Etramp5 as a useful serological marker in children to assess the immediate effects of mass drug campaigns for malaria.

INTRODUCTION: Serological methods provide useful metrics to estimate age-specific period prevalence in settings of low malaria transmission; however, evidence on the use of seropositivity as an endpoint remains scarce in studies to evaluate combinations of malaria control measures, especially in children. This study aims to evaluate the immediate effects of a targeted mass drug administration campaign (tMDA) in Haiti by using serological markers. METHODS: The tMDA was implemented in September-October 2018 using sulfadoxine-pyrimethamine and single low-dose primaquine. A natural quasi-experimental study was designed, using a pretest and posttest in a cohort of 754 randomly selected school children, among which 23% reported having received tMDA. Five antigens were selected as outcomes (MSP1-19, AMA-1, Etramp5 antigen 1, HSP40, and GLURP-R0). Posttest was conducted 2-6 weeks after the intervention. RESULTS: At baseline, there was no statistical difference in seroprevalence between the groups of children that were or were not exposed during the posttest. A lower seroprevalence was observed for markers informative of recent exposure (Etramp5 antigen 1, HSP40, and GLURP-R0). Exposure to tMDA was significantly associated with a 50% reduction in the odds of seropositivity for Etramp5 antigen 1 and a 21% reduction in the odds of seropositivity for MSP119. CONCLUSION: Serological markers can be used to evaluate the effects of interventions against malaria on the risk of infection in settings of low transmission. Antibody responses against Etramp5 antigen 1 in Haitian children were reduced in the 2-6 weeks following a tMDA campaign, confirming its usefulness as a short-term marker in child populations.

The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015.

Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

Effects on vitamin A deficiency in children of periodic high-dose supplements and of fortified oil promotion in a deficient area of the Philippines.

Regular semi-annual distribution of high-dose (200,000 IU) vitamin A capsules (VACs) to children 1 - 5 years of age (previously identified as underweight), in Leyte Province, the Philippines, was compared to providing extra VACs to give three-monthly dosing, and to vitamin A-fortified cooking oil (VAFO) promotion (with continued VACs every 6 months). Serum retinol (SR) was measured at baseline and after 12 or 18 months (for VAFO). No sustained increase in SR was determined from the three-month VAC dosing regimen, and the prevalence of vitamin A deficiency (VAD) as assessed by SR (< 20 mcg / dL) remained around 30 % (in line with national survey estimates over the previous 15 years). The major difference found was that 18 months of VAFO (of which 9 months had sustained promotion) was associated with reducing the prevalence of VAD to < 10 %. The effective fortification and lack of effect of semi-annual VAC results are in line with previous studies; testing with dosing of VAC every three months is a new intervention. The results imply that promotion of fortified oil would reduce VAD in these conditions; whether it can replace or needs to be added to semi-annual VAC dosing remains to be determined. A phased changeover to reliance on fortified commodities (including oil) with careful monitoring of VAD trends is indicated.

Aflatoxin B1 induction of hepatocellular carcinoma in the embryos of rainbow trout (Salmo gairdneri).

Liver cancer in rainbow trout was induced by exposure of fertile eggs to an aqueous, 0.5 ppm (microgram/ml) solution of aflatoxin B1 (AFB1) for 1 hour. Single treatments, given on alternate days during the embryonic period, produced a low cancer incidence (less than 20%) prior to formation of the embryonic liver on day 14, but a steadily increasing incidence from day 15 (31.7%) until day 23 (58.3%), in fish examined 1 year later. Treatment of trout eggs with [14C]AFB1 was used to quantitate the amount of AFB1 absorbed by the eggs. Twenty-one-day-old rainbow trout eggs absorbed approximately 30 ng of [14C]AFB1 during a 1-hour exposure to 0.5 ppm aqueous [14C]AFB1. After 1 day 85-90% of the [14C]AFB1 was either metabolized and excreted or leached from the egg. The residual [14C]AFB1 remained constant until hatching when an additional 50% was lost. Comparison of the amount of AFB1 absorbed by eggs with the amount of AFB1 consumed per fish during a 1-year feeding trial at 4 ppb in the diet indicates that the trout embryo is even more sensitive than juvenile trout to the carcinogenic properties of AFB1.

