Acute pulmonary embolectomy.

Acute pulmonary embolism (PE) is a common condition frequently associated with a high mortality worldwide. It can be classified into non-massive, sub-massive and massive, based on the degree of haemodynamic compromise. Surgical pulmonary embolectomy, despite having been in existence for over 100 years, is generally regarded as an option of last resort, with expectedly high mortality rates. Recent advances in diagnosis and recognition of key qualitative predictors of mortality, such as right ventricular stress on echocardiography, have enabled the re-exploration of surgical pulmonary embolectomy for use in patients prior to the development of significant circulatory collapse, with promising results. We aim to review the literature and discuss the indications, perioperative workup and outcomes of surgical pulmonary embolectomy in the management of acute PE.

Population-based registration of phenotypic anatomic and familial data for melanoma: results from a Swiss multicentric study

CONTEXT AND OBJECTIVES: A multicentric study was set up to assess the feasibility for Swiss cancer registries of actively retrieving 3 additional variables of epidemiological and a etiological relevance for melanoma, and of potential use for the evaluation of prevention campaigns. MATERIAL AND METHODS: The skin type, family history of melanoma and precise anatomical site were retrieved for melanoma cases registered in 5 Swiss cantons (Neuchâtel, St-Gall and Appenzell, Vaud and Wallis) over 3 to 6 consecutive years (1995-2002). Data were obtained via a short questionnaire administered by the physicians - mostly dermatologists - who originally excised the lesions. As the detailed body site was routinely collected in Ticino, data from this Cancer Registry were included in the body site analysis. Relative melanoma density (RMD) was computed by the ratio of observed to expected numbers of melanomas allowing for body site surface areas, and further adjusted for site-specific melanocyte density. RESULTS: Of the 1,645 questionnaires sent, 1,420 (86.3%) were returned. The detailed cutaneous site and skin type were reliably obtained for 84.7% and 78.7% of questionnaires, and family history was known in 76% of instances. Prevalence of sun-sensitive subjects and patients with melanoma affected first-degree relatives, two target groups for early detection and surveillance campaigns were 54.1% and 3.4%, respectively. After translation into the 4th digit of the International Classification of Diseases for Oncology, the anatomical site codes from printed (original information) and pictorial support (body chart from the questionnaire) concurred for 94.6% of lesions. Discrepancies occurred mostly for lesions on the upper, outer part of the shoulder for which the clinician's textual description was "shoulder blade". This differential misclassification suggests under-estimation by about 10% of melanomas of the upper limbs and an over-estimation of 5% for truncal melanomas. Sites of highest melanoma risk were the face, the shoulder and the upper arm for sexes, the back for men and the leg for women. Three major features of this series were: (1) an unexpectedly high RMD for the face in women (6.2 vs 4.2 in men), (2) the absence of a male predominance for melanomas on the ears, and (3) for the upper limbs, a steady gradient of increasing melanoma density with increasing proximity to the trunk, regardless of sex. DISCUSSION AND CONCLUSION: The feasibility of retrieving the skin type, the precise anatomical location and family history of melanoma in a reliable manner was demonstrated thanks to the collaboration of Swiss dermatologists. Use of a schematic body drawing improves the quality of the anatomical site data and facilitate the reporting task of doctors. Age and sex patterns of RMD paralleled general indicators of sun exposure and behaviour, except for the hand (RMD=0.2). These Swiss results support some site or sun exposure specificity in the aetiology of melanoma.

Quantifying intracellular protein binding thermodynamics during mechanotransduction based on FRET spectroscopy.

Mechanical force modulates myriad cellular functions including migration, alignment, proliferation, and gene transcription. Mechanotransduction, the transmission of mechanical forces and its translation into biochemical signals, may be mediated by force induced protein conformation changes, subsequently modulating protein signaling. For the paxillin and focal adhesion kinase interaction, we demonstrate that force-induced changes in protein complex conformation, dissociation constant, and binding Gibbs free energy can be quantified by lifetime-resolved fluorescence energy transfer microscopy combined with intensity imaging calibrated by fluorescence correlation spectroscopy. Comparison with in vitro data shows that this interaction is allosteric in vivo. Further, spatially resolved imaging and inhibitor assays show that this protein interaction and its mechano-sensitivity are equal in the cytosol and in the focal adhesions complexes indicating that the mechano-sensitivity of this interaction must be mediated by soluble factors but not based on protein tyrosine phosphorylation.

