Inhibition of bicarbonate transport protects embryonic heart against reoxygenation-induced dysfunction.

It has not been well established whether the mechanisms participating in pH regulation in the anoxic-reoxygenated developing myocardium resemble those operating in the adult. We have specially examined the importance of Na+/H+ exchange (NHE) and HCO3-dependent transports in cardiac activity after changes in extracellular pH (pHo). Spontaneously contracting hearts isolated from 4-day-old chick embryos were submitted to single or repeated anoxia (1 min) followed by reoxygenation (10 min). The chronotropic, dromotropic and inotropic responses of the hearts were determined in standard HCO3- buffer at pHo 7.4 and at pHo 6.5 (hypercapnic acidosis). In distinct experiments, acidotic anoxia preceded reoxygenation at pHo 7.4. NHE was blocked with amiloride derivative HMA (1 micro mol/l) and HCO3-dependent transports were inactivated by replacement of HCO3 or blockade with stilbene derivative DIDS (100 micro mol/l). Anoxia caused transient tachycardia, depressed mechanical function and induced contracture. Reoxygenation temporarily provoked cardiac arrest, atrio-ventricular (AV) block, arrhythmias and depression of contractility. Addition of DIDS or substitution of HCO3 at pHo 7.4 had the same effects as acidosis per se, i.e. shortened contractile activity and increased incidence of arrhythmias during anoxia, prolonged cardioplegia and provoked arrhythmias at reoxygenation. Under anoxia at pHo 6.5/reoxygenation at pHo 7.4, cardioplegia, AV block and arrhythmias were all markedly prolonged. Interestingly, in the latter protocol, DIDS suppressed AV block and arrhythmias during reoxygenation, whereas HMA had no effect. Thus, intracellular pH regulation in the anoxic-reoxygenated embryonic heart appears to depend predominantly on HCO3 availability and transport. Furthermore, pharmacological inhibition of anion transport can protect against reoxygenation-induced dysfunction.

Survival of zirconia- and metal-supported fixed dental prostheses: a systematic review

Purpose: The aim of this review was to systematically evaluate and compare the frequency of veneer chipping and core fracture of zirconia fixed dental prostheses (FOPS) and porcelain-fused-to-metal (PFM) FDPs and determine possible influencing factors. Materials and Methods: The SCOPUS database and International Association of Dental Research abstracts were searched for clinical studies involving zirconia and PFM FDPs. Furthermore, studies that were integrated into systematic reviews on PFM FDPs were also evaluated. The principle investigators of any clinical studies on zirconia FDPs were contacted to provide additional information. Based on the available information for each FOP, a data file was constructed. Veneer chipping was divided into three grades (grade 1 = polishing, grade 2 = repair, grade 3 = replacement). To assess the frequency of veneer chipping and possible influencing factors, a piecewise exponential model was used to adjust for a study effect. Results: None of the studies on PFM FDPs (reviews and additional searching) sufficiently satisfied the criteria of this review to be included. Thirteen clinical studies on zirconia FDPs and two studies that investigated both zirconia and PFM FDPs were identified. These studies involved 664 zirconia and 134 PFM FDPs at baseline. Follow-up data were available for 595 zirconia and 127 PFM FDPs. The mean observation period was approximately 3 years for both groups. The frequency of core fracture was less than 1% in the zirconia group and 0% in the PFM group. When all studies were included, 142 veneer chippings were recorded for zirconia FDPs (24%) and 43 for PFM FDPs (34%). However, the studies differed extensively with regard to veneer chipping of zirconia: 85% of all chippings occurred in 4 studies, and 43% of all chippings included zirconia FDPs. If only studies that evaluated both types of core materials were included, the frequency of chipping was 54% for the zirconia-supported FDPs and 34% for PFM FDPs. When adjusting the survival rate for the study effect, the difference between zirconia and PFM FDPs was statistically significant for all grades of chippings (P = .001), as well as for chipping grade 3 (P = .02). If all grades of veneer chippings were taken into account, the survival of PFM FDPs was 97%, while the survival rate of the zirconia FDPs was 90% after 3 years for a typical study. For both PFM and zirconia FDPs, the frequency of grades 1 and 2 veneer chippings was considerably higher than grade 3. Veneer chipping was significantly less frequent in pressed materials than in hand-layered materials, both for zirconia and PFM FDPs (P = .04). Conclusions: Since the frequency of veneer chipping was significantly higher in the zirconia FDPs than PFM FDPs, and as refined processing procedures have started to yield better results in the laboratory, new clinical studies with these new procedures must confirm whether the frequency of veneer chipping can be reduced to the level of PFM. Int J Prosthodont 2010;23:493-502