Rat urinary metabolites of [9,10-methylene-14C] sterculic acid.

1. The metabolism of [9,10-methylene-14C] sterculic acid was studied in corn oil and Stercula foetida oil fed rats. The majority of the radioactivity was excreted into the urine as short chain dicarboxylic acids. The main urinary metabolites were cis-3,4-methylene adipic acid, cis-3,4-methylene suberic acid, trans-3,4-methylene adipic acid, cis-3,4-methylene pimelic acid, and cis-3,4-methylene azelic acid. 2. Formation of these urinary metabolites requires alpha-, beta-, and omega-oxidation plus reduction of the cyclopropene ring to a cyclopropane ring. Sterculic acid must be transported through both mitochondrial and microsomal systems. 3. Other non-radioactive urinary compounds were also identified. A proposed pathway for the metabolism of sterculic acid and possible detrimental effects caused by these metabolites is discussed.

Association analysis of genes involved in cholesterol metabolism located within the linkage region on chromosome 10 and Alzheimer's disease.

Epidemiological studies identified a higher risk of developing Alzheimer's disease (AD) among subjects with elevated cholesterol levels. This association may be caused by a modulation of the amyloid precursor protein (APP) processing in response to the cellular cholesterol content. High cholesterol levels may favor the amyloidogenic pathway by inhibition of the alpha-secretase probably leading to elevated beta-Amyloid (Abeta) production. The identification of a linkage peak on chromosome 10q using high Abeta as quantitative trait led us to examine polymorphisms of genes located on chromosome 10 involved in cholesterol metabolism, like Lipase A (LIPA), Cholesterol 25 hydroxylase (CH25H), and FLJ22476, a high density lipoprotein binding related protein. Using 286 patients with AD and 162 controls we analyzed several single nucleotide polymorphisms (SNPs) within LIPA, CH25H, and FLJ22476. None of the polymorphisms showed significant association with AD which contradicts recent findings on CH25H. From our results we conclude that the investigated genetic variations do not contribute to the genetic risk of AD.

Pattern recognition system for focal liver lesions using "crisp" and "fuzzy" classifiers.

RATIONALE AND OBJECTIVES: To determine the diagnostic performance of an artificial intelligence system for classification of focal liver lesions, in comparison to human observers. METHODS: One hundred forty-three focal hepatic lesions were evaluated with dynamic computed tomography. The study comprised 59 hemangiomas, 24 other benign lesions (focal nodular hyperplasia, adenoma), and 60 malignant liver lesions (18 primary, 42 secondary). All lesions but the hemangiomas were histologically examined by needle biopsy. For delineation of the lesion, a region of interest was defined interactively. The pattern recognition was performed in two steps with initial extraction of textural features: training of a classifier and classification of the lesions. The accuracy of classification of hepatic lesions into three groups (hemangioma, other benign processes, malignant lesions) was tested. The results were compared with those achieved by human observers using receiver operating characteristic statistical analysis. RESULTS: The accuracy (total rate of correct diagnoses) was 90.2%. False classifications were found owing to small size, weak contrast enhancement after bolus injection, respiratory movement, and atypical morphology of the lesion. The area under the receiver operating characteristic curve was not significantly different for computer and human observers. CONCLUSIONS: The system demonstrated a diagnostic accuracy comparable to human observers. Further improvement with increasing numbers of typical computed tomographic series for training of the classifier can be expected.

Lack of association between a single nucleotide polymorphism within the choline acetyltransferase gene and patients with Alzheimer's disease.

