Targeting Enterococcus faecalis Biofilms with Phage Therapy.

Phage therapy has been proven to be more effective, in some cases, than conventional antibiotics, especially regarding multidrug-resistant biofilm infections. The objective here was to isolate an anti-Enterococcus faecalis bacteriophage and to evaluate its efficacy against planktonic and biofilm cultures. E. faecalis is an important pathogen found in many infections, including endocarditis and persistent infections associated with root canal treatment failure. The difficulty in E. faecalis treatment has been attributed to the lack of anti-infective strategies to eradicate its biofilm and to the frequent emergence of multidrug-resistant strains. To this end, an anti-E. faecalis and E. faecium phage, termed EFDG1, was isolated from sewage effluents. The phage was visualized by electron microscopy. EFDG1 coding sequences and phylogeny were determined by whole genome sequencing (GenBank accession number KP339049), revealing it belongs to the Spounavirinae subfamily of the Myoviridae phages, which includes promising candidates for therapy against Gram-positive pathogens. This analysis also showed that the EFDG1 genome does not contain apparent harmful genes. EFDG1 antibacterial efficacy was evaluated in vitro against planktonic and biofilm cultures, showing effective lytic activity against various E. faecalis and E. faecium isolates, regardless of their antibiotic resistance profile. In addition, EFDG1 efficiently prevented ex vivo E. faecalis root canal infection. These findings suggest that phage therapy using EFDG1 might be efficacious to prevent E. faecalis infection after root canal treatment.

Viticultura de precisión: predicción de cosecha a partir de variables del cultivo e índices de vegetación

El presente trabajo muestra los resultados provisionales de un proyecto de viticultura de precisión, llevado a cabo entre la Universidad de Lleida y la empresa Codorníu, S.A., con el objeto de predecir el rendimiento, de forma localizada, de diferentes variedades de viña para la producción de vinos y cavas de calidad. Las variables de cultivo muestreadas de forma detallada han sido: número de yemas, número de brotes, número de racimos, peso de la poda, vigor del cultivo y cosecha del año anterior (2003). El vigor del cultivo se ha extraído de una imagen multiespectral Quickbird 2. Estas variables se han analizado en un modelo de regresión múltiple con la cosecha del año 2004 (variable dependiente), ofreciendo diferentes ajustes según la variedad considerada y variables incorporadas en el análisis.

Loss of the RNA polymerase III repressor MAF1 confers obesity resistance.

MAF1 is a global repressor of RNA polymerase III transcription that regulates the expression of highly abundant noncoding RNAs in response to nutrient availability and cellular stress. Thus, MAF1 function is thought to be important for metabolic economy. Here we show that a whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity and nonalcoholic fatty liver disease by reducing food intake and increasing metabolic inefficiency. Energy expenditure in Maf1(-/-) mice is increased by several mechanisms. Precursor tRNA synthesis was increased in multiple tissues without significant effects on mature tRNA levels, implying increased turnover in a futile tRNA cycle. Elevated futile cycling of hepatic lipids was also observed. Metabolite profiling of the liver and skeletal muscle revealed elevated levels of many amino acids and spermidine, which links the induction of autophagy in Maf1(-/-) mice with their extended life span. The increase in spermidine was accompanied by reduced levels of nicotinamide N-methyltransferase, which promotes polyamine synthesis, enables nicotinamide salvage to regenerate NAD(+), and is associated with obesity resistance. Consistent with this, NAD(+) levels were increased in muscle. The importance of MAF1 for metabolic economy reveals the potential for MAF1 modulators to protect against obesity and its harmful consequences.

Mechanisms of action of brief alcohol interventions remain largely unknown - a narrative review.

