[Making innovation in teaching measurable : Psychometric validation of the "Radio-Prak": a questionnaire using the example of a clinical practical seminar in interventional radiology]. / Innovationen in der Lehre messbar machen : Psychometrische Validierung des Messinstrumentes "Radio-Prak" am Beispiel eines klinisch-praktischen Seminars der interventionellen Radiologie.

BACKGROUND: As part of the reform of medical education with a stronger focus on clinical-practical skills, a restructured seminar on interventional radiology was evaluated using a newly developed questionnaire. OBJECTIVES: Because knowledge in medical education is increasingly transferred by means of application-based teaching formats, a suitable evaluation tool is essential to assess the quality of newly implemented teaching courses. The aim of this study was to evaluate the seminar on interventional radiology and to validate the "Radio-Prak" questionnaire psychometrically in the process. MATERIALS AND METHODS: In the summer semester of 2018, 123 students participating in the newly established seminar were asked to document their satisfaction using the "Radio-Prak" questionnaire with 23 items employing a 5-point Likert scale. We evaluated the questionnaire psychometrically by performing exploratory factor (EFA) and reliability analysis and examined differential validity by group differences. RESULTS: The newly structured seminar on interventional radiology was met with great approval by students (mean global rating = 1.31, on a grading scale where 1 = very good, 5 = insufficient). EFA revealed that the questionnaire consisted of two main factors "didactic quality" and "practical quality" (five items each, α = 0.68). The seminar was rated more positively when students perceived the time for practice as sufficient (p < 0.05). Furthermore, female students demonstrated significantly less self-esteem, identified by the item "I have improved my spatial ability through the seminar," (p < 0.05). CONCLUSION: The "Radio-Prak" questionnaire is both reliable and valid as an instrument to evaluate the quality of a clinical-practical seminar. The students assessed the didactic dimension, but also rated the practical component as important in the assessment.

Effect of divalent versus monovalent cations on the MS2 retention capacity of amino-functionalized ceramic filters.

Ceramic capillary membranes conditioned for virus filtration via functionalization with n-(3-trimethoxysilylpropyl)diethylenetriamine (TPDA) are analyzed with respect to their virus retention capacity when using feed solutions based on monovalent and divalent salts (NaCl, MgCl2). The log reduction value (LRV) by operating in dead-end mode using the model bacteriophage MS2 with a diameter of 25 nm and an IEP of 3.9 is as high as 9.6 when using feeds containing MgCl2. In contrast, a lesser LRV of 6.4 is observed for feed solutions based on NaCl. The TPDA functionalized surface is simulated at the atomistic scale using explicit-solvent molecular dynamics in the presence of either Na+ or Mg2+ ions. Computational prediction of the binding free energy reveals that the Mg2+ ions remain preferentially adsorbed at the surface, whereas Na+ ions form a weakly bound dissolved ionic layer. The charge shielding between surface and amino groups by the adsorbed Mg2+ ions leads to an upright orientation of the TPDA molecules as opposed to a more tilted orientation in the presence of Na+ ions. The resulting better accessibility of the TPDA molecules is very likely responsible for the enhanced virus retention capacity using a feed solution with Mg2+ ions.

Cellular uptake of coumarin-6 under microfluidic conditions into HCE-T cells from nanoscale formulations.

