Unprecedented Benzoquinone Motifs Reveal Post-Oligomerizational Modification of Proanthocyanidins.

Proanthocyanidins (PACs) are complex flavan-3-ol polymers with stunning chemical complexity due to oxygenation patterns, oxidative phenolic ring linkages, and intricate stereochemistry of their heterocycles and inter-flavan linkages. Being promising candidates for dental restorative biomaterials, trace analysis of dentin bioactive cinnamon PACs now yielded novel trimeric ( and ) and tetrameric () PACs with unprecedented - and benzoquinone motifs (benzoquinonoid PACs). Challenges in structural characterization, especially their absolute configuration, prompted the development of a new synthetic-analytical approach involving comprehensive spectroscopy, including NMR with quantum mechanics-driven H iterative functionalized spin analysis (HifSA) plus experimental and computational electronic circular dichroism (ECD).

Anti-Microbial Activity of Aliphatic Alcohols from Chinese Black Cardamom (Amomum tsao-ko) against Mycobacterium tuberculosis H37Rv.

The fruits of Amomun tsao-ko (Chinese black cardamom; Zingiberaceae) contain an abundance of essential oils, which have previously demonstrated significant antimicrobial activity. In our preliminary search for natural anti-tuberculosis agents, an acetone extract of A. tsao-ko (AAE) exhibited strong antibacterial activity against Mycobacterium tuberculosis H37Rv.

Hypertension-mediated organ damage in masked hypertension.

Objectives: Masked hypertension - a blood pressure (BP) phenotype characterized by a clinic BP in the normal range but elevated BP outside the office - is associated with early hypertension-mediated organ damage. This study examined early target organ manifestations of masked hypertension diagnosed by home (HBPM) and ambulatory (ABPM) BP monitoring.

Methods: Left ventricular (LV) structure and diastolic function measured by echocardiography, microalbuminuria, and coronary artery calcification were evaluated in 420 patients with high clinic BP (SBP 120-150 mmHg or DBP 80-95 mmHg).

Coronary Artery Calcifications and Cardiac Risk After Radiation Therapy for Stage III Lung Cancer.

Purpose: Heart dose and heart disease increase the risk for cardiac toxicity associated with radiation therapy. We hypothesized that computed tomography (CT) coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease.

Methods And Materials: We analyzed the cumulative incidence of cardiac events in patients with stage III non-small cell lung cancer receiving median 74 Gy on prospective dose-escalation trials.

Design of Novel Phosphopantetheine Adenylyltransferase Inhibitors: A Potential New Approach to Tackle Mycobacterium tuberculosis.

Background: Tuberculosis (TB) has been a challenging disease worldwide, especially for the neglected poor populations. Presently, there are approximately 2 billion people infected with TB worldwide and 10 million people in the world fell ill with active TB, leading to 1.5 million deaths.

Antimycobacterial Rufomycin Analogues from Strain MJM3502.

This study represents a systematic chemical and biological study of the rufomycin (RUF) class of cyclic heptapeptides, which our anti-TB drug discovery efforts have identified as potentially promising anti-TB agents that newly target the caseinolytic protein C1, ClpC1. Eight new RUF analogues, rufomycins NBZ1-NBZ8 (-), as well as five known peptides (-) were isolated and characterized from the strain MJM3502. Advanced Marfey's and X-ray crystallographic analysis led to the assignment of the absolute configuration of the RUFs.

Diagnostic performance of an artificial intelligence-driven cardiac-structured reporting system for myocardial perfusion SPECT imaging.

Objectives: To describe and validate an artificial intelligence (AI)-driven structured reporting system by direct comparison of automatically generated reports to results from actual clinical reports generated by nuclear cardiology experts.

Background: Quantitative parameters extracted from myocardial perfusion imaging (MPI) studies are used by our AI reporting system to generate automatically a guideline-compliant structured report (sR).

Method: A new nonparametric approach generates distribution functions of rest and stress, perfusion, and thickening, for each of 17 left ventricle segments that are then transformed to certainty factors (CFs) that a segment is hypoperfused, ischemic.

