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Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease.In this prospective cohort study, we followed up healthy, South African adolescents aged 12-18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex quantitative real-time PCR (qRT-PCR), the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease.Between July 6, 2005, and April 23, 2007, we enrolled 6363 participants from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% CI 63·2-68·9) and a specificity of 80·6% (79·2-82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6-64·3) and a specificity of 82·8% (76·7-86) in the 12 months preceding tuberculosis.The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease.BillMelinda Gates Foundation, the National Institutes of Health, Aeras, the European Union, and the South African Medical Research Council.

MSc (Pharmaceutics), North-West University, Potchefstroom Campus The use of herbal medicines is currently experiencing a revival of sorts. However, this resurgence in popularity is casting a much needed light on safety issues relevant to the use thereof, since many herbal products remain untested with regards to their toxicological properties. Siphonochilus aethiopicus, or African ginger, is one of the most desired medicinal plants at South African muthi markets. Traditional uses vary from malaria to various inflammatory related conditions such as asthma and dysmenorrhoea. Though African ginger has shown auspicious potential in several pharmacological studies - possessing anti-inflammatory, anti-trypanosomal and antimalarial activity (to name only a few) — information relating to its cytotoxicity is limited. When considering the wide range of commercially available products containing this plant, this raises concern for consumer safety. The main aim of the current study is to investigate the in vitro cytotoxicity of several S. aethiopicus extracts, alone and in combination with chitosan and Pharmacel® 101 fillers for tableting, on human hepatocellular liver carcinoma (HepG2) and human epithelial colorectal adenocarcinoma (Caco-2) cell lines since they represent the oral route of administration. Organic extracts were prepared by solvent extraction and compared with an aqueous extract and traditional infusion. These extracts were, subsequently, characterised with ultra-performance liquid chromatography quadruple time of flight mass spectrometry (UPLC-Q-TOF/MS) through the identification of AG 1—4, previously identified marker compounds. Standard cytotoxicity assays with different endpoints were selected and included the tetrazolium reduction (MTT) and lactate dehydrogenase (LDH) assays, as well as flow cytometry with fluorescent annexin V / propidium iodide (PI). UPLC chromatograms of extracts revealed organic extracts (ethanol and diethyl ether) to contain all four isolated African ginger compounds (AG 1—4). Aqueous extracts only contained AG 1 and AG 2 in small amounts and did not contain AG 3 or AG 4. MTT assays proved organic extracts to reduce cell viability, despite interference, whereas aqueous extracts did not cause interference; nor did it reduce cell viability. LDH data also indicated only organic extracts to cause LDH release on both cell lines. During both assays Caco-2 cells proved to be less sensitive to the effects of the extracts, compared to HepG2 cells, since cell viability only decreased at considerably higher concentrations. Fillers seldom, if at all, caused a significant (p ≤ 0.05) alteration of the effects caused by extracts. Subsequently, flow cytometric analysis was performed on organic extracts alone. Results indicated a definite decrease in cell viability of both cell lines following exposure, with a concomitant increase in apoptotic and necrotic cell populations. Therefore, it can be concluded that aqueous extracts do not possess cytotoxic properties, whereas organic extracts caused apoptotic and necrotic cell death. Considering the difference in phytochemical composition of these extracts, one cannot help to consider the possibility of AG 3 and AG 4, compounds only present in organic extracts, to be partly responsible for the observed cytotoxicity. Consequently, it is suggested to further isolate the major compounds present in S. aethiopicus and investigate their individual cytotoxicity. Selectivity of crude extracts and isolated compounds should, moreover, be investigated. Finally, development of polymer nanoparticle formulations are furthermore recommended as it might reduce toxicity. Masters