UNLABELLED: In vitro studies of ocular bioavailability of active pharmaceutical ingredients (API) from colloidal drug delivery systems do not consider physiological shear stress generated by eyelid wiping and tear flow. The present study introduces a live cell imaging approach which enables the investigation of model drug uptake from various formulations under shear stress by using custom-made microchannels for the cultivation of human corneal epithelial cells (HCE-T). Coumarin-6 (C-6) was used as a model API incorporated into solid lipid nanoparticles and liposomes, and as an aqueous crystalline suspension. Confocal laser scanning microscopy visualized C-6 uptake into HCE-T cells in a time-resolved manner with an applied shear stress of 0.1 Pa. Static conditions were also studied for comparative purposes. Additionally, solid lipid nanoparticles (SLN) were labeled with a fluorescent phospholipid to check whether C-6 uptake was associated with SLN incorporation into the cells. RESULTS: Intact SLN were not incorporated into the cells, i.e., C-6 was passively redistributed from SLN to lipophilic cellular compartments. C-6 was enriched up to a given limit in HCE-T cells within 5 min of contact with the dispersions both under static and under flow conditions. The C-6 delivery rate from liposomes was superior to that from SLN whereby the suspension exhibited the lowest rate. C-6 release rates were comparable for static and flow conditions. Alternate flushing with formulations and buffer revealed that cells accumulated C-6. The results suggest that combining microfluidics with live cell imaging provides a valuable option for in vitro studies of ocular drug delivery.

[Avoidable visual impairment among residents in care institutions: lessons from an intervention project in the Den Bosch region]. / Onnodige slechtziendheid onder ouderen in zorginstellingen: lessen uit een interventieproject in de regio Den Bosch.

INTRODUCTION: Many elderly in care institutions in The Netherlands are visually impaired (visual acuity < 0.3). They fall more frequently, are more depressed and require more care. In this project visually impaired residents were identified and referred for adequate eye care. The aim of this study is to evaluate the intervention, including validation of the screening, assessment of the prevalence and causes of visual impairment as well as the outcome of the treatment. The effectiveness of the care chain is also evaluated. MATERIALS AND METHODS: 640 residents were offered a basic eye examination and 210 of them were referred, via their general practitioner, to an optometrist (10), ophthalmologist (98), or centre for visually impaired persons (1). RESULTS: Compliance in this study was poor. The prevalence of visual impairment (24%) was lower than in comparable studies. Cataract was the main cause in 51%. Overall 17 (8.1%) residents were treated by ophthalmologists and nine (4.3%) were referred to optical shops. Constraints in the care chain are identified. DISCUSSION: Vision screening in care institutions for elderly is feasible and useful. The care chain should be shorter and simpler. That will increase the effectiveness of this intervention, and thereby the quality of life for many residents.

The pharmacological control of neuronal excitability in the retinal spreading depression model of migraine.

Spreading Depression is the underlying patho physiological mechanism for the neurological symptoms of migraine aura and is thought to play a major role in triggering migraine. Therefore it seems reasonable to use the Spreading Depression as a pharmacological tool for anti migraine drugs. Drugs that are able to alter parameters of Spreading Depression should also influence appearance and course of migraine attacks. Concerning the classification on the different mechanisms of drug action, especially the retinal Spreading Depression is useful, due to the separation of vascular and neuronal effects. In this study we investigated substances from different classes of common anti migraine drugs on different parameters of the retinal spreading depression. The results are discussed according to the classification of the drug.

Dermal fibroblasts from acute inflamed atopic dermatitis lesions display increased eotaxin/CCL11 responsiveness to interleukin-4 stimulation.

BACKGROUND: The presence of eosinophils and/or eosinophil-derived products in the dermis is characteristic for involved skin of patients with atopic dermatitis and contributes to the observed tissue injury. CCL11 is a potent chemoattractant and activator of human eosinophils and interleukin (IL)-4 is a potent inducer of CCL11 expression in dermal fibroblasts. OBJECTIVES: As increased fibroblast CCL11 expression may explain eosinophilic infiltration of involved skin areas in atopic dermatitis, we asked whether dermal fibroblasts from atopic patients differ from fibroblasts of healthy individuals in their ability to express CCL11. METHODS: We compared IL-4-induced CCL11 mRNA expression using reverse transcription-polymerase chain reaction from cultured dermal fibroblasts derived from biopsies of chronic lesional and acute lesional atopic skin as well as from skin biopsies derived from normal skin of healthy donors. RESULTS: Considerable variability in IL-4-induced relative CCL11 mRNA expression was detected in fibroblasts derived from biopsies of different individuals. The lowest median IL-4 concentration inducing half maximal CCL11 mRNA expression (EC(50)) was found in fibroblasts derived from acute inflamed atopic lesions. CONCLUSIONS: Inducibility of CCL11 in dermal fibroblasts upon stimulation with Th2 cytokines explains the tissue eosinophilia observed in the presence of Th2 cytokines and the localization of eosinophils to the dermis. Decreased EC(50) values of IL-4-induced CCL11 expression in fibroblasts from acute inflamed atopic skin lesions indicates increased IL-4 responsiveness in these lesions and further substantiates the special role for IL-4-induced dermal fibroblast CCL11 expression in acute lesions. Variable CCL11 expression in fibroblasts from different patients with atopic dermatitis indicates heterogeneity of factors determining atopic phenotype in atopic dermatitis.

