Chapter~1. Alkylation chemistry of the camphor imine of tert-butyl glycinate and its derivatives. Chapter~2. Synthesis and reactions of a new carbon(2) symmetric ketone.

Factors which influence the diastereoselectivity in the alkylation of the (R)-camphor imine of tert-butyl glycinate (24) were investigated in order to further refine the alkylation model. It was demonstrated that when alkylating 24 with various benzyl bromides or allyl bromide that the diastereoselectivity was dependent on the $\pi$-electron density of the alkylating agent, the metal cation of the enolate and the cosolvent used. Inferior selectivities (de\u27s $$ 95%) were obtained when using HMPA as the cosolvent, Li or Na as the metal cation and alkylating agents with electron rich $\pi$-systems. Further study included the preparation of several camphor derivatives (ketopinic acid, methyl ketopinate, 3-hydroxycamphor, 1-hydroxymethyl camphor) which were utilized as chiral auxiliaries in the alkylation of their corresponding imines of tert-butyl glycinate. These investigations lead to the discovery of two new and unexpected reactions of the camphor skeleton. Finally, a new C\sb2 symmetric ketone, cis,anti,cis-tricyclo (6.3.0.0\sp{3,7}\rbrackundecan-2-one (91) was prepared in 91% ee. Initial efforts to use this ketone as a chiral auxiliary in the alkylation of chiral imines of tert-butyl glycinate failed since condensation of 91 with several amines was not possible. This lead to an investigation into the utility of cis,anti,cis-tricyclo (6.3.0.0\sp{3,7}\rbrackundecan-2-ol (92) as a chiral auxiliary. Source: Dissertation Abstracts International, Volume: 53-12, Section: B, page: 6300. Thesis (Ph.D.)--University of Windsor (Canada), 1992

Dietary flavonoid intake and weight maintenance: three prospective cohorts of 124,086 US men and women followed for up to 24 years

Objective: To examine whether dietary intake of specific flavonoid sub-classes is associated with weight change over time, including flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, and flavonoid polymers. Design: Three prospective cohort studies. Setting: Health professionals in the United States. Participants: 124,086 men and women participating in the Health Professionals Follow-up Study (HPFS), Nurses’ Health Study (NHS), and Nurses’ Health Study II (NHS II). Main outcome measure: Self-reported change in weight over multiple 4-year time intervals between 1986 and 2011. Results: Increased consumption of most flavonoid sub-classes, including flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers was inversely associated with weight change over 4-year time intervals, after adjustment for simultaneous changes in other lifestyle factors including other aspects of diet, smoking status, and physical activity. In the pooled results, the greatest magnitude of association was observed for anthocyanins (-0.22 lbs, 95% CI -0.30 to -0.15 lbs per additional SD/day, 10 mg), flavonoid polymers (-0.18 lbs, 95% CI -0.28 to -0.08 lbs per additional SD/day, 138 mg), and flavonols (-0.16 lbs, 95% CI -0.26 to -0.06 lbs per additional SD/day, 7 mg). After additional adjustment for fiber intake associations remained significant for anthocyanins, proanthocyanidins, and total flavonoid polymers but were attenuated and no longer statistically significant for other sub-classes. Conclusions: Higher intake of foods rich in flavonols, flavan-3-ols, anthocyanins, and flavonoid polymers, may contribute to weight maintenance in adulthood, and may help to refine dietary recommendations for the prevention of obesity and its potential sequelae

Mycobacterial infections in a large Virginia hospital, 2001-2009

<p>Abstract</p> <p>Background</p> <p>In areas where both tuberculosis (TB) and nontuberculous mycobacteria (NTM) are prevalent, descriptive studies of the clinical features of individual mycobacteria are needed to inform clinical triage.</p> <p>Methods</p> <p>We queried the University of Virginia Clinical Data Repository for all mycobacterial infections from 2001-2009.</p> <p>Results</p> <p>Of 494 mycobacterial infections in 467 patients there were 22 species. Patients with pulmonary Tb were more likely to be reported as immigrants (p < 0.001) and less likely to have a predisposing risk factor for NTM (pre-existing lung disease or host predisposition; p = 0.002). Review of chest CT scans revealed that TB infection was more likely to exhibit cavities and pleural effusion than NTM infection (p < 0.05). Among NTM infections <it>M. kansasii</it>, <it>M. xenopi</it>, and <it>M. fortuitum </it>were more likely than MAC to have cavities. There were at least 83 patients that met criteria for NTM lung disease and these were caused by 9 species. <it>M. abscessus </it>infection was associated with cystic fibrosis and <it>M. xenopi </it>infection was associated with male gender.</p> <p>Conclusions</p> <p>In our center mycobacterial infections were common and of diverse species. Immigrant status, cavities, and effusion were associated with TB vs. NTM.</p

Difference in the Pharmacokinetics and Hepatic Metabolism of Antidiabetic Drugs in Zucker Diabetic Fatty and Sprague-Dawley Rats

ABSTRACT The Zucker diabetic fatty (ZDF) rat, an inbred strain of obese Zucker fatty rat, develops early onset of insulin resistance and displays hyperglycemia and hyperlipidemia. The phenotypic changes resemble human type 2 diabetes associated with obesity and therefore the strain is used as a pharmacological model for type 2 diabetes. The aim of the current study was to compare the pharmacokinetics and hepatic metabolism in male ZDF and Sprague-Dawley (SD) rats of five antidiabetic drugs that are known to be cleared via various mechanisms. Among the drugs examined, metformin, cleared through renal excretion, and rosiglitazone, metabolized by hepatic cytochrome P450 2C, did not exhibit differences in the plasma clearance in ZDF and SD rats. In contrast, glibenclamide, metabolized by hepatic CYP3A, canagliflozin, metabolized mainly by UDP-glucuronosyltransferases (UGT), and troglitazone, metabolized by sulfotransferase and UGT, exhibited significantly lower plasma clearance in ZDF than in SD rats after a single intravenous administration. To elucidate the mechanisms for the difference in the drug clearance, studies were performed to characterize the activity of hepatic drug-metabolizing enzymes using liver S9 fractions from the two strains. The results revealed that the activity for CYP3A and UGT was decreased in ZDF rats using the probe substrates, and decreased unbound intrinsic clearance in vitro for glibenclamide, canagliflozin, and troglitazone was consistent with lower plasma clearance in vivo. The difference in pharmacokinetics of these two strains may complicate pharmacokinetic/ pharmacodynamic correlations, given that ZDF is used as a pharmacological model, and SD rat as the pharmacokinetics and toxicology strain

U.S. Billion-ton Update: Biomass Supply for a Bioenergy and Bioproducts Industry

The Report, Biomass as Feedstock for a Bioenergy and Bioproducts Industry: The Technical Feasibility of a Billion-Ton Annual Supply (generally referred to as the Billion-Ton Study or 2005 BTS), was an estimate of “potential” biomass within the contiguous United States based on numerous assumptions about current and future inventory and production capacity, availability, and technology. In the 2005 BTS, a strategic analysis was undertaken to determine if U.S. agriculture and forest resources have the capability to potentially produce at least one billion dry tons of biomass annually, in a sustainable manner—enough to displace approximately 30% of the country’s present petroleum consumption. To ensure reasonable confidence in the study results, an effort was made to use relatively conservative assumptions. However, for both agriculture and forestry, the resource potential was not restricted by price. That is, all identified biomass was potentially available, even though some potential feedstock would more than likely be too expensive to actually be economically available. In addition to updating the 2005 study, this report attempts to address a number of its shortcoming

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care