Alterations of the cholinergic system may account for typical clinical and pathophysiological disturbances of Alzheimer's disease (AD). In particular, a marked decline of choline acetyltransferase activity (CHAT) and as a consequence of acetylcholine during the course of the disease has been described. Due to the chromosomal localization of CHAT at 10q11.23 and its possible role in the pathophysiology of AD, CHAT may represent an appropriate candidate gene conferring risk to AD. In fact, a recent study identified a functional single nucleotide polymorphism (SNP) within the first common exon of CHAT, which was associated with AD giving an odds ratio of 3.8 (Neurosci. Lett. 333 (2002) 9). Because of the potential importance of this finding we analyzed this SNP and another functional SNP within exon 9 (rs868749) of the CHAT gene using a German case control sample consisting of 242 patients with AD and 143 cognitively healthy controls. No statistically significant differences were obtained for the previously described polymorphism. In addition, the exon 9 SNP (rs868749) was not polymorphic in the studied population. We conclude that the previously identified polymorphism is not associated with AD.

The effect of indole-3-carbinol, an aflatoxin B1 hepatocarcinoma inhibitor, and other indole analogs on the rainbow trout hepatic mixed function oxidase system.

Rainbow trout were fed diets containing 3.4 mmol of indole-3-carbinol, indole-3-ethanol, indole-3-aldehyde, or indole-3-acetic acid in 100 g salmon oil/kg diet for 3 weeks. The indoles did not increase hepatic microsomal cytochrome(s) P-450 or P-448 nor induce the associated mixed function oxidase enzyme activities as measured by ethoxyresorufin-O-deethylase (EROD) and benzphetamine-N-demethylase activities. Indole-3-carbinol did not alter the in vitro metabolism of aflatoxin B1 to aflatoxicol and aflatoxin M1; but the other indoles did suppress the formation of aflatoxin M1 from aflatoxin B1. The results suggest that the mechanism by which indole-3-carbinol protected rainbow trout from aflatoxin B1 (AFB1) hepatocarcinogenesis was not via the alteration of the mixed function oxidase system.

Synthesis of a thio-linked Lewis A (Le(a)) epitope.

The synthesis of heptyl (alpha-L-fucopyransoyl)-(1-->4)-S-[(beta-D-galactopyranosyl)-(1--> 3)] -1,4-dithio-beta-D-glucopyranoside (2), as thio-linked Lewis A analogue was based on thexyldimethylsilyl 3-O-allyl-2-O-benzoyl-6-O-(4-methoxybenzyl)-4-thio-beta-D-glucopyranosid e (15) which was readily obtained from D-galactose. Reaction of 15 with O-3,4-di-O-acetyl-2-O-(4-methoxybenzyl)-alpha-L-fucopyranosyl trichloroacetimidate (8) as fucosyl donor afforded the alpha-(1-->4)-thio-linked disaccharide. Replacement of the 4-methoxybenzyl groups by acetyl groups and removal of the 3a-O-allyl group afforded as 3a-O-unprotected acceptor thexyldimethylsilyl (2,3,4-tri-O-acetyl-alpha-L-fucopyranosyl)-(1-->4)-S-6-O-acetyl-2-O-benz oyl -4-thio-beta-D-glucopyranoside (19), which gave with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl trichloroacetimidate as galactosyl donor (20) the trisaccharide. Transformation into a trichloroacetimidate as glycosyl donor, glycosylation of heptylmercaptan, and then removal of the O-acyl protective groups afforded target molecule 2.

Carbohydrate and acid contents of Gala apples and Bartlett pears from regular and controlled atmosphere storage.

Gala apples and Bartlett pears were harvested over two crop seasons at different maturities and growing sources then stored in refrigerated storage alone and in controlled atmosphere storage (1% O(2) plus 1% CO(2) or 2% O(2) plus 3% CO(2)). Before and after storage of 45 or 90 days, the juice from the fruit was examined for carbohydrate and acid compositions and contents. For Gala apples, the type and length of storage had no significant effect on juice carbohydrate and acid contents and compositions, whereas the time of harvest greatly influenced both parameters. Storage atmosphere did not affect the carbohydrate and acid contents and compositions of Bartlett pear juice; however, the source of the fruit and subsequent amount of ripening did appear to significantly cause changes in the same parameters. The carbohydrate and acid compositions and contents of Gala apple juice were within the compositional range for worldwide apple juice. Bartlett pear juice contained significantly greater concentrations of citric acid than shown in previously published studies.

