Alcaraz J, Ikemori R, Llorente A, Díaz-Valdivia N, Reguart N, Vizoso M. Epigenetic reprogramming of tumor-associated fibroblasts in lung cancer: therapeutic opportunities. Cancers. 2021;13:3782.Download referencesWe thank Raimon Sunyer, Pere Roca-Cusachs, Patricia Fernández, Kate Neal , Zanetta Zoi and Joan Montero for technical support, and Ramon Farré for support.
Natalia Díaz-Valdivia, Alejandro Llorente, Rafael Ikemori, Alejandro Bernardo, Marselina Arshakyan & Jordi Alcaraz Institute for Bioengineering of Catalonia , The Barcelona Institute for Science and Technology , 08028, Barcelona, SpainPathology Service, Hospital Clínic de Barcelona, 08036, Barcelona, SpainJosep Ramírez, Noemí Reguart & Jordi Alcaraz
Department of Medical Oncology, Catalan Institute of Oncology, L’Hospitalet de Llobregat , 08908, Barcelona, SpainPreclinical and Experimental Research in Thoracic Tumors group, Oncobell Program, Bellvitge Biomedical Research Institute , L’Hospitalet de Llobregat , 08908, Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer , Barcelona, 08036, Spain
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Pre-hyperglycemia immune cell trafficking underlies subclinical diabetic cataractogenesis - Journal of Biomedical ScienceBackground This work elucidates the first cellular and molecular causes of cataractogenesis. Current paradigm presupposes elevated blood glucose as a prerequisite in diabetic cataractogenesis. Novel evidence in our model of diabetic cataract challenges this notion and introduces immune cell migration to the lens and epithelial-mesenchymal transformation (EMT) of lens epithelial cells (LECs) as underlying causes. Methods Paucity of suitable animal models has hampered mechanistic studies of diabetic cataract, as most studies were traditionally carried out in acutely induced hyperglycemic animals. We introduced diabetic cataract in the Nile grass rat (NGR) that spontaneously develops type 2 diabetes (T2D) and showed its closeness to the human condition. Specialized stereo microscopy with dual bright-field illumination revealed novel hyperreflective dot-like microlesions in the inner cortical regions of the lens. To study immune cell migration to the lens, we developed a unique in situ microscopy technique of the inner eye globe in combination with immunohistochemistry. Results Contrary to the existing paradigm, in about half of the animals, the newly introduced hyper reflective dot-like microlesions preceded hyperglycemia. Even though the animals were normoglycemic, we found significant changes in their oral glucose tolerance test (OGTT), indicative of the prediabetic stage. The microlesions were accompanied with significant immune cell migration from the ciliary bodies to the lens, as revealed in our novel in situ microscopy technique. Immune cells adhered to the lens surface, some traversed the lens capsule, and colocalized with apoptotic nuclei of the lens epithelial cells (LECs). Extracellular degradations, amorphous material accumulations, and changes in E-cadherin expressions showed epithelial-mesenchymal transformation (EMT) in LECs. Subsequently, lens fiber disintegration and cataract progression extended into cortical, posterior, and anterior subcapsular catar
Source: BioMedCentral - 🏆 22. / 71 Read more »
Migraine attacks are of peripheral origin: the debate goes on - The Journal of Headache and PainBackground Despite the pervasiveness of migraine, the underlying pathophysiological mechanisms initiating migraine attacks are far from well understood and are matter of scientific debate. Objective In this narrative review, we discuss key evidence for that suggest a peripheral origin or central origin and provide directions for future studies that may provide further clarification. Discussion Migraine pathogenesis is considered to involve the trigeminovascular system, a term that encompasses the trigeminal nerve and its axonal projections to the intracranial blood vessels. Beyond any doubt both peripheral and central mechanisms are involved in migraine pathogenesis, but an unresolved question is the how the initial activation occurs in a migraine attack. Evidence favoring a peripheral origin of migraine attacks, i.e., initial events occur outside of the blood–brain barrier, include the importance of sensitization of perivascular sensory afferents early on in a migraine attack. Evidence favoring a central origin include the occurrence of prodromal symptoms, migraine aura, and activation of structures within