Residual Complexity Does Impact Organic Chemistry and Drug Discovery: The Case of Rufomyazine and Rufomycin.

Residual complexity (RC) involves the impact of subtle but critical structural and biological features on drug lead validation, including unexplained effects related to unidentified impurities. RC commonly plagues drug discovery efforts due to the inherent imperfections of chromatographic separation methods. The new diketopiperazine, rufomyazine (6), and the previously known antibiotic, rufomycin (7), represent a prototypical case of RC that (almost) resulted in the misassignment of biological activity.

QSAR-driven design, synthesis and discovery of potent chalcone derivatives with antitubercular activity.

New anti-tuberculosis (anti-TB) drugs are urgently needed to battle drug-resistant Mycobacterium tuberculosis strains and to shorten the current 6-12-month treatment regimen. In this work, we have continued the efforts to develop chalcone-based anti-TB compounds by using an in silico design and QSAR-driven approach. Initially, we developed SAR rules and binary QSAR models using literature data for targeted design of new heteroaryl chalcone compounds with anti-TB activity.

The Generally Useful Estimate of Solvent Systems (GUESS) method enables the rapid purification of methylpyridoxine regioisomers by countercurrent chromatography.

The TLC-based Generally Useful Estimate of Solvent Systems (GUESS) method was employed for countercurrent chromatography solvent system selection, in order to separate the three synthetic isomers: 3-O-methylpyridoxine, 4'-O-methylpyridoxine (ginkgotoxin), and 5'-O-methylpyridoxine. The Rf values of the three isomers indicated that ChMWat+2 (chloroform-methanol-water 10:5:5, v/v/v) was appropriate for the countercurrent separation. The isomer separation was highly selective and demonstrated that the TLC-based GUESS method can accelerate solvent system selection for countercurrent separation.

Looking afield: debt collection tips hospitals can borrow from banks.

When developing strategies for collecting on patient debt, hospitals can benefit from following the example of the banking industry: Banks take a "do-it-yourself" approach, working delinquent accounts in-house for as long as practical. They embrace technology to give in-house debt collectors optimal opportunity to connect with customers to work out terms for resolving debt. They strategically leverage outside collections agencies based on the makeup of their debt portfolio.

Reproducibility of masked hypertension among adults 30 years or older.

Objective: Masked hypertension (MH) refers to nonelevated office blood pressure (BP) with elevated out-of-office BP, but its reproducibility has not been conclusively established. We examined 1-week reproducibility of MH by home BP monitoring (HBPM) and ambulatory BP monitoring (ABPM).

Methods: We recruited 420 adults not on BP-lowering medication, with recent clinic BP between 120/80 and 149/95 mmHg.

Clinical decision support systems in myocardial perfusion imaging.

Diagnostic imaging is becoming more complicated, physicians are also required to master an ever-expanding knowledge base and take into account an ever increasing amount of patient-specific clinical information while the time available to master this knowledge base, assemble the relevant clinical data, and apply it to specific tasks is steadily shrinking. Compounding these problems, there is an ever increasing number of aging "Baby Boomers" who are becoming patients coupled with a declining number of cardiac diagnosticians experienced in interpreting these studies. Hence, it is crucial that decision support tools be developed and implemented to assist physicians in interpreting studies at a faster rate and at the highest level of up-to-date expertise.

Quantification of a botanical negative marker without an identical standard: ginkgotoxin in Ginkgo biloba.

A new strategy for the analysis of natural products uses a combination of quantitative (1)H NMR (qHNMR) and adsorbent-free countercurrent separation (CS) methodology to establish a quantification method for ginkgotoxin (4'-O-methylpyridoxine) in Ginkgo biloba preparations. The target analyte was concentrated in a one-step CS process using the ChMWat +2 solvent system (CHCl3-MeOH-H2O, 10:5:5) and subsequently assayed by qHNMR. While commercial G.

A novel indigoid anti-tuberculosis agent.

The structure of a novel indigoid component was characterized by X-ray crystallography. This compound exhibited excellent anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv in whole cell culture showing a submicromolar minimum inhibitory concentration (MIC). A synthesis of this molecule was designed and carried out to produce sufficient material for further testing.