Psoriasin (S100A7) is a principal antimicrobial peptide of the human tongue.

The human tongue is particularly resistant to bacterial infections although the mouth is continuously exposed to a complex and abundant ensemble of microbes, such as the common intestinal bacterium Escherichia coli. We show that lingual epithelia produce and release, as a primary E. coli-killing compound, the S100 protein psoriasin. No significant reduction in psoriasin release could be achieved through repeated rinsing of the epithelial surface of the tongue. Psoriasin is produced in the upper layers of the lingual epithelia but is lacking in the most superficial and basal cells. It displays a gradient pattern of expression with decreasing expression from the anterior one-third to the posterior portion of the tongue. Thus, psoriasin may be the key to the resistance of the human tongue toward E. coli.

Social exclusion decreases prosocial behavior.

In 7 experiments, the authors manipulated social exclusion by telling people that they would end up alone later in life or that other participants had rejected them. Social exclusion caused a substantial reduction in prosocial behavior. Socially excluded people donated less money to a student fund, were unwilling to volunteer for further lab experiments, were less helpful after a mishap, and cooperated less in a mixed-motive game with another student. The results did not vary by cost to the self or by recipient of the help, and results remained significant when the experimenter was unaware of condition. The effect was mediated by feelings of empathy for another person but was not mediated by mood, state self-esteem, belongingness, trust, control, or self-awareness. The implication is that rejection temporarily interferes with emotional responses, thereby impairing the capacity for empathic understanding of others, and as a result, any inclination to help or cooperate with them is undermined.

Association between body weight of newborn rats and density of serotonin transporters in the frontal cortex at adulthood.

Persisting alterations in monoaminergic innervation patterns have been observed following various environmental manipulations and neuro-psychopharmacological treatments during fetal or early postnatal life. The present study investigates the question how differences in initial growth conditions at birth might interfere with subsequent development of both serotonergic and noradrenergic innervation in the rat frontal cortex (FC) and brain stem. For this purpose, newborn rat littermates were divided into two groups, a low and a high birth weight group, and the densities of both serotonin (5-HT) and norepinephrine (NE) transporters in the FC and brain stem were analyzed at adulthood. 5-HT transporter density in the FC was significantly higher in the high birth weight group as compared with the low birth weight group. No significant differences were observed between both groups in the density of 5-HT transporters in the brain stem and in the densities of NE transporters in FC and brain stem. It is discussed that differences in birth weight may affect the postnatal development of 5-HT projections to the frontal cortex.

Identification of growth phenotype-related genes in Aspergillus oryzae by heterologous macroarray and suppression subtractive hybridization.

Aspergillus oryzae requires polarized growth for colonization of solid substrates, and this growth phenotype differs from that seen in liquid medium. Various experimental approaches were used to identify genes that are differentially expressed when A. oryzae is grown on wheat kernels and in a wheat-based liquid medium. Hybridization of A. oryzae RNAs to a macroarray bearing cDNAs isolated from a library representing at least 16% of the total number of A. niger genes identified 14 differentially expressed cDNA clones, showing that heterologous macroarray analysis with an A. niger cDNA library can be used to identify regulated gene transcripts in the related species A. oryzae. Moreover, Northern analysis with a selection of eight probes for A. niger genes encoding proteins involved in morphological development and cell wall biosynthesis identified five more differentially expressed genes. A suppression subtractive hybridization procedure revealed another 12 differentially expressed genes. The results presented show that, of the 29 identified genes which are expressed at higher levels during growth on wheat kernels, six encode proteins that are functionally related to polarized growth, four encode products known to be involved in morphogenesis, three code for proteins related to cell wall composition, and nine of the cDNA clones encode novel proteins. These findings pinpoint genes associated with the changes in cellular morphogenesis seen in A. oryzae grown on wheat kernels as opposed to wheat-based liquid medium.

