The implementation of knowledge dissemination in the prevention of occupational skin diseases.

BACKGROUND: Occupational skin diseases (OSD) have a high medical, social, economic and political impact. Knowledge dissemination from research activities to key stakeholders involved in health care is a prerequisite to make prevention effective. OBJECTIVES: To study and prioritize different activity fields and stakeholders that are involved in the prevention of OSD, to reflect on their inter-relationships, to develop a strategic approach for knowledge dissemination and to develop a hands-on tool for OSD prevention projects METHODS: Seven different activity fields that are relevant in the prevention of OSD have been stepwise identified. This was followed by an impact analysis. Fifty-five international OSD experts rated the impact and the influence of the activity fields for the prevention of OSD with a standardized questionnaire. RESULTS: Activity fields identified to have a high impact in OSD prevention are the political system, mass media and industry. The political system has a strong but more indirect effect on the general population via the educational system, local public health services or the industry. The educational system, mass media, industry and local public health services have a strong direct impact on the OSD 'at risk' worker. Finally, a hands-on tool for future OSD prevention projects has been developed that addresses knowledge dissemination and different stakeholder needs. CONCLUSION: Systematic knowledge dissemination is important to make OSD prevention more effective and to close the gap between research and practice. This study provides guidance to identify stakeholders, strategies and dissemination channels for systematic knowledge dissemination which need to be adapted to country-specific structures, for example the social security system and healthcare systems. A key for successful knowledge dissemination is building linkages among different stakeholders, building strategic partnerships and gaining their support right from the inception phase of a project.

[Individual prevention of occupational contact dermatitis: protective gloves and skin protection recommendations as part of the patient management scheme by the public statutory employers' liability insurance]. / Individualprävention beruflicher Kontaktekzeme: Schutzhandschuhe und Hautschutzempfehlungen im berufsgenossenschaftlichen Heilverfahren.

The dermatologist's procedure is a pivotal tool for early recognition of occupational contact dermatitis (OCD), for reporting OCD cases to the statutory accident insurance and for treating the diseases. The employer is in charge of implementing skin protection measures at the workplace. However, in terms of an individual prevention approach it may be necessary to propose targeted skin protection recommendations in specific patient cases. The patient's own skin protection behavior significantly contributes to regenerating and maintaining healthy skin. This behavior includes the use of occupational skin products, and in particular the correct use of appropriately selected protective gloves. Protective gloves are the most important personal protective measure in the prevention of OCD. Prevention services, occupational health and safety specialists, occupational physicians and centers specialized in occupational dermatology can support the identification of suitable protective measures. Nowadays, suitable protective gloves exist for (almost) every occupational activity and exposure. However, improper use in practice can become a risk factor by itself for the skin (e. g., incorrectly used gloves). Therefore, it is of utmost importance to identify application errors, to educate patients in terms of skin protection and to motivate them to perform an appropriate skin protection behavior. With particular focus on protective gloves, this article gives an overview of various types, materials and potentially glove-related allergens, presents strategies for reducing occlusion effects and discusses some typical application errors and solutions.

[Occupational skin cancer : Prevention and recommendations for UV protection as part of the treatment approved by the public statutory employers' liability insurance]. / Beruflicher Hautkrebs : Prävention und UV-Schutzempfehlungen im berufsgenossenschaftlichen Heilverfahren.

In Germany, approximately 2 to 3 million employees work in outdoor professions. They are exceptionally exposed to solar ultraviolet (UV) radiation for a large part of their daily working time. Cumulative UV exposure is associated with a significantly increased risk of skin cancer for outdoor workers from various occupational groups (e. g. landscape and horticulture, agriculture and forestry, fisheries and seafaring, construction and trade, as well as sports teachers, lifeguards and mountain guides). Since 1 January 2015, squamous cell carcinoma and multiple actinic keratosis due to natural UV radiation can be recognised as occupational disease No. 5103 by the German statutory social accident insurance. Reducing cumulative UV exposure is the main prevention aspect of this type of skin damage. Therefore, technical, organisational and personal UV protection measures should be implemented in the professional and private environment. Moreover, they have to be regularly used in an appropriate way. In addition to guideline-oriented therapy, training and counselling of patients with already existing actinic skin damage or a recognised occupational disease No. 5103 is therefore of particular importance. The focus should be on improving the individual UV protection behaviour. This article gives an overview of current recommendations for UV protection in the professional environment. It outlines possible solutions for patient counselling in terms of UV protection in everyday practice.

