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The access of ring junction functionalized 5,6-hydrindanone systems has been elusive in the realm of synthetic methodology, and the functionalization of a pre-built ring system rarely explored. These 5,6-hydridanone systems are prevalent in a variety of terpenoid ring systems, especially that of steroidal molecules. Previous synthetic methods to reach these systems using a Diels-Alder cycloaddition proved to be difficult and lacked labile functional groups that would be useful for substitution after the cycloaddition. The design of the α-nitrile cyclopentenone dienophile allows for both post-cyclization adduct functionalization, as well as lowering the energy barrier of the cycloaddition itself. In this work, it is shown that the Lewis acid promoted Diels-Alder reaction with α-nitrile β-methyl cyclopentenone dienophile can be performed under standard temperatures and pressures unlike previously established methods.1 This reaction can generate four chiral centers in a single synthetic step when the starting materials are prochiral. After the generation of 5,6-hydrindanone systems, radical cleavage of the nitrile functionality also allowed for electrophile trapping at the ring junction. This radical cleavage and electrophile trapping pathway allows for functionalization of a quaternary carbon at the ring junction, a method that should be fruitful in the generation of difficult to synthesize steroidal and other terpenoid molecules. In the work on synthetic cell penetrating peptides, camptothecin whilst a notably effective topoisomerase I inhibitor, has never quite reached it’s potential as a therapeutic due to its poor solubility in living systems. Previously, cationic amphiphilic polyproline helices (CAPH) molecules from the Chmielewski lab have been hydrophobically functionalized through O-alkylation of hydroxyprolines at specific regions within the peptide to generate a hydrophobic face. The combination of the cationic faces and the hydrophobic face have made the CAPH molecules notably cell penetrant and tunable. With camptothecin’s notable insolubility in water, it may serve as valuable surrogate to the hydrophobic groups on CAPH molecules and allowing it to be delivered intracellularly. Using an endogenously cleavable linker, we have worked towards a CPP that acts as a drug delivery vehicle. Acting as a replacement of the hydrophobic residue of a CAPH molecule, camptothecin will be chaperoned into the cell and should be released through the action of intracellular esterases.

To further engineer dienones with optimal combinations of potency and bioavailability, thirty-four asymmetric 1,5-diarylpenta-1,4-dien-3-ones ( 25 – 58 ) have been designed and synthesized for the evaluation of their in vitro anti-proliferative activity in three human prostate cancer cell lines and one non-neoplastic prostate epithelial cell line. All these asymmetric dienones are sufficiently more potent than curcumin and their corresponding symmetric counterparts. The optimal dienone 58 , with IC 50 values in the range of 0.03–0.12 μM, is 636-, 219-, and 454-fold more potent than curcumin in three prostate cancer cell models. Dienones 28 and 49 emerged as the most promising asymmetric dienones that warrant further preclinical studies. The two lead compounds demonstrated substantially improved potency in cell models and superior bioavailability in rats, while exhibiting no acute toxicity in the animals at the dose of 10 mg/kg. Dienones 28 and 46 can induce PC-3 cell cycle regulation at the G 0 /G 1 phase. However, dienone 28 induces PC-3 cell death in a different way from 46 even though they share the same scaffold, indicating that terminal heteroaromatic rings are critical to the action of mechanism for each specific dienone.