Our objective was to estimate core body temperature (T(b) ) from facial skin temperature (T(fs) ) in mixed-sex broilers. Chickens were obtained at hatch (d0) and grown in floor pens. At d34, temperature loggers were surgically placed into the abdominal cavity of anesthetized broilers. On d42, 43, 44, 45, and 49, all chickens (n=6/sex) were exposed to ambient temperatures (T(a) ) of 21, 26, 30, and 35°C each day, with d46 through 48 as a 21°C de-acclimation period. Core body temperature was measured using implanted data loggers and T(fs) was measured using an infrared camera. A multiple linear regression prediction equation was developed via Proc Reg using d42 through 45 data, and T(b), T(fs), and the T(b)/T(fs) ratio data from d42 through d45 were analyzed with Proc Glimmix in SAS 9.4 with day as a repeated measure. For the T(b) prediction all parameters were significant yielding the equation T(b)=16.435 + 0.622 ± 0.02(T(fs))+0.346 ± 0.05(sex)-0.086 ± 0.02(day) with R(2)= 0.87, sex = 0 for males and 1 for females, and day = 1 to 4 for T(a) exposure time. Calculated T(b) from d49 were similar to measured T(b) values from d49, averaging 100.03 ± 0.10% of measured d49 T(b) values. Females had greater T(b) (P=0.005; 0.32°C) and T(b)/T(fs) ratio (P

© The Author 2015. Published by Oxford University Press on behalf of the Infectious. Objective.To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)-infected women during pregnancy and post partum. Methods.HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated. Results.Eighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval,. 60-.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58-0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03-0.56). The viral load close to delivery was

The asymmetric Heck reaction is a powerful method for the synthesis of both tertiary and quaternary chiral carbon centers, with an enantiomeric excess often greater than 80%, and in some cases much higher (up to 99% ee). A variety of carbocyclic and heterocyclic systems can be constructed, including spirocyclic systems. The scope of the reaction with respect to the product alkene isomerization is somewhat limited by problems of regioselectivity, however, these problems are surmountable, and a new generation of ligands that dissociate more rapidly from the products, might improve both enantio- and regiocontrol. A variety of chiral compounds prepared by the asymmetric Heck reaction were successfully utilized in the enantioselective syntheses of complex natural products.

The catalytic enantioselective meso-epoxide ring opening reaction with phenolic oxygen nucleophile (4-methoxyphenol) is described for the first time herein. This reaction was first found to be promoted by (R)-GaLB (Ga = gallium, L = lithium, B = (R)-BINOL), giving a variety of epoxide opening products in good to high ee (67−93% ee). However, chemical yield was only modest (yield 31−75%), despite the use of more than 20 mol % GaLB. This was due to the undesired ligand exchange between BINOL and 4-methoxyphenol, which resulted in the decomplexation of GaLB. Application of various known chiral ligands such as 6,6‘-bis((triethylsilyl)ethynyl)-BINOL and H8-BINOL were examined, but satisfactory results were not obtained. To overcome this problem a novel linked-BINOL containing coordinative oxygen atom in the linker has been developed. By linking two BINOL units in GaLB, the stability of the Ga-complex was greatly improved. Using 3−10 mol % (R,R)-Ga-Li-linked-BINOL complex, a variety of epoxide opening reactions...

The enantioselective Heck reaction is a powerful method for the synthesis of both tertiary and quaternary chiral carbon centres, with enantiomeric excesses (ees) often around 80% and in some cases much higher. A variety of carbocyclic and heterocyclic systems can be constructed or modified including spirocyclic systems. Although problems of regioselectivity with respect to the product alkene continue to limit the scope of the reaction somewhat, there are indications that these may be surmountable and that a new generation of ligands and a refined methodology, may improve both enantio- and regiocontrol. All the relevant literature is discussed.

The synthesis of new C 2 -symmetric chiral ligands consisting of two binaphthol units linked by a short bridge is described. These ligands can be used for investigating catalytic asymmetric reactions which utilize BINOL or related ligands as was demonstrated for the ring opening reaction of cyclohexene oxide with 4-methoxyphenol.

4,6-Bis(diphenylphosphanyl)dibenzofuran (1), despite its large P…P distance of 5.74 A and its bite angle of ca. 131° was found to be Capable of tridentate coordination to ruthenium (II) chloride. Single crystal X-ray structure analyses of the new ruthenium (II) complexes 3,4 and 5 revealed that the ligand 1 coordinates to a single ruthenium atom with both phosphorus centers and the dibenzofuran oxygen atom. The remarkable ligand deformation resulting from the coordination is evident from the decrease of the P…P distance by 1 A to 4.75 A and the increase of the bite angle (P–Ru–P) by 25° to 155°−157. The unprecedented in-plane coordination of the dibenzofuran oxygen atom to ruthenium is interesting in view of the hybridisation of the oxygen.

