Activity coefficients of binary methanol alcohol mixtures from cluster weighting.

The hydrogen bond network of different small alcohols is investigated via cluster analysis. Methanol/alcohol mixtures are studied with increasing chain length and branching of the molecule. Those changes can play an important role in different fields, including solvent and metal extraction. The extended tight binding method GFN2-xTB allows the evaluation and geometry optimization of thousands of clusters built via a genetic algorithm. Interaction energies and geometries are evaluated and discussed for the neat systems. Thermodynamic properties, such as vaporization enthalpies and activity coefficients, are calculated with the binary quantum cluster equilibrium (bQCE) approach using our in-house code peacemaker 2.8. Combined distribution functions of the distances against the angles of the hydrogen bonds are evaluated for neat and mixed clusters and weighted by the equilibrium populations achieved from bQCE calculations.

TRAVIS-A free analyzer for trajectories from molecular simulation.

TRAVIS ("Trajectory Analyzer and Visualizer") is a program package for post-processing and analyzing trajectories from molecular dynamics and Monte Carlo simulations, mostly focused on molecular condensed phase systems. It is an open source free software licensed under the GNU GPL, is platform independent, and does not require any external libraries. Nine years after the original publication of TRAVIS, we highlight some of the recent new functions and features in this article. At the same time, we shortly present some of the underlying algorithms in TRAVIS, which contribute to make trajectory analysis more efficient. Some modern visualization techniques such as Sankey diagrams are also demonstrated. Many analysis functions are implemented, covering structural analyses, dynamical analyses, and functions for predicting vibrational spectra from molecular dynamics simulations. While some of the analyses are known since several decades, others are very recent. For example, TRAVIS has been used to compute the first ab initio predictions in the literature of bulk phase vibrational circular dichroism spectra, bulk phase Raman optical activity spectra, and bulk phase resonance Raman spectra within the last few years.

The effect of repeated testing vs repeated practice on skills learning in undergraduate dental education.

OBJECTIVES: Recent studies in undergraduate medical education have demonstrated the advantage of repeated testing over repeated practice with regard to knowledge and skills retention. The aim of this study was to investigate whether this "testing effect" also applies to skills retention in undergraduate dental education. METHODS: In this prospective, randomised controlled trial, fourth-year dental students at Göttingen University Medical Centre participated in a training session on surgical suturing in winter term 2014/2015. Following this, they were either assigned to two sessions of additional skills training (group A) or two sessions of skills assessment with feedback (group B). These sessions were spaced over a period of 4 weeks. Skills retention was assessed in a summative objective structured clinical examination (OSCE) at the end of term, that is 6 months after the initial teaching session. RESULTS: A total of 32 students completed the study. With regard to suturing, OSCE performance was significantly better in group B than group A (81.9±13.1% vs 63.0±15.4%; P=0.001; Cohen's d=1.33). There was no significant OSCE performance difference in the two groups with regard to other learning objectives that were addressed in the end-of-term examination. Thus, the group difference was specific to suturing skills. CONCLUSIONS: This is the first study to demonstrate that in dental education, repeated testing produces more favourable skills retention than repeated practice. Test-enhanced learning might be a viable concept for skills retention in undergraduate dentistry education.

Effect of magnetic stimulation on the gene expression profile of in vitro cultured neural cells.

Transcranial magnetic stimulation is a non-invasive tool in clinical diagnostics and therapy for physiological and psychological diseases and has an increased application in experimental neurophysiology. Despite this, the mechanisms of magnetic stimulation of the central nervous system remain still unclear. We applied sinus-shaped high frequency magnetic fields in different stimulation patterns and repeated treatments to cell cultures derived from frontal cortex of murine embryos (BALB/cOlaHsd mice) to elucidate the effects of repetitive magnetic stimulation on the gene expression of in vitro cultured neural cells. Gene expression profiling was performed by using qRT-PCR array and single qRT-PCR analyses. Our methodological approach using microelectrode arrays data recording and analysis minimizes variations in transcriptome analysis arising from cell differentiation status and tissue complexity. With 10 significant changes in gene expression out of 171 genes using Alzheimer disease and neurodegeneration related qRT-PCR arrays we demonstrate significant impact of repetitive magnetic stimulation on the mRNA transcript of neural cell cultures. Sixteen candidate genes were analyzed using single qRT-PCR in a replicated statistical design, which provided more precise estimates of differences in expression profiles. We discussed the utility of the experimental methods used for cell culture selection and the changes in gene expression considering physiological aspects.

Quantification noise in single cell experiments.

