Estimating estuarine residence times in the Westerschelde (The Netherlands) using a box model with fixed dispersion coefficients

The residence time of the water masses in the Westerschelde estuary was determined using a simple compartment-model that simulates the advective-diffusive transport of a conservative dissolved substance (chlorinity). The residence time of a water parcel in the upstream part of the estuary (i.e. the time needed for this water parcel to leave the estuary) varied from about 50 days in winter to about 70 days in summer. The most seaward compartment had residence times of about 10-15 days.Dispersive coefficients that are fixed in time were able to reproduce the observed salinity distributions very well in the Westerschelde. They were obtained by calibration on observed chlorinities. It is argued that the apparent relationship of dispersive coefficients with freshwater flow, which is observed in certain studies, could (partly) reflect the deviation from steady state conditions which are required assumptions to calculate these dispersive coefficients directly from salinity profiles.     

Postmortem diagnosis and toxicological validation of illicit substance use.

The present study examines the diagnostic challenges of identifying ante-mortem illicit substance use in human postmortem cases. Substance use, assessed by clinical case history reviews, structured next-of-kin interviews, by general toxicology of blood, urine and/or brain, and by scalp hair testing, identified 33 cocaine, 29 cannabis, 10 phencyclidine and nine opioid cases. Case history identified 42% cocaine, 76% cannabis, 10% phencyclidine and 33% opioid cases. Next-of-kin interviews identified almost twice as many cocaine and cannabis cases as Medical Examiner (ME) case histories, and were crucial in establishing a detailed lifetime substance use history. Toxicology identified 91% cocaine, 68% cannabis, 80% phencyclidine and 100% opioid cases, with hair testing increasing detection for all drug classes. A cocaine or cannabis use history was corroborated by general toxicology with 50% and 32% sensitivity, respectively, and with 82% and 64% sensitivity by hair testing. Hair testing corroborated a positive general toxicology for cocaine and cannabis with 91% and 100% sensitivity, respectively. Case history corroborated hair toxicology with 38% sensitivity for cocaine and 79% sensitivity for cannabis, suggesting that both case history and general toxicology underestimated cocaine use. Identifying ante-mortem substance use in human postmortem cases are key considerations in case diagnosis and for characterization of disorder-specific changes in neurobiology. The sensitivity and specificity of substance use assessments increased when ME case history was supplemented with structured next-of-kin interviews to establish a detailed lifetime substance use history, while comprehensive toxicology, and hair testing in particular, increased detection of recent illicit substance use.     

Extensively high load of internal tumors determined by whole body MRI scanning in a patient with neurofibromatosis type 1 and a non-LCR-mediated 2-Mb deletion in 17q11.2

Deletions in 17q11.2 affecting the NF1 gene and surrounding regions occur in 5% of patients with NF1. The two major types of NF1 deletions encompass 1.4-Mb and 1.2-Mb, respectively, and have breakpoints in the NF1 low-copy repeats or in the JJAZ gene and its pseudogene. Deletions larger than 1.4-Mb are rare, and only seven cases have been reported so far. Here, we describe a 26-year-old NF1 patient with an atypical NF1 deletion of 2-Mb. In contrast to the 1.4-Mb deletions, which preferentially occur by interchromosomal recombination during maternal meiosis, the deletion described here occurred intrachromosomally on the paternal chromosome. The centromeric deletion breakpoint lies in an L1-element located 1.3-Mb proximal to the NF1 gene. The telomeric deletion boundary is located in a single copy segment between an AT-rich segment and an AluSx-element in intron 15 of the JJAZ1 gene. Structural analysis implies that non-B DNA conformations at the breakpoints destabilized the duplex DNA and caused double-strand breaks. Although the breakpoints of this 2-Mb deletion are not recurrent, it is conspicuous that one breakpoint is located in the JJAZ1 gene. Paralogous recombination between the JJAZ1 gene and its pseudogene causes the recurrent 1.2 Mb deletions. The genomic architecture of the NF1 gene region, influenced by paralogous sequences such as the JJAZ1 gene and its pseudogene, seems also to stimulate the occurrence of non-recurrent deletions mediated by non-homologous end joining. Patient 442 described here suffers from a very high burden of subdermal neurofibromas. Magnetic resonance imaging of the whole body revealed numerous internal tumors, mainly plexiform neurofibromas and spinal tumors. This demonstrates the value of whole-body MRI scanning in determining the total tumor load, which is an important aspect in genotype/phenotype correlations with regard to large NF1 deletions.     

Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices

Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β₁ augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin) after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A) or TGF-β receptor kinase (SB431542) prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl) mimicked the effects of methacholine. Collectively, bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling.     

X-chromosome polysomy in the male

Summary A review of 569 male patients with X-chromosome polysomies (544 Klinefelter and 25 patients with other types of X-chromosome polysomy) is presented here. These patients were detected among the 77000 persons karyotyped in the Leuven cytogenetic center between the years 1966 and 1987. In the group of 544 Klinefelter patients special attention was paid to (1) the age at diagnosis, (2) social and marital status of the postpubertal males, (3) physical and intellectual abilities of the prepubertal boys, (4) delineation of the concurrence of Klinefelter syndrome and fragile X syndrome, and (5) the frequency of malignancies. In 25 patients with other X-chromosome polysomies (2 n48 chromosomes) genotype/phenotype correlation is reviewed, especially for the patients with 48,XXYY and 49,XXXXY karyotypes. Finally, double aneuploidy and rare structural X-chromosome aberrations are briefly discussed.     

N NMR studies of the binding of CN with gold(I) drugs

¹⁵N NMR studies of the interaction of ¹⁵N cyanide ion with gold(I)-thiomalate (Autm) and gold(I)-thioglucose (Autg) have been carried out at pH* 7.40. The chemical shifts of the two ¹⁵N ions containing species Au(C¹⁵N)₂⁻ and RS-Au-C¹⁵N⁻ (where RS⁻ = tm⁻ or tg⁻) were identified at 265.94 and 260.30 ppm, respectively. From the broadened ¹⁵N NMR signals, approximate life times of the RS-Au-CN⁻ species were calculated.     

Human non-secretory ribonucleases. II. Structural characterization of theN-glycans of the kidney, liver and spleen enzymes by NMR spectroscopy and electrospray mass spectrometry

The N-glylycans have been removed by peptide-N-glycosidase F(PNGase F) from purified human non-secretory RNases derivedfrom kidney, liver and spleen. The spleen RNase was purifiedby two procedures, one of which did not include the usual acidtreatment step (0.25 M H₂SO₄, 45 min, 4C), to determine ifacid treatment alters the carbohydrate moieties. TheN-glycansof the RNases were fractionated by Bio-Gel P-4 chromatographyand analysed by 600 MHz ¹H-NMR spectroscopy and electrospraymass spectrometry. All four non-secretory RNase preparationscontained the following structures: The relative amounts of the trisaccharide, pentasaccharide andhexasaccharide appeared to vary slightly in the different tissueRNases. The overall results indicate: (i) that acid treatmentduring purification does not alter the N-glycans of non-secretoryRNases; (ii) that the N-glycans from kidney, liver and spleennon-secretory RNases are very similar, if not identical, toone another, but different from the N-glycan structures reportedfor secretory RNase. N-glycans non-secretory RNases     

Public Beliefs on Antibiotics and Symptoms of Respiratory Tract Infections among Rural and Urban Population in Poland: A Questionnaire Study

Introduction

General public views and expectations around the use of antibiotics can influence general practitioners'' antibiotic prescribing decisions. We set out to describe the knowledge, attitudes and beliefs about the use of antibiotics for respiratory tract infections in adults in Poland, and explore differences according to where people live in an urban-rural continuum.

Material and Methods

Face to face survey among a stratified random sample of adults from the general population.

Results

1,210 adults completed the questionnaire (87% response rate); 44.3% were rural; 57.9% were women. 49.4% of rural respondents and 44.4% of urban respondents had used an antibiotic in the last 2 years. Rural participants were less likely to agree with the statement “usually I know when I need an antibiotic,” (53.5% vs. 61.3% respectively; p = 0.015) and reported that they would consult with a physician for a cough with yellow/green phlegm (69.2% vs. 74.9% respectively; p = 0.004), and were more likely to state that they would leave the decision about antibiotic prescribing to their doctor (87.5% vs. 85.6% respectively; p = 0.026). However, rural participants were more likely to believe that antibiotics accelerate recovery from sore throat (45.7% vs. 37.1% respectively; p = 0.017). Use of antibiotic in the last 2 years, level of education, number of children and awareness of the problem of developing antimicrobial resistance predicted accurate knowledge about antibiotic effectiveness.

Conclusions

There were no major differences in beliefs about antibiotics between urban and rural responders, although rural responders were slightly less confident in their knowledge about antibiotics and self-reported greater use of antibiotics. Despite differences in the level of education between rural and urban responders, there were no significant differences in their knowledge about antibiotic effectiveness.