Spheresomes are the main extracellular vesicles in low-grade gliomas

Cancer progression and its impact on treatment response and prognosis is deeply regulated by tumour microenvironment (TME). Cancer cells are in constant communication and modulate TME through several mechanisms, including transfer of tumour-promoting cargos through extracellular vesicles (EVs) or oncogenic signal detection by primary cilia. Spheresomes are a specific EV that arise from rough endoplasmic reticulum–Golgi vesicles. They accumulate beneath cell membrane and are released to the extracellular medium through multivesicular spheres. This study describes spheresomes in low-grade gliomas using electron microscopy. We found that spheresomes are more frequent than exosomes in these tumours and can cross the blood–brain barrier. Moreover, the distinct biogenesis processes of these EVs result in unique cargo profiles, suggesting different functional roles. We also identified primary cilia in these tumours. These findings collectively contribute to our understanding of glioma progression and metastasis

The importance of organizational variables in treatment time for patients with ST-elevation acute myocardial infarction improve delays in STEMI

Background: The time between arrival at the emergency department (ED) and balloon (D2B) in STEMI is one of the best indicators of the quality of care. Our aim is to describe treatment times and evaluate the causes of delay. Methods: This is an observational retrospective study, including all consecutive STEMI code patients ≥18 years old treated in the ED from 2013 to 2016.All the patients were stratified into two groups: delayed group with D2B > 70 min and non-delayed ≤70. The primary variable was D2B time. Findings: In total 327 patients were included, stratified according to their D2B as follows: 166 (67·48%) in the delayed group and 80 (32·52%) in the non-delayed group. The delayed group was older (p = 0·005), with more females (p = 0·060) and more atypical electrocardiogram (ECG) STEMI signs or symptoms (p = 0·058) (p = 0·087). Predictors of shorter D2B time were: typical STEMI ECG signs and short training sessions for nurses on identifying STEMI patients. Interpretation: There are delays particularly in specific groups with atypical clinical presentations. Short training sessions aimed at emergency nurses correlate with shorter delay. This suggests that continuing training for emergency nurses, along with organizational strategies, can contribute to increasing the quality of care. Clinical trial number: NCT0433338

Novel ball head screw and screwdriver design for implant-supported prostheses with angled channels: a finite element analysis

The primary objective of this study was to design the optimal geometry of a novel screwdriver, create the grooves on a ball head screw, and demonstrate its resistance to a torque of up to 40 Ncm at angulations of 0°, 15°, and 30° by using nonlinear finite element analysis. A secondary objective was to create a foolproof, easily recognizable system. The grooved ball head screw and geometry of the screwdriver, functioning from an angulation of 0° to 30°, was generated using Pro-ENGINEER Wildfire 5.0 software. Static structural analyses among bodies in contact were performed at different angles of 0°, 15°, and 30° at a torque of 20 Ncm and 40 Ncm using nonlinear finite element simulation by means of ANSYS 12.0. The maximum stress supported by the ball head screw and screwdriver was similar at 20 Ncm and 40 Ncm. Although greater deformations were found at 40 Ncm, these were small and might not affect the performance of the system. Further, the rupture torque value for the M2 connection was 55 Ncm for 0° and 30°, and 47.5 Ncm for 15°. Numerical simulation showed that the ball head system design can achieve the mechanical strength requirements expected for screws used in implant-supported restorations at an angulation of up to 30°. Finite element analysis showed this novel ball head screw and screwdriver system to be a good solution for angled screw channels in implant-supported prostheses

Strategies and methods to study sex differences in cardiovascular structure and function: a guide for basic scientists

<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease remains the primary cause of death worldwide. In the US, deaths due to cardiovascular disease for women exceed those of men. While cultural and psychosocial factors such as education, economic status, marital status and access to healthcare contribute to sex differences in adverse outcomes, physiological and molecular bases of differences between women and men that contribute to development of cardiovascular disease and response to therapy remain underexplored.</p> <p>Methods</p> <p>This article describes concepts, methods and procedures to assist in the design of animal and tissue/cell based studies of sex differences in cardiovascular structure, function and models of disease.</p> <p>Results</p> <p>To address knowledge gaps, study designs must incorporate appropriate experimental material including species/strain characteristics, sex and hormonal status. Determining whether a sex difference exists in a trait must take into account the reproductive status and history of the animal including those used for tissue (cell) harvest, such as the presence of gonadal steroids at the time of testing, during development or number of pregnancies. When selecting the type of experimental animal, additional consideration should be given to diet requirements (soy or plant based influencing consumption of phytoestrogen), lifespan, frequency of estrous cycle in females, and ability to investigate developmental or environmental components of disease modulation. Stress imposed by disruption of sleep/wake cycles, patterns of social interaction (or degree of social isolation), or handling may influence adrenal hormones that interact with pathways activated by the sex steroid hormones. Care must be given to selection of hormonal treatment and route of administration.</p> <p>Conclusions</p> <p>Accounting for sex in the design and interpretation of studies including pharmacological effects of drugs is essential to increase the foundation of basic knowledge upon which to build translational approaches to prevent, diagnose and treat cardiovascular diseases in humans.</p

