Immune-mediated gene therapy using adenovirus expressing Flt3 ligand and thymidine kinase followed by ganciclovir administration (Flt3/TK) effectively elicits tumor regression in preclinical glioma models. Herein, we assessed new strategies to optimize Flt3L/TK therapeutic efficacy in a refractory RG2 orthotopic glioblastoma model. Specifically, we aimed to optimize the therapeutic efficacy of Flt3L/TK treatment in the RG2 model by overexpressing the following genes within the brain tumor microenvironment: 1) a TK mutant with enhanced cytotoxicity (SR39 mutant TK), 2) Flt3L-IgG fusion protein that has a longer half-life, 3) CD40L to stimulate DC maturation, 4) T helper cell type 1 polarizing dendritic cell cytokines interleukin-12 or C-X-C motif ligand 10 chemokine (CXCL)-10, 5) C-C motif ligand 2 chemokine (CCL2) or C-C motif ligand 3 chemokine (CCL3) to enhance dendritic cell recruitment into the tumor microenvironment, 6) T helper cell type 1 cytokines interferon-γ or interleukin-2 to enhance effector T-cell functions, and 7) IκBα or p65RHD (nuclear factor kappa-B [NF-κB] Neurotherapeutics (2012) 9:827-843 DOI 10.1007 immunity and tumor specific effector T-cell functions were assessed by cytotoxic T lymphocyte assay and intracellular IFN-γ staining. Our data showed that overexpression of interferon-γ or interleukin-2, or inhibition of the nuclear factor kappa-B within the tumor microenvironment, enhanced cytotoxic T lymphocyte-mediated immune responses and successfully extended the median survival of rats bearing intracranial RG2 when combined with Flt3L/TK. These findings indicate that enhancement of T-cell functions constitutes a critical therapeutic target to overcome immune evasion and enhance therapeutic efficacy for brain cancer. In addition, our study provides novel targets to be used in combination with immunetherapeutic strategies for glioblastoma, which are currently being tested in the clinic.

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Introduction: Traumatic brain injury (TBI) is a public health problem with higher impact in low and middle income countries. Surgical management of TBI in Colombia is a common intervention performed by neurosurgeons but there is little knowledge about their preferences and trends during the care. Materials and methods:We designed a 19 questions survey based on previous studies in high income settings. Through the Colombian Association of Neurosurgery website contact list, we submit the survey to 324 registered neurosurgeons. Statistical analysis was performed using frequencies of nominal and quantitative data. Results:The response number was 47 (14.8%). Around 97.8% were males and 66% have more than 5 years in practice. Thirty percent operate between 50 and 100 cases of TBI and 65.9% work in at least two facilities. The 95.74% consider that trauma surgery is not well paid by the system. Only 12.5% of the neurosurgeons are more devoted to neurotrauma and 20.8% are practicing more spine surgery. The 36.1% will choose not to do trauma neurosurgery if they have the opportunity. Resources for emergency craniotomies in their facilities were considered adequate by 93.6% of the responders. Conclusion:Caring for patients with neurotrauma is not an attractive option for some practicing neurosurgeons in Colombia. Traumatic brain injury cases are frequent in daily practice but some neurosurgeons prefer not to do trauma surgery if they have the option. Institutions have basic resources to perform trauma neurosurgery but the surgery is not well paid by the health system according to the neurosurgeons perspective.

Introduction Poor sleep during pregnancy is common and associated with increased risk of adverse perinatal outcomes. Racial/ethnic minoritized groups in the United States experience worse sleep than non-Hispanic Whites (nHW), likely due to downstream effects of systemic and structural discrimination. Nonetheless, the extent of sleep disparities in the perinatal period remains understudied. In this analysis we estimated the prevalence of subjective measures of sleep in a multi-racial/ethnic pregnant population from the Environmental influences on Child Health Outcomes (ECHO) program. Methods Participants self-reported their race and ethnicity and were grouped into four categories: 1)nHW, 2)non-Hispanic Black/African American (nHB/AA), 3)Hispanic, 4)non-Hispanic Asian (nHA). Our analysis examined trimester-specific nocturnal sleep duration, sleep quality, and sleep disturbances (derived from the Pittsburgh Sleep Quality Index and the ECHO maternal sleep health questionnaire) by race/ethnicity. A total of 1119,2409 and 1284 participants in the first (T1), second (T2) and third trimesters (T3) reported on sleep duration. 1107,1742 and 783 participants in T1,T2 and T3 reported on sleep quality. 1112,1758, and 787 participants in T1,T2 and T3 reported on sleep disturbances Linear or multinomial regression were used to estimate associations between race/ethnicity and each sleep domain by trimester, controlling for body mass index (BMI) and age. We repeated analyses within education strata (high school degree, GED/equivalent; some college and above) Results nHB/AA participants reported shorter sleep duration (T2: β=-0.55 [-0.80,-0.31]: T3: β=-0.65 [-0.99,-0.31]), and more sleep disturbances (T2:β=1.92 [1.09,2.75]; T3:β=1.41 [0.09,2.74]) compared to nHW. Hispanic participants reported longer duration compared to nHW (T1: β=0.22 [0.00004, 0.44];T2: β=0.61 [0.47,0.76];T3: β=0.46 [0.22,0.70]), better sleep quality (Compare to Very good quality OR for Fairly good T1: OR=0.48 [0.32,0.73], T2: OR=0.36 [0.26,0.48], T3: OR=0.31 [0.18,0.52]; Fairly bad T1:OR=0.27 [0.16,0.44], T2:OR=0.46 [0.31,0.67], T3: OR=0.31[0.17,0.55]), and fewer sleep disturbances (T2 β=-0.5 [-1.0,-0.12]; T3 β=-1.21 [-2.07,-0.35]). Differences persisted within the subsample of high SES women. Conclusion These findings highlight racial/ethnic disparities across multiple domains of sleep health during pregnancy. Given the stark racial/ethnic disparities in perinatal outcomes and their associations with sleep health, further research is warranted to investigate the determinants of these disparities, such as downstream effects of systemic and structural discrimination Support (If Any)