[Longterm Homecare Augmentation Program in Alpha-1-Antitrypsin Deficient Patients]. / Langzeit-Augmentationstherapie von Patienten mit Alpha-1-Antitrypsin-Mangel in der häuslichen Pflege.

BACKGROUND: Augmentation with human alpha-1 proteinase inhibitor is the only specific treatment for Alpha-1-Antitrypsin Deficiency (AATD), a rare genetic disease with symptoms of progressive COPD. OBJECTIVES: A prospective long-term exploration of outcomes during the "Alpha-1-Mobile" home care AAT augmentation program in seven advanced-stage patients. METHODS: Patients received weekly i. v. AAT augmentation and COPD therapy. Symptoms, lung function, health status, quality-of-life aspects, and safety were documented continuously. Outcomes during six years of home care augmentation therapy were observed and evaluated on an inter- and intraindividual basis. FEV1 profiles were compared to pre-program data. RESULTS: The seven patients had a mean age of 56.7 (40-68) years and had previously received augmentation for 8.8 (1-19) years. Compared to the three-year preprogram period, functional decline of FEV1 (ΔFEV1 0.47 L vs 0.17 L) slowed. Mean QoL scores showed seasonal fluctuations in the first three years of observation, and then stabilized. All blood samples tested exceeded the protective threshold of 50 mg/dL with a dose of 60 mg AAT/kg/week. Less than one exacerbation-related hospitalization occurred per patient-year. No adverse events of related to augmentation therapy were observed. CONCLUSIONS: Home care with i. v. augmentation therapy by medical professionals contributes to optimum care through consistent treatment and close health-status monitoring in our collective. Exacerbation-related hospitalizations were largely avoided. "Alpha-1-Mobile" was well accepted, practical, and safe.

[Intravascular papillary endothelial hyperplasia (IPEH) : Masson's pseudoangiosarcoma on the forefoot]. / Intravaskuläre papilläre endotheliale Hyperplasie (IPEH) : Masson-Pseudoangiosarkom am Vorfuß.

Intravascular papillary endothelial hyperplasia (IPEH)/Masson's pseudoangiosarcoma is a rare (orphan) disease of the forefoot that has not yet been described in Europe. The pathoanatomic examination of a young patient with a vague interdigital space-consuming lesion revealed a intravascular papillary endothelial hyperplasia/Masson's pseudoangiosarcoma. The intravascular papillary endothelial hyperplasia can be mainly detected in the upper limbs as well as cervically. Heretofore, the intravascular papillary endothelial hyperplasia has only been described in Japan and the USA. For Europe, our case report is the first description of the clinical course of IPEH.

[Prospective evaluation of clinical parameters of AAT patients with i. v. prolastin therapy in a homecare setting]. / Prospektive Untersuchung klinischer Verlaufsparameter von Patienten mit Alpha-1-Antitrypsinmangelsyndrom unter i. v. Prolastin-Heimtherapie.

Prognostic parameters and indicators of deterioration of prolastin substituted alpha 1 antitrypsin deficient COPD (AAT) are poorly defined. In particular, there is a lack of information how patients with AAT report exacerbations or how intravenous therapy with prolastin is tolerated and leads to a stabilization of the clinical course of the disease. In a prospective study seven patients were followed over 36 months who received i. v. prolastin at home. Both clinical parameters such as exacerbations and spirometric lung function tests were used to monitor the clinical course of the disease. During the time period given 2.1 exacerbations/year were documented, the average lung function loss over the period of 36 month was mean FEV1 1.02 ± 0.61 l/s to 0.94 ± 0.63 l/s and mean vital capacity 2.95 ± 0.82 l to 2.87 ± 0.81 l. Complications related to home based infusion therapy did not occur. No non elective hospitalisations were reported. Taken together, this prospective feasibility trial could show that home based i. v. therapy in patients with AAT is safe and leads to less exacerbations and loss of lung function as compared to the historical cohort.

[German guideline for diagnosis and management of idiopathic pulmonary fibrosis]. / S2K-Leitlinie zur Diagnostik und Therapie der idiopathischen Lungenfibrose.