A growing body of evidence has shown the efficacy of brief intervention (BI) for hazardous and harmful alcohol use in primary health care settings. Evidence for efficacy in other settings and effectiveness when implemented at larger scale are disappointing. Indeed, BI comprises varying content; exploring BI content and mechanisms of action may be a promising way to enhance efficacy and effectiveness. Medline and PsychInfo, as well as references of retrieved publications were searched for original research or review on active ingredients (components or mechanisms) of face-to-face BIs [and its subtypes, including brief advice and brief motivational interviewing (BMI)] for alcohol. Overall, BI active ingredients have been scarcely investigated, almost only within BMI, and mostly among patients in the emergency room, young adults, and US college students. This body of research has shown that personalized feedback may be an effective component; specific MI techniques showed mixed findings; decisional balance findings tended to suggest a potential detrimental effect; while change plan exercises, advice to reduce or stop drinking, presenting alternative change options, and moderation strategies are promising but need further study. Client change talk is a potential mediator of BMI effects; change in norm perceptions and enhanced discrepancy between current behavior and broader life goals and values have received preliminary support; readiness to change was only partially supported as a mediator; while enhanced awareness of drinking, perceived risks/benefits of alcohol use, alcohol treatment seeking, and self-efficacy were seldom studied and have as yet found no significant support as such. Research is obviously limited and has provided no clear and consistent evidence on the mechanisms of alcohol BI. How BI achieves the effects seen in randomized trials remains mostly unknown and should be investigated to inform the development of more effective interventions.

Promotion of physical activity in the primary care setting : the situation in Switzerland

Although many harmful effects of a sedentary lifestyle on health are well known, we still need to better understand how regular physical activity in the general population can be promoted effectively. Among the currently explored strategies, screening for sedentary lifestyle and promoting physical activity in the primary care setting seem promising. Despite recommendations from governmental agencies and professional associations in favor of physical activity counseling, this approach has not been widely adopted so far. This article summarizes the steps taken in Switzerland with the aim of developing physical activity counseling in the primary care setting. It describes how the early implication of primary care physicians influenced in a concrete way the development of the project.

A wolf in sheep"s clothing: carnivory in dominant sea urchins in the Mediterranean

Arbacia lixula and Paracentrotus lividus are the dominant sea urchins in the Mediterranean sublittoral, where they are key structuring species due to their grazing activity. It has been commonly accepted that competition between both species is minimized by specializing in different algal foods. A. lixula is considered to feed mainly on encrusting coralline algae, while P. lividus prefers fleshy macroalgae. We used stable isotope analysis to test if these species occupy different trophic positions at 3 locations in the western Mediterranean and one in Macaronesia. Our results show unambiguously that A. lixula always occupies a higher trophic level than P. lividus, with a δ15N comparable in some locations to strict carnivores such as Actinia schmidti or Marthasterias glacialis. A temporal monitoring at one locality showed that this signature of a higher trophic level is consistent throughout the year. These results are incompatible with the current belief of an herbivorous diet for A. lixula and suggest that it must be considered an omnivore tending to carnivory in Mediterranean ecosystems, feeding at least partially on sessile animals such as Cirripedia, Hydrozoa or Bryozoa. A parallel analysis of gut contents showed a predominance of vegetal items in both species, although A. lixula consistently had a higher abundance of animal components than P. lividus. Our results challenge the validity of using gut content observations alone for characterizing the trophic behaviour of omnivorous marine invertebrates that feed on a variety of food sources with different digestibility.

TGF-β dependent regulation of oxygen radicals during transdifferentiation of activated hepatic stellate cells to myofibroblastoid cells