Classical parameters of Shadowlands by Richard Attenborough (On C. S. Lewis's Life and Work)

The aim of this article is to show the classical parameters of Shadowlands by R. Attenborough, with a screenplay by W. Nicholson, on C. S. Lewis's life and work. Based upon an accurate reading of Lewis's works, the author of this article proposes to interpret the opposition Lewis / Gresham as the translation into the real life of the opposition between the Platonic or idealistic and the Aristotelian or materialistic temperaments which was already maintained by Coleridge. In any case, there are many classical references which must be taken into account in order to understand to what extent C. S. Lewis's Christianity is also a classic Christianity, that is, a Greek and Latin one.

Cooperative kinking at distant sites in mechanically stressed DNA.

In cells, DNA is routinely subjected to significant levels of bending and twisting. In some cases, such as under physiological levels of supercoiling, DNA can be so highly strained, that it transitions into non-canonical structural conformations that are capable of relieving mechanical stress within the template. DNA minicircles offer a robust model system to study stress-induced DNA structures. Using DNA minicircles on the order of 100 bp in size, we have been able to control the bending and torsional stresses within a looped DNA construct. Through a combination of cryo-EM image reconstructions, Bal31 sensitivity assays and Brownian dynamics simulations, we have been able to analyze the effects of biologically relevant underwinding-induced kinks in DNA on the overall shape of DNA minicircles. Our results indicate that strongly underwound DNA minicircles, which mimic the physical behavior of small regulatory DNA loops, minimize their free energy by undergoing sequential, cooperative kinking at two sites that are located about 180° apart along the periphery of the minicircle. This novel form of structural cooperativity in DNA demonstrates that bending strain can localize hyperflexible kinks within the DNA template, which in turn reduces the energetic cost to tightly loop DNA.

La traducció del castellà al català en l'àmbit oral col·loquial: una aproximació pràctica

Treball en què que s'analitza la traducció del castellà al català en l'àmbit oral col·loquial a partir d'un exemple real pràctic (una pel·lícula) per tal de determinar els problemes més comuns d'aquest tipus de traducció i de quina manera s’hi ha d’enfrontar el traductor per aconseguir un producte final satisfactori.

Traducción comentada del ámbito biomédico:«La integración de los genomas»

El presente trabajo consiste en la traducción comentada de un artículo científico. Nuestros objetivos son reflexionar sobre las características y problemas de la traducción especializada, analizar las estrategias y las soluciones propuestas, y producir un texto meta ‘adecuado’ teniendo en cuenta la tipología textual y el ámbito al que pertenece.

Differential effects of immunosuppressive drugs on effector and regulatory T cells.

Purpose: Current experimental data suggest that CD4+CD25+Foxp3+regulatory T cells (Tregs) based immunotherapy would be of greatinterest to promote donor-specific immune tolerance in transplantation(Tx). Whether and how adoptive transfer of Tregs could be bestcombined with current immunosuppressive regimens in clinicalsettings remains to be defined. Using an experimental Tx model,we had previously shown that the transfer of antigen-specific Tregspromoted long-term skin allograft acceptance in lymphopenic mice,in the absence of any immunosuppressive drug. However, allograftsurvival was only slightly prolonged when Tregs were transferredalone into non-lymphopenic mice, suggesting that in more stringentconditions such as in clinical settings adjuvant therapies may beneeded to effectively control alloreactive T cells (Teff).Methods and Materials: Here we have investigated the effects ofvarious immunosuppressive drugs on the survival, proliferation andeffector function of Teff and Tregs in response to alloantigens in in vitroassays and in our in vivo Tx model.Results: Teff proliferation was inhibited in a dose-dependant mannerby rapamycin and cyclosporine A, while anti-CD154 only marginallyaffected Teff proliferation and survival in vitro. Rapamycin promotedapoptosis of Teff as compared to Tregs that were more resistant underthe same culture conditions. In vivo, the transfer of donor-specificTregs could be advantageously combined with rapamycin andanti-CD154 to significantly prolong MHC-mismatched skin allograftsurvival in non-lymphopenic recipients.Conclusion: Taken together, our data indicate thatimmunosuppressive drugs differentially target T-cell subsets and couldpromote Tregs expansion and/or function while controlling the Teff pool.