[A horse with a badly-healing wound? A case report]. / Een paard met een slecht genezende wond? Een case report.

A 14-year-old Haflinger mare was presented with a wound on the right metatarsus which it had sustained 3 years earlier. The wound had never completely healed but had only recently become a problem. Over a period of several months, the wound became larger, produced a lot of exudate, and the horse became lame on the affected limb. Clinical examination and radiographs failed to reveal the cause of the deterioration. Histological evaluation of tissue removed during debridement of the wound revealed squamous cell carcinoma. Because the tumour had already invaded the bone, the prognosis was unfavourable and the horse was euthanised. Necropsy showed the tumour to have metastasised to the right inguinal area and the adjacent mammary gland.

Psoriasis scales contain C5a as the predominant chemotaxin for monocyte-derived dendritic cells.

Dendritic cells seem to be of major importance for the pathogenesis of psoriasis. They are increased in number in lesional psoriatic skin which is thought to be due to an increased influx from the peripheral blood regulated by chemotaxins. Using a biological/biochemical approach we have addressed the question whether psoriasis scale extracts contain proteinaceous chemotaxins for dendritic cells. Human monocytes differentiated into dendritic cells by culture with GM-CSF and IL-4 (MoDC) served as responder cells. Chemotactic activity for MoDC was purified by several HPLC-steps. The results of our study show that C5a/C5adesarg is the major chemotactic peptide for MoDC in psoriasis scale extracts. In comparison to other stimuli such as fMLP or monocyte chemotactic peptide 1 (MCP-1) C5a proved to be a most potent and efficient chemotaxin for MoDC. C5a co-eluted with MRP14/calgranulin B which is present in large amounts in psoriasis scale extracts as identified by amino acid sequencing. However, MRP14/calgranulin B did not possess any chemotactic activity for MoDC. Our results provide evidence that C5a/C5adesarg although not specific for dendritic cells seems to be the major chemoattractant for these cells in lesional psoriasis skin.

Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic.

The growing public health problem of infections caused by multiresistant Gram-positive bacteria, in particular Staphylococcus aureus, prompted us to screen human epithelia for endogenous S. aureus-killing factors. A novel 5-kDa, nonhemolytic antimicrobial peptide (human beta-defensin-3, hBD-3) was isolated from human lesional psoriatic scales and cloned from keratinocytes. hBD-3 demonstrated a salt-insensitive broad spectrum of potent antimicrobial activity against many potentially pathogenic microbes including multiresistant S. aureus and vancomycin-resistant Enterococcus faecium. Ultrastructural analyses of hBD-3-treated S. aureus revealed signs of cell wall perforation. Recombinant hBD-3 (expressed as a His-Tag-fusion protein in Escherichia coli) and chemically synthesized hBD-3 were indistinguishable from naturally occurring peptide with respect to their antimicrobial activity and biochemical properties. Investigation of different tissues revealed skin and tonsils to be major hBD-3 mRNA-expressing tissues. Molecular cloning and biochemical analyses of antimicrobial peptides in cell culture supernatants revealed keratinocytes and airway epithelial cells as cellular sources of hBD-3. Tumor necrosis factor alpha and contact with bacteria were found to induce hBD-3 mRNA expression. hBD-3 therefore might be important in the innate epithelial defense of infections by various microorganisms seen in skin and lung, such as cystic fibrosis.

Adolescents' perception of living with end stage renal disease.