Embedded bleeding detector into a PMMA applicator for electron intraoperative radiotherapy

Purpose: The aim of this work is to present a ready to industrialize low-cost and easy-to-install bleeding detector for use in intraoperative electron radiation therapy (IOERT). The detector works in stand-alone mode and is embedded into a translucent polymethylmethacrylate (PMMA) applicator avoiding any contact with the patient, which represent a novelty compared to previous designs. The use of this detector will prevent dose misadministration during irradiation in the event of accumulation of fluids in the applicator. Methods: The detector is based on capacitive sensor and wireless power-supply electronics. Both sensor and electronics have been embedded in the applicator, so that any contact with the patient would be avoided. Since access to the tumor can be done through different trajectories, the detector has been calibrated for different tilting angles. Results: The result of the calibration provides us with a fit curve that allows the interpolation of the results at any angle. Comparison of estimated fluid height vs real height gives an error of 1 mm for tilting angles less than 10º and 2 mm for tilting angles greater than 15º. This accuracy is better than the one required by clinic. Conclusions: The performance of the bleeding detector was evaluated in situ. No interference was observed between the detector and the beam. In addition, a user-friendly mobile application has been developed to help the surgical team making decisions before and during irradiation. The measurement provided by the mobile application was stable during the irradiation process

Cellulose dissolution and regeneration using a non-aqueous, non-stoichiometric protic ionic liquid system

The solubility of cellulose has been studied as a function of composition in the binary mixture of 1,1,3,3-tetramethylguanidine and propionic acid. In amine-rich compositions, greater quantities of cellulose can be dissolved than in the equimolar composition, a.k.a. the protic ionic liquid [TMGH][OPr]. By applying a methodology of a short period of heating followed by cooling, similar concentrations of cellulose can be achieved in a much shorter time period. Finally, regeneration of cellulose from solution can be achieved by altering the acid:amine molar ratio. In comparison to cellulose regenerated from these solutions using water as an antisolvent, cellulose regenerated with propionic acid exhibit a lower crystallinity as inferred from x-ray diffractometry, but a greater average molecular weight as inferred from gel permeation chromatography

Spain

This chapter presents a review of the situation concerning the various geomorphological hazards in the country, including some information about existing programmes for research, control and mitigation. With its great variety of climatic, geological and morphodynamic environments, Spain is subject to every kind of natural hazard: tsunamis, floods, volcanism, and mass movements. The whole of the territory is prone to some kind of geomorphological hazard but it is in the eastern and southern coastal strips that the risks are greatest. One of the main problems for the mitigation of geomorphological hazards in Spain is the lack of an appropriate regulatory framework for the incorporation of natural hazard assessments into land-use planning and management at the macro-, meso- and micro-planning levels. The coverage of hazard mapping is still far from complete or adequate, and much work remains to be done. There has been considerable diversity in the methods used for risk assessment and for the cartographic representation of natural hazards. An urgent need is to establish common, accepted methodologies and criteria, based on indicators defined as clearly as possible, and to standardize map legends and scales for different planning levels. Information programmes for the general public also need to be considerably expanded

mTOR Controls Ovarian Follicle Growth by Regulating Granulosa Cell Proliferation

We have shown that inhibition of mTOR in granulosa cells and ovarian follicles results in compromised granulosa proliferation and reduced follicle growth. Further analysis here using spontaneously immortalized rat granulosa cells has revealed that mTOR pathway activity is enhanced during M-phase of the cell cycle. mTOR specific phosphorylation of p70S6 kinase and 4E-BP, and expression of Raptor are all enhanced during M-phase. The predominant effect of mTOR inhibition by the specific inhibitor Rapamycin (RAP) was a dose-responsive arrest in the G1 cell cycle stage. The fraction of granulosa cells that continued to divide in the presence of RAP exhibited a dose-dependent increase in aberrant mitotic figures known as anaphase bridges. Strikingly, estradiol consistently decreased the incidence of aberrant mitotic figures. In mice treated with RAP, the mitotic index was reduced compared to controls, and a similar increase in aberrant mitotic events was noted. RAP injected during a superovulation regime resulted in a dose-dependent reduction in the numbers of eggs ovulated. Implications for the real-time regulation of follicle growth and dominance, including the consequences of increased numbers of aneuploid granulosa cells, are discussed