Distribution of esterase activity in porcine ear skin, and the effects of freezing and heat separation

Porcine ear skin is widely used to study skin permeation and absorption of ester compounds, whose permeation and absorption profiles may be directly influenced by in situ skin esterase activity. Importantly, esterase distribution and activity in porcine ear skin following common protocols of skin handling and storage have not been characterised. Thus, we have compared the distribution and hydrolytic activity of esterases in freshly excised, frozen, heated and explanted porcine ear skin. Using an esterase staining kit, esterase activity was found to be localised in the stratum corneum and viable epidermis. Under frozen storage and a common heating protocol of epidermal sheet separation, esterase staining in the skin visibly diminished. This was confirmed by a quantitative assay using HPLC to monitor the hydrolysis of aspirin, in freshly excised, frozen or heated porcine ear skin. Compared to vehicle-only control, the rate of aspirin hydrolysis was approximately three-fold higher in the presence of freshly excised skin, but no different in the presence of frozen or heated skin. Therefore, frozen and heat-separated porcine ear skin should not be used to study the permeation of ester-containing permeants, in particular co-drugs and pro-drugs, whose hydrolysis or degradation can be modulated by skin esterases.

The TGR5 receptor mediates bile acid-induced itch and analgesia

Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal cord that transmit itch and pain, and in dermal macrophages that contain opioids. Bile acids and a TGR5-selective agonist induced hyperexcitability of dorsal root ganglia neurons and stimulated the release of the itch and analgesia transmitters gastrin-releasing peptide and leucine-enkephalin. Intradermal injection of bile acids and a TGR5-selective agonist stimulated scratching behavior by gastrin-releasing peptide- and opioid-dependent mechanisms in mice. Scratching was attenuated in Tgr5-KO mice but exacerbated in Tgr5-Tg mice (overexpressing mouse TGR5), which exhibited spontaneous pruritus. Intraplantar and intrathecal injection of bile acids caused analgesia to mechanical stimulation of the paw by an opioid-dependent mechanism. Both peripheral and central mechanisms of analgesia were absent from Tgr5-KO mice. Thus, bile acids activate TGR5 on sensory nerves, stimulating the release of neuropeptides in the spinal cord that transmit itch and analgesia. These mechanisms could contribute to pruritus and painless jaundice that occur during cholestatic liver diseases.

Climate change policy and business climate strategies: EU cement companies' response to climate change and barriers against action

The paper provides a descriptive analysis of the carbon management activities of the cement industry in Europe based on a study involving the four largest producers of cement in the world. Based on this analysis, the paper explores the relationship between managerial perception and strategy with particular focus on the impact of government regulation and competitive dynamics. The research is based on extensive documentary analysis and in-depth interviews with senior managers from the four companies who have been responsible for and/or involved in the development of climate change strategies. We find that whilst the cement industry has embraced climate change and the need for action, their remains much scope for action in their carbon management activities with current effort concentration on hedging practices and win-win efficiency programs. Managers perceive that inadequate and unfavourable regulatory structure is the key barrier against more action to achieve emission reduction within the industry. EU Cement companies are also shifting their CO2 emissions to less developed countries of the South.

Measuring students' emotions in the early years: the Achievement Emotions Questionnaire-Elementary School (AEQ-ES)

This article reports about the development and validation of a measurement instrument assessing elementary school students' achievement emotions (Achievement Emotions Questionnaire-Elementary School, AEQ-ES). Specifically, the instrument assesses students' enjoyment, anxiety, and boredom pertaining to three types of academic settings (i.e., attending class, doing homework, and taking tests and exams). Scale construction was based on Pekrun's (2006) control-value theory of achievement emotions. The instrument was tested using samples from German and American elementary school classrooms. The results of Study 1 (German sample) corroborate the reliability and structural validity of the new emotion measure. Moreover, they show that students' achievement emotions were linked with their control and value appraisals as well as their academic performance, thus supporting the external validity of the measure as well as propositions of Pekrun's (2006) control-value theory of achievement emotions. Study 2 (American sample) corroborated the cross-cultural equivalence of the measure and the generalizability of findings across the German and American samples. Implications for research on achievement emotions and educational practice are discussed. (PsycINFO Database Record (c) 2013 APA, all rights reserved)(journal abstract)

