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A strategically novel synthesis of nano-sized, asymmetrically functionalized double-decker shaped silsesquioxanes (DDSQ) is reported. Selective protection with a boronic acid affords the crucial mono-protected intermediate en route to the asymmetric products. Generation of symmetric by-products is minimized by judicious choice of base, and high recovery of recyclable starting DDSQ tetraol is achieved.

Background: Ensuring malaria commodity availability at health facilities is a cornerstone of malaria control. Since 2013, the Guinea National Malaria Control Programme has been routinely collecting data on stock levels of key malaria commodities through a monthly routine malaria information system (RMIS). In parallel, biannual end-user verification (EUV) surveys have also assessed malaria commodity availability at a subset of health facilities, potentially representing a duplication of efforts., Methods: Data on 12 malaria commodity stock levels verified during four EUV surveys conducted between 2014 and 2016 was compared to data for the corresponding months submitted by the same health facilities through the RMIS. The sensitivity and specificity of the RMIS in detecting stock-outs was calculated, as was the percent difference between average stock levels reported through the two systems., Results: Of the 171 health facilities visited during the four EUV surveys, 129 (75%) had data available in the RMIS. Of 351 commodity stock-outs observed during the EUV in the sampled reporting health facilities, 256 (73%) were also signaled through the corresponding RMIS reports. When the presence of malaria commodity stocks was confirmed during the EUV surveys, the RMIS also reported available stock 87% (677/775) of the time. For all commodities, the median percent difference in average stock levels between the EUV and RMIS was 4% (interquartile range - 7 to 27%)., Conclusion: The concordance between stock levels reported through the RMIS and those verified during the EUV visits provides certain evidence that RMIS data can inform quantification and procurement decisions. However, lower than acceptable rates of reporting and incomplete detection of stock-outs from facilities that do report suggest that further systems strengthening is needed to improve RMIS reporting completeness and data quality.

An atom-economic route to benzo[f]-1-indanone frameworks has been developed starting from the readily available gem-dialkylthio trienynes by intramolecular annulations. The chemoselectivity of the intramolecular cyclizations can be regulated by both the base and the type of gas atmosphere used in the reaction, thus allowing the divergent synthesis of the corresponding functionalized benzo[f]-1-indanones in good to excellent yields.

The effect of lactose at the concentration typically found in milk (134 mM) on the ability of ricin to inhibit protein synthesis in HeLa cells was studied. Ricin (0.001 to 300 μg/ml) that was either not treated or treated with 134 mM lactose was added to test tubes containing 1 ml of HeLa cells (approximately 3 × 10(5) cells in a low-leucine medium). After 2 h of incubation at 37°C, 0.5 μCi of L-[U-(14)C]-leucine was added to each tube and incubated for another 60 min. The cells were harvested by centrifugation and lysed, and cellular proteins were separated. The amount of radioactivity incorporated into the proteins was determined by liquid scintillation. The biological activity of ricin, i. e., the amount of radioactivity in a sample relative to that of the control (cells not treated with ricin), was calculated for each treatment. The inhibitory effect of 134 mM lactose on the biological activity of ricin was only significant at concentrations of ricin below 1 μg/ml. At higher ricin concentrations, the effect of 134 mM lactose decreased as the concentration of ricin increased, resulting in an increase in the inhibition of proteins synthesis. Our results also indicated that bovine milk, when used in place of 134 mM lactose, was more effective for reducing the activity of ricin at concentrations below 1 μg/ml but was ineffective against ricin concentrations greater than 1 μg/ml. These results suggest that milk may not protect against ricin intoxication at the concentration (0.89 μg/ml) equivalent to the lowest limit of its 50 % lethal dose for a 20-kg child consuming 225 ml (8 oz) of milk.

Aldehyde Termination: A novel copper-catalyzed transformation from methyl ketones into aldehydes has been accomplished. This method is applicable to a wide range of aromatic and aliphatic methyl ketones and chemoselectively produces aldehydes, accompanied by the release of hydrogen (H2 ) and carbon dioxide (CO2 ) as by-products., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel and efficient method for the construction of α-(1,3-dithiolan-2-ylidene) δ-lactam and δ-lactone rings has been developed. It involves the regiospecific 6-endo-annulation of in situ generated 2-(1,3-dithiolan-2-ylidene)-3,4-dienamides/acids from the dehydrative coupling of α-oxo ketene dithioacetals with tertiary propargyl alcohols promoted by BF3·Et2O. A range of α-(1,3-dithiolan-2-ylidene) δ-lactams and δ-lactones are obtained in good to high yields. In addition, indenes are prepared by using α-acetyl ketene dithioacetal as the precursor.

gem-Dialkylthio vinylallenes were obtained for the first time and applied to the divergent synthesis of fully-substituted pyrroles and thiophenes by domino cyclizations. These two cyclization pathways were regulated by alkylthio groups. Plausible reaction mechanisms were presented and supported by DFT calculations. An unprecedented metal-free carbothiolation was discovered in the formation of thiophenes.

