Non-targeted and suspect screening analysis using ion exchange chromatography-Orbitrap tandem mass spectrometry reveals polar and very mobile xenobiotics in Danish drinking water.

Non-targeted and suspect screening analysis is gaining approval across the scientific and regulatory community to monitor the chemical status in the environment and thus environmental quality. These holistic screening analyses provides the means to perform suspect screening and go beyond to discover previously undescribed chemical pollutants in environmental samples. In a case study, we developed and optimized a high-resolution tandem mass spectrometry platform hyphenated with anion exchange chromatography to screen drinking water samples in Denmark. The optimized non-targeted screening method was able to detect anionic and polar compounds and was successfully applied to drinking water from two drinking water facilities. Following a data analysis pipeline optimization, anionic pesticide residues and other environmental contaminants were detected at confidence identification level 1 such as dimethachlor ESA, mecoprop, and dichlorprop in drinking water. In addition to these three substances, it was possible to detect another 1662 compounds, of which 97 were annotated at confidence identification level 2. More research is urgently needed to health risk prioritize the detected substances and to determine their concentrations.

Maternal Anaemia in Pregnancy: A Significantly Greater Risk Factor for Anaemia in Australian Aboriginal Children than Low Birth Weight or Prematurity.

OBJECTIVES: To identify maternal and perinatal risk factors associated with childhood anaemia. METHODS: A retrospective cohort study was conducted in three remote Katherine East Aboriginal communities in Northern Territory, Australia. Children born 2004-2014 in Community A and 2010-2014 in Community B and C, and their respective mothers were recruited into the study. Maternal and child data were linked to provide a longitudinal view of each child for the first 1000 days from conception to 2-years of age. Descriptive analyses were used to calculate mean maternal age, and proportions were used to describe other antenatal and perinatal characteristics of the mother/child dyads. The main outcome was the prevalence of maternal anaemia in pregnancy and risk factors associated with childhood anaemia at age 6 months. RESULTS: Prevalence of maternal anaemia in pregnancy was higher in the third trimester (62%) compared to the first (46%) and second trimesters (48%). There was a strong positive linear association (R2 = 0.46, p < 0.001) between maternal haemoglobin (Hb) in third trimester pregnancy and child Hb at age 6 months. Maternal anaemia in pregnancy (OR 4.42 95% CI 2.08-9.36) and low birth weight (LBW, OR 2.62, 95% CI 1.21-5.70) were associated with an increased risk of childhood anaemia at 6 months of age. CONCLUSIONS FOR PRACTICE: This is the first study to identify the association of maternal anaemia with childhood anaemia in the Australian Aboriginal population. A review of current policies and practices for anaemia screening, prevention and treatment during pregnancy and early childhood would be beneficial to both mother and child. Our findings indicate that administering prophylactic iron supplementation only to children who are born LBW or premature would be of greater benefit if expanded to include children born to anaemic mothers.

Prediction of outcome in patients with low back pain--A prospective cohort study comparing clinicians' predictions with those of the Start Back Tool.

The clinical course of low back pain (LBP) cannot be accurately predicted by existing prediction tools. Therefore clinicians rely largely on their experience and clinical judgement. The objectives of this study were to investigate 1) which patient characteristics were associated with chiropractors' expectations of outcome from a LBP episode, 2) if clinicians' expectations related to outcome, 3) how accurate clinical predictions were as compared to those of the STarT Back Screening Tool (SBT), and 4) if accuracy was improved by combining clinicians' expectations and the SBT. Outcomes were measured as LBP intensity (0-10) and disability (RMDQ) after 2-weeks, 3-months, and 12-months. The course of LBP in 859 patients was predicted to be short (54%), prolonged (36%), or chronic (7%). Clinicians' expectations were most strongly associated with education, LBP history, radiating pain, and neurological signs at baseline and related to all outcomes. The accuracies of predictions made by clinicians (AUC .58-.63) and the SBT (AUC .50-.61) were comparable and low. No substantial increase in the predictive capability was achieved by combining clinicians' expectations and the SBT. In conclusion, chiropractors' predictions were associated with well-established prognostic factors but not simply a product of these. Chiropractors were able to predict differences in outcome on a group level, but prediction of individual patients' outcomes were inaccurate and not substantially improved by the SBT. It is worth investigating if more accurate tools can be developed to assist clinicians in prediction of outcome.

