The Expression of Connexins and SOX2 Reflects the Plasticity of Glioma Stem-Like Cells

Glioblastoma (GBM) is the most malignant primary brain tumor, with an average survival rate of 15 months. GBM is highly refractory to therapy, and such unresponsiveness is due, primarily, but not exclusively, to the glioma stem-like cells (GSCs). This subpopulation express stem-like cell markers and is responsible for the heterogeneity of GBM, generating multiple differentiated cell phenotypes. However, how GBMs maintain the balance between stem and non-stem populations is still poorly understood. We investigated the GBM ability to interconvert between stem and non-stem states through the evaluation of the expression of specific stem cell markers as well as cell communication proteins. We evaluated the molecular and phenotypic characteristics of GSCs derived from differentiated GBM cell lines by comparing their stem-like cell properties and expression of connexins. We showed that non-GSCs as well as GSCs can undergo successive cycles of gain and loss of stem properties, demonstrating a bidirectional cellular plasticity model that is accompanied by changes on connexins expression. Our findings indicate that the interconversion between non-GSCs and GSCs can be modulated by extracellular factors culminating on differential expression of stem-like cell markers and cell-cell communication proteins. Ultimately, we observed that stem markers are mostly expressed on GBMs rather than on low-grade astrocytomas, suggesting that the presence of GSCs is a feature of high-grade gliomas. Together, our data demonstrate the utmost importance of the understanding of stem cell plasticity properties in a way to a step closer to new strategic approaches to potentially eliminate GSCs and, hopefully, prevent tumor recurrence

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Integrated palliative care networks from the perspectives of patients:A cross-sectional explorative study in five European countries

Background: Although examining perspectives of patients on integrated palliative care organisation is essential, available literature is largely based on administrative data or healthcare professionals’ perspectives. Aim: (1) Providing insight into the composition and quality of care networks of patients receiving palliative care and (2) describing perceived integration between healthcare professionals within these networks and its association with overall satisfaction. Design: Cross-sectional explorative design. Setting/participants: We recruited 157 patients (62% cancer, 25% chronic obstructive pulmonary disease, 13% chronic heart failure, mean age 68 years, 55% female) from 23 integrated palliative care initiatives in Belgium, Germany, the United Kingdom, Hungary and the Netherlands. Results: About 33% reported contact with a palliative care specialist and 48% with a palliative care nurse. Relationships with palliative care specialists were rated significantly higher than other physicians (p <0.001). Compared to patients with cancer, patients with chronic obstructive pulmonary disease (odds ratio = 0.16, confidence interval (0.04; 0.57)) and chronic heart failure (odds ratio = 0.11, confidence interval (0.01; 0.93)) had significantly lower odds of reporting contact with palliative care specialists and patients with chronic obstructive pulmonary disease (odds ratio = 0.23, confidence interval (0.08; 0.71)) had significantly lower odds of reporting contact with palliative care nurses. Perceptions of main responsible healthcare professionals or caregivers in patient’s care networks varied across countries. Perceived integration was significantly associated with overall satisfaction. Conclusion: Palliative care professionals are not always present or recognised as such in patients’ care networks. Expert palliative care involvement needs to be explicated especially for non-cancer patients. One healthcare professional should support patients in understanding and navigating their palliative care network. Patients seem satisfied with care provision as long as continuity of care is provided

Bridging gaps in everyday life : a free-listing approach to explore the variety of activities performed by physiotherapists in specialized palliative care

BACKGROUND: A growing body of studies indicate benefits of physiotherapy for patients in palliative care, for symptom relief and wellbeing. Though physiotherapists are increasingly acknowledged as important members of palliative care teams, they are still an underutilized source and not fully recognized. The aim of this study was to explore the variety of activities described by physiotherapists in addressing the needs and problems of patients and their families in specialized palliative care settings. METHODS: Using a free-listing approach, ten physiotherapists working in eight specialized palliative care settings in Sweden described as precisely and in as much detail as possible different activities in which patients and their families were included (directly or indirectly) during 10 days. The statements were entered into NVivo and analysed using qualitative content analysis. Statements containing more than one activity were categorized per activity. RESULTS: In total, 264 statements, containing 504 varied activities, were coded into seven categories: Counteracting a declining physical function; Informing, guiding and educating; Observing, assessing and evaluating; Attending to signs and symptoms; Listening, talking with and understanding; Caring for basic needs; and Organizing, planning and coordinating. In practice, however, the activities were intrinsically interwoven. The activities showed how physiotherapists aimed, through care for the body, to address patients' physical, psychological, social and existential needs, counteracting the decline in a patient's physical function and wellbeing. The activities also revealed a great variation, in relation not only to what they did, but also to their holistic and inseparable nature with regard to why, how, when, where, with whom and for whom the activities were carried out, which points towards a well-adopted person-centred palliative care approach. CONCLUSIONS: The study provides hands-on descriptions of how person-centred palliative care is integrated in physiotherapists' everyday activities. Physiotherapists in specialized palliative care help patients and families to bridge the gap between their real and ideal everyday life with the aim to maximize security, autonomy and wellbeing. The concrete examples included can be used in understanding the contribution of physiotherapists to the palliative care team and inform future research interventions and outcomes