Induction Chemotherapy Prior to Endoscopic Resection of Alveolar Rhabdomyosarcoma.

Head and neck rhabdomyosarcoma (HNRMS) is a rare type of soft tissue tumor that affects both adults and children with an overall incidence of 0.041 per 100,000 people. Adults make up approximately 31.2% of all HNRMS diagnoses and have an overall survival rate between 20% and 40%. We present a case of a 46-year-old male who initially presented with nasal congestion and vision changes. Maxillofacial computed tomography and magnetic resonance imaging of the brain showed involvement of the orbital apex, abutment of the planum sphenoidale, and extension to the foramen rotundum (FR). Nasal endoscopy with biopsy confirmed the diagnosis of T2aN0M0 parameningeal HNRMS. The patient underwent induction chemotherapy, followed by endoscopic resection, which resulted in negative intraoperative margins. Subsequently, he underwent adjuvant concurrent chemotherapy and proton beam radiation after positive microscopic positive margins were found on the optic nerve. The patient did not experience any significant complications, and he is currently without radiographic or clinical recurrence 18 months after the treatment. He was able to maintain his vision throughout the treatment. In adults, HNRMS is usually treated with chemoradiotherapy based on pediatric protocols, since there are limited data available for adult treatment protocols and outcomes. Although surgery has been associated with positive outcomes in adult patients, there are no previous reports of its use with either neoadjuvant or adjuvant treatment. This type of treatment protocol has never been described for adult HNRMS. We hope that our report can add more data to the growing body of literature on HNRMS treatment protocols.

ß-Cyclodextrin-poly (ß-Amino Ester) Nanoparticles Are a Generalizable Strategy for High Loading and Sustained Release of HDAC Inhibitors.

Therapeutic development of histone deacetylase inhibitors (HDACi) has been hampered by a number of barriers to drug delivery, including poor solubility and inadequate tissue penetration. Nanoparticle encapsulation could be one approach to improve the delivery of HDACi to target tissues; however, effective and generalizable loading of HDACi within nanoparticle systems remains a long-term challenge. We hypothesized that the common terminally ionizable moiety on many HDACi molecules could be capitalized upon for loading in polymeric nanoparticles. Here, we describe the simple, efficient formulation of a novel library of ß-cyclodextrin-poly (ß-amino ester) networks (CDN) to achieve this goal. We observed that network architecture was a critical determinant of CDN encapsulation of candidate molecules, with a more hydrophobic core enabling effective self-assembly and a PEGylated surface enabling high loading (up to ∼30% w/w), effective self-assembly of the nanoparticle, and slow release of drug into aqueous media (up to 24 days) for the model HDACi panobinostat. We next constructed a library of CDNs to encapsulate various small, hydrophobic, terminally ionizable molecules (panobinostat, quisinostat, dacinostat, givinostat, bortezomib, camptothecin, nile red, and cytarabine), which yielded important insights into the structural requirements for effective drug loading and CDN self-assembly. Optimized CDN nanoparticles were taken up by GL261 cells in culture and a released panobinostat was confirmed to be bioactive. Panobinostat-loaded CDNs were next administered by convection-enhanced delivery (CED) to mice bearing intracranial GL261 tumors. These studies confirm that CDN encapsulation enables a higher deliverable dose of drug to effectively slow tumor growth. Matrix-assisted laser desorption/ionization (MALDI) analysis on tissue sections confirms higher exposure of tumor to drug, which likely accounts for the therapeutic effects. Taken in sum, these studies present a novel nanocarrier platform for encapsulation of HDACi via both ionic and hydrophobic interactions, which is an important step toward better treatment of disease via HDACi therapy.

Electronic media time and sedentary behaviors in children: Findings from the Built Environment and Active Play Study in the Washington DC area.