Comparative Analysis of ESBL-Positive Escherichia coli isolates from Animals and Humans from the UK, the Netherlands and Germany

The putative virulence and antimicrobial resistance gene contents of extended spectrum β-lactamase (ESBL)-positive E. coli (n=629) isolated between 2005 and 2009 from humans, animals and animal food products in Germany, The Netherlands and the UK were compared using a microarray approach to test the suitability of this approach with regard to determining their similarities. A selection of isolates (n=313) were also analysed by multilocus sequence typing (MLST). Isolates harbouring blaCTX-M-group-1 dominated (66%, n=418) and originated from both animals and cases of human infections in all three countries; 23% (n=144) of all isolates contained both blaCTX-M-group-1 and blaOXA-1-like genes, predominantly from humans (n=127) and UK cattle (n=15). The antimicrobial resistance and virulence gene profiles of this collection of isolates were highly diverse. A substantial number of human isolates (32%, n=87) did not share more than 40% similarity (based on the Jaccard coefficient) with animal isolates. A further 43% of human isolates from the three countries (n=117) were at least 40% similar to each other and to five isolates from UK cattle and one each from Dutch chicken meat and a German dog; the members of this group usually harboured genes such as mph(A), mrx, aac(6’)-Ib, catB3, blaOXA-1-like and blaCTX-M-group-1. forty-four per cent of the MLST-typed isolates in this group belonged to ST131 (n=18) and 22% to ST405 (n=9), all from humans. Among animal isolates subjected to MLST (n=258), only 1.2% (n=3) were more than 70% similar to human isolates in gene profiles and shared the same MLST clonal complex with the corresponding human isolates. The results suggest that minimising human-to-human transmission is essential to control the spread of ESBL-positive E. coli in humans.

Blockade of ActRIIB signaling triggers muscle fatigability and metabolic myopathy

Myostatin regulates skeletal muscle size via the activin receptor IIB (ActRIIB). However, its effect on muscle energy metabolism and energy dependent muscle function remains largely unexplored. This question needs to be solved urgently since various therapies for neuromuscular diseases based on blockade of ActRIIB signaling are being developed. Here we show in mice that four months of pharmacological abrogation of ActRIIB signaling by treatment with soluble ActRIIB-Fc triggers extreme muscle fatigability. This is associated with elevated serum lactate levels and a severe metabolic myopathy in the mdx mouse, an animal model of Duchenne muscular dystrophy. Blockade of ActRIIB signaling down-regulates Porin, a crucial ADP/ATP shuttle between cytosol and mitochondrial matrix leading to a consecutive deficiency of oxidative phosphorylation as measured by in vivo Phophorus Magnetic Resonance Spectroscopy (31P-MRS). Further, ActRIIB blockade reduces muscle capillarization, which further compounds the metabolic stress. We show that ActRIIB regulates key determinants of muscle metabolism, such as Pparβ, Pgc1α, and Pdk4 thereby optimizing different components of muscle energy metabolism. In conclusion, ActRIIB signaling endows skeletal muscle with high oxidative capacity and low fatigability. The severe metabolic side effects following ActRIIB blockade caution against deploying this strategy, at least in isolation, for treatment of neuromuscular disorders.

Diversity of STs, plasmids and ESBL genes among Escherichia coli from humans, animals and food in Germany, the Netherlands and the UK

This study aimed to compare ESBL-producing Escherichia coli causing infections in humans with infecting or commensal isolates from animals and isolates from food of animal origin in terms of the strain types, the ESBL gene present and the plasmids that carry the respective ESBL genes. A collection of 353 ESBL-positive E. coli isolates from the UK, the Netherlands and Germany were studied by MLST and ESBL genes were identified. Characterization of ESBL gene-carrying plasmids was performed using PCR-based replicon typing. Moreover, IncI1-Iγ and IncN plasmids were characterized by plasmid MLST. The ESBL-producing E. coli represented 158 different STs with ST131, ST10 and ST88 being the most common. Overall, blaCTX-M-1 was the most frequently detected ESBL gene, followed by blaCTX-M-15, which was the most common ESBL gene in the human isolates. The most common plasmid replicon type overall was IncI1-Iγ followed by multiple IncF replicons. ESBL genes were present in a wide variety of E. coli STs. IncI1-Iγ plasmids that carried the blaCTX-M-1 gene were widely disseminated amongst STs in isolates from animals and humans, whereas other plasmids and STs appeared to be more restricted to isolates from specific hosts.

