Tracking of Normal and Malignant Progenitor Cell Cycle Transit in a Defined Niche.

While implicated in therapeutic resistance, malignant progenitor cell cycle kinetics have been difficult to quantify in real-time. We developed an efficient lentiviral bicistronic fluorescent, ubiquitination-based cell cycle indicator reporter (Fucci2BL) to image live single progenitors on a defined niche coupled with cell cycle gene expression analysis. We have identified key differences in cell cycle regulatory gene expression and transit times between normal and chronic myeloid leukemia progenitors that may inform cancer stem cell eradication strategies

Los Peligros Escondidos de las Playas: Parada Cardiorespiratória

Thermal shock is widely recognized by modern medicine. Its pathophysiological mechanisms are known, as are its possible consequences, but scientific reports in the literature about clinical cases with severe consequences are sparse. The authors present a case of cardiorespiratory arrest after prolonged sun exposure followed by a dive in the ocean. Other aetiological causes were ruled out, by exclusion, leading to the diagnosis of cardiorespiratory arrest caused by thermal shock. It is important to inform the public in general of the risks of negligent behaviour on the beach.info:eu-repo/semantics/publishedVersio

Management of ibrutinib treatment in patients with B-cell malignancies: clinical practice in Portugal and multidisciplinary recommendations

Objectives: Ibrutinib, a potent inhibitor of the Bruton tyrosine kinase, has revolutionized the treatment of many B-cell malignancies. Ibrutinib has an established favorable toxicity profile with up to 8 years of experience in clinical trials; however, despite ibrutinib’s favorable toxicity profile, dose reductions and treatment discontinuations are becoming more evident in clinical practice, particularly in the setting of specific clinical contexts and patient characteristics. This manuscript is set to provide practical recommendations on the management of patients treated with this agent in daily practice. Methods: A group of multidisciplinary experts from Portugal met to discuss and highlight practical recommendations, supported on both literature and clinical insights, for the management of the treatment with ibrutinib. Results/discussion: Handling of both toxicities and drug–drug interactions during ibrutinib treatment poses several challenges to healthcare providers and can benefit from a multidisciplinary approach. The involvement of specialties, such as cardiology, infectiology and pharmacology, can bring an added value to patient care, not only in anticipating/managing safety issues and dose adjustments but also in enhancing adherence to treatment, ultimately improving the risk/benefit balance. Conclusion: By involving a multidisciplinary group of experts, this work provides a set of key recommendations to optimize care and outcomes for ibrutinib-treated patients. Despite not being a fully comprehensive review on the topic, it is intended as a framework to hematologists and other healthcare professionals who manage these patients in their daily clinical practice.The project received financial support from Janssen for logistics of expert meetings and editorial support. The sponsor had no influence on the opinions expressed here, which are those of the authors

The Psy-Security-Curriculum ensemble: British Values curriculum policy in English schools

Framed as being in response to terrorist attacks and concerns about religious bias in some English schools, ‘British Values’ (BV) curriculum policy forms part of the British Government’s Counter-Terrorism and Security Act, 2015. This includes a Duty on teachers in England to actively promote British Values to deter students from radicalisation. This paper, first, traces the history of Britishness in the curriculum to reveal a prevalence of nationalistic, colonial values. Next, an ensemble of recent policies and speeches focusing on British Values is analysed, using a psycho-political approach informed by anti-colonial scholarship. Finally, we interrogate two key critiques of the British Values curriculum discourse: the universality of British Values globally, and concerns over the securitisation of education. Findings indicate that the constitution of white British supremacist subjectivities operate through curriculum as a defence mechanism against perceived threats to white privilege, by normalising a racialised state-controlled social order. The focus is on ‘British’ values, but the analytic framework and findings have wider global significance

Effects of external nutrient sources and extreme weather events on the nutrient budget of a Southern European coastal lagoon

The seasonal and annual nitrogen (N), phosphorus (P), and carbon (C) budgets of the mesotidal Ria Formosa lagoon, southern Portugal, were estimated to reveal the main inputs and outputs, the seasonal patterns, and how they may influence the ecological functioning of the system. The effects of extreme weather events such as long-lasting strong winds causing upwelling and strong rainfall were assessed. External nutrient inputs were quantified; ocean exchange was assessed in 24-h sampling campaigns, and final calculations were made using a hydrodynamic model of the lagoon. Rain and stream inputs were the main freshwater sources to the lagoon. However, wastewater treatment plant and groundwater discharges dominated nutrient input, together accounting for 98, 96, and 88 % of total C, N, and P input, respectively. Organic matter and nutrients were continuously exported to the ocean. This pattern was reversed following extreme events, such as strong winds in early summer that caused upwelling and after a period of heavy rainfall in late autumn. A principal component analysis (PCA) revealed that ammonium and organic N and C exchange were positively associated with temperature as opposed to pH and nitrate. These variables reflected mostly the benthic lagoon metabolism, whereas particulate P exchange was correlated to Chl a, indicating that this was more related to phytoplankton dynamics. The increase of stochastic events, as expected in climate change scenarios, may have strong effects on the ecological functioning of coastal lagoons, altering the C and nutrient budgets.Portuguese Science and Technology Foundation (FCT) [POCI/MAR/58427/2004, PPCDT/MAR/58427/2004]; Portuguese Science and Technology Foundation (FCT