4,029 research outputs found

    The central nervous system source modulates microglia function and morphology in vitro

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    The regional heterogeneity of microglia was first described a century ago by Pio del Rio Hortega. Currently, new information on microglia heterogeneity throughout central nervous system (CNS) regions is being revealed by high-throughput techniques. It remains unclear whether these spatial specificities translate into different microglial behaviors in vitro. We cultured microglia isolated from the cortex and spinal cord and analyzed the effect of the CNS spatial source on behavior in vitro by applying the same experimental protocol and culture conditions. We analyzed the microglial cell numbers, function, and morphology and found a distinctive in vitro phenotype. We found that microglia were present in higher numbers in the spinal-cord-derived glial cultures, presenting different expressions of inflammatory genes and a lower phagocytosis rate under basal conditions or after activation with LPS and IFN-γ. Morphologically, the cortical microglial cells were more complex and presented longer ramifications, which were also observed in vivo in CX3CR1+/GFP transgenic reporter mice. Collectively, our data demonstrated that microglial behavior in vitro is defined according to specific spatial characteristics acquired by the tissue. Thus, our study highlights the importance of microglia as a source of CNS for in vitro studies.This work was funded by the Santa Casa Neuroscience Awards—Prize Melo e Castro for Spinal Cord Injury Research (MC-18-2021), and it was partially funded by the Wings for Life Spinal Cord Research Foundation (WFL-ES-03/19). This work was also funded by national funds through the Foundation for Science and Technology (FCT)—projects UIDB/50026/2020, UIDP/50026/2020, and EXPL/MED-PAT/0931/2021, and by the project NORTE-01-0145-FEDER-000039, supported by the Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF). We would like to acknowledge the support given by the Portuguese Foundation of Science and Technology to AGP (2020.07534.BD), AM (UMINHO/BIL-CNCG/2022/16), SM (CEECIND/01902/2017), and NAS (CEECIND/04794/2007)

    Survival following gamma knife radiosurgery for brain metastasis from breast cancer

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    BACKGROUND: Breast cancer is the second most common cause of brain metastases in the United States. Although breast cancer induced brain metastases represent an incurable condition, some patients experience prolonged survival. In this retrospective study, we examine a cohort of patients with brain metastases from breast cancer treated with Gamma Knife stereotactic radiosurgery to identify factors that predict better outcomes. METHODS: A retrospective database of 100 patients treated for brain metastases due to breast cancer via Gamma Knife radiosurgery (GKS) from July 1998 through March 2009 was reviewed. Patients who received radiosurgery as sole treatment, as a planned boost after whole brain radiotherapy or surgical resection, or as salvage after prior whole brain radiation therapy (WBRT) or surgical resection were included. Prognostic factors identified to be significant for survival in previous brain metastasis studies were analyzed for significance by univariate and multivariate Cox analysis. RESULTS: Overall, the median brain progression-free survival time was 7.1 months and the median survival time was 12.3 months. No prognostic variables were significant for brain progression-free survival. For patients treated with a planned GKS after WBRT, GKS as sole treatment, GKS salvage after WBRT, GKS boost after surgery, or GKS for surgical salvage the median survival times (MSTs) were as follows: 12.2 months, 12.4 months, 9.5 months, 27.6 months and 33.4 months respectively. Differences between the groups were not significant (p = 0.06); however, GKS boost after surgery and GKS for salvage after surgery did have a trend toward better overall survival. The MST for patients of age <65 years was 14.5 months, compared to age ≥65 which was 7.7 months (p = 0.06) and remained a significant prognostic factor for overall survival on multivariate analysis. The MST for patients with a single lesion was 16.9 months, not significantly different than the MST of 14.5 months for patients with 2–3 lesions. However patients with >3 lesions had a MST of 5.9 months, which was significantly worse. Breast cancer subtype as approximated by biomarkers and KPS were not significant predictors of overall survival and stage at initial diagnosis was inversely associated with survival. CONCLUSION: Stereotactic radiosurgery offers good local control and prolonged survival in selected patients. Age and number of lesions are strong predictors of overall survival

    Negative Consequences of Innovation-Igniting Urban Developments: Empirical Evidence from Three US Cities

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    Emergent economic development policies reflect the challenges urban growth coalitions face in attracting the footloose tech-entrepreneurs of the global economy. This convergence between the focus on place and the harnessing of global capital has led to the proliferation of innovation-igniting urban developments (IIUD)—place-based economic development strategies to boost the local knowledge economy. Economic developers are using IIUD strategies to convert areas of the city into entrepreneurial “launch pads” for innovation. However, because these developments remain young, considerations to implement IIUDs lack an evidence-base to show the potential for negative consequences on the communities where they are embedded. This research addresses this gap through: 1) a review of studies of similar developments to identify negative consequences; and 2) using a quasi-experimental method composed of Propensity Score Matching and Average Treatment Effect analyses from IIUDs in three US cities (Boston, MA, St. Louis, MO, and Buffalo, NY). Combined, results demonstrate that the greatest implications of IIUDs are the increased polarized division of labor, housing unaffordability, and income inequality. As IIUDs gain in popularity, it is critical to correlate negative consequences with IIUDs to inform economic developers in assessing trade-offs

    Measuring Patient and Clinician Perspectives to Evaluate Change in Health-Related Quality of Life Among Patients with Chronic Obstructive Pulmonary Disease