Chlorinated coumarins from the polypore mushroom Fomitopsis officinalis and their activity against Mycobacterium tuberculosis.

An EtOH extract of the polypore mushroom Fomitopsis officinalis afforded two new naturally occurring chlorinated coumarins, which were identified as the previously synthesized compounds 6-chloro-4-phenyl-2H-chromen-2-one (1) and ethyl 6-chloro-2-oxo-4-phenyl-2H-chromen-3-carboxylate (2). The structures of the two isolates were deduced by ab initio spectroscopic methods and confirmed by chemical synthesis. In addition, an analogue of each was synthesized as 7-chloro-4-phenyl-2H-chromen-2-one (3) and ethyl 7-chloro-2-oxo-4-phenyl-2H-chromen-3-carboxylate (4).

Lone atrial fibrillation is associated with pectus excavatum.

Background: Pectus excavatum is a skeletal abnormality that may have cardiac manifestations.

Objective: To determine whether pectus excavatum is associated with lone atrial fibrillation (AF).

Methods: The pectus severity index (PSI) is the ratio of the lateral diameter of the chest to the distance between the sternum and the spine on computed tomography scan.

Synthesis of Substituted Isatins.

Isatins are valuable intermediates for heterocyclic chemistry. Most of the common methods for their production are less than adequate when the number and lipophilicity of substituents on the targeted isatin are increased. Our group desired such molecules and identified an alternative method for their production.

P1-substituted symmetry-based human immunodeficiency virus protease inhibitors with potent antiviral activity against drug-resistant viruses.

Because there is currently no cure for HIV infection, patients must remain on long-term drug therapy, leading to concerns over potential drug side effects and the emergence of drug resistance. For this reason, new and safe antiretroviral agents with improved potency against drug-resistant strains of HIV are needed. A series of HIV protease inhibitors (PIs) with potent activity against both wild-type (WT) virus and drug-resistant strains of HIV was designed and synthesized.

Image-guided optimization of the ECG trace in cardiac MRI.

Improper electrocardiogram (ECG) lead placement resulting in suboptimal gating may lead to reduced image quality in cardiac magnetic resonance imaging (CMR). A patientspecific systematic technique for rapid optimization of lead placement may improve CMR image quality. A rapid 3 dimensional image of the thorax was used to guide the realignment of ECG leads relative to the cardiac axis of the patient in forty consecutive adult patients.

Identification of proteasome gene regulation in a rat model for HIV protease inhibitor-induced hyperlipidemia.

Patients treated with highly active antiretroviral therapy may develop metabolic side effects such as hyperlipidemia, insulin resistance, lipoatrophy and lactic acidosis. The pathophysiology of these metabolic abnormalities is unknown, although some, e.g.

Synthesis and evaluation of inhibitors of cytochrome P450 3A (CYP3A) for pharmacokinetic enhancement of drugs.

The HIV protease inhibitor ritonavir (RTV) is also a potent inhibitor of the metabolizing enzyme cytochrome P450 3A (CYP3A) and is clinically useful in HIV therapy in its ability to enhance human plasma levels of other HIV protease inhibitors (PIs). A novel series of CYP3A inhibitors was designed around the structural elements of RTV believed to be important to CYP3A inhibition, with general design features being the attachment of groups that mimic the P2-P3 segment of RTV to a soluble core. Several analogs were found to strongly enhance plasma levels of lopinavir (LPV), including 8, which compares favorably with RTV in the same model.

Synthesis and biological characterization of B-ring amino analogues of potent benzothiadiazine hepatitis C virus polymerase inhibitors.

Benzothiadiazine inhibitors of the HCV NS5B RNA-dependent RNA polymerase are an important class of non-nucleoside inhibitors that have received considerable attention in the search for novel HCV therapeutics. Research in our laboratories has identified a novel series of tetracyclic benzothiadiazine inhibitors of HCV polymerase bearing a benzylamino substituent on the B-ring. Compounds in this series exhibit low-nanomolar activities in both genotypes 1a and 1b polymerase inhibition assays and subgenomic replicon assays.