In quantitative single-cell studies, the critical part is the low amount of nucleic acids present and the resulting experimental variations. In addition biological data obtained from heterogeneous tissue are not reflecting the expression behaviour of every single-cell. These variations can be derived from natural biological variance or can be introduced externally. Both have negative effects on the quantification result. The aim of this study is to make quantitative single-cell studies more transparent and reliable in order to fulfil the MIQE guidelines at the single-cell level. The technical variability introduced by RT, pre-amplification, evaporation, biological material and qPCR itself was evaluated by using RNA or DNA standards. Secondly, the biological expression variances of GAPDH, TNFα, IL-1ß, TLR4 were measured by mRNA profiling experiment in single lymphocytes. The used quantification setup was sensitive enough to detect single standard copies and transcripts out of one solitary cell. Most variability was introduced by RT, followed by evaporation, and pre-amplification. The qPCR analysis and the biological matrix introduced only minor variability. Both conducted studies impressively demonstrate the heterogeneity of expression patterns in individual cells and showed clearly today's limitation in quantitative single-cell expression analysis.

Quantum Cluster Equilibrium Theory Applied in Hydrogen Bond Number Studies of Water. 1. Assessment of the Quantum Cluster Equilibrium Model for Liquid Water.

Different cluster sets containing only 2-fold coordinated water, 2- and 3-fold coordinated water, and 2-fold, 3-fold, and tetrahedrally coordinated water molecules were investigated by applying second-order Møller-Plesset perturbation theory and density functional theory based on generalized gradient approximation functionals in the framework of the quantum cluster equilibrium theory. We found an improvement of the calculated isobars at low temperatures if tetrahedrally coordinated water molecules were included in the set of 2-fold hydrogen-bonded clusters. This was also reflected in a reduced parameter for the intercluster interaction. If all parameters were kept constant and only the electronic structure methods were varied, large basis set dependencies in the liquid state for the density functional theory results were found. The behavior of the intercluster parameter was also examined for the case that cooperative effects were neglected. The values were 3 times as large as in the calculations including the total electronic structure. Furthermore, these effects are more severe in the tetrahedrally coordinated clusters. Different populations were considered, one weighted by the total number of clusters and one depending on the monomers.

Quantum Cluster Equilibrium Theory Applied in Hydrogen Bond Number Studies of Water. 2. Icebergs in a Two-Dimensional Water Continuum?

With the aid of the quantum cluster equilibrium method, we calculate thermodynamic properties for a new water cluster set containing 2-fold and additional tetrahedrally hydrogen-bonded water molecules on the basis of accurate correlated electronic structure calculations. The addition of clusters with 4-fold coordinated water molecules leads to an improved thermodynamical description of the liquid phase in comparison to experimental values. The comparison of the obtained isobars from the pure 2-fold cluster set with the mixed cluster set shows improved results for the mixed set. Furthermore, the results of the liquid-phase entropy calculation compare excellently with experiment if the mixed cluster set is applied. The calculated populations allow us to determine hydrogen bond numbers, resulting in a temperature-dependent average hydrogen bond number. We observe a decreasing average hydrogen bond number of 2.77 at 274 K to 2.26 at 373 K and a dominance of 75% 2-fold hydrogen-bonded water molecules at room temperature for the mixed cluster set.

Why are ionic liquid ions mainly associated in water? A Car-Parrinello study of 1-ethyl-3-methyl-imidazolium chloride water mixture.

In this study we present the results of a first principles molecular dynamics simulation of a single 1-ethyl-3-methyl-imidazolium chloride [C(2)C(1)im][Cl] ion pair dissolved in 60 water molecules. We observe a preference of the in plane chloride coordination with respect to the cation ring plane as compared to the energetic slightly more demanding on top coordination. Evaluation of the different radial distribution functions demonstrates that the structure of the hydration shell around the ion pair differs significantly from bulk water and that no true ion pair dissociation in terms of completely autonomous solvation shells takes place on the timescale of the simulation. In addition, dipole moment distributions of the solvent in distinct solvation shells around different functional parts of the [C(2)C(1)im][Cl] ion pair are calculated from maximally localized Wannier functions. The analysis of these distributions gives evidence for a depolarization of water molecules close to the hydrophobic parts of the cation as well as close to the anion. Examination of the angular distribution of different OH(H(2)O)-X angles in turn shows a linear coordination of chloride accompanied by a tangential orientation of water molecules around the hydrophobic groups, being a typical feature of hydrophobic hydration. Based on these orientational aspects, a structural model for the obvious preference of ion pair association is developed, which justifies the associating behavior of solvated [C(2)C(1)im][Cl] ions in terms of an energetically favorable interface between the solvation shells of the anion and the hydrophobic parts of the cation.