the central nervous system early in and during a migraine attack. Conclusions Both peripheral and central mechanisms are likely involved in a migraine attack, e.g., peripheral nociceptive input is necessary for pain transmission and cortical activity is necessary for pain perception. Yet, the debate of whether migraine attacks are initiated a peripheral or central site remains unresolved. The increased focus on prodromal symptoms and on the development of a human model of migraine aura will possibly provide key arguments needed to answer this question in the near future. Until then, we cannot draw firm conclusions and the debate goes on. Video link Video recording of the debate held at the 1st International Conference on Advances in Migraine Sciences (ICAMS 2022, Copenhagen, Denmark) is available at: https://www.youtube.com/watch?v=NC0nlcKohz0 . Graphical Abstrac
Source: BioMedCentral - 🏆 22. / 71 Read more »
COVID-19 Symptom Monitoring and Social Distancing in a University Population - Journal of Healthcare Informatics ResearchThis paper reports on our efforts to collect daily COVID-19-related symptoms for a large public university population, as well as study relationship between reported symptoms and individual movements. We developed a set of tools to collect and integrate individual-level data. COVID-19-related symptoms are collected using a self-reporting tool initially implemented in Qualtrics survey system and consequently moved to .NET framework. Individual movement data are collected using off-the-shelf tracking apps available for iPhone and Android phones. Data integration and analysis are done in PostgreSQL, Python, and R. As of September 2020, we collected about 184,000 daily symptom responses for 20,000 individuals, as well as over 15,000 days of GPS movement data for 175 individuals. The analysis of the data indicates that headache is the most frequently reported symptom, present almost always when any other symptoms are reported as indicated by derived association rules. It is followed by cough, sore throat, and aches. The study participants traveled on average 223.61 km every week with a large standard deviation of 254.53 and visited on average 5.77 ± 4.75 locations each week for at least 10 min. However, there is no evidence that reported symptoms or prior COVID-19 contact affects movements (p | 0.3 in most models). The evidence suggests that although some individuals limit their movements during pandemics, the overall study population do not change their movements as suggested by guidelines. AI would be a great doctor, interpreting results and symptoms better than humans. The problem is that it will be programmed by pharmaceutical companies and they will program it so that AI will make mistakes.
Source: medical_xpress - 🏆 101. / 51 Read more »
US general warns British Army no longer top-level fighting force, defence sources revealRishi Sunak risks failing in his role as 'wartime prime minister' unless he takes urgent action given the growing security threat posed by Vladimir Putin, it has been warned, with calls for a significant hike in spending. Who cares, so long as it’s diverse and inclusive! 🌈 QueerFuselier Ok fine So basically Sky News is telling us they have sources inside the MOD/Govt who are leaking details of private conversations 🤔 I am more concerned that the Official Secrets Act is being broken by these sources. Who else are those sources leaking information too wondering 🤔
Source: SkyNews - 🏆 35. / 67 Read more »
'Holocaust denier kept British girls in cellar'The man arrested on suspicion of keeping six young British children in his wine cellar for nine months has been identified as a conspiracy theorist and alleged Holocaust denier. It's never just one thing with these right wing scumbags. I'd be check the internet history and cellars of all the ones on GBNews and Talk 'shite' Radio/TV. Horrific. Keeping girls in cellars must be a pass time occupation for the nation's cranked heads till they are free. Then the whole nation joins in what they make is a big spectator events on tabloids. Surely time has come for a new law requiring check on every cellar once a year!
Source: LBCNews - 🏆 75. / 59 Read more »
Royal Mint launches new coin collection featuring British monarchCOINS featuring a remastered portrait of Henry VIII have been unveiled by the Royal Mint. It’s the fifth coin in the British Monarchs collection and the second to feature a king from the Hous…
Source: TheSun - 🏆 64. / 61 Read more »