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Introduction: Modeling the blood-brain barrier has long been a challenge for pharmacological studies. Up to the present, numerous attempts have been devoted to recapitulating the endothelial barrier in vitro to assess drug delivery vehicles’ efficiency for brain disorders. In the current work, we presented a new approach for analyzing the morphometric parameters of the cells of an insert coculture blood-brain barrier model using rat brain astrocytes, rat brain microvascular endothelial cells, and rat brain pericytes. This analytical approach could aid in getting further information on drug trafficking through the blood-brain barrier and its impact on the brain indirectly. Methods: In the current work, we cultured rat brain astrocytes, rat brain microvascular endothelial cells, and rat brain pericytes and then used an insert well to culture the cells in contact with each other to model the blood-brain barrier. Then, the morphometric parameters of the porous membrane of the insert well, as well as each cell type were imaged by digital holographic microscopy before and after cell seeding. At last, we performed folate conjugation on the surface of the EVs we have previously tested for glioma therapy in our previous work called VEGF-A siDOX-EVs and checked how the trafficking of EVs improves after folate conjugation as a clathrin-mediated delivery setup. the trafficking and passage of EVs were assessed by flow cytometry and morphometric analysis of the digital holographic microscopy holograms. Results: Our results indicated that EVs successfully entered through the proposed endothelial barrier assessed by flow cytometry analysis and furthermore, folate conjugation significantly improved EV passage through the blood-brain barrier. Moreover, our results indicated that the VEGF-A siDOX-EVs insert cytotoxic impact on the cells of the bottom of the culture plate. Conclusion: folate-conjugation on the surface of EVs improves their trafficking through the blood-brain barrier and by using digital holographic microscopy analysis, we could directly assess the morphometric changes of the blood-brain barrier cells for pharmacological purposes as an easy, labelfree, and real-time analysis. [ABSTRACT FROM AUTHOR]

Childhood obesity has become a serious public health challenge during the past few decades, calling for policies to incorporate physical activity into students' routines. This study is an effort to contribute to the current literature of school travels by analyzing how improving safety of different neighborhoods in Chicago, Illinois would encourage students toward shifting to active modes, and how this interrelationship is affected by the severe weather conditions during the cold winters of the region. The results are complemented by multiple sensitivity analyses to quantify how these shifts would help different students burn extra walking calories (i.e. the extra calories each student burns due to walking more). We estimate multiple discrete continuous extreme value models to understand how flexible a student is in combining his/her most preferred transportation mode with other choices. Various sources of inter-personal heterogeneity are also captured by using a latent-classification framework as well as differentiating the before-school from after-school trip chains to consider the behavioral distinction, explicitly. Several explanatory variables are incorporated into the models, including socio-demographics of students and their household, land-use, crime prevalence, and seasonal/weather conditions. Per the results, improving safety of Chicago from its current condition to the national median, would encourage students to be up to 40% more active. This extra active travel demand would provide obese students aged 14–18 with 18% of the calorie burn they need to lose weight to the obesity cutoff and 13% of the calorie burn required for losing weight from the obesity cutoff to overweight. [ABSTRACT FROM AUTHOR]

Background: Cancer cells bear various metabolic alterations in order to survive and progress. Neoplastic cells rewire their metabolic pathways for fermentation of glucose and production of more lactate. Microenvironment acidification is a common feature of many neoplastic lesions. In other words, most cancer cells produce energy ineffectively, by aerobic glycolysis, considered as "Warburg effect". Mounting on previous evidence, hypoxia also induces tumor stemness, diminished apoptosis, and more invasive behavior as well as angiogenesis. In this study, we aimed to investigate whether more lactate concentration in stereotactic puncture specimen of various brain lesions can be an alarming sign of malignancy and higher grades. The current study aims at providing a rapid prognostic biomarker of higher grades for cystic brain lesions approached stereotactically before the complete pathologic grading report is prepared. Methods: We investigated the biochemical cyst content of 44 patients with astrocytomas, 8 craniopharyngiomas, 1 oligodendroglioma and 2 cases with metastatic lesions after stereotactic surgery (47 patients were enrolled in the study). Cyst fluid was analyzed for pH, total protein concentration, cytology, and lactate. The association of these parameters was explored relative to tumor behavior (e.g., tumor grade, type, and cyst progression). The current study was conducted at Firoozgar hospital, Tehran, Iran. Patients were followed for any possible progression from 2014 to 2017. Results: The analyses revealed a significant and positive correlation between grade and lactate concentration (P ≤ 0.001); as well as between grade and mean total protein concentration (P = 0.046). This suggests that more lactate and total protein concentration in stereotactic specimen can be an alarming sign of higher grades and poor outcome in astrocytoma cysts. However, craniopharyngiomas; as benign lesions; had significantly lower lactate (P ≤ 0.001) and total protein concentrations (P = 0.018) than astrocytomas. Conclusion: Higher total protein and lactate concentrations in the stereotactic biopsy specimens are alarming signs of poor outcome and higher grades in astrocytomas. Trial Ethics Registration: IR.IUMS.FMD.REC 1396.88215207. [ABSTRACT FROM AUTHOR]