BACKGROUND: End stage renal disease (ESRD) is a serious chronic condition, requiring life-long treatment and management to survive. It is unclear how the unique developmental needs of adolescents influence their ability to maintain the complex medical treatment regimen associated with ESRD. PURPOSE: The purpose of this study was to explore the perception of adolescents living with ESRD. Ascertaining the subjective perspectives of the adolescent provides insight into the effects of the chronic condition on their development and well-being. METHOD: Q-methodology was used to assess the adolescent's perception of living with ESRD. Thirty-five adolescents, 13 to 18 years, who were on renal dialysis or had received a renal transplant served as participants. FINDINGS: The results of the analysis identified four significant factors. The factors represented four distinct perspectives held by these adolescents living with ESRD: (a) normalization, (b) illness intrusion: barrier to normalcy; (c) illness management: parent-focused; and (d) illness management: self-focused. CONCLUSION: Overall, the majority of the adolescents in this study held a more positive perspective of living with ESRD than what has been described previously in the literature. The findings of this exploratory study provide direction for future research and nurses in practice.

Mucoid Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia.

Cultured lung epithelial cells release antibacterial activity upon contact with Pseudomonas aeruginosa (PA), which is impaired in cystic fibrosis (CF). In order to identify the factors responsible for killing PA by a biochemical approach, we purified antimicrobial activity from supernatants of the A549 lung epithelial cell line, previously stimulated with PA bacteria, by subsequent high performance liquid chromatography. NH(2)-terminal sequencing of a major bactericidal compound revealed it to be identical with human beta-defensin-2 (hBD-2). A mucoid phenotype of PA, but not two nonmucoid PA strains, high concentrations (> 10 microg/ml) of PA lipopolysaccharide, tumor necrosis factor alpha, and interleukin (IL)-1beta, but not IL-6, dose-dependently induced hBD-2 messenger RNA in cultured normal bronchial, tracheal, as well as normal and CF-derived nasal epithelial cells. Genomic analysis of hBD-2 revealed a promoter region containing several putative transcription factor binding sites, including nuclear factor (NF) kappaB, activator protein (AP)-1, AP-2, and NF-IL-6, known to be involved in the regulation of inflammatory responses. Thus, hBD-2 represents a major inducible antimicrobial factor released by airway epithelial cells either on contact with mucoid PA or by endogenously produced primary cytokines. Therefore, it might be important in lung infections caused by mucoid PA, including those seen in patients with CF.

Outcomes assessment: implications for nursing education.

In response to public criticisms about the outcomes of higher education, colleges and universities have implemented comprehensive assessment programs. In nursing education, outcomes assessment has become a criteria for accreditation. Yet, currently no guidelines exist describing "best practices" in nursing education outcomes assessment. Experts in educational assessment provide helpful guidelines for nurse educators as they establish comprehensive assessment plans. The authors provide a review of the literature in the field of assessment and offer strategies for developing successful assessment programs in nursing education.

Th1- and Th2-type cytokines regulate the expression and production of eotaxin and RANTES by human lung fibroblasts.

Eosinophils (Eos) and fibroblasts are known to play a major role in the pathogenesis of bronchial asthma and fibrotic lung disease. Therefore, we investigated whether Th1 and Th2 cytokines stimulate the production of Eo-activating chemokines by lung fibroblasts. Analyses of the culture supernatant using multiple steps of high-performance liquid chromatography demonstrated that interleukin (IL)-4 preferentially stimulates lung fibroblasts to secrete a peak of eosinophil chemotactic activity (ECA) which, upon N-terminal analyses, showed similar sequence to eotaxin, whereas interferon (IFN)-gamma had negligible effect on the release of this chemokine. In contrast, tumor necrosis factor (TNF)-alpha stimulated lung fibroblasts to release two peaks of activity that were found to correspond to eotaxin and regulated on activation, normal T cells expressed and secreted (RANTES), respectively. Interestingly, IL-4 synergized with TNF-alpha to increase greatly the production of three biochemically distinct eotaxin forms. In contrast, IFN-gamma synergized with TNF-alpha to increase RANTES production. Neither IL-2, IL-5, IL-6 nor IL-10 had an effect on lung fibroblasts' capacity to express or release eotaxin and RANTES. Upon appropriate cytokine stimulation, lung fibroblasts were also found to express messenger RNA for monocyte chemotactic protein (MCP)-3 and MCP-4 but not eotaxin-2. However, no ECA like MCP-3 or MCP-4 was detected. These observations suggest that the release of Th1 or Th2 cytokines in the lung tissue polarizes lung fibroblasts to produce either RANTES or eotaxin as major Eo attractants.