Idiopathic pulmonary fibrosis is a fatal lung disease with a variable and unpredictable natural history and limited treatment options. Since publication of the ATS-ERS statement on IPF in the year 2000 diagnostic standards have improved and a considerable number of randomized controlled treatment trials have been published necessitating a revision. In the years 2006 - 2010 an international panel of IPF experts produced an evidence-based guideline on diagnosis and treatment of IPF, which was published in 2011. In order to implement this evidence-based guideline into the German Health System a group of German IPF experts translated and commented the international guideline, also including new publications in the field. A consensus conference was held in Bochum on December 3rd 2011 under the protectorate of the "Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin (DGP)" and supervised by the "Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften" (AWMF). Most recommendations of the international guideline were found to be appropriate for the german situation. Based on recent clinical studies "weak negative" treatment recommendations for pirfenidone and anticoagulation were changed into "weak positive" for pirfenidone and "strong negative" for anticoagulation. Based on negative results from the PANTHER-trial the recommendation for the combination therapy of prednisone plus azathiorpine plus N-acetlycsteine was also changed into strong negative für patients with definite IPF. This document summarizes essential parts of the international IPF guideline and the comments and recommendations of the German IPF consensus conference.

[Total hip arthroplasty by neuromuscular impairment: functional outcome]. / Hüftendoprothetik bei neuromuskulärem Impairment: Funktionelles Outcome.

INTRODUCTION: Studies which deal with the problems of total hip arthoplasty (THA) in patients with neuromuscular impairments are rare. The aim of this study was to examine whether THA for painful coxarthrosis in such patients relieved pain and improved functional outcome and how high the complication rate was. MATERIAL AND METHODS: For this study 10 patients (13 hips) with neuromuscular impairment who had received a total hip arthroplasty for painful coxarthrosis were retrospectively identified. A chart review determined the preoperative functional level. For postoperative evaluation all patients completed a questionnaire, including a self-created modified hip score. RESULTS: The average age of the patients at the time of follow-up was 42.1 years (range 26.5-62.2 years, standard deviation SD 9.9 years) and the minimum follow-up was 24 months (average 80.3 months, range 24-143 months, SD 47 months). Pain relief was obtained for all patients but two patients had a postoperative dislocation and four patients had a major complication (infection) requiring removal of the implant. Therefore, the follow-up rate at the final examination with completed questionnaires was 69% (9 out of 13 excluding patients with removal of THA). These patients showed an improved function from 42.2-83.66 points in the hip score (p=0.0006) and there was general satisfaction with the procedure. DISCUSSION: Total hip arthroplasty can provide improved function in patients with neuromuscular impairment and severe coxarthrosis. The rate of complications was moderate in this series; however, the high infection rate in these patients should be kept in mind.

[Optimized dermatologist's report and hierarchical multi-step invention. Randomized evaluation of the cornerstones of preventive occupational dermatology]. / Optimiertes Hautarztverfahren und Stufenverfahren Haut. Randomisierte Evaluation der Eckpfeiler der berufsdermatologischen Prävention.

Parallel to the introduction of the optimized dermatologist's report in 2006, a hierarchical multi-step intervention approach to occupational dermatitis (OD) was launched within the statutory accident insurance bodies. It is aimed at ensuring that OD patients can be allocated to dermatological consultations and preventive measures quickly and in a manner appropriate to the severity of their OD. At present, a study ("EVA Haut") is being conducted at the University of Osnabrueck in which about 10% of the annually reported cases in Germany with suspected OD in 2007 have been selected at random (N=1,600). All randomized notifications are reviewed by occupational dermatologists; in parallel, the implementation of the hierarchical multi-step intervention scheme by the insurance-administrations is evaluated. Main criteria are the course of OD, job loss and costs of the procedures (follow-up 1 year). The random quota sample reveals the number of cases in which dermatological and/or preventive intervention were initiated by the administrations ("dermatologist's procedure"; N=995), in these cases patients and dermatologists involved are interviewed by a standardized questionnaire. In the remaining N=556 cases, no intervention has taken place so far; these cases are also analyzed. The study offers the unique opportunity to analyze the quality and interaction of dermatological and administrative procedures in the management of occupational dermatoses in Germany and to define criteria for further improvement.