Evidence of evolving extraintestinal enteroaggregative Escherichia coli ST38 clone

BACKGROUND: Several clones of extended-spectrum β-lactamase (ESBL)–producing extraintestinal pathogenic Escherichia coli (ExPEC) have globally expanded their distribution. ExPEC infections often originate from the patient’s own intestinal flora, although the degree of overlap between diarrheagenic E. coli and ExPEC pathotypes is unclear. Relatively little is known about antimicrobial drug resistance in the most common diarrheagenic E. coli groups, including enteroaggregative E. coli (EAEC), and bacterial gastroenteritis is generally managed without use of antimicrobial drugs. APPROACHES: We conducted this study to establish the presence and characteristics of ESBL-producing EAEC in a well-defined collection of ESBL-producing isolates. The isolates were from human and animal sources in Germany, the Netherlands, and the United Kingdom. DNA from 359 ESBL isolates was screened for the presence of the EAEC transport regulator gene (aggR), located on the EAEC plasmid, using a real-time PCR assay and the phylogroup was determined for each positive isolate. A microarray was used to detect ESBL genes, such as blaCTX-M, at the group level, as previously described. The antimicrobial drug susceptibilities of EAEC isolates were determined and virulence factors associated with intestinal and extraintestinal infection and with EAEC were investigated . RESULTS AND CONCLUSIONS: We assigned a virulence score (total number of virulence factor genes detected; maximum possible score 22) and a resistance score (total number of drug classes; maximum score 11) to each isolate. We isolated 11 EAEC from humans. Eight of the EAEC were isolated from urine specimens, and 1 was isolated from a blood culture; 63% belonged to phylogroup D (Table). EAEC ST38, the most common (55%) ST, was significantly associated with extraintestinal sites in the subset of 140 human isolates (Fisher exact test, p<0.0001)

The Climate-system Historical Forecast Project: do stratosphere-resolving models make better seasonal climate predictions in boreal winter?

Using an international, multi-model suite of historical forecasts from the World Climate Research Programme (WCRP) Climate-system Historical Forecast Project (CHFP), we compare the seasonal prediction skill in boreal wintertime between models that resolve the stratosphere and its dynamics (“high-top”) and models that do not (“low-top”). We evaluate hindcasts that are initialized in November, and examine the model biases in the stratosphere and how they relate to boreal wintertime (Dec-Mar) seasonal forecast skill. We are unable to detect more skill in the high-top ensemble-mean than the low-top ensemble-mean in forecasting the wintertime North Atlantic Oscillation, but model performance varies widely. Increasing the ensemble size clearly increases the skill for a given model. We then examine two major processes involving stratosphere-troposphere interactions (the El Niño-Southern Oscillation/ENSO and the Quasi-biennial Oscillation/QBO) and how they relate to predictive skill on intra-seasonal to seasonal timescales, particularly over the North Atlantic and Eurasia regions. High-top models tend to have a more realistic stratospheric response to El Niño and the QBO compared to low-top models. Enhanced conditional wintertime skill over high-latitudes and the North Atlantic region during winters with El Niño conditions suggests a possible role for a stratospheric pathway.