Elevated hepatocyte paraffin 1 and neprilysin expression in hepatocellular carcinoma are correlated with longer survival

Résumé de l'article Le carcinome hépatocellulaire reste une tumeur maligne de mauvais pronostic. Le but de cette étude rétrospective est d'étudier l'expression immunohistochimique semi-quantitative d'Hep Par 1 (hepatocyte paraffin 1) et de CD 10 (CALLA ou neprilysin) et leur valeur pronostique sur un collectif de 97 patients avec un carcinome hépatocellulaire traité à visée curative. Hep Par 1 réagit avec un épitope spécifique de l'hépatocyte au niveau de la membrane mitochondriale et se présente sous forme d'un marquage cytoplasmique diffus d'intensité variable, le foie non tumoral exprimant un marquage granulaire servant de contrôle interne positif. Le CD 10 correspond ä une metallopeptidase de la membrane cellulaire participant au processus de sécrétion hormonale et l'immunoréaction colore spécifiquement la portion luminale des canalicules biliaires du foie non tumoral, qui sert ainsi de contrôle interne positif. Le foie tumoral exprime ou non un marquage canaliculaire (CD 10 can), similaire au foie non tumoral, ou cytoplasmique (CD 10 cyt). Le marquage immunohistochimique est quantifié pour les 3 différents marqueurs (Hep Par 1, CD10 can et CD10 cyt) en fonction du pourcentage de cellules tumorales positives (score de 0 à 3 établi pour chaque marqueur immunohistochimique). L'élaboration d'un score combiné immunohistochimique (CIS) est obtenu en additionnant les scores d'Hep Par 1 et de CD10 con et en soustrayant le score de CD10 cyt. Dans l'analyse univariée, la survie globale des patients est prolongée de manière significative en cas de forte expression tumorale par Hep Par 1 (p=0,0005) et CD10 can (p=0,02). Dans l'analyse multivariée, la combinaison du CIS avec les autres paramètres histopathologiques pronostiques classiques du carcinome hépatocellulaire comme la taille tumorale, l'invasion vasculaire, la multifocalité de la tumeur et le grade tumoral montre que le score immunohistochimique combiné (CIS) reste le facteur pronostique le plus important (p=0,001). Les patients avec un CIS bas (<4) avec une survie moyenne de 17 mois ont 3,5 fois plus de risque de décès comparés à ceux avec un CIS élevé (>4) avec une survie moyenne de plus de 80 mois. En conclusion, une expression immunohistochimique élevée d'Hep Par 1 et de CD10 can en l'absence d'expression de CD10 cyt sont des facteurs pronostiques favorables pour les patients présentant un carcinome hépatocellulaire. La combinaison des marqueurs immunohistochimiques dans un score combiné pourrait être utilisé dans la prise en charge des patients avec un hépatocarcinome àvisée curative. Toutefois des études prospectives restent nécessaires pour confirmer l'utilité pronostique du CIS.

The JAK2/STAT3 pathway in the embryonic chick heart submitted to anoxia, reoxygenation and oxidant stress

