Tumorigenic Potential of Olfactory Bulb-Derived Human Adult Neural Stem Cells Associates with Activation of TERT and NOTCH1

BACKGROUND: Multipotent neural stem cells (NSCs) have been isolated from neurogenic regions of the adult brain. Reportedly, these cells can be expanded in vitro under prolonged mitogen stimulation without propensity to transform. However, the constitutive activation of the cellular machinery required to bypass apoptosis and senescence places these cells at risk for malignant transformation. METHODOLOGY/PRINCIPAL FINDINGS: Using serum-free medium supplemented with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), we established clonally derived NS/progenitor cell (NS/PC) cultures from the olfactory bulb (OB) of five adult patients. The NS/PC cultures obtained from one OB specimen lost growth factor dependence and neuronal differentiation at early passage. These cells developed glioblastoma tumors upon xenografting in immunosuppressed mice. The remaining NS/PC cultures were propagated either as floating neurospheres or as adherent monolayers with maintenance of growth factor dependence and multipotentiality at late passage. These cells were engrafted onto the CNS of immunosuppressed rodents. Overall, the grafted NS/PCs homed in the host parenchyma showing ramified morphology and neuronal marker expression. However, a group of animals transplanted with NS/PCs obtained from an adherent culture developed fast growing tumors histologically resembling neuroesthesioblastoma. Cytogenetic and molecular analyses showed that the NS/PC undergo chromosomal changes with repeated in vitro passages under mitogen stimulation, and that up-regulation of hTERT and NOTCH1 associates with in vivo tumorigenicity. CONCLUSIONS/SIGNIFICANCE: Using culturing techniques described in current literature, NS/PCs arise from the OB of adult patients which in vivo either integrate in the CNS parenchyma showing neuron-like features or initiate tumor formation. Extensive xenografting studies on each human derived NS cell line appear mandatory before any use of these cells in the clinical setting

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

INTRACEREBRAL HEMORRHAGE: A TRANSITION PHASE TOWARD BETTER PROGNOSIS

BACKGROUND: In the United States, data on patient outcomes after operative management of nontraumatic intracerebral hemorrhage (ICH) have been largely derived from tertiary care academic institutions. Given that outcomes of patients treated at these specialized centers may differ from those treated at community hospitals, our aim was to report patient outcomes on a population-based, national level. METHODS: The Nationwide Inpatient Sample (NIS) was utilized to identify all patients with a primary diagnosis of nontraumatic ICH (431.xx) who underwent a craniotomy or craniectomy (ICD-9 CCS code 1). Univariate and multivariate analyses were performed to analyze the effects of patient and hospital characteristics on outcome measures. RESULTS: NIS estimated that 657,428 patients with a primary diagnosis of nontraumatic ICH were admitted between 1993 and 2003 in the United States, 45,159 (6.9%) of whom underwent surgical treatment. The in-hospital mortality rate for surgically treated patients was 27.2%, and the complication rate was 41.2%. The most common complications reported were pulmonary (30.4%), renal (3.2%), and thromboembolic (2.9%). A single postoperative complication increased the mortality rate by 29% and lengthened the hospital stay by 5 days. Multivariate logistic regression demonstrated that complications and mortality were more likely in patients of African-American descent, and in subjects with 1 or more pre-existing comorbidity. Additionally, the mortality rate was lowest in hospitals that performed the highest volume of operations for nontraumatic ICH (odds ratio 0.8; 95% confidence interval 0.68 to 0.99). CONCLUSIONS: Patients with intracerebral hemorrhage who undergo craniotomy or craniectomy have a high morbidity and mortality. Male gender, preoperative comorbidities, complications, and low hospital volume were associated with an increased risk of in-hospital mortality