Synthesis and pharmacological evaluation of N-benzyl substituted 4-bromo-2,5-dimethoxyphenethylamines as 5-HT2A/2C partial agonists.

N-Benzyl substitution of phenethylamine 5-HT2A receptor agonists has dramatic effects on binding affinity, receptor selectivity and agonist activity. In this paper we examine how affinity for the 5-HT2A/2C receptors are influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine derivatives. Special attention is given to the 2' and 3'-position of the N-benzyl as such compounds are known to be very potent. We found that substitutions in these positions are generally well tolerated. The 2'-position was further examined using a range of substituents to probe the hydrogen bonding requirements for optimal affinity and selectivity, and it was found that small changes in the ligands in this area had a profound effect on their affinities. Furthermore, two ligands that lack a 2'-benzyl substituent were also found to have high affinity contradicting previous held notions. Several high-affinity ligands were identified and assayed for functional activity at the 5-HT2A and 5-HT2C receptor, and they were generally found to be less efficacious agonists than previously reported N-benzyl phenethylamines.

Measurement and prediction of the acceptable noise level for single-microphone noise reduction algorithms.

OBJECTIVE: To measure the acceptable noise level (ANL) with and without noise reduction algorithms (NRAs), and to predict ΔANL, i.e. the difference in acceptable noise level with and without NRAs. DESIGN: The ANL test was applied to three NRAs. Furthermore, the measured ΔANL was predicted using several methods based on either the calculation of the signal-to-noise ratio or correlation methods of the processed signals with an unprocessed reference signal. STUDY SAMPLE: Ten normal-hearing and eleven hearing-impaired subjects accomplished the ANL test. RESULTS: In general, the ANL test could determine an increased acceptance of noise with some NRAs. However, great inter-individual differences also resulted that were attributed to audible distortions when an NRA was used. Prediction of the mean measured DANL was possible, but individual prediction of DANL failed due to inter-individual differences. Mean DANL was predicted more accurately for hearing-impaired subjects when individual hearing loss was taken into account. CONCLUSIONS: The ANL test is a suitable tool for measuring the advantage of one NRA. A prediction of the measured individual ΔANL failed. However, mean DANL could be predicted with some methods. Furthermore, the individual hearing loss should be taken into account for a more accurate prediction for hearing-impaired subjects.

Recording and classification of the acoustic environment of hearing aid users.

This article investigates the different acoustic signals that hearing aid users are exposed to in their everyday environment. Binaural microphone signals from recording positions close to the microphone locations of behind-the-ear hearing aids were recorded by 20 hearing aid users during daily life. The recorded signals were acoustically analyzed with regard to narrowband short-term level distributions. The subjects also performed subjective assessments of their own recordings in the laboratory using several questions from the Glasgow Hearing Aid Benefit Profile (GHABP) questionnaire. Both the questionnaire and the acoustic analysis data show that the importance, problems, and hearing aid benefit as well as the acoustic characteristics of the individual situations vary a lot across subjects. Therefore, in addition to a nonlinear hearing aid fitting, further signal classification and signal/situation-adaptive features are highly desirable inside modern hearing aids. These should be compatible with the variability of the individual sound environments of hearing-impaired listeners.

A single, bi-functional aquaglyceroporin in blood-stage Plasmodium falciparum malaria parasites.

The malaria parasite Plasmodium falciparum faces drastic osmotic changes during kidney passages and is engaged in the massive biosynthesis of glycerolipids during its development in the blood-stage. We identified a single aquaglyceroporin (PfAQP) in the nearly finished genome of P. falciparum with highest similarity to the Escherichia coli glycerol facilitator (50.4%), but both canonical Asn-Pro-Ala (NPA) motifs in the pore region are changed to Asn-Leu-Ala (NLA) and Asn-Pro-Ser (NPS), respectively. Expression in Xenopus oocytes renders them highly permeable for both water and glycerol. Sugar alcohols up to five carbons and urea pass the pore. Mutation analyses of the NLA/NPS motifs showed their structural importance, but the symmetrical pore properties were maintained. PfAQP is expressed in blood-stage parasites throughout the development from rings via trophozoites to schizonts and is localized to the parasite but not to the erythrocyte cytoplasm or membrane. Its unique bi-functionality indicates functions in the protection from osmotic stress and efficiently provides access to the serum glycerol pool for the use in ATP generation and primarily in the phospholipid synthesis.