Kompostointilaitoksen lopputuotteen käyttömahdollisuudet. Case: Himanka

Työssä selvitetään kompostointilaitoksen lopputuotteen erilaisia käyttömahdollisuuksia. Yleisten käyttökohteiden pohjalta on luotu malli Vapo Oy Biotech:n toimittaman Himangan kompostointilaitoksen kompostin hyödyntämiselle. Laitos sijaitsee Himangan kunnassa Keski- Pohjanmaalla. Laitoksella kompostoidaan pääasiassa Himangan ja ympäröivien kuntien jätevesilietteitä turkiseläinlantaa. Jätehuolto Suomessa ja koko EU:n alueella elää voimakasta muutoskautta. Orgaanisten jätteiden vienti kaatopaikoille pyritään tulevaisuudessa lopettamaan kokonaan, mikä on lisännyt niiden käsittelyä mm. kompostoimalla. Kompostoinnin lopputuotteena saadaan ravinteikasta, humuspitoista ainesta. Kompostoinnin yhtenä tavoitteena on tuottaa hyötykäyttöön soveltuvaa tuotetta, joten käyttökohteen löytäminen kompostille on laitoksen toiminnan kannalta erittäin tärkeää. Kompostin käyttömahdollisuuksiin vaikuttavat lainsäädäntö, kompostin ominaisuudet sekä paikalliset olosuhteet. Käyttökohteet on työssä jaettu ei-energiakäyttöön ja energiakäyttöön. Ei-energiakäyttöön kuuluvat maanparannuskäyttö, lannoitekäyttö, käyttö kasvualustassa, maisemointi ja julkinen rakentaminen sekä joitakin erityissovelluksia. Energiakäytön puolella on tarkasteltu kompostin soveltuvuutta erilaisille polttotekniikoille sekä vertailtu kompostia muihin kiinteisiin polttoaineisiin. Kompostien soveltuvuutta eri kohteisiin on arvioitu kompostin analyysi- ja kasvatuskoetulosten pohjalta. Kompostin ei-energiakaytössa on saatu eri tutkimuksissa lupaavia tuloksia. Kompostin on todettu soveltuvan erittäin hyvin mm. perunanviljelyyn, viljan ja nurmikasvien viljelyyn ja erilaisiin maisemointikohteisiin sekä kotipuutarhakäyttöön. Kompostin käyttöä polttoaineena ei ole vielä kokeiltu missään. Kompostin polton suurimmat ongelmat ovat korkea tuhka-, rikki- ja typpipitoisuus sekä epätasainen laatu.

Les traduccions al català de Marguerite Yourcenar: edicions i recepció crítica

Dins el marc d’un projecte més ampli que vol abastar l’anàlisi de les traduccions d’obres literàries escrites per dones, l'objectiu d’aquest article és establir l’estat de la qüestió de les traduccions al català de l’obra de Marguerite Yourcenar i oferir una primera aproximació a la recepció crítica que aquestes traduccions han tingut a la premsa catalana. Per això hem ordenat l’estudi en tres apartats: a) cronologia de les traduccions de Yourcenar al català; b) referències bibliogràfiques de les obres de Marguerite Yourcenar traduïdes al català i/o al castellà; c) recepció de les traduccions catalanes de Yourcenar a la premsa de Catalunya.

Aerosol therapy in intensive and intermediate care units: prospective observation of 2808 critically ill patients.

PURPOSE: Unlike in the outpatient setting, delivery of aerosols to critically ill patients may be considered complex, particularly in ventilated patients, and benefits remain to be proven. Many factors influence aerosol delivery and recommendations exist, but little is known about knowledge translation into clinical practice. METHODS: Two-week cross-sectional study to assess the prevalence of aerosol therapy in 81 intensive and intermediate care units in 22 countries. All aerosols delivered to patients breathing spontaneously, ventilated invasively or noninvasively (NIV) were recorded, and drugs, devices, ventilator settings, circuit set-up, humidification and side effects were noted. RESULTS: A total of 9714 aerosols were administered to 678 of the 2808 admitted patients (24 %, CI95 22-26 %), whereas only 271 patients (10 %) were taking inhaled medication before admission. There were large variations among centers, from 0 to 57 %. Among intubated patients 22 % (n = 262) received aerosols, and 50 % (n = 149) of patients undergoing NIV, predominantly (75 %) inbetween NIV sessions. Bronchodilators (n = 7960) and corticosteroids (n = 1233) were the most frequently delivered drugs (88 % overall), predominantly but not exclusively (49 %) administered to patients with chronic airway disease. An anti-infectious drug was aerosolized 509 times (5 % of all aerosols) for nosocomial infections. Jet-nebulizers were the most frequently used device (56 %), followed by metered dose inhalers (23 %). Only 106 (<1 %) mild side effects were observed, despite frequent suboptimal set-ups such as an external gas supply of jet nebulizers for intubated patients. CONCLUSIONS: Aerosol therapy concerns every fourth critically ill patient and one-fifth of ventilated patients.

Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells.

Tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily members play essential roles in the development of the different phases of the immune response. Mouse LIGHT (TNFSF14) is a type II transmembrane protein with a C-terminus extracellular TNF homology domain (THD) that assembles in homotrimers and regulates the course of the immune responses by signaling through 2 receptors, the herpes virus entry mediator (HVEM, TNFSFR14) and the lymphotoxin β receptor (LTβR, TNFSFR3). LIGHT is a membrane-bound protein transiently expressed on activated T cells, natural killer (NK) cells and immature dendritic cells that can be proteolytically cleaved by a metalloprotease and released to the extracellular milieu. The immunotherapeutic potential of LIGHT blockade was evaluated in vivo. Administration of an antagonist of LIGHT interaction with its receptors attenuated the course of graft-versus-host reaction and recapitulated the reduced cytotoxic activity of LIGHT-deficient T cells adoptively transferred into non-irradiated semiallogeneic recipients. The lack of LIGHT expression on donor T cells or blockade of LIGHT interaction with its receptors slowed down the rate of T cell proliferation and decreased the frequency of precursor alloreactive T cells, retarding T cell differentiation toward effector T cells. The blockade of LIGHT/LTβR/HVEM pathway was associated with delayed downregulation of interleukin-7Rα and delayed upregulation of inducible costimulatory molecule expression on donor alloreactive CD8 T cells that are typical features of impaired T cell differentiation. These results expose the relevance of LIGHT/LTβR/HVEM interaction for the potential therapeutic control of the allogeneic immune responses mediated by alloreactive CD8 T cells that can contribute to prolong allograft survival.

Towards automated specifications of scenarios in enhanced learning technology

Recent standardization efforts in e-learning technology have resulted in a number of specifications, however, the automation process that is considered essential in a learning management system (LMS) is a lessexplored one. As learning technology becomes more widespread and more heterogeneous, there is a growing need to specify processes that cross the boundaries of a single LMS or learning resource repository. This article proposes to obtain a specification orientated to automation that takes on board the heterogeneity of systems and formats and provides a language for specifying complex and generic interactions. Having this goal in mind, a technique based on three steps is suggested. The semantic conformance profiles, the business process management (BPM) diagram, and its translation into the business process execution language (BPEL) seem to be suitable for achieving it.

Negative Regulation of Receptor Tyrosine Kinases by T-cell Protein Tyrosine Phosphatase

Protein tyrosine phosphorylation controls a wide array of cellular responses such as growth, migration, proliferation, differentiation, metabolism and cytoskeletal organisation. Tyrosine phosphorylation is a dynamic process involving the competing activities of protein tyrosine kinases and protein tyrosine phosphatases. The protein tyrosine kinases are further divided into non-receptor- and receptor tyrosine kinases. The latter are transmembrane glycoproteins activated by the binding of specific ligands, mostly growth factors, to their extracellular domain, transmitting different signals to the cell. Growth factor receptors such as the epidermal growth factor receptor, vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor β, belong to the receptor tyrosine kinases, the signalling of which is often disturbed in various diseases, including cancer. This has led to the development of receptor tyrosine kinase antagonists for use as anti-cancer drugs. As the receptor tyrosine kinases, also the protein tyrosine phosphatases can be divided into receptor- and non-receptor types. The protein tyrosine phosphatases have attained much less attention than the receptor tyrosine kinases partly because they were identified later. However, accumulating evidence shows that the protein tyrosine phosphatases have important roles as specific and active regulators of tyrosine phosphorylation in cells and of physiological processes. Consequently, the protein tyrosine phosphatases are receiving arising interest as novel drug targets. The aim of this work was to elucidate the negative regulation of receptor tyrosine kinases by one non-receptor protein tyrosine phosphatase, T-cell protein tyrosine phosphatase TCPTP. The results show that TCPTP activated by cell adhesion receptor integrin α1 functions as a negative regulator of the epidermal growth factor receptor. It was also found that TCPTP affects vascular endothelial growth factor receptor 2 signalling and angiogenesis. Lastly, a High-throughput screen with 64,280 compounds was performed to identify novel TCPTP activators, resulting in identification of one small molecule compound capable of exerting similar effects on TCPTP signalling as integrin α1. This compound is shown to downregulate signalling of epidermal growth factor receptor and platelet-derived growth factor receptor β, as well as to inhibit cell proliferation and angiogenesis. Our results suggest that a suitable small-molecule TCPTP activator could be utilized in the development of novel anti-cancer drugs.