Services. Every year, OSA status will be assessed by full sleep study and blood samples will be obtained for immediate standard biochemistry, hematology, inflammatory cytokines and cytometry analysis. For biobanking, aliquots of serum, plasma, urine, mRNA and DNA are also obtained. Bilateral carotid echography will be performed to assess subclinical atherosclerosis and atherosclerosis progression. OSA patients are treated according with national guidelines. Discussion EPIOSA will enable the prospective evaluation of inflammatory and epigenetics mechanism involved in cardiovascular complication of treated and non-treated patients with OSA compared with non OSA subjects

A phase 2 study of ibrutinib in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma

Objective: We evaluated ibrutinib, a once-daily inhibitor of Bruton's tyrosine kinase, combined with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma who had received 1-3 prior therapies. Methods: This was a phase 2, single-arm, open-label, multicentre study (NCT02902965). The primary endpoint was progression-free survival (PFS). Results: Seventy-six patients were enrolled; 74 received ≥1 dose of study treatment. After median follow-up of 19.6 months, median PFS was 8.5 months (95% CI: 6.2-10.8); median overall survival was not reached. Overall response rate was 57% (95% CI: 45-68), and median duration of response was 9.5 months (95% CI: 6.9-10.6). Grade 3/4 AEs occurred in 73% of patients and fatal AEs occurred in 15% of patients. Incidence of major haemorrhage was 5%; one patient died from cerebral haemorrhage. After an observed increased incidence of serious (42%) and fatal (11%) infections, enrolment was suspended to implement risk-minimisation measures. The safety profile was otherwise consistent with known safety profiles of the individual drugs. Conclusion: Ibrutinib combined with bortezomib and dexamethasone elicited clinical responses. However, efficacy assessments conducted at potential restart of enrolment indicated that the targeted PFS could not be reached with additional patient enrolment, and the study was terminated

EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA); Scientific Opinion on establishing Food-Based Dietary Guidelines

This Opinion of the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) provides guidance on the translation of nutrient based dietary advice into guidance, intended for the European population as a whole, on the contribution of different foods or food groups to an overall diet that would help to maintain good health through optimal nutrition (food-based dietary guidelines). The main focus of this Opinion is put on the scientific process of developing food-based dietary guidelines (FBDG) for the diverse European populations, following a stepwise approach which should ideally consist of: 1) Identification of diet-health relationships, 2) Identification of country specific diet-related health problems, 3) Identification of nutrients of public health importance, 4) Identification of foods relevant for FBDG, 5) Identification of food consumption patterns, 6) Testing and optimising FBDG and 7) Graphical representations of FBDG. FBDG should focus on the diet-disease relationships of particular relevance to the specific population and should be developed using a multi-disciplinary approach. The early involvement of stakeholders is recommended to promote the acceptance of the outcome. FBDG should be consistent with other public policies that have an impact on food availability and be integrated with other policies related to health promotion. Once established, FBDG should be implemented and their impact monitored and evaluate