Acid-treated carbon nanotubes have been decorated with nanoscale Au, Pt and Ag clusters by employing several procedures. The nature and extent of metal coverage can be varied by changing the concentration of the metal compound or by mild sonication (treatment with ultrasound). The metal clusters seem to get deposited on the acidic surface sites of the nanotubes.

Reaction of Co2(CO)8 with 4,6-bis(diphenylphosphino)dibenzofuran (1) in diethylether gives the dinuclear complex 4,6-bis(diphenylphosphino)dibenzofurandicobalthexacarbonyl (2). The solid state structures of 1 and 2 have been established by X-ray crystallography. Low temperature 13C-NMR spectroscopy was used to analyse 2 in solution.

No Abstract.

The synthesis of new C 2 -symmetric chiral ligands consisting of two binaphthol units linked by a short bridge is described. These ligands can be used for investigating catalytic asymmetric reactions which utilize BINOL or related ligands as was demonstrated for the ring opening reaction of cyclohexene oxide with 4-methoxyphenol.

A general protocol for the Pd-catalyzed-arylation of nitroalkanes is described. Substituted aryl bromides as well as aryl chlorides can be coupled efficiently with a variety of nitroalkanes under mild conditions to selectively yield the monoarylated products. This method tolerates a number of functional groups including ketones, esters, and olefins. Notably, the arylation of nitroalkanes can be effected chemoselectively over ketone and ester arylation.

Statistics showing that only 3.8% of consumers who have applied for debt review in terms of the National Credit Act 34 of 2005 (NCA) have succeeded to have their cases adjudicated by the court, indicate that the process is not functioning effectively. In January 2009, the Law Clinic of the University of Pretoria was commissioned by the National Credit Regulator (NCR) to conduct an assessment on the reasons for the ineffectiveness of the debt counselling process. The research report indicated that credit providers not co-operating in the process and not-complying with the NCA and Regulations and the so-called work stream agreement reached between major credit providers, established debt counsellors and the National Credit Regulator, were the main reasons for the ineffectiveness of the debt counselling process. Second on the list of so-called major obstacles were the vagueness and insufficiency of the NCA and Regulations. The main purpose of this article, which is based on chapter 2 of the research report mentioned above, is to identify the loopholes in the NCA which cause the lack of legal certainty and which contribute to the ineffectiveness of the debt counselling process. Although the work stream guidelines are to be welcomed because they attempt to find a solution for the vagueness and insufficiency of the NCA and Regulations, it is submitted that the situation is still not desirable. Many credit providers and debt counsellors did not form part of the work stream processes and therefore cannot be bound by these agreements. The NCR's application to the High Court for a declaratory order in terms of section 16(1)(b)(ii) may shed some light on the problems currently experienced, however, it is submitted that the best solution is for the legislator to address these shortcomings in order to bring about a proper and effective debt counselling process. By also taking the Draft Debt Counselling Regulations into consideration, certain issues which, in our view, should be addressed by the legislator are identified and proposals for the amendment of provisions of the NCA are made. Ultimately, the effectiveness of the NCA's provisions to provide debt relief to the over-indebted consumer depends on the co-operation of the different role players and compliance with the spirit of the Act in terms of section 86(5)(b) to participate in good faith in the review and in the negotiations for debt rearrangement. It is submitted that in theses negotiations the purpose of the Act, namely to protect consumers, should constantly be kept in mind. Credit providers will have to change their attitudes and appreciate the fact that they will have to take greater responsibility for the negative consequences of credit granting. It is furthermore submitted that more should still be done to prevent over-indebtedness and to reduce the need for consumers to resort to the debt relief mechanisms of the Act. The apparent need for consumer education at both the adult and school level should therefore be addressed.

18 status: published

Hollow nanotubes of SiO2, Al2O3, V2O5, and MoO3 have been prepared using carbon nanotubes as templates. The procedure involves coating the carbon nanotubes with tetraethylorthosilicate, aluminum isopropoxide, or vanadium pentoxide gel, followed by calcination and heating at higher temperatures in air to oxidize the carbon. SiO2 nanotubes containing transition metal ions have been prepared by this procedure since such materials may be of use in catalysis.