The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice.

Modulation of tumour cell growth by tumour-infiltrating leucocytes is of high importance for the biological behaviour of malignant neoplasms. In melanoma, tumour-associated macrophages (TAM) and tumour-infiltrating lymphocytes (TIL) are of particular interest as inhibitors or enhancers of cell growth. Recruitment of leucocytes from the peripheral blood into the tumour site is mediated predominantly by chemotaxins, particularly by the group of chemokines. The aim of this study was to identify peptides released by human melanoma cells with monocyte chemotactic properties. To assure the presence of biologically active mediators, biochemical purification and biological characterization of peptides was based on a detection system dependent on bioactive, monocyte chemotactic activity in vitro. Cell culture supernatants of melanoma cells were fractioned by heparin-sepharose followed by preparative reversed-phase HPLC steps to enrich monocyte chemotactic activity in one single band on a sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) gel. These purified fractions were shown to react with RANTES-specific antibodies in an enzyme-linked immunosorbent assay (ELISA) as well as in Western blot analysis. Amino acid sequencing of the N-terminal protein fragment confirmed 100% homology to the RANTES protein. Further analysis showed that four out of eight melanoma cell lines constitutively expressed and secreted the beta-chemokine RANTES as detected by ELISA. The amount of RANTES protein secreted (up to 50 ng ml(-1)) was about 5-50 times higher than interleukin 8 (IL-8), determined in the same supernatant samples. Tumour necrosis factor alpha, (TNF-alpha), not, however, IL-2, interferon-gamma (IFN-gamma), or (alpha-melanocyte-stimulating hormone (alpha-MSH) was able to up-regulate RANTES and interleukin 8 secretion. Furthermore, higher levels of RANTES secretion in vitro were associated with increased tumour formation upon s.c. injection of six human melanoma cell lines in nude mice. Our data provide evidence that a subset of melanoma cells express mRNA and secrete RANTES protein which may be partly responsible for the recruitment of monocytes, T-cells and dendritic cells into the tumours. However, transplantation experiments in nude mice suggest that effects of RANTES may also benefit tumour progression. Further studies are needed to dissect the underlying mechanisms.

Genomic organization, sequence analysis and transcriptional regulation of the human MCP-4 chemokine gene (SCYA13) in dermal fibroblasts: a comparison to other eosinophilic beta-chemokines.

The eosinophil chemotactic beta-chemokine MCP-4 is assumed to be involved in the accumulation of eosinophils characteristic for eosinophilic inflammatory diseases. We here describe the genomic organisation (3 exons of 138, 115 and 578 bp, 2 introns of 867 and 437 bp and 1.4 kb of regulatory sequences from the immediate 5' upstream region), sequence (genomic and transcribed) and mRNA expression of the human MCP-4 gene in dermal fibroblasts. Among the promoter elements potentially regulating MCP-4 gene expression and/or mediating the effects of anti-inflammatory drugs we identified consensus sequences known to interact with nuclear factors like NF-IL6, AP-2, a NF-kappaB like consensus sequence, gamma-interferon- response and YY-1 elements as well as glucocorticoid response elements. Like MCP-3, MCP-4 mRNA expression in dermal fibroblasts is upregulated by TNF-alpha, IL-1alpha, IFN-gamma or IL-4 and differs from RANTES and eotaxin mRNA expression in its response to IFN-gamma and/or IL-4.