BACKGROUND There are no clinical guidelines on best practices for the use of bronchoscopy and esophagoscopy in diagnosing head and neck cancer. This retrospective cohort study examined variation in the use of bronchoscopy and esophagoscopy across hospitals in Michigan. METHODS A total of 17,828 patients were identified with head and neck cancer in the 2006 to 2010 Michigan State Ambulatory Surgery Databases. A hierarchical, mixed-effect logistic regression was used to examine whether a hospital's risk-adjusted rate of concurrent bronchoscopy or esophagoscopy was associated with its case volume (< 100, 100-999, or ≥ 1000 cases per hospital) for those undergoing diagnostic laryngoscopy. RESULTS Of 9218 patients undergoing diagnostic laryngoscopy, 1191 (12.9%) received concurrent bronchoscopy and 1675 (18.2%) underwent concurrent esophagoscopy. The median hospital rate of bronchoscopy was 2.7% (range, 0%-61.1%), and low-volume (odds ratio [OR] = 27.1; 95% confidence interval [CI] = 1.9, 390.7) and medium-volume (OR = 28.1; 95% CI = 2.0, 399.0) hospitals were more likely to perform concurrent bronchoscopy compared to high-volume hospitals. The median hospital rate of esophagoscopy was 5.1% (range, 0%-47.1%), and low-volume (OR = 9.8; 95% CI = 1.5, 63.7) and medium-volume (OR = 8.5; 95% CI = 1.3, 55.0) hospitals were significantly more likely to perform concurrent esophagoscopy relative to high-volume hospitals. CONCLUSIONS Patients with head and neck cancer who are undergoing diagnostic laryngoscopy are much more likely to undergo concurrent bronchoscopy and esophagoscopy at low- and medium-volume hospitals than at high-volume hospitals. Whether this represents overuse of concurrent procedures or appropriate care that leads to earlier diagnosis and better outcomes merits further investigation. Cancer 2014;120:61–67. © 2013 American Cancer Society.

A method for producing a hybrid electrolyte including preparing a housing, positioning a solid lithium ion conductor in the housing, and at least partially filling the housing with an organic liquid lithium ion conductor.

Evaluation of floating treatment wetlands in stormwater retention ponds on poultry farms to reduce nutrient loading Best management practices (BMPs) such as stormwater retention ponds are implemented to collect runoff and drainage from poultry farms and provide a possible intervention point for water treatment. Floating treatment wetlands (FTWs) are thought to remove pollutants from surrounding water columns. The majority of research conducted on FTWs focuses on nutrient removal via plant uptake. The results of prior studies conclude that plant uptake of nutrients alone is not a reliable source of nutrient removal because macrophytes and microalgae only temporarily immobilize N; this conclusion suggests that without periodic harvesting of plants, nutrient cycling would occur, while permanent removal of N is dependent upon denitrification. Floating treatment wetlands were evaluated to see if they could be used as a BMP. Denitrification potential was evaluated in the sediment and FTW through a denitrification enzyme assay by measuring the maximum potential of the microbial community at sample collection. Denitrification potentials among the FTWs were 5 to 7 times higher than rates found among pond sediments. Although significant denitrification was present, maximum nutrient removal could only take place if plants were harvested from FTWs in addition to microbial denitrification. The combination of plants and organisms within FTW matrices could potentially reduce nitrogen concentrations within stormwater retention ponds. Floating treatment wetlands provide a new tool that could assist in the uptake of nutrients, especially those associated with eutrophication. Floating treatment wetlands should be further analyzed but could potentially serve as a successful BMP in low flow systems within the Chesapeake Bay Watershed., (M.S.) -- Towson University, 2013.

6044 Background: Hospital variation in bronchoscopy and esophagoscopy rates while diagnosing head and neck cancer may reflect professional uncertainty about the effectiveness of these procedures and a lack of clinical guidelines on best practices. Furthermore, high-volume hospitals have demonstrated better outcomes for select oncologic procedures. We examined the association between hospital case volume and diagnostic bronchoscopy and esophagoscopy rates. Methods: This retrospective cohort study used the 2006-2010 Michigan State Ambulatory Surgery Databases, capturing all outpatient surgical cases in Michigan. Eligible cases included head and neck cancer patients who underwent laryngoscopy, bronchoscopy, and/or esophagoscopy. The primary outcome measure was the likelihood that a patient who underwent laryngoscopy during head and neck cancer diagnostic workup also underwent either bronchoscopy or esophagoscopy. We used hierarchical, mixed-effect logistic regression to measure the association between the primary outcome and hospital case volume (