Background: The activation of hepatic stellate cells (HSCs) plays a pivotal role during liver injury because the resulting myofibroblasts (MFBs) are mainly responsible for connective tissue re-assembly. MFBs represent therefore cellular targets for anti-fibrotic therapy. In this study, we employed activated HSCs, termed M1-4HSCs, whose transdifferentiation to myofibroblastoid cells (named M-HTs) depends on transforming growth factor (TGF)-β. We analyzed the oxidative stress induced by TGF-β and examined cellular defense mechanisms upon transdifferentiation of HSCs to M-HTs. Results: We found reactive oxygen species (ROS) significantly upregulated in M1-4HSCs within 72 hours of TGF-β administration. In contrast, M-HTs harbored lower intracellular ROS content than M1-4HSCs, despite of elevated NADPH oxidase activity. These observations indicated an upregulation of cellular defense mechanisms in order to protect cells from harmful consequences caused by oxidative stress. In line with this hypothesis, superoxide dismutase activation provided the resistance to augmented radical production in M-HTs, and glutathione rather than catalase was responsible for intracellular hydrogen peroxide removal. Finally, the TGF-β/NADPH oxidase mediated ROS production correlated with the upregulation of AP-1 as well as platelet-derived growth factor receptor subunits, which points to important contributions in establishing antioxidant defense. Conclusion: The data provide evidence that TGF-β induces NADPH oxidase activity which causes radical production upon the transdifferentiation of activated HSCs to M-HTs. Myofibroblastoid cells are equipped with high levels of superoxide dismutase activity as well as glutathione to counterbalance NADPH oxidase dependent oxidative stress and to avoid cellular damage.

Lämmöntalteenottokattilan dynaaminen simulointimalli

Työssä mallinnettiin kombivoimalaitoksen lämmöntalteenottokattila Apros-simulointiohjelmalla. Simulointimalli valmistettiin vastaamaan Helsingin Energian Vuosaari B:n voimalaitoksen lämmöntalteenottokattilaa, joka toimii kahdella painetasolla. Kattila on Foster Wheelerin valmistama. Ennen mallinnuksen aloittamista tutustuttiin laitoksen termodynamiikkaan, jolloin saatiin riittävä teoreettinen tieto koko laitoksen toiminnasta. Kattilan reunaehtoina ovat kaasuturbiiniprosessi ja laitoksen höyrykierto. Kaasuturbiini korvattiin laskentayhtälöillä, jotka antavat alkuarvot mm. savukaasun massavirralle ja lämpötilalle ennen kattilaa kaasuturbiinin tehon funktiona. Kattila liitetään höyrykiertoon tuorehöyry- ja syöttövesilinjasta, jolloin reunaehtoina annetaan lämpötilat ja paineet massavirroille. Valmistettua mallia testattiin ylösajo- ja kuormanmuutostilanteessa. Ylösajotilanteessa saatuja laskentatuloksia verrattiin todellisen laitoksen mittaustuloksiin, jolloin varmistuttiin simulointimallin oikeasta fysikaalisesta toiminnasta. Kuormanmuutostilanteissa kaasuturbiinin tehoa muutettiin ja samalla seurattiin kattilan reagointia muutostilanteessa. Kuormanmuutosmittauksessa varmistettiin vielä, että kattila reagoi kuormanmuutokseen oikealla tavalla, eikä muutos aiheuta kattilan toiminnalle haitallista värähtelyä.

Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial.

BACKGROUND: The recent large randomized controlled trial of glutamine and antioxidant supplementation suggested that high-dose glutamine is associated with increased mortality in critically ill patients with multiorgan failure. The objectives of the present analyses were to reevaluate the effect of supplementation after controlling for baseline covariates and to identify potentially important subgroup effects. MATERIALS AND METHODS: This study was a post hoc analysis of a prospective factorial 2 × 2 randomized trial conducted in 40 intensive care units in North America and Europe. In total, 1223 mechanically ventilated adult patients with multiorgan failure were randomized to receive glutamine, antioxidants, both glutamine and antioxidants, or placebo administered separate from artificial nutrition. We compared each of the 3 active treatment arms (glutamine alone, antioxidants alone, and glutamine + antioxidants) with placebo on 28-day mortality. Post hoc, treatment effects were examined within subgroups defined by baseline patient characteristics. Logistic regression was used to estimate treatment effects within subgroups after adjustment for baseline covariates and to identify treatment-by-subgroup interactions (effect modification). RESULTS: The 28-day mortality rates in the placebo, glutamine, antioxidant, and combination arms were 25%, 32%, 29%, and 33%, respectively. After adjusting for prespecified baseline covariates, the adjusted odds ratio of 28-day mortality vs placebo was 1.5 (95% confidence interval, 1.0-2.1, P = .05), 1.2 (0.8-1.8, P = .40), and 1.4 (0.9-2.0, P = .09) for glutamine, antioxidant, and glutamine plus antioxidant arms, respectively. In the post hoc subgroup analysis, both glutamine and antioxidants appeared most harmful in patients with baseline renal dysfunction. No subgroups suggested reduced mortality with supplements. CONCLUSIONS: After adjustment for baseline covariates, early provision of high-dose glutamine administered separately from artificial nutrition was not beneficial and may be associated with increased mortality in critically ill patients with multiorgan failure. For both glutamine and antioxidants, the greatest potential for harm was observed in patients with multiorgan failure that included renal dysfunction upon study enrollment.