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    CONTEXT: Many treatments aim to improve patients’ health-related quality of life (HRQoL), and many care guidelines suggest assessing symptoms and their impact on HRQoL. However, there is a lack of consensus regarding which HRQoL outcome measures are appropriate to assess, and how much change on those measures depict significant HRQoL improvement. OBJECTIVE: We used triangulation methods to identify and understand clinically important differences (CIDs) for the amount of change in HRQoL that reflects both health professionals and patients’ values, among patients with chronic obstructive pulmonary disease (COPD). DESIGN, SETTING, AND PARTICIPANTS: We incorporated three perspectives: (1) an expert panel of physicians familiar with the measurement of HRQoL in COPD patients; (2) 610 primary care COPD outpatients who completed baseline and bimonthly follow-up HRQoL interviews over the 12-month study; and (3) the primary care physicians (PCPs; n = 43) of these outpatients who assessed their patients’ disease at baseline and at subsequent PCP visits during the year long study. MEASUREMENTS: The Chronic Respiratory Disease Questionnaire (CRQ), the Medical Outcomes Study Short Form 36-item survey (SF-36, version 2.0), and global assessments of change from each of the three perspectives for all HRQoL domains. RESULTS: With few exceptions, the CRQ was able to detect small changes at levels reported by the patients (1–2 points) and their PCPs (1–5 points). These results confirm minimal important difference standards developed in 1989 by Jaeschke et al. anchored on patient-perceived changes in HRQoL. In general, the expert panel and PCP CIDs were larger than the patient CIDs. CONCLUSION: This triangulation methodology yielded improved interpretation, understanding, and insights on stakeholder perspectives of CIDs for patient-reported outcomes

    The phantom of Palais Brongniart economic patriotism and the Paris stock exchange

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    French governments are famous for promoting national champions, notably by preventing foreign takeovers, but in 2005-2006, the Villepin administration allowed the New York Stock Exchange to take control of Euronext, a French-led pan-European company that includes the Paris Bourse. By mapping the public discourse surrounding this striking case of non-intervention, we explain why opponents of the transatlantic merger failed in their appeals to economic patriotism. Discursive strategies designed to justify discrimination against territorially defined outsiders ran into several hurdles, including weak patriotic sentiments for the company concerned; a lack of patriotic alternatives to the proposed merger; and the questionable patriotic credentials of those demanding intervention. Our findings advance research on the demand side of economic patriotism including its discursive dimension. Beyond that, they inform research on business-government relations, and on the political implications of corporate ownership structures. -- Französische Regierungen sind eigentlich dafür bekannt, dass sie einheimische Unternehmen vor Auslandsübernahmen schützen. Im Jahr 2005-2006 gestattete Villepins Regierung jedoch der New York Stock Exchange die Übernahme von Euronext, einer paneuropäischen Gesellschaft unter französischer Leitung, zu der auch die Pariser Börse gehört. Der öffentliche Diskurs zu diesem bedeutenden Fall von Nichtintervention gibt Aufschluss darüber, warum die Gegner der transatlantischen Fusion mit ihren Forderungen nach Wirtschaftspatriotismus scheiterten. Diskursiven Strategien zur Rechtfertigung von Diskriminierung gegen territorial definierte Außenseiter standen mehrere Hindernisse im Weg, etwa unzureichend ausgeprägte patriotische Gefühle für den Übernahmekandidaten, der Mangel patriotischer Alternativen zu einer transatlantischen Fusion und die mangelnde patriotische Glaubwürdigkeit derer, die eine staatliche Einmischung forderten. Der vorliegende Aufsatz ergänzt mit seinem diskursiven Schwerpunkt die aktuelle Forschung zu Wirtschaftspatriotismus. Außerdem trägt er zur Forschung über die Beziehungen zwischen Staat und Unternehmen und über die politischen Auswirkungen von Veränderungen in der Struktur von Unternehmenseigentum bei.

    Spring Newsletter 2001

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    Genotoxicity of multi-walled carbon nanotubes at occupationally relevant doses

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    Carbon nanotubes are commercially-important products of nanotechnology; however, their low density and small size makes carbon nanotube respiratory exposures likely during their production or processing. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In this study, we examined whether multi-walled carbon nanotubes (MWCNT) cause mitotic spindle damage in cultured cells at doses equivalent to 34 years of exposure at the NIOSH Recommended Exposure Limit (REL). MWCNT induced a dose responsive increase in disrupted centrosomes, abnormal mitotic spindles and aneuploid chromosome number 24 hours after exposure to 0.024, 0.24, 2.4 and 24 ÎĽg/cm2 MWCNT. Monopolar mitotic spindles comprised 95% of disrupted mitoses. Three-dimensional reconstructions of 0.1 ÎĽm optical sections showed carbon nanotubes integrated with microtubules, DNA and within the centrosome structure. Cell cycle analysis demonstrated a greater number of cells in S-phase and fewer cells in the G2 phase in MWCNT-treated compared to diluent control, indicating a G1/S block in the cell cycle. The monopolar phenotype of the disrupted mitotic spindles and the G1/S block in the cell cycle is in sharp contrast to the multi-polar spindle and G2 block in the cell cycle previously observed following exposure to SWCNT. One month following exposure to MWCNT there was a dramatic increase in both size and number of colonies compared to diluent control cultures, indicating a potential to pass the genetic damage to daughter cells. Our results demonstrate significant disruption of the mitotic spindle by MWCNT at occupationally relevant exposure levels
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