This study was conducted to compare the identification of Shiga toxin 1 (Stx1) based on its specific biological activity and based on results of a commercial enzyme-linked immunosorbent assay (ELISA) kit. Stx1 was thermally treated for various periods in phosphate-buffered saline, milk, and orange juice. The residual Stx1 concentration was determined with the commercial ELISA kit, and its residual enzymatic activity (amount of adenine released from a 2,551-bp DNA substrate) was determined with a biological activity assay (BAA). Regression analysis indicated that the inactivation of Stx1 as a function of time followed first-order kinetics. The half-lives determined at 60, 65, 70, 75, 80, and 85°C were 9.96, 3.19, 2.67, 0.72, 0.47, and 0.29 min, respectively, using the BAA. The half-lives determined by the ELISA with thermal treatments at 70, 75, 80, and 85°C were 40.47, 11.03, 3.64, and 1.40 min, respectively. The Z, Q(10), and Arrhenius activation energy values derived by both assays were dissimilar, indicating that the rate of inactivation of the active site of Stx1 was less sensitive to temperature change than was denaturation of the epitope(s) used in the ELISA. These values were 10.28°C and 9.40 and 54.70 kcal/mol, respectively, with the ELISA and 16°C and 4.11 and 34 kcal/mol, respectively, with the BAA. Orange juice enhanced Stx1 inactivation as a function of increasing temperature, whereas inactivation in 2% milk was not very much different from that in phosphate-buffered saline. Our investigation indicates that the ELISA would be a reliable method for detecting the residual toxicity of heat-treated Stx1 because the half-lives determined with the ELISA were greater than those determined with the BAA (faster degradation) at all temperatures and were highly correlated (R(2) = 0.994) with those determined with the BAA.

In this study, saxitoxin dihydrochloride in skim milk was reacted with sodium hydroxide and hydrogen peroxide to yield nontoxic 8-amino-6-hydroxymethyl-iminopurine-3(2H)-propionic acid (AHIPA), which was quantified by fluorescence spectroscopy using excitation and emission wavelengths of 330 and 425 nm, respectively. Samples of saxitoxin dihydrochloride (in 20% ethanol, vol/vol) were used as controls. The limits of detection of AHIPA, based on the concentration of saxitoxin prior to inactivation, were 5 and 10 μg/ml for the control and skim milk, respectively. These values are considerably below the concentration of saxitoxin that corresponds to the lethal dosage of 1 mg for an adult of average weight (70 kg). The inactivation of saxitoxin proceeded at a lower rate in skim milk than in the control, as its reaction rate constant was only 0.004 min(-1) compared with 0.011 min(-1) for the control. We were unable to detect AHIPA in 2% milk contaminated with saxitoxin because of possible interference from what we believed were products of secondary reactions involving milk fat and sodium hydroxide. Our results also indicated that the conversion of saxitoxin to AHIPA increased initially with temperature up to 40°C but decreased thereafter. We observed a decrease in the formation of AHIPA when the concentration of hydrogen peroxide was increased except at 22°C, where there was an initial increase in AHIPA formation between 1.2 and 2.4 mg/ml hydrogen peroxide but its formation decreased thereafter.

The regiospecific β-lactam ring-opening/recyclization reaction of N-aryl-3-spirocyclic-β-lactams, made by the one-pot cyclization reaction of acetoacetanilides, has been achieved for the first time using a Lewis-Brønsted acids combined superacid catalyst system, thus providing an efficient entry to 3-spirocyclicquinolin-4(1H)-ones. A mechanism involving superacid-catalysis was proposed.

A novel copper-mediated chelation-assisted ortho C-H nitration of (hetero)arenes has been developed for the first time, which used dioxygen as terminal oxidant and 1,2,3-TCP as solvent, leading to the synthesis of nitroaromatics with excellent regioselectivity and in good yields. Mechanistic investigations indicate a mechanism involving a four-centered transition state, with simultaneous cleavage of an ortho C-H bond and a N-O bond of the nitrate anion on the 2-arylpyridine-coordinated copper(II) complex.

Background: Although surgery is increasingly recognized as an essential component of primary health care, there has been little documentation of surgical programs in low- and middle-income countries. Surgeons OverSeas (SOS) is a New York-based organization with a mission to save lives in developing countries by improving surgical care. This article highlights the surgical program in Sierra Leone as a possible model to improve access to surgery., Methods: An SOS team conducted a needs assessment of surgical capacity in Sierra Leone in February 2008. Interventions were then developed and programs were implemented. A follow-up assessment was conducted in December 2009, which included interviews of key Sierra Leone hospital personnel and a review of operating room log books., Results: Based on an initial needs assessment, a program was developed that included training, salary support, and the provision of surgical supplies and equipment. Two 3-day workshops were conducted for a total of 44 health workers, salary support given to over 100 staff, and 2 containers of supplies and equipment were donated. Access to surgery, as measured by the number of major operations at Connaught Hospital, increased from 460 cases in 2007 to 768 cases in 2009., Conclusions: The SOS program in Sierra Leone highlights a method for improving access to surgery that incorporates an initial needs assessment with minimal external support and local staff collaboration. The program functions as a catalyst by providing training, salary support, and supplies. The beneficial results of the program can then be used to advocate for additional resources for surgery from policy makers. This model could be beneficial in other resource-poor countries in which improved access to surgery is desired., (Copyright 2010 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)