Användning av arkiv i samhällskunskapsundervisningen på gymnasiet

Syftet med denna uppsats är att undersöka om, och i så fall hur, man på ett fruktbart sätt kan göra de kommunala arkiven (och ev. andra arkiv) användbara i ämnet samhällskunskap A på gymnasiet. Detta test sker utifrån ett pedagogiskt undervisningsmaterial, närmare bestämt en portfölj tillsammans med en undervisningsplanering i samhällskunskap på gymnasiet. För denna uppsats har en forskarpraktiserande metod använts. Den används för att kunna uppnå syftet med skapandet av ett pedagogiskt undervisningsmaterial (portföljen) för gymnasieungdomar i samhällskunskap A. Utgångspunkterna för undersökningen är för det fösta att samhällskunskap är idag ett tvärvetenskapligt ämne som t.ex. består av ekonomi och politik och historia, geografi m.m. Den andra är att ingen forskare, enligt min vetskap, tidigare har genomfört ett projekt där kommunarkiven har involverats i samhällkunskap. Däremot använder lärare och forskare arkivinformation inom ämnen såsom historia och geografi. Källorna i undersökningen är läromedlet Reflex A, styrdokumenten och arkivhandlingar från 1878, 1970-2000 och forskning från pedagoger och arkivpedagoger. Denna forskning har legat till grund för den framtagna undervisningsplaneringen samt den pedagogiska portföljen. Arbetet gick ut på att skapa en portfölj med arkivhandlingar som skulle användas i samhällkunskap A. De övergripande målen som ex styrdokumenten visa på att det finns inga direkta konkreta direktiv som sa att läraren inte kunde använda arkivhandlingar. Det står tydligt att eleverna skall ha ett dåtida, nutida och framtida perspektiv och att de skall lära sig använda flera källor samt vara källkritiska. Resultatet är även det som finns i portföljen och är portföljen med dess handbok. Introduceringen av arkiven sker utifrån ett pedagogiskt undervisningsmaterial och en undervisningsplanering. Det krävs emellertid att läraren får den tid för att sammanställa ett fungerande material för användandet av arkiven i undervisningen.

Livskvalitet i familjer med barn och ungdomar med astma : en systematisk litteraturstudie

Syftet med litteraturstudien var att beskriva vilken livskvalitet barn och ungdomar med astma och deras föräldrar hade. Till resultatet användes tretton vetenskapliga artiklar publicerade tidigast år 2000. Databaserna Elin, Blackwell Synergy och Ebsco Host användes vid artikelsökningen och en manuell sökning gjordes via www.asthma.se. Sökorden asthma, child, parents, quality of life, experience och coping användes i olika kombinationer. Artikelurvalet gjordes för att passa litteraturstudiens syfte och frågeställningar och det vetenskapliga värdet i artiklarna skattades med hjälp av modifierade granskningsmallar. Resultatet visade att barn och ungdomar med astma hade relativt högt skattad livskvalitet och hade lärt sig att hitta strategier för att hantera sin sjukdom och därmed kunna leva ett så normalt liv som möjligt. Många av barnen och ungdomar testade gränser för hur mycket kroppen tålde genom påfrestande fysiska aktiviteter. För de ungdomarna som hade lågt skattad livskvalitet kunde orsakerna härledas till dålig kontrollerade astmasymtom eller då omgivningen påverkade barnet negativt. Flickor hade lägre livskvalitet än pojkar i studierna. Föräldrarna till barn och ungdomar med astma var generellt mer påverkade av barnets sjukdom än barnen själva. De fanns vissa skillnader mellan föräldrarna, mödrarna var mer bekymrade och oroade medan fäderna hade ett mer avslappnat förhållande till barnet och sjukdomen.

Lekens betydelse : En studie av fem pedagogers uppfattning om lekens betydelse för lärandet i förskoleklass

Denna undersökning handlar om pedagogers uppfattning om lekens betydelse för barns lärande. Undersökningen har gjorts i en förskoleklass. Vi har intervjuat fem pedagoger, tre förskollärare, en barnskötare och en outbildad pedagog om deras syn på lekens betydelse för lärandet i förskoleklassen. Intervjuerna bandades och vissa passager som vi ansåg hade med undersökningsfrågorna att göra skrevs ut. Resultatet visade på att pedagogerna ger stor betydelse åt lek för lärande i förskoleklassen. Pedagogerna anser att lek och lärande hör ihop i förskoleklass då man i de yngre åldrarna lär och utvecklas genom lek. Vår slutsats är att leken finns i stor grad i den här förskoleklassen där vi gjort vår undersökning. Vi anser att det är en balans mellan lek och lärande.

