No abstract

Nonnicotine factors in tobacco smoking produce important right brain effects. Nicotine is a pharmacological factor during tobacco smoking that releases bilateral striatal DA, but more in the left brain.

Objective: To explore temporal trends in tissue plasminogen activator (tPA) administration for acute ischemic stroke (AIS) in a biethnic community without an academic medical center and variation in trends by age, sex, ethnicity, and stroke severity.Methods: Cases of AIS were identified from 7 hospitals in the Brain Attack Surveillance in Corpus Christi (BASIC) project, a population-based surveillance study between January 1, 2000, and June 30, 2012. tPA, demographics, and stroke severity as assessed by the NIH Stroke Scale (NIHSS) were ascertained from medical records. Temporal trends were explored using generalized estimating equations, and adjustment made for age, sex, ethnicity, and NIHSS. Interaction terms were included to test for effect modification.Results: There were 5,277 AIS cases identified from 4,589 unique individuals. tPA use was steady at 2% and began increasing in 2006, reaching 11% in subsequent years. Stroke severity modified temporal trends (p 5 0.003) such that cases in the highest severity quartile (NIHSS . 8) had larger increases in tPA use than those in lower severity quartiles. Although ethnicity did not modify the temporal trend, Mexican Americans (MAs) were less likely to receive tPA than nonHispanic whites (NHWs) due to emerging ethnic differences in later years.Conclusions: Dramatic increases in tPA use were apparent in this community without an academic medical center. Primary stroke center certification likely contributed to this rise. Results suggest that increases in tPA use were greater in higher severity patients compared to lower severity patients, and a gap between MAs and NHWs in tPA administration may be emerging. Neurology ® 2016;87:2184-2191 GLOSSARY AIS 5 acute ischemic stroke; BASIC 5 Brain Attack Surveillance in Corpus Christi; ED 5 emergency department; EMS 5 emergency medical services; GAM 5 generalized additive models; GEE 5 generalized estimating equations; ICD-9 5 International Classification of Diseases-9; IQR 5 interquartile range; IRB 5 internal review board; MA 5 Mexican American; NHW 5 non-Hispanic white; NIHSS 5 NIH Stroke Scale; PSC 5 primary stroke centers; RR 5 relative rate; tPA 5 tissue plasminogen activator.Stroke is a leading cause of death and long-term adult disability in the United States. 1,2 Due to reductions in stroke mortality and increased life expectancy, the prevalence of stroke is climbing and predicted to increase by 20.5% by 2030, with the largest increase among Hispanic men (29%). 1 Disparities exist in stroke care in the United States with differences in tissue plasminogen activator (tPA) use based on sex and race-ethnicity demonstrated in academic settings. [3][4][5][6][7] Temporal trends show that tPA use has more than doubled at large, high-volume academic hospitals since the early 2000s, with data suggesting that treatment gaps based on age and race are narrowing. [8][9][10] Yet there is a paucity of information concerning trends in community hospitals, which have been shown to exhibit different trends than academic centers....

Gliomas represent the most common malignant primary brain tumors, and a high-grade subset of these tumors including glioblastoma are particularly refractory to current standard-of-care therapies including maximal surgical resection and chemoradiation. The prognosis of patients with these tumors continues to be poor with existing treatments and understanding treatment failure is required. The dynamic interplay between the tumor and its microenvironment has been increasingly recognized as a key mechanism by which cellular adaptation, tumor heterogeneity, and treatment resistance develops. Beyond ongoing lines of investigation into the peritumoral cellular milieu and microenvironmental architecture, recent studies have identified the growing role of mechanical properties of the microenvironment. Elucidating the impact of these biophysical factors on disease heterogeneity is crucial for designing durable therapies and may offer novel approaches for intervention and disease monitoring. Specifically, pharmacologic targeting of mechanical signal transduction substrates such as specific ion channels that have been implicated in glioma progression or the development of agents that alter the mechanical properties of the microenvironment to halt disease progression have the potential to be promising treatment strategies based on early studies. Similarly, the development of technology to measure mechanical properties of the microenvironment in vitro and in vivo and simulate these properties in bioengineered models may facilitate the use of mechanical properties as diagnostic or prognostic biomarkers that can guide treatment. Here, we review current perspectives on the influence of mechanical properties in glioma with a focus on biophysical features of tumor-adjacent tissue, the role of fluid mechanics, and mechanisms of mechanical signal transduction. We highlight the implications of recent discoveries for novel diagnostics, therapeutic targets, and accurate preclinical modeling of glioma.