Dietary antioxidant effects on the hepatic mixed-function oxidase system of rainbow trout (Salmo Gairdneri).

Rainbow trout (Salmo gairdneri) were fed a control diet with or without an antioxidant--3,5-di-tert-butyl-4-hydroxytoluene (BHT), 2(3)-tert-butyl-4-hydroxyanisole (BHA), mono-tert-butylhydroquinone (TBHQ) or ethoxyquin (EQ)--at a level of 5.56 mmol in 100 g oil/kg diet for 6 wk. The treated trout had reduced liver weight/body weight ratios. In comparison with trout fed control diet, microsomal protein content was lowered by 13% in TBQH-fed trout and elevated by 28% in EQ-fed trout, cytochrome P-450 content was 21% lower in BHA- and TBHQ-fed and 18% lower in EQ-fed trout and cytochrome b5 content was 46% lower in EQ-fed trout. Activities of benzo[a]pyrene hydroxylase, epoxide hydratase and ethoxycoumarin-O-deethylase were, respectively, 3.2-4.8, 1.2-1.7 and 1.3-5.5 times higher in antioxidant-fed trout. NADPH-cytochrome c reductase was elevated 1.2-1.3 times over the control value with dietary BHA, TBHQ and BHT, but was lowered with EQ. p-Nitroanisole-O-demethylase activity was completely suppressed in antioxidant-fed trout. The content of post-mitochondrial acid-soluble sulphydryl groups was 42% lower in BHA- and BHT-fed trout. Alterations in the enzyme activities of the mixed-function oxidase system, changes in the ethyl isocyanide binding ratio and decreases in cytochrome P-450 content suggest that dietary antioxidants could alter carcinogen activation and/or detoxification mechanisms in the hepatic microsomes of rainbow trout.

Effect of cyclopropenoid fatty acids on the hepatic microsomal mixed-function-oxidase system and aflatoxin metabolism in rabbits.

Male New Zealand weanling rabbits were fed a diet containing 0.25% cyclopropenoid fatty acids for 28 days. Compared with the controls, the rabbits given cyclopropenoid fatty acids showed retarded growth, some moderate liver histological damage, altered hepatic mixed-function-oxidase activities and minor variations in vitro [14C]aflatoxin B1 metabolism. In in vitro assays the major hepatic metabolite of aflatoxin B1 (AFB1) was aflatoxicol (AFL) and the major AFL metabolite was AFB1. Minor amounts of aflatoxin M1 and a metabolite believed to be AFL-M1 were formed. The similarity of this AFB1 metabolite pattern to that in rainbow trout, taken together with the apparent absence of AFB1 detoxification products is consistent with the sensitivity of both species to the acute effects of AFB1.

[The diagnosis of focal liver lesions by the texture analysis of dynamic computed tomograms]. / Diagnostik fokaler Leberläsionen durch Texturanalyse von dynamischen Computertomogrammen.

Characterisation of focal liver lesions on computed tomography (CT) depends on correct interpretation of morphology and dynamic changes during bolus injection of contrast medium. The aim of this study was to develop a texture analysis concept for computer based interpretation of dynamic CT images. 148 focal liver lesions were investigated by serial CT. The study comprised 61 haemangiomas, 25 other benign lesions (FNH/adenomas) and 62 malignant lesions (primary or secondary). FNH, adenomas and malignant lesions were histologically proven. Diameter was 8-145 mm (mean 31 mm). Regions of interest were interactively defined. After extraction of characteristic textural features, a pattern classifier was trained. All CT series were evaluated using the "leaving-one-out" method. 134 of the 148 lesions were correctly classified (positive predictive value 0.9). Sensitivity for the presence of malignancy was 0.93 (80/86), specificity was 0.9 (56/62). False classification of a lesion was found to depend strongly on the quality of the examination (bolus intensity, positional change of the lesion due to respiratory movements).