Kvinnors upplevelser av missfall : och dess påverkan på nästkommande graviditet

En övervägande stor grupp kvinnor drabbas av missfall, antingen tidigt eller sent i graviditeten, ochför många är det en traumatisk upplevelse. Syftet med denna litteraturstudie var att beskriva aktuellforskning om hur kvinnor upplever ett missfall och hur den upplevelsen påverkar den psykiskahälsan i nästkommande graviditet. Litteraturöversikten baserades på tjugotre vetenskapliga artiklarpublicerade mellan 1995 och 2007. Sökning har skett i fyra olika databaser med ett antalsökkombinationer.Resultatet visade att missfall är ett komplext tillstånd där många olika känslor är involverade.Blandade känslor i form av sorg, oro, förtvivlan, depression och skuld beskrevs av kvinnorna. Vidnästkommande graviditet upplevdes en stark oro och ett hot mot graviditeten och barnet. Studiervisade även en lägre grad av prenatal anknytning till barnet hos de kvinnor som upplevt missfall.Upplevelsen av att sakna stöd efter missfallet och under nästkommande graviditet påtalades avföräldrarna. Skillnad i sorgearbete mellan kvinnan och mannen beskrevs, liksom att kvinnan visadehögre grad av depression och oro än mannen. Flera studier betonar vikten av planerad uppföljningefter ett missfall.Nyckelord; missfall, kvinnors upplevelse, oro, sorg, skuld och nästkommande graviditet.

Granskning av kvalitetssäkringsarbetet vid en ICC-profilbaserad trycksaksproduktion

To make your company change from a conventional workflow to an ICC-based workflow you need tomake investments in time and money. On the other hand you get your reward in terms of a stable andquality safe production. To choose this way of adjusting your company to new routines requires accuracyas well as a great deal of commitment. It is not only about having the right equipment. There area lot of factors that affect the quality of production.Our ambition with this report is to bring out the importance of general thinking when it comes toICC-profiling and to discuss on which basis printing profiles should be created. Quality parameters asfor example roughness and whiteness of paper are also discussed. To be able to investigate these mattersin detail we have taken a closer look at two companies, which have chosen to commit themselvesto achive better quality through color management but still feel that they have some problems withtheir workflow.One of the conclusions that are made in this report is that both companies should extend their investmentsin education of employees to become less independent of consultants, but also to increase theinterest in changes within the company. It is also stressed that an ICC-profile only can be efficient if acompany commits itself to accuracy regarding routines, control and calibration.

Omvårdnadsåtgärder som stärker egenvården hos patienter med Irritable Bowel Syndrome

Syftet med denna systematiska litteraturstudie var att belysa hur sjuksköterskans omvårdnad kan stödja egenvårdsförmågan hos patienter med IBS. Den viktigaste omvårdnadsåtgärden var att tidigt i samband med diagnostiseringen av IBS, ge information och kunskap om sjukdomen, dess prognos samt behandling, vilket visades förbättra upplevd livskvalitet samt ge symtom-lindring. IBS skolor startade av sjuksköterskor förbättrade patienternas hälsobeteende samt minskade symtomen. Genom introduktion av guidebok innehållande råd om kost, motion, stresshantering samt symtomkontroll upplevde patienterna en minskning av symtom, vilket även ledde till en minskning av antalet besök inom sjukvården. När sjuksköterskan använde olika frågeformulär i kontakten med patienter med IBS kunde patienternas problem identifieras och strategier för egenvården planeras samt individuella handlingsplaner skapas. Sjuksköterskans kunskap och förståelse om patientens egen sjukdomsupplevelse samt copingstrategi ledde till att patienten tog en mer aktiv roll i sjukdomshantering. Patienters behandling borde inriktas på livsstilsförändringar, som till exempel psykosocial arbetsmiljö, kost, fysisk aktivitet, samt stresshantering. Genom att patienten förde dagbok över kostintag och sedan gjorde jämförelser med ökade eller minskade symtom kunde faktorer identifieras i matvanor samt kostintag som inverkade på symtomen. Dorotea Orems omvårdnadsmodell har legat till grund för denna studie där tron på människans egna resurser framhålls.