Taajuusmuuttajan verkkovirran yliaallot pienitehoisissa kolmivaihekäytöissä

Pienitehoisessa taajuusmuuttajassa verkkojännite tasasuunnataan yleisesti diodisillalla. Taajuusmuuttajaa kuormitettaessa diodisilta aiheuttaa sen, että verkosta otettava virta on epäsinimuotoista ja sisältää runsaasti eri kertalukujen yliaaltoja. Tällainen virta vääristää verkon jännitettä sekä aiheuttaa häviöitä, resonansseja ja toimintaepävarmuutta sähkönjakeluverkkoon liitetyissä laitteissa ja komponenteissa. Työssä on tarkasteltu pienitehoisen kolmivaiheisen taajuusmuuttajan tulovirrassa esiintyviä yliaaltoja ja keinoja niiden rajoittamiseksi. Laitevalmistajien osalta syynä aiheen tutkimiseen ja kiinnostavuuteen ovat lähinnä uudet yliaaltoja käsittelevät standardit. Työssä onkin tutustuttu tarvittavin osin standardoinnin nykytilaan sekä seurattu standardeja valmistelevien työryhmien työtä ja tätä kautta perehdytty alaa käsittelevien standardien tulevaisuudennäkymiin Euroopan Unionin alueella. Käsittely on kohdistettu kolmivaiheisiin laitteisiin. Standardi IEC 61000-3-2 asettaa yliaaltorajat ammattikäyttöön tarkoitetuille laitteille, kun laitteen tuloteho on korkeintaan 1 kW. Tällä tehoalueella riittää kolmivaihelaitteille kuristimilla suoritettu passiivinen suodatus täyttämään asetetut viranomaisvaatimukset. Tähän liittyen on suunniteltu kolmivaihekuristin, joka on tarkoitettu käytettäväksi taajuusmuuttajasarjan lisävarusteena tehoalueella 0.12…2.2 kW.

Biogeochemical processes controlling oxygen and carbon isotopes of diatom silica in Late Glacial to Holocene lacustrine rhythmites

Biogeochemical cycles and sedimentary records in lakes are related to climate controls on hydrology and catchment processes. Changes in the isotopic imposition of the diatom frustules (δ 18 O diatom and δ 13 C diatom ) in lacustrine sediments can be used to reconstruct palaeoclimatic and palaeoenvironmental changes. The Lago Chungará (Andean Altiplano, 18°15 ′ S, 69°10 ′ W, 4520 masl) diatomaceous laminated sediments are made up of white and green multiannual rhythmites. White laminae were formed during short-term diatom super-blooms, and are composed almost exclusively of large-sized Cyclostephanos andinus.These diatoms bloom during mixing events when recycled nutrients from the bottom waters are brought to the surface and/or when nutrients are introduced from the catchment during periods of strong runoff. Conversely, the green laminae are thought to have been deposited over several years and are composed of a mixture of diatoms (mainly smaller valves of C. andinus and Discostella stelligera ) and organic matter. These green laminae reflect the lake's hydrological recovery from a status favouring the diatom super-blooms (white laminae) towards baseline conditions. δ 18 O diatom and δ 13 C diatom from 11,990 to 11,530 cal years BP allow us to reconstruct shifts in the precipitation/evaporation ratio and changes in the lake water dissolved carbon concentration, respectively. δ 18 O diatom values indicate that white laminae formation occurred mainly during low lake level stages, whereas green laminae formation generally occurred during high lake level stages. The isotope and chronostratigraphical data together suggest that white laminae deposition is caused by extraordinary environmental events. El Niño-Southern Oscillation and changes in solar activity are the most likely climate forcing mechanisms that could trigger such events, favouring hydrological changes at interannual-to-decadal scale. This study demonstrates the potential for laminated lake sediments to document extreme pluriannual events.