SUMMARYAim: The embryonic/fetal heart is highly sensitive to oxygenation level and a transient uteroplacental hypoperfusion can lead to oxyradicals overproduction. Information about the molecular mechanisms underlying ischemia-reperfusion (I-R) injury in the developing heart is lacking. The Janus Kinase 2 / Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway, required for cardiogenesis and involved in protection of the adult heart against I-R, could also play a key role in the response of the fetal myocardium to transient oxygen deprivation. The aim of the study was to characterize the involvement of JAK2/STAT3 pathway and its interaction with other signalling pathways in the developing heart transiently submitted to anoxia. Furthermore, the response of the embryonic heart to an exogenous oxidant stress (H2O2) in comparison to reoxygenation-induced endogenous oxyradicals has been investigated.Methods: Hearts isolated from 4-day-old chick embryos were submitted to anoxia (30min) and reoxygenation (80min) with or without the antioxidant MPG, the JAK2/STAT3 inhibitor AG490 or exposed to H202 (50|iM-lmM). The time course of phosphorylation of STAT3atyr0Sine7 and Reperfusion Injury Salvage Kinase (RISK) proteins (PI3K, Akt, GSK3B, Glycogen Synthase and ERK2) was determined in homogenate" and in enriched nuclear and cytoplasmic fractions. The STAT3 DNA-binding was determined by EMSA and the expression of STAT3 specific target genes by RT-PCR. The chrono-, dromo- and inotropic disturbances were also investigated by ECG and mechanical recordings.Results: Phosphorylation of STATSaP (P-Tyr STAT3a) was increased by reoxygenation and reduced by MPG or AG490. STAT3 and GSK36 were detected both in nuclear and cytoplasmic fractions while PI3K, Akt, GS and ERK2 were restricted to cytoplasm. Reoxygenation led to nuclear accumulation of STAT3 but unexpectedly without DNA- binding. AG490 decreased the reoxygenation-induced phosphorylation of STABa^, Akt, GS and ERK2 and phosphorylation/inhibition of GSK3B in the nucleus, exclusively. Inhibition of JAK2/STAT3 delayed recovery of atrial rate, worsened RR. variability and prolonged arrhythmias compared to control hearts. Cardiac activity was altered only at concentrations >500μΜ of H2O2. Moreover, ImM of H2O2 suppressed atrial activity in 45% of the hearts, atrioventricular conduction in 66% and augmented P-Tyr STAT3awhich led to an increase in the DNA-binding but no change in the expression of three STAT3 specific target genes (iNOS, MnSOD, Cox-2).Conclusion: In the developing heart, besides its nuclear translocation without transcriptional activity, ROS-activated STAT3a can rapidly interact with RISK proteins present in nucleus and cytoplasm and reduce the anoxia-reoxygenation-induced arrhythmias. Moreover, the embryonic heart is highly resistant to H2O2 and the atrial region is the less affected. The role of JAK2/STAT3 in the response to reoxygenation-induced oxyradicals is different from the response to strong exogenous oxidant stress where STAT3 DNA-binding activity is increased. Such findings provide a first step in understanding the modulation of signalling cascades in the fetal heart submitted to transient intrauterine oxygen deprivation.RESUMEIntroduction: Le coeur embryonnaire et foetal est très sensible au manque d'oxygène et une hypoperfusion utéroplacentaire transitoire peut conduire à une surproduction d'espèces radicalaires (ROS). Dans le coeur en développement les mécanismes moléculaires impliqués en situation d'ischémie-reperfusion (I-R) ne sont pas connus. La voie de signalisation JAK2/STAT3 (Janus Kinase 2 / Signal Transducer and Activator of Transcription 3), impliquée aussi bien dans la cardiogenèse précoce que dans la protection du coeur adulte contre l'I-R, pourrait jouer un rôle clé dans la réponse du myocarde foetal à un déficit en oxygène. Cette étude a permis d'étudier le rôle de la voie JAK2/STAT3 et son interaction avec d'autres voies de signalisation dans un modèle de coeur embryonnaire soumis à un épisode anoxique. En outre, les effets du stress oxydant endogène provoqué par la réoxygénation ont été comparés à ceux du stress oxydatif exogène induit par du peroxyde d'hydrogène (H2O2).Méthodes: Des coeurs isolés d'embryons de poulet âgés de 4 jours ont été soumis à une anoxie (30min) suivie d'une réoxygénation (80min) en présence ou non de l'antioxydant MPG et de l'inhibiteur de JAK2/STAT3 AG490 ou exposés à de 1Ή202 (50μΜ-1πιΜ). L'évolution temporelle de la phosphorylation de 8ΤΑΤ3α*ΓΟδίη6705 (P-Tyr STAT3a) et celle de la phosphorylation des protéines de la voie RISK (Reperfusion Injury Salvage Kinase: PI3K, Akt, GSK3B, glycogène synthase GS et ERK2) ont été déterminés dans l'homogénat et dans les fractions nucléaire et cytopiasmique du myocarde. La liaison de STAT3 à l'ADN a été déterminée par EMSA et l'expression de gènes cibles de STAT3 (iNOS, MnSOD, Cox2) par RT-PCR. Les effets chrono-, dromo- et inotropes ont été déterminés par les enregistrements de l'ECG et de l'activité contractile ventriculaire.Résultats: STAT3 et GSK3B étaient présents dans les fractions nucléaire et cytopiasmique tandis que PI3K, Akt, GS et ERK2 n'étaient détectées que dans la fraction cytopiasmique. L'augmentation de P-Tyr STAT3a provoquée par la réoxygénation était significativement réduite par le MPG ou PAG490. La réoxygénation entraînait l'accumulation nucléaire de STAT3, mais étonnamment sans liaison avec l'ADN. A la réoxygénation TAG490 diminuait la phosphorylation d'Akt, GS et ERK2 ainsi que celle de GSK36 mais exclusivement dans la fraction nucléaire. L'inhibition de JAK2/STAT3 retardait également la récupération du rythme cardiaque et prolongeait la durée des arythmies. L'activité cardiaque n'était perturbée par de ΓΗ2Ο2 qu'à des concentrations >500μΜ. A ImM, ΓΗ2Ο2 supprimait l'activité auriculaire dans 45% des coeurs et la conduction auriculo-ventriculaire dans 66% et augmentait la formation de P-Tyr STAT3a et sa liaison à l'ADN sans modifier l'expression des gènes cibles.Conclusion: Les ROS produits par l'anoxie-réoxygénation activent STAT3a qui subit une translocation dans le noyau sans se lier à l'ADN et interagit rapidement avec des protéines de la voie RISK dans les compartiments nucléaire et cytopiasmique du coeur embryonnaire. Ce dernier, en particulier au niveau des oreillettes, se révèle très résistant au puissant stress oxydatif de l'H202 qui se différencie du stress lié à la réoxygénation en favorisant la liaison de STAT3 à l'ADN. Ces résultats originaux permettent une meilleure compréhension des mécanismes qui peuvent améliorer la récupération du coeur en développement après un épisode hypoxique intra-utérin.