The metagenomics RAST server - a public resource for the automatic phylogenetic and functional analysis of metagenomes.

BACKGROUND: Random community genomes (metagenomes) are now commonly used to study microbes in different environments. Over the past few years, the major challenge associated with metagenomics shifted from generating to analyzing sequences. High-throughput, low-cost next-generation sequencing has provided access to metagenomics to a wide range of researchers. RESULTS: A high-throughput pipeline has been constructed to provide high-performance computing to all researchers interested in using metagenomics. The pipeline produces automated functional assignments of sequences in the metagenome by comparing both protein and nucleotide databases. Phylogenetic and functional summaries of the metagenomes are generated, and tools for comparative metagenomics are incorporated into the standard views. User access is controlled to ensure data privacy, but the collaborative environment underpinning the service provides a framework for sharing datasets between multiple users. In the metagenomics RAST, all users retain full control of their data, and everything is available for download in a variety of formats. CONCLUSION: The open-source metagenomics RAST service provides a new paradigm for the annotation and analysis of metagenomes. With built-in support for multiple data sources and a back end that houses abstract data types, the metagenomics RAST is stable, extensible, and freely available to all researchers. This service has removed one of the primary bottlenecks in metagenome sequence analysis - the availability of high-performance computing for annotating the data. http://metagenomics.nmpdr.org.

The relationship of mucosal bacteria to duodenal histopathology, cytokine mRNA, and clinical disease activity in cats with inflammatory bowel disease.

Feline inflammatory bowel disease (IBD) is the term applied to a group of poorly understood enteropathies that are considered a consequence of uncontrolled intestinal inflammation in response to a combination of elusive environmental, enteric microbial, and immunoregulatory factors in genetically susceptible cats. The present study sought to examine the relationship of mucosal bacteria to intestinal inflammation and clinical disease activity in cats with inflammatory bowel disease. Duodenal biopsies were collected from 27 cats: 17 undergoing diagnostic investigation of signs of gastrointestinal disease, and 10 healthy controls. Subjective duodenal histopathology ranged from normal (10), through mild (6), moderate (8), and severe (3) IBD. The number and spatial distribution of mucosal bacteria was determined by fluorescence in situ hybridization with probes to 16S rDNA. Mucosal inflammation was evaluated by objective histopathology and cytokine profiles of duodenal biopsies. The number of mucosa-associated Enterobacteriaceae was higher in cats with signs of gastrointestinal disease than healthy cats (P<0.001). Total numbers of mucosal bacteria were strongly associated with changes in mucosal architecture (P<0.001) and the density of cellular infiltrates, particularly macrophages (P<0.002) and CD3(+)lymphocytes (P<0.05). The number of Enterobacteriaceae, E. coli, and Clostridium spp. correlated with abnormalities in mucosal architecture (principally atrophy and fusion), upregulation of cytokine mRNA (particularly IL-1, -8 and -12), and the number of clinical signs exhibited by the affected cats. These data establish that the density and composition of the mucosal flora is related to the presence and severity of intestinal inflammation in cats and suggest that mucosal bacteria are involved in the etiopathogenesis of feline IBD.

An overview of the safety pharmacology society strategic plan.

Safety Pharmacology studies are conducted to characterize the confidence by which biologically active new chemical entities (NCE) may be anticipated as safe. Non-clinical safety pharmacology studies aim to detect and characterize potentially undesirable pharmacodynamic activities using an array of in silico, in vitro and in vivo animal models. While a broad spectrum of methodological innovation and advancement of the science occurs within the Safety Pharmacology Society, the society also focuses on partnerships with health authorities and technology providers and facilitates interaction with organizations of common interest such as pharmacology, physiology, neuroscience, cardiology and toxicology. Education remains a primary emphasis for the society through content derived from regional and annual meetings, webinars and publication of its works it seeks to inform the general scientific and regulatory community. In considering the future of safety pharmacology the society has developed a strategy to successfully navigate forward and not be mired in stagnation of the discipline. Strategy can be defined in numerous ways but generally involves establishing and setting goals, determining what actions are needed to achieve those goals, and mobilizing resources within the society to accomplish the actions. The discipline remains in rapid evolution and its coverage is certain to expand to provide better guidance for more systems in the next few years. This overview from the Safety Pharmacology Society will outline the strategic plan from 2016 to 2018 and beyond and provide insight into the future of the discipline which builds upon a previous strategic plan established in 2009.