Metallisten kuluttajamaalipakkausten kierrätys.

Metalliset maalipurkit valmistetaan tinalla molemmin puolin päällystetystä pellistä. Tina on terästeollisuudelle haitallinen aine raaka-aineen seassa ja tästä syystä tinapellille on ollut vaikeuksia löytää hyötykäyttäjää. Metallipakkauksien osalta on sitouduttu hyötykäyttötavoitteisiin ja niihin pääsemiseksi tulee kerätä myös tinapeltipakkauksia, koska ne muodostavat huomattavan osan vuosittain käytettävistä metallipakkauksista. Suurilta ammattikäyttäjiltä maalipakkauksia on kerätty jo vuodesta 1998 ja pienkuluttajia varten keräyskokeilu aloitettiin vuoden 1999 alkupuolella. Tämä tutkimus käsittelee kuluttajille suunnattua keräyskokeilua ja tutkimuksen tavoitteena on laatia suosituksia ja ohjeita kuluttajamaalipakkausten keräilyn järjestämiseksi Suomessa. Kokeilua varten perustettiin muutamia keräyspisteitä, ensin Suur-Helsingin alueelle ja myöhemmin myös muualle Etelä-Suomeen. Kaikki perustetut keräyspisteet sijaitsivat maalia myyvän kaupan yhteydessä. Kuluttajat suhtautuivat palautusmahdollisuuteen erittäin myönteisesti ja kokeilussa mukana olevat liikkeet saivat positiivista julkisuutta. Keräyspisteisiin pääsääntöisesti palautetut maalipurkit olivat tyhjiä tai niissä oli vain hieman maalia jäljellä. Kaupoissa sijaitsevien keräyspisteiden lisäksi on tarvetta myös kunnallisille keräyspisteille. Kuusakoski Oy on nykyisin ainoa tinapellin käsittelijä Suomessa. Myös Onni Forsell Oy on kehittelemässä tinapellin käsittelymenetelmää. Kuusakosken murskauskäsittelyn ympäristövaikutukset selvitettiin tutkimuksessa ja tulosten mukaan käsittelyssä syntyvä jäte on kaatopaikkakelpoista. Tinapeltimurskeen hyötykäyttäjää ei Suomesta tällä hetkellä löydy, joten murske viedään ulkomaille hyötykäytettäväksi.