Derivation of traceable and transplantable photoreceptors from mouse embryonic stem cells.

Retinal degenerative diseases resulting in the loss of photoreceptors are one of the major causes of blindness. Photoreceptor replacement therapy is a promising treatment because the transplantation of retina-derived photoreceptors can be applied now to different murine retinopathies to restore visual function. To have an unlimited source of photoreceptors, we derived a transgenic embryonic stem cell (ESC) line in which the Crx-GFP transgene is expressed in photoreceptors and assessed the capacity of a 3D culture protocol to produce integration-competent photoreceptors. This culture system allows the production of a large number of photoreceptors recapitulating the in vivo development. After transplantation, integrated cells showed the typical morphology of mature rods bearing external segments and ribbon synapses. We conclude that a 3D protocol coupled with ESCs provides a safe and renewable source of photoreceptors displaying a development and transplantation competence comparable to photoreceptors from age-matched retinas.

The direct effects of tacrolimus and cyclosporin A on isolated human islets: A functional, survival and gene expression study.

The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to β-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of isolated human islets to therapeutical levels of tacrolimus (Tac) or cyclosporin A (CsA). Islets were isolated from the pancreas of multiorgan donors by enzymatic digestion and density gradient centrifugation. Functional, survival and molecular studies were then performed after 4 days of incubation with therapeutical concentrations of Tac or  CsA. Glucose-induced insulin secretion was significantly decreased in Tac, but not in CsA exposed islets, which was associated with a reduction of the amount of insulin granules as shown by electron microscopy. The percentage of apoptotic β-cells was higher in Tac than CsA exposed islets. Microarray experiments followed by Gene Set Enrichment Analysis revealed that gene expression was more markedly affected upon Tac treatment. In conclusion, Tac and CsA affect features of beta-cell differently, with several changes occurring at the molecular level.

Homeostatic proliferation and survival of naïve and memory T cells.

The immune system relies on homeostatic mechanisms in order to adapt to the changing requirements encountered during steady-state existence and activation by antigen. For T cells, this involves maintenance of a diverse repertoire of naïve cells, rapid elimination of effector cells after pathogen clearance, and long-term survival of memory cells. The reduction of T-cell counts by either cytotoxic drugs, irradiation, or certain viruses is known to lead to lymphopenia-induced proliferation and restoration of normal T-cell levels. Such expansion is governed by the interaction of TCR with self-peptide/MHC (p/MHC) molecules plus contact with cytokines, especially IL-7. These same ligands, i.e. p/MHC molecules and IL-7, maintain naïve T lymphocytes as resting cells under steady-state T-cell-sufficient conditions. Unlike naïve cells, typical "central" memory T cells rely on a combination of IL-7 and IL-15 for their survival in interphase and for occasional cell division without requiring signals from p/MHC molecules. Other memory T-cell subsets are less quiescent and include naturally occurring activated memory-phenotype cells, memory cells generated during chronic viral infections, and effector memory cells. These subsets of activated memory cells differ from central memory T cells in their requirements for homeostatic proliferation and survival. Thus, the factors controlling T-cell homeostasis can be seen to vary considerably from one subset to another as described in detail in this review.

The role of smoking in changes in the survival curve: an empirical study in 10 European countries.