An objective of the Built Environment and Active Play (BEAP) Study was to examine whether home built environment, bedroom electronic presence, parental rules and demographics predicted children's sedentary behavior (SB). In 2014, BEAP Study questionnaires were mailed to 2000 parents of children (7-12 years) within the Washington DC area. SB-Duration (hours/day) and SB-Frequency (days/week) were assessed by two questions with multiple subparts relating to SB activity type (e.g. car riding) and SB companionship (e.g. friends). Built environment, bedroom electronic presence, parental rules and demographic data were obtained through questionnaire items and ordered logistic regression models were used to examine whether these variables were associated with SB. Study sample included 144 children (female (50%); average age (9.7 years); White (56.3%); Black/African-American (23.7%); Asian-Americans (10.4%)). Nearly 40% of the sample reported daily solitary SB with car riding being the most frequently reported type of SB. Children living on streets without a dead-end/cul-de-sac exhibited a higher odds in SB-Duration using electric media [2.61 (CI: 1.31, 5.18)] and having no television in a child's bedroom was associated with a lower odds in SB-Frequency [0.048 (CI: 0.006, 0.393)] and SB-Duration [0.085 (CI: 0.018, 0.395)]. Non-Hispanic/Latino children were also found to have higher odds in solitary SB-Frequency when parental rules of electronic use were modeled [8.56 (CI: 1.11, 66.01)]. Based on results from this cross-sectional study, home neighborhood built environment, bedroom electronic presence and absence of parental rules can significantly predict children's SB.

Parental perceived built environment measures and active play in Washington DC metropolitan children.

OBJECTIVE: Previous research identified associations between perceived built environment and adult physical activity; however, fewer studies have explored associations in children. The Built Environment and Active Play (BEAP) Study examined relationships between children's active play and parental perceptions of home neighborhood built environments within the Washington, DC metropolitan area (DMV). METHODS: With this cross-sectional study, a questionnaire was administered in 2014 to parents of children (7-12 years old) residing in the DMV. Data were collected on children's active play, home built environment parental perceptions, and demographics. Active play response data were dichotomized by whether the child did or did not meet the 60-min/day Physical Activity Guidelines for Americans (PAGAs) recommendation. Perceived home neighborhood built environment data were also dichotomized. Chi-square tests determined differences in parental perceived built environment measures between active and non-active child groups. Logistic regression assessed the association of parental perceived built environment variables with active play while adjusting for demographic variables. RESULTS: The BEAP Study population (n = 144) included a uniquely diverse population of children with 23.7% African Americans and 10.4% Asian Americans. A statistically significant greater proportion of active children's parents agreed with the importance of neighborhood esthetics, active play areas, walkability and safety as compared to the parents of non-active children. Fully adjusted logistic regression models demonstrated that some parental perceived built environment measures (e.g. access to play equipment) were predictors of their children meeting the 60-min/day PAGA recommendation. CONCLUSION: Our findings support the important role of home neighborhood built environment perceptions on childhood active play.

Built environment and active play among Washington DC metropolitan children: A protocol for a cross-sectional study.

BACKGROUND: Research has demonstrated that children who participate in active play are more likely to be physically active, thereby improving long-term health outcomes. Many adult studies have also shown that neighborhood built environments can encourage or discourage routine physical activity. Limited evidence has demonstrated that children who reside in neighborhoods with a built environment that is more inviting to active play exhibit lower overweight and obesity rates as well as an overall better state of well-being. This Built Environment and Active Play (BEAP) Study aims to develop a neighborhood playability rating system in the Washington, DC (DMV) area. Similar to walkability scores, these playability scores will estimate how affable a neighborhood is to active play. The BEAP Study will attempt to provide a broad view of factors influencing the level and type of active play among children. METHODS/DESIGN: Using a cross-sectional design, the BEAP Study will collect data using a mail questionnaire administered to the parents and/or guardians of 2000 children aged 7-12 years residing in select DMV areas in October of 2014. Questionnaire data, including information on active play, home and neighborhood characteristics, parental perceptions, and sociodemographic characteristics will be merged through a geographic information system (GIS) with objective built environment measures in the participants' neighborhoods. An ordered logit model will be used to regress an ordinal active play outcome on built environment exposure variables while adjusting for potential confounders. Upon the construction of the final model, predictor coefficients will be used as parameters in the scoring system to develop neighborhood playability scores. DISCUSSION: The BEAP Study intends to generate a neighborhood playability index by characterizing and quantifying children's active play using parent-reported physical activity data in children, GIS data and built environment measures in participant neighborhoods. The BEAP Study will improve our understanding of the built environment and childhood playability relationship while also contributing to the body of evidence-based built environment and physical activity research.