BRIGEP--the BRIDGE-based genome-transcriptome-proteome browser.

The growing amount of information resulting from the increasing number of publicly available genomes and experimental results thereof necessitates the development of comprehensive systems for data processing and analysis. In this paper, we describe the current state and latest developments of our BRIGEP bioinformatics software system consisting of three web-based applications: GenDB, EMMA and ProDB. These applications facilitate the processing and analysis of bacterial genome, transcriptome and proteome data and are actively used by numerous international groups. We are currently in the process of extensively interconnecting these applications. BRIGEP was developed in the Bioinformatics Resource Facility of the Center for Biotechnology at Bielefeld University and is freely available. A demo project with sample data and access to all three tools is available at https://www.cebitec.uni-bielefeld.de/groups/brf/software/brigep/. Code bundles for these and other tools developed in our group are accessible on our FTP server at ftp.cebitec.uni-bielefeld.de/pub/software/.

Seed Transmission of Fusarium verticillioides in Maize Plants Grown Under Three Different Temperature Regimes.

Fusarium verticillioides can be seed transmitted and cause systemic infection of maize; however, the frequency of these phenomena has varied widely among and within individual studies. In order to better understand this variability, we evaluated the effect of temperature on the first step in the systemic infection process, the transmission of F. verticillioides from seed to seedling. Seed of a commercial maize hybrid were inoculated with a strain of F. verticillioides that had been transformed with a gene for green fluorescent protein (GFP). The seed were planted in a greenhouse potting mix and incubated in growth chambers. Plants were incubated at one of three temperature regimes designed to simulate average and extreme temperatures occurring in Iowa during the weeks following planting. Root, mesocotyl, and stem tissues were sampled at growth stages V2 and V6, surface disinfested, and cultured on a semiselective medium. At V2, >90% of root and mesocotyl tissues was infected by the GFP-expressing strain at all three temperature regimes. Also at V2, infection was detected in 68 to 75% of stems. At V6, infection of root and mesocotyl tissues persisted and was detected in 97 to 100% of plants at all three temperature regimes. Plants also had symptomless systemic infection of belowground and aboveground internodes at V6. Infection of the three basal aboveground internodes was 24, 6, and 3% for the low-temperature regime; 35, 9, and 0% for the average-temperature regime; and 46, 24, and 9% for the high-temperature regime. Seed transmission and systemic infection occurred at all temperatures and did not differ significantly among treatments. These results indicate that, if maize seed is infected with F. verticillioides, seed transmission is common and symptomless systemic infection can be initiated under a broad range of temperature conditions.

Effects of hyperthermia on blood flow and cis-diamminedichloroplatinum(II) pharmacokinetics in murine mammary adenocarcinomas.

The effect of localized hyperthermia on blood flow and cis-diamminedichloroplatinum(II) (CDDP) pharmacokinetics in 7,12-dimethylbenz[a]anthracene-induced mammary adenocarcinomas was studied. Blood flow was determined in rat tumors and normal tissue immediately and 1, 2, and 3 h after local hyperthermia treatment (43 degrees C, 1 h) as well as in unheated tumors of rats. The rate of blood flow in the tumor was increased 1.9 times at the end of treatment relative to control values and returned to the control values by 3 h after hyperthermia. Similarly, the rate of blood flow in the peripheral skin around the tumor immediately after hyperthermia was 2.2 times greater than that of unheated skin and returned to near normal values by 3 h after heating. Tumor-bearing rats received CDDP 1 h before, at the beginning of, at the end of, and 1 h after hyperthermia administration. The CDDP plasma concentration versus time profiles for rats did not vary statistically between treatment groups. Two h after CDDP administration, the mean tumor CDDP concentration of the rats which received drug at the beginning of hyperthermia was statistically greater (P less than 0.05) than tumor CDDP concentrations in rats which received drug at the end of heat treatment. The latter group was given CDDP when tumor blood flow was the greatest; however, mean tumor drug concentration was lowest of all the groups. The mean drug concentration in tumor tissues of rats which received drug 1 h after hyperthermia was comparable to rats which received drug at the beginning of hyperthermia. This suggests that drug delivery or uptake in tumors may be altered when local hyperthermia is administered concurrently or sequentially.