What keeps ionic liquids in flow?

The elimination of a hydrogen bond in imidazolium based ionic liquids which results in an increased melting point is investigated by means of static quantum chemical and molecular dynamics simulations.

[Exposure testing with powdered gloves in 60 health care workers with latex allergy]. / Expositionstestungen mit gepuderten Handschuhen bei 60 Latexallergikern aus dem Gesundheitswesen.

BACKGROUND AND OBJECTIVE: Type 1 sensitization to natural rubber latex occurs in up to 22% of health care workers. Most sensitizations are due to the use of powdered latex gloves. Work place-associated exposure tests were performed to ascertain how frequently persons who developed breathing difficulties, rhinitis/conjunctivitis or obstructive respiratory tract illness when using powdered latex gloves are allergic to latex. PATIENTS AND METHODS: 60 persons (48 women and 12 men; mean age 29 +/- 7 years) with type 1 sensitization to natural rubber latex were studied. The past history was obtained through a questionnaire specially designed for those with latex allergy. Diagnostic measures included prick tests with different latex allergens, measuring the concentrations of total and latex-specific IgE and exposure trials, related to the work place, with powdered vinyl and latex gloves. RESULTS: The prick tests with various latex allergens produced significant skin reactions in 59 subjects, 58 had latex-specific IgE antibodies (0.47 kU/l- > 100 kU/l). Exposure tests with powdered latex gloves produced rhinitis in 55 and conjunctivitis in 38 persons, urticaria in 3 and cough in 19. Whole-body plethysmography demonstrated a significant rise in respiratory tract resistance in 13, a reduction in 1-second expiratory volume of at least 20% in 15. Abnormal values in both tests were noted in 8 subjects. CONCLUSION: The breathing difficulty reported by all subjects was in most cases due not to bronchial obstruction but to obstructed nasal breathing. In cases with breathing difficulty on exposure to latex gloves a latex allergy should be considered as the cause. Powdered latex gloves present a danger to health care personnel and should no longer be used.

[The latency period between exposure and the symptoms in allergy to natural latex. Suggestions for prevention]. / Latenzzeit zwischen Exposition und Symptomen bei Allergie gegen Naturlatex. Vorschläge zur Prävention.

BASIC PROBLEM AND OBJECTIVE OF STUDY: Among persons working in the health care system allergies caused by natural rubber latex (NRL) are more common than among the general population, because the frequent use of latex gloves and other latex articles may cause sensitisation. A retrospective study was undertaken to determine the period before such an allergy occurs. PATIENTS AND METHODS: 63 patients (53 women and 10 men; mean age 31.3 +/- 8.3 years) with symptoms of type 1 (immediate response; IgE-mediated) allergy to NRL filled in a special questionnaire asking, among other items, about occupational history, duration and frequency of contact with latex gloves, as well as the course of occupational or other symptoms. All but five of the group had been in their job for less than 15 years. A prick test with 21 ubiquitous environmental allergens was performed on 62 of the patients. RESULTS: Two thirds of the patients had atopy. First symptoms of an allergy to latex developed at an average of 5 years (58.7 +/- 59.3 months) after starting work involving contact with latex products. In 59 persons the first symptoms were contact urticaria, in some together with rhinitis or dyspnea. The interval until onset of symptoms relating to the lower respiratory tract averaged a further 25.3 +/- 34.6 months. Symptoms developed earlier in patients with atopy than in those without (51.9 +/- 54.3 vs 76 +/- 69 months). CONCLUSIONS: The use of powdered natural rubber latex gloves should be discontinued to prevent the increasing incidence of sensitization to aerogenic latex and to protect those already sensitized from developing allergic bronchial asthma.

Use of vancomycin hydrochloride for treatment of Clostridium difficile enteritis in Syrian hamsters.

As part of an 18-month carcinogenicity study, 680 Syrian hamsters (Mesocricetus auratus) received daily gavage doses of fenazaquin, an experimental miticide. Mortality associated with severe enteritis was noticed beginning when the hamsters were 4 months old and ranged from one to five deaths per month until the hamsters were about 10 months old, when 41 deaths occurred in a 1-month period. Ante- and postmortem findings were consistent with those reported for antibiotic-induced enteritis in hamsters. Clostridium difficile was isolated from 12 of the 13 samples of cecal contents analyzed. Toxin assays of C. difficile isolates collected from 11 affected animals were positive for both cyto- and enterotoxins. Daily oral administration of vancomycin hydrochloride at a dose of 20 mg/kg was initiated when the hamsters were about 10 months old. Deaths due to C. difficile enteritis were significantly decreased within 2 weeks, and treatment was continued for 3 months. A trial withdrawal period for a subset of 64 hamsters (approximately 16% of the total population) was initiated to evaluate survival after discontinuation of the antibiotic treatment. Clostridium difficile enteritis recurred within 2 weeks and caused 19 deaths during the next month; therefore, these hamsters were returned to daily vancomycin treatment for the remainder of the study. With the exception of severe gaseous distention of the ceca, which caused death in 17 (< 4% of the total population) of the affected hamsters, vancomycin treatment did not cause any major adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraoperative, probe-guided curettage of osteoid osteoma.