Uuttoprosessin suunnittelu

Teknologian kehitys ja prosessien tiukempi valvonta ovat alentaneet selluteollisuuden häviöitä tehden prosesseista suljetumpia. Valitettavasti nämä edistysaskeleet teknologiassa ovat lisänneet prosessiin kuulumattomien yhdisteiden määrää kemikaalien talteenottokierrossa. Näistä kemikaaleista haitallisimpia ovat kloridi- ja kaliumyhdisteet, jotka tulevat prosessiin raaka-aineiden ja prosessikemikaalien mukana. Kloridi ja kalium muodostavat emäksisissä liuoksissa epäorgaanisia liukoisia yhdisteitä, jotka rikastuvat lipeäkiertoon. Soodakattilassa kloridien läsnäolo alentaa tuhkan sulamislämpötilaa sekä tarttumispistettä, lisää korroosiota ja saostumien muodostumista kattilan pinnalle. Nämä seuraukset voivat vähentää vuosituotantoa ja nostaa korjauskustannuksia. Kaliumin ja kloridin rikastumista talteenottokiertoon voidaan estää poistamalla ne prosessista. Prosessiin kuulumattomat yhdisteet tulisi poistaa talteenottoprosessista ja säilyttää samalla korkea kemikaalien talteenottoprosentti. Koska kaliumin ja kloridin rikastumiskertoimet soodakattilan tuhkassa ovat korkeita, on tuhkan käsittely tehokasta. Kloridin ja kaliumin poistoon on kehitetty menetelmiä, joilla voidaan vähentää hyödyllisten kemikaalien häviöitä. Näitä menetelmiä ovat uutto, ioninvaihto, elektrodialyysi, jäähdytyskiteytys ja haihdutuskiteytys. Menetelmissä tuhka jaetaan kloridi- ja kaliumpitoiseen osaan ja natriumsulfaattipitoiseen osaan. Kloridi ja kalium poistetaan prosessista ja loput palautetaan lipeäkiertoon. Kloridin ja kaliumin poistoa tuhkasta tutkittiin uuttamalla tuhkaa vedellä. Parhaissa käyttöolosuhteissa natriumsulfaatin liukoisuus veteen on huomattavasti alhaisempi kuin kaliumkloridin liukoisuus veteen. Optimaalinen uuttolämpötila ja tuhka-vesisuhde määritettiin siten, että kloridi- ja kaliumpitoisuudet suodoksessa olivat mahdollisimman korkeat sekä natriumin ja muiden anioneiden pitoisuudet suodoksessa mahdollisimman alhaiset. Saatuja tuloksia käytettiin jatkuvatoimisen uuttoprosessin suunnittelussa.

Cannabis Users Identifying Themselves as Non-Cigarette Smokers : Who Are They?

Introduction and Aims. About 20% of cannabis consumers report not smoking cigarettes. Studies that have compared cannabis and cigarette smokers, cigarette smokers, and cannabis users who do not smoke cigarettes (CNSs) have shown that CNSs have better outcomes across a range of indicators compared to the others. Therefore, we conducted a qualitative study to determine why CNSs did not smoke cigarettes and how they managed to resist cigarette smoking in order to better inform prevention efforts. Design and Methods. We conducted five focus groups (FG) with a total of 19 CNSs between ages 16 and 25. A narrative analysis of FGs was conducted using qualitative analysis software. Results. CNSs' non-smoking choice was rooted in a negative opinion of cigarettes and a harm-reduction strategy. They were unique cases within their peer groups, but there were no CNSs groups. All participants were confronted to the mulling paradox. Discussion and Conclusions. While tobacco-use prevention seems to have been successful, CNSs need to be informed of harmful consequences of chronic cannabis use. Given their habit of adding tobacco to cannabis, CNSs need to be alerted that they may be nicotine dependent even though they do not smoke tobacco on its own. This exploratory study brings essential insight concerning this specific population of cannabis consumers which future research should continue to develop.

Defining ecologically relevant water quality targets for lakes in Europe

1. The implementation of the Water Framework Directive requires EU member states to establish and harmonize ecological status class boundaries for biological quality elements. In this paper, we describe an approach for defining ecological class boundaries that delineates shifts in lake ecosystem functioning and, therefore, provides ecologically meaningful targets for water policy in Europe. 2. We collected an extensive data set of 810 lake-years from nine Central European countries, and we used phytoplankton chlorophyll a, a metric widely used to measure the impact of eutrophication in lakes. Our approach establishes chlorophyll a target values in relation to three significant ecological effects of eutrophication: the decline of aquatic macrophytes, the dominance of potentially harmful cyanobacteria and the major functional switch from a clear water to a turbid state. 3. Ranges of threshold chlorophyll a concentrations are given for the two most common lake types in lowland Central Europe: for moderately deep lakes (mean depth 3–15 m), the greatest ecological shifts occur in the range 10–12 lg L 1 chlorophyll a, and for shallow lakes (<3 m mean depth), in the range 21–23 lg L 1 chlorophyll a. 4. Synthesis and applications. Our study provides class boundaries for determining the ecological status of lakes, which have robust ecological consequences for lake functioning and which, therefore, provide strong and objective targets for sustainable water management in Europe. The results have been endorsed by all participant member states and adopted in the European Commission legislation, marking the first attempt in international water policy to move from physico-chemical quality standards to harmonized ecologically based quality targets.