The health planning process: are consumers really in control?

This study of the governing board of a Health Systems Agency tends to support those who argue that a numerical majority of consumers does not guarantee consumer control of the decision-making process. Empirical support stems from the fact that consumers, relative to providers, appeared to be at a decided disadvantage in three areas: 1. Consumers see themselves as experiencing greater communication problems. 2. Consumers are more likely to perceive their knowledge as being inadequate. 3. Consumers are more likely to feel intimidated by other governing board members. The consumers' disadvantages in these three areas likely diminish the amount of influence they hold. Indeed, both provider and consumer board members felt consumers held less than one-fourth of the influence on the governing board. Although consumers wanted more influence they did not desire majority control. Staff was seen as exerting most of the influence within the HSA.

Determination of D-malic acid in apple juice by liquid chromatography: collaborative study.

Eleven laboratories collaboratively studied a liquid chromatographic (LC) method for determination of D-malic acid in apple juice. The mobile phase consisted of mM L-valine and 8 mM copper acetate adjusted to pH 5.5 with NaOH. The UV detector was set at 330 nm, and a single reversed-phase LC column was used. Seven paired samples containing various amounts of D-malic acid ranging from 0 to 188 mg/100 mL of 12 Brix pasteurized apple juice were tested by each collaborator. Repeatability and reproducibility coefficients of variation ranged from 1.0 to 3.5% and 7.7 to 11.7%, respectively, within the range of 26 to 188 mg D-malic acid/100 mL of 12 Brix apple juice. The collaborative study results demonstrated that the method could quantitate the economic adulteration of apple juice with DL-malic acid at lower levels than those reported with previous methods. The LC method for determination of D-malic acid in apple juice has been adopted first action by AOAC INTERNATIONAL.

Quantification of dabsylated di- and tri-peptides in fermented milk.

An improved HPLC method using pre-column dabsyl chloride derivatisation for the separation and quantification of antihypertensive di- and tri-peptides in fermented milk products was established. The dabsylated peptides Val-Pro-Pro (VPP), Ile-Pro-Pro (IPP), Leu-Pro-Pro (LPP) and Phe-Pro (FP) were separated on a C18-column coupled to UV/VIS and mass spectrometric detector, respectively. Due to the derivatisation of the peptides, an HPLC base line separation was achieved and the peak width was improved. The VIS-spectrometry did not allow a good quantification of these peptides since more than one peptide co-eluted under one single peak. In contrast applying LC-ESI-MS with a single quadrupole much better quantification of the dabsylated peptides was done. In Evolus® (Valio Ltd., Finland), a fermented milk drink, 6.9 mg L(-1) for VPP, 6.1 mg L(-1) for IPP, 0.8 mg L(-1) for LPP and 3.2 mg L(-1) for FP were determined. In fermented reconstituted milk (Lactobacillus helveticus, 37°C, 48 h) lower concentrations of these peptides were determined (0.7, 0.6, 0.0 and 2.2 mg L(-1), respectively).

No association of lipase C polymorphisms with Alzheimer's disease.

Hepatic lipase, also known as hepatic triglyceride lipase (LIPC), much like the major genetic risk factor for Alzheimer's disease (AD), apolipoprotein E (APOE), is associated with altered lipid metabolism. As such this link makes LIPC a potential functional candidate for AD risk. Previously, three single nucleotide polymorphisms (SNPs) have been investigated in AD with a lack of association reported. To rule out a possible contribution of other variants in LIPC, located at 15q21-q23, we used a detailed fine mapping approach in a German case-control sample. Genotyping of 25 single nucleotide polymorphisms covering the complete LIPC gene and haplotypic analysis revealed no association with AD. Thus, we conclude that LIPC can be excluded as a major functional candidate gene conferring risk to AD.