PURPOSE: We examined the role of smoking in the two dimensions behind the time trends in adult mortality in European countries, that is, rectangularization of the survival curve (mortality compression) and longevity extension (increase in the age-at-death). METHODS: Using data on national sex-specific populations aged 50 years and older from Denmark, Finland, France, West Germany, Italy, the Netherlands, Norway, Sweden, Switzerland, and the United Kingdom, we studied trends in life expectancy, rectangularity, and longevity from 1950 to 2009 for both all-cause and nonsmoking-related mortality and correlated them with trends in lifetime smoking prevalence. RESULTS: For all-cause mortality, rectangularization accelerated around 1980 among men in all the countries studied, and more recently among women in Denmark and the United Kingdom. Trends in lifetime smoking prevalence correlated negatively with both rectangularization and longevity extension, but more negatively with rectangularization. For nonsmoking-related mortality, rectangularization among men did not accelerate around 1980. Among women, the differences between all-cause mortality and nonsmoking-related mortality were small, but larger for rectangularization than for longevity extension. Rectangularization contributed less to the increase in life expectancy than longevity extension, especially for nonsmoking-related mortality among men. CONCLUSIONS: Smoking affects rectangularization more than longevity extension, both among men and women.

Global surveillance of cancer survival 1995-2009 : analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75 000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems. FUNDING: Canadian Partnership Against Cancer (Toronto, Canada), Cancer Focus Northern Ireland (Belfast, UK), Cancer Institute New South Wales (Sydney, Australia), Cancer Research UK (London, UK), Centers for Disease Control and Prevention (Atlanta, GA, USA), Swiss Re (London, UK), Swiss Cancer Research foundation (Bern, Switzerland), Swiss Cancer League (Bern, Switzerland), and University of Kentucky (Lexington, KY, USA).

Meckel-Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe.

Meckel-Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11-36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.

Extensive microRNA-mediated crosstalk between lncRNAs and mRNAs in mouse embryonic stem cells.

Recently, a handful of intergenic long noncoding RNAs (lncRNAs) have been shown to compete with mRNAs for binding to miRNAs and to contribute to development and disease. Beyond these reports, little is yet known of the extent and functional consequences of miRNA-mediated regulation of mRNA levels by lncRNAs. To gain further insight into lncRNA-mRNA miRNA-mediated crosstalk, we reanalyzed transcriptome-wide changes induced by the targeted knockdown of over 100 lncRNA transcripts in mouse embryonic stem cells (mESCs). We predicted that, on average, almost one-fifth of the transcript level changes induced by lncRNAs are dependent on miRNAs that are highly abundant in mESCs. We validated these findings experimentally by temporally profiling transcriptome-wide changes in gene expression following the loss of miRNA biogenesis in mESCs. Following the depletion of miRNAs, we found that >50% of lncRNAs and their miRNA-dependent mRNA targets were up-regulated coordinately, consistent with their interaction being miRNA-mediated. These lncRNAs are preferentially located in the cytoplasm, and the response elements for miRNAs they share with their targets have been preserved in mammals by purifying selection. Lastly, miRNA-dependent mRNA targets of each lncRNA tended to share common biological functions. Post-transcriptional miRNA-mediated crosstalk between lncRNAs and mRNA, in mESCs, is thus surprisingly prevalent, conserved in mammals, and likely to contribute to critical developmental processes.

Survival after surgical drainage of malignant pericardial effusion.

OBJECTIVES: Management of malignant pericardial effusion (PE) is complex. Cardiac surgeons are not necessarily familiar with or are challenged by the many underlying etiologies. Analyzing risk factors for mortality may help to estimate the benefit of surgery in high-risk patients. METHODS: Patients undergoing a surgical pericardiotomy for malignant PE, between 2001 and 2011, were included. The influence of tumor type, disease extension, intra-pericardial tumor infiltration on early mortality and long-term survival as well as freedom from symptoms after drainage, and the use of sclerosing agents on PE recurrence rates was analyzed. RESULTS: PE drainage was performed on 46 patients 12 ± 30 months after tumor diagnosis. Malignant diseases were lung cancers (50 %), breast cancers (15 %), lymphoma and leukemia (13 %), cancers of the digestive tract (13 %), and others (9 %). 80 % of patients were symptomatic and symptom relief was achieved in 65 %. Nobody died during surgery. Recurrence rate was 4 %. Early in-hospital mortality was 22 %. After 1 year, 29 % of patients were alive. Eleven patients (24 %) had a complete tumor regression. Metastatic spread (p < 0.001), pericardial infiltration (p = 0.02), and intra-pericardial Bleomycin (p = 0.01) injection were associated with increased mortality. Hematological malignancies had a better prognosis for survival. CONCLUSION: Surgical pericardiotomy is safe, associated with a low recurrence rate and symptom relief in the majority of dyspneic patients. Intra-pericardial Bleomycin may reduce recurrent effusion but does not ameliorate survival. Long-term survival rate was low with an increased mortality in cases of metastatic spreading, pericardial infiltration, and as the tumor of origin: breast cancers. Leukemic and lymphatic tumors have better prognosis.