The only curative approach for osteoid osteoma is operative removal of the nidus, but intraoperative detection of the nidus is difficult even when an X-ray amplifier is used. A simple probe-guided operative procedure using technetium-99m methylene diphosphonate is described, and the results and follow-up in 12 patients are reported. In addition physical properties of the probe have been evaluated by phantom measurements.

N-(2-diethylaminoethyl)-4-[123I]iodobenzamide as a tracer for the detection of malignant melanoma: simple synthesis, improved labelling technique and first clinical results.

In order to evaluate the behaviour of N-(2-diethylaminoethyl)-4-[123I]iodobenzamide in malignant melanotic disease, we synthesized the bromo compound in a simple one-step reaction. Labelling was performed by non-isotopic bromine-iodine-123 exchange in radiochemical yields up to 60%. By means of isocratic high-performance liquid chromatography, the iodinated product could be isolated with high apparent specific activity. First clinical studies in patients with malignant melanoma using N-(2-diethylaminoethyl)-4-[123I]iodobenzamide showed moderate uptake of the tracer in the tumour and the suspected metastases in all patients. Most of the lesions were detectable with technetium-99m-diethylene triamine penta-acetic acid (DTPA) scintigraphy too, but we were able to detect additional, previously unidentified metastases with benzamide scintigraphy. This changed the therapeutic procedure in two of the five cases investigated so far.

[The value of sequential scintigraphy of the liver in postactinic liver lesions]. / Wertigkeit der Lebersequenzszintigraphie bei postaktinischen Leberläsionen.

Dynamic hepatobiliary scintigraphy is the only method which enables non-invasive monitoring of regional function of liver parenchyma. It allows early detection of functional impairment due to radiation hepatitis. This method is simple and reproducible and is therefore suitable for follow-up of this disease.

[Atypical bone metastases in prostate cancer]. / Atypische Skelettmetastasierung bei Prostatakarzinom.

Two cases of prostatic cancer with single bone metastasis in the tibia are discussed. The intense uniform involvement of a solitary limb bone with high perfusion and blood pool activity in the 3-phase bone scan and the positive white blood cell scan (observed in one case) were not typical for a metastatic bone lesion. Conventional radiomorphology--lamellar, periosteal reaction, disseminated medullar sclerosis, no localized lesion--also led to other differential considerations such as osteomyelitis and malignant lymphoma, which could not be specified by CT and MRI. Even if there is no typical morphology in scintigraphic and radiologic imaging, biopsy should be performed to exclude bone metastasis in prostatic cancer.

Spontaneous bronchopneumonia in laboratory dogs infected with untyped Mycoplasma spp.

Three Mycoplasma spp. were isolated from five colony bred laboratory dogs (Canis familiaris) obtained from a single vendor. Four of these animals were Beagles and one was a mongrel. Three displayed clinical signs of respiratory disease including dyspnea, chronic coughing and moist rales, while the other two dogs were observed during thoracic surgery to have macroscopic lesions suggestive of pneumonia. All five dogs were submitted for diagnostic necropsy during which they were cultured for bacteria and mycoplasma. Mycoplasma spp. having three distinct colonial forms were isolated from the lungs of each of the animals. These three isolates were sent to the National Cancer Institute Diagnostic Microbiology Laboratory and to the National Institutes of Health, NIAID, Mycoplasmology Laboratory. Neither laboratory could serotype these isolates against antisera to 73 Mycoplasma spp., including the common canine mycoplasmas, and nine Acholeplasma spp. Histologically, the bronchopneumonia was characterized by bronchiectasis, purulent bronchiolitis, bronchial and bronchiolar epithelial hyperplasia, chronic non-suppurative peribronchiolitis and perivasculitis, bronchiolitis obliterans, and acute to subacute purulent pneumonia. The similarity between the pathologic findings in these animals and those observed in respiratory mycoplasmosis of other species, e.g. the rat, suggests a causal relationship between the isolated mycoplasmas and the pulmonary disease observed in these dogs.