The association of ambient air pollution and physical inactivity in the United States.

BACKGROUND: Physical inactivity, ambient air pollution and obesity are modifiable risk factors for non-communicable diseases, with the first accounting for 10% of premature deaths worldwide. Although community level interventions may target each simultaneously, research on the relationship between these risk factors is lacking. OBJECTIVES: After comparing spatial interpolation methods to determine the best predictor for particulate matter (PM2.5; PM10) and ozone (O3) exposures throughout the U.S., we evaluated the cross-sectional association of ambient air pollution with leisure-time physical inactivity among adults. METHODS: In this cross-sectional study, we assessed leisure-time physical inactivity using individual self-reported survey data from the Centers for Disease Control and Prevention's 2011 Behavioral Risk Factor Surveillance System. These data were combined with county-level U.S. Environmental Protection Agency air pollution exposure estimates using two interpolation methods (Inverse Distance Weighting and Empirical Bayesian Kriging). Finally, we evaluated whether those exposed to higher levels of air pollution were less active by performing logistic regression, adjusting for demographic and behavioral risk factors, and after stratifying by body weight category. RESULTS: With Empirical Bayesian Kriging air pollution values, we estimated a statistically significant 16-35% relative increase in the odds of leisure-time physical inactivity per exposure class increase of PM2.5 in the fully adjusted model across the normal weight respondents (p-value<0.0001). Evidence suggested a relationship between the increasing dose of PM2.5 exposure and the increasing odds of physical inactivity. CONCLUSIONS: In a nationally representative, cross-sectional sample, increased community level air pollution is associated with reduced leisure-time physical activity particularly among the normal weight. Although our design precludes a causal inference, these results provide additional evidence that air pollution should be investigated as an environmental determinant of inactivity.

Antiangiogenic drugs synergize with a membrane macrophage colony-stimulating factor-based tumor vaccine to therapeutically treat rats with an established malignant intracranial glioma.

Combining a T9/9L glioma vaccine, expressing the membrane form of M-CSF, with a systemic antiangiogenic drug-based therapy theoretically targeted toward growth factor receptors within the tumor's vasculature successfully treated >90% of the rats bearing 7-day-old intracranial T9/9L gliomas. The antiangiogenic drugs included (Z)-3-[4-(dimethylamino)benzylidenyl]indolin-2-one (a platelet-derived growth factor receptor beta and a fibroblast growth factor receptor 1 kinase inhibitor) and oxindole (a vascular endothelial growth factor receptor 2 kinase inhibitor). A total of 20-40% of the animals treated with the antiangiogenic drugs alone survived, while all nontreated controls and tumor vaccine-treated rats died within 40 days. In vitro, these drugs inhibited endothelial cells from proliferating in response to the angiogenic factors produced by T9/9L glioma cells and prevented endothelial cell tubulogenesis. FITC-labeled tomato lectin staining demonstrated fewer and constricted blood vessels within the intracranial tumor after drug therapy. Magnetic resonance imaging demonstrated that the intracranial T9 glioma grew much slower in the presence of these antiangiogenic drugs. These drugs did not affect in vitro glioma cell growth nor T cell mitogenesis. Histological analysis revealed that the tumor destruction occurred at the margins of the tumor, where there was a heavy lymphocytic infiltrate. Real-time PCR showed more IL-2-specific mRNA was present within the gliomas in the vaccinated rats treated with the drugs. Animals that rejected the established T9/9L glioma by the combination therapy proved immune against an intracranial rechallenge by T9/9L glioma, but showed no resistance to an unrelated MADB106 breast cancer.