Effect of hyperthermia on normal tissue toxicity and on adriamycin pharmacokinetics in dogs.

This study examined the effects of Adriamycin (ADR) (30 mg/m2), whole-body hyperthermia (WBH) (42 degrees C for 1 h), and the combination of the two (ADR plus WBH) on gastrointestinal and hematopoietic toxicity and the effects of WBH on ADR pharmacokinetics in the normal dog (n = 5/treatment group). Duodenal biopsies were collected from animals in each group via endoscopy and were incubated in the presence of [3H]thymidine as an index of cell turnover. Additional duodenal biopsies were assayed for the enzymes gamma-glutamyltranspeptidase, N-acetyl-beta-D-glucosaminidase, and succinate dehydrogenase. Complete blood chemistry profiles and differential blood cell counts were done prior to and following treatment. Cell turnover was most depressed 3 days after ADR or ADR plus WBH; WBH alone had little effect on cell turnover. Neither gamma-glutamyltranspeptidase, N-acetyl-beta-D-glucosaminidase, nor succinate dehydrogenase activities were significantly altered by any of the treatment protocols. High performance liquid chromatography was used to quantify Adriamycin and adriamycinol in samples collected up to 6 h after drug administration. Duodenal biopsies were collected immediately and 1 h after drug administration for measurement of tissue concentrations of Adriamycin. A significant increase in the apparent volume of distribution and whole-body clearance and decrease in area under the plasma Adriamycin concentration versus time curve occurred when drug was administered concurrently with WBH. This differs from results reported in some other mammalian species.

Expression of heme oxygenase-1 protects endothelial cells from irradiation-induced apoptosis.

A common side effect of therapeutic use of ionizing irradiation is endothelial cell damage resulting in a variety of clinical complications. Thus, preservation of endothelial function after irradiation could potentially limit toxicity. Using the murine endothelioma cell line bEnd2 we show here that induction of heme oxygenase-1 (HO-1) by cobalt protoporphyrine IX (CoPP) inhibits irradiation-induced apoptosis. In contrast, HO-1 induction by tin protoporphyrine IX (SnPP), a HO-1 inhibitor, does not affect survival after irradiation. The protective effects of CoPP could be partially reversed by blockade of HO-1 function with SnPP after induction by CoPP. Vice versa, blockade of HO-1 function by SnPP was reversible using CoPP. Treatment with CoPP inhibited cytochrome c release induced by irradiation. These results demonstrate that HO-1 induction and activation prior to irradiation inhibits endothelial apoptosis and might be used for possible cell protection in vivo.

[Cytokine profile of a human bone marrow cell culture under the influence of UHMW-PE wear particles]. / Zytokinprofil einer humanen Knochenmarkzellkultur unter dem Einfluss von UHMW-PE Abriebpartikeln.

There is considerable evidence that orthopaedic wear debris plays a crucial role in the pathology of aseptic loosening of joint prostheses. The purpose of the present study was to evaluate the influence of ultra-high-molecular-weight polyethylene (UHMW-PE) on the cytokine response in a modified in vitro model. UHMW-PE particles (psi < 7.5 microm) were suspended in soluble collagen type I and subsequently solidified in different concentrations (105,106 and 107 particles per well) on the bottom of the wells. Human bone marrow cells in a concentration of 3 x 106 cells per well were seeded on the collagen-particle substrata and maintained for up to 12 days. The cytokine response (IL-1_, IL-6 and TNF-_) of the cells to the particles were examined by ELISA compared to cells on control collagen surfaces without any particles. Assays for viability using LDH activity were done immediately. Light and scanning microscopic evaluation revealed that the UHMWPE particles, which have built large conglomerates (psi7.5_m), were mainly surrounded by the cells and less phagocytosed. The results of the cytokine release revealed significant differences in interleukin (IL)6, tumor necrosis factor (TNF)- _ and IL-1beta. The cell viability was not affected by the UHMW-PE particles. The results demonstrate that the particle induced cytokine response by UHMW-PE is mainly by the release of Interleukin 6 and TNF- _. Moreover the results confirm that the present method is useful to evaluate the in vitro effects of UHMW-PE wear particles with direct particle cell contact.