3D-QSAR and molecular modeling studies on 2,3-dideoxy hexenopyranosid-4-uloses as anti-tubercular agents targeting alpha-mannosidase.

Ligand-based and structure-based methods were applied in combination to exploit the physicochemical properties of 2,3-dideoxy hex-2-enopyranosid-4-uloses against Mycobacterium tuberculosis H37Rv. Statistically valid 3D-QSAR models with good correlation and predictive power were obtained with CoMFA steric and electrostatic fields (r(2) = 0.797, q(2) = 0.589) and CoMSIA with combined steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (r(2) = 0.867, q(2) = 0.570) based on training set of 33 molecules with predictive r(2) of 0.808 and 0.890 for CoMFA and CoMSIA respectively. The results illustrate the requirement of optimal alkyl chain length at C-1 position and acceptor groups along hydroxy methyl substituent of C-6 to enhance the anti-tubercular activity of the 2,3-dideoxy hex-2-enopyranosid-4-uloses while any substitution at C-3 position exert diminishing effect on anti-tubercular activity of these enulosides. Further, homology modeling of M. tuberculosis alpha-mannosidase followed by molecular docking and molecular dynamics simulations on co-complexed models were performed to gain insight into the rationale for binding affinity of selected inhibitors with the target of interest. The comprehensive information obtained from this study will help to better understand the structural basis of biological activity of this class of molecules and guide further design of more potent analogues as anti-tubercular agents.

Universal Precautions Plus: Physician-Directed Strategies for Improving Patient Health Literacy in the Emergency Department.

Working on the frontlines with safety-net populations, emergency physicians are uniquely positioned to take on a greater role in addressing the current health literacy crisis and specific barriers that may exist. Here, we review the concept of universal health literacy precautions and explore the application of these universal precautions in conjunction with other patient-centered strategies. More specifically, to improve patient understanding and outcomes, emergency physicians can pair universal health literacy precautions with strategies including multiple learning techniques, dual-code theory, empowerment counseling, family buy-in, and hands-on practice. We provide two examples of emergency department encounters where this combined approach was used differently yet successfully and efficiently. Ultimately, we aim to highlight the value of emergency physicians being equipped with basic skills in health literacy educational strategies.

Chiral pyridin-3-ones and pyridines: syntheses of enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones, 2,3-disubstituted 4-iodopyridines, and enantiopure 2,3-disubstituted 4-pyridinemethanols.

The development of an innovative method to access enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones starting from D-glucal via the aza-Achmatowicz transformation has been described. These highly functionalized pyridin-3-ones have been utilized for the synthesis of contiguously substituted pyridines through a rapid and efficient Et(3)N/Ac(2)O promoted cyclo-elimination, aromatization cascade, allowing the facile assembly of important pyridine-based building blocks like 2-substituted 3-acetoxy-4-iodopyridines and enantiopure 2-substituted 3-acetoxy-4-pyridinemethanols possessing benzylic stereogenic centers, whose synthesis otherwise would be tedious. The utilization of commercially available sugars as starting materials, mild reaction conditions, catalytic transfer hydrogen (CTH) of α-furfuryl azide derivatives, transfer of chiral aryl/alkyl methanols from enulosides to pyridin-3-ones and pyridines, high yields, and short reaction times are key features of this method. The utility of the method has been further exemplified by demonstrating the usage of the 2-substituted 3-acetoxy-4-iodopyridine for the construction of biologically significant molecules like 2,7-disubstituted furo[2,3-c]pyridines and 7,7'-disubstituted 2,2'-bifuro[2,3-c]pyridines.

Impact of Hurricane Harvey on Healthcare Utilization and Emergency Department Operations.

INTRODUCTION: Hurricanes have increased in severity over the past 35 years, and climate change has led to an increased frequency of catastrophic flooding. The impact of floods on emergency department (ED) operations and patient health has not been well studied. We sought to detail challenges and lessons learned from the severe weather event caused by Hurricane Harvey in Houston, Texas, in August 2017. METHODS: This report combines narrative data from interviews with retrospective data on patient volumes, mode of arrival, and ED lengths of stay (LOS). We compared the five-week peri-storm period for the 2017 hurricane to similar periods in 2015 and 2016. RESULTS: For five days, flooding limited access to the hospital, with a consequent negative impact on provider staffing availability, disposition and transfer processes, and resource consumption. Interruption of patient transfer capabilities threatened patient safety, but flexibility of operations prevented poor outcomes. The total ED patient census for the study period decreased in 2017 (7062 patients) compared to 2015 (7665 patients) and 2016 (7770) patients). Over the five-week study period, the arrival-by-ambulance rate was 12.45% in 2017 compared to 10.1% in 2016 (p < 0.0001) and 13.7% in 2015 (p < 0.0001). The median ED length of stay (LOS) in minutes for admitted patients was 976 minutes in 2015 (p < 0.0001) compared to 723 minutes in 2016 and 591 in 2017 (p < 0.0001). For discharged patients, median ED LOS was 336 minutes in 2016 compared to 356 in 2015 (p < 0.0001) and 261 in 2017 (p < 0.0001). Median boarding time for admitted ED patients was 284 minutes in 2016 compared to 470 in 2015 (p < 0.0001) and 234.5 in 2017 (p < 0.001). Water damage resulted in a loss of 133 of 179 inpatient beds (74%). Rapid and dynamic ED process changes were made to share ED beds with admitted patients and to maximize transfers post-flooding to decrease ED boarding times. CONCLUSION: A number of pre-storm preparations could have allowed for smoother and safer ride-out functioning for both hospital personnel and patients. These measures include surplus provisioning of staff and supplies to account for limited facility access. During a disaster, innovative flexibility of both ED and hospital operations may be critical when disposition and transfer capibilities or bedding capacity are compromised.

Facile synthesis of enantiomerically pure 2- and 2,3-disubstituted furans catalysed by mixed Lewis acids: an easy route to 3-iodofurans and 3-(hydroxymethyl)furans.

Simple and efficient syntheses, catalysed by a mixed Lewis acid system (ZrCl(4)/ZnI(2)), of enantiomerically pure 2- and 2,3-disubstituted furan derivatives--including important synthons such as 3-iodofuran and 3-(hydroxymethyl)furan derivatives--from commercially available 3,4,6-tri-O-acetyl-D-glucal are described. The transformation is achieved through a synergistic interaction between ZrCl(4) and ZnI(2) in catalytic amounts.

2,3-dideoxy hex-2-enopyranosid-4-uloses as promising new anti-tubercular agents: design, synthesis, biological evaluation and SAR studies.

The alarming resurgence of tuberculosis (TB) underlines the urgent need for development of new and potent anti-TB drugs. Towards this goal we herein report the design and synthesis of 2,3-dideoxy hex-2-enopyranosid-4-uloses as promising new anti-tubercular agents. These easily accessible, small molecules were found to exhibit in vitro activity against Mycobacterium tuberculosis H37Rv in a MIC range of 0.78 µg/mL to 25 µg/mL. A detailed SAR study on these hex-2-enopyranosid-4-uloses led to the identification of compound 5g (S007-724) which on the basis of low MIC (0.78 µg/mL-M. tuberculosis H37Rv; 1.56 µg/mL-MDR, SDR strains of M. tuberculosis; 0.78 µg/mL-inhibition of intracellular replication of M. tuberculosis) and SI value of 13.5 has been identified as a promising lead molecule.