bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asxl1 deficiency in embryonic fibroblasts leads to cellular senescence via impairment of the AKT-E2F pathway and Ezh2 inactivation
Authors: Youn Hye Sook , Kim Tae-Yoon , Park Ui-Hyun , Moon Seung-Tae , An So-Jung , Lee Yong-Kyu , Hwang Jin-Taek , Kim Eun-Joo , Um Soo-Jong 
Published: July 2017

AbstractAlthough ASXL1 mutations are frequently found in human diseases, including myeloid leukemia, the cell proliferation–associated function of ASXL1 is largely unknown. Here, we explored the molecular mechanism underlying the growth defect found in Asxl1-deficient mouse embryonic fibroblasts (MEFs). We found that Asxl1, through amino acids 371 to 655, interacts with the kinase domain of AKT1. In Asxl1-null MEFs, IGF-1 was unable to induce AKT1 phosphorylation and activation; p27Kip1, which forms a ternary complex with ASXL1 and AKT1, therefore remained unphosphorylated. Hypophosphorylated p27Kip1 is able to enter the nucleus, where it prevents the phosphorylation of Rb; this ultimately leads to the down-regulation of E2F target genes as confirmed by microarray analysis. We also found that senescence-associated (SA) genes were upregulated and that SA β-gal staining was increased in Asxl1−/− MEFs. Further, the treatment of an AKT inhibitor not only stimulated nuclear accumulation of p27Kip1 leading to E2F inactivation, but also promoted senescence. Finally, Asxl1 disruption augmented the expression of p16Ink4a as result of the defect in Asxl1-Ezh2 cooperation. Overall, our study provides the first evidence that Asxl1 both activates the AKT-E2F pathway and cooperates with Ezh2 through direct interactions at early embryonic stages, reflecting that Asxl1 disruption causes cellular senescence.
Clostridium perfringens α-toxin impairs erythropoiesis by inhibition of erythroid differentiation
Authors: Takagishi Teruhisa , Takehara Masaya , Seike Soshi , Miyamoto Kazuaki , Kobayashi Keiko , Nagahama Masahiro 
Published: July 2017

AbstractClostridium perfringens α-toxin induces hemolysis of erythrocytes from various species, but it has not been elucidated whether the toxin affects erythropoiesis. In this study, we treated bone marrow cells (BMCs) from mice with purified α-toxin and found that TER119+ erythroblasts were greatly decreased by the treatment. A variant α-toxin defective in enzymatic activities, phospholipase C and sphingomyelinase, had no effect on the population of erythroblasts, demonstrating that the decrease in erythroblasts was dependent of its enzymatic activities. α-Toxin reduced the CD71+TER119+ and CD71–TER119+ cell populations but not the CD71+TER119− cell population. In addition, α-toxin decreased the number of colony-forming unit erythroid colonies but not burst-forming unit erythroid colonies, indicating that α-toxin preferentially reduced mature erythroid cells compared with immature cells. α-Toxin slightly increased annexinV+ cells in TER119+ cells. Additionally, simultaneous treatment of BMCs with α-toxin and erythropoietin greatly attenuated the reduction of TER119+ erythroblasts by α-toxin. Furthermore, hemin-induced differentiation of human K562 erythroleukemia cells was impaired by α-toxin, whereas the treatment exhibited no apparent cytotoxicity. These results suggested that α-toxin mainly inhibited erythroid differentiation. Together, our results provide new insights into the biological activities of α-toxin, which might be important to understand the pathogenesis of C. perfringens infection.
Alpha Power Predicts Persistence of Bistable Perception
Authors: Piantoni Giovanni , Romeijn Nico , Gomez-Herrero German , Van Der Werf Ysbrand D. , Van Someren Eus J. W. 
Published: July 2017

AbstractPerception is strongly affected by the intrinsic state of the brain, which controls the propensity to either maintain a particular perceptual interpretation or switch to another. To understand the mechanisms underlying the spontaneous drive of the brain to explore alternative interpretations of unchanging stimuli, we repeatedly recorded high-density EEG after normal sleep and after sleep deprivation while participants observed a Necker cube image and reported the durations of the alternating representations of their bistable perception. We found that local alpha power around the parieto-occipital sulcus within the first second after the emergence of a perceptual representation predicted the fate of its duration. An experimentally induced increase in alpha power by means of sleep deprivation increased the average duration of individual representations. Taken together, these findings show that high alpha power promotes the stability of a perceptual representation and suppresses switching to the alternative. The observations support the hypothesis that synchronization of alpha oscillations across a wide neuronal network promotes the maintenance and stabilization of its current perceptual representation. Elevated alpha power could also be key to the poorly understood cognitive deficits, that typically accompany sleep deprivation, such as the loss of mental flexibility and lapses of responsiveness.
Early intervention with Bifidobacterium lactis NCC2818 modulates the host-microbe interface independent of the sustained changes induced by the neonatal environment
Authors: Lewis Marie C. , Merrifield Claire A. , Berger Bernard , Cloarec Olivier , Duncker Swantje , Mercenier Annick , Nicholson Jeremy K. , Holmes Elaine , Bailey Mick 
Published: July 2017

AbstractInflammatory and metabolic diseases can originate during early-life and have been correlated with shifts in intestinal microbial ecology. Here we demonstrate that minor environmental fluctuations during the early neonatal period had sustained effects on the developing porcine microbiota and host-microbe interface. These inter-replicate effects appear to originate during the first day of life, and are likely to reflect very early microbiota acquisition from the environment. We statistically link early systemic inflammation with later local increases in inflammatory cytokine (IL-17) production, which could have important enteric health implications. Immunity, intestinal barrier function, host metabolism and host-microbiota co-metabolism were further modified by Bifidobacterium lactis NCC2818 supplementation, although composition of the in situ microbiota remained unchanged. Finally, our robust model identified novel, strong correlations between urinary metabolites (eg malonate, phenylacetylglycine, alanine) and mucosal immunoglobulin (IgM) and cytokine (IL-10, IL-4) production, thus providing the possibility of the development of urinary ‘dipstick’ tests to assess non-accessible mucosal immune development and identify early precursors (biomarkers) of disease. These results have important implications for infants exposed to neonatal factors including caesarean delivery, antibiotic therapy and delayed discharge from hospital environments, which may predispose to the development of inflammatory and metabolic diseases in later life.
The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells
Authors: Muluhngwi Penn , Alizadeh-Rad Negin , Vittitow Stephany L. , Kalbfleisch Ted S. , Klinge Carolyn M. 
Published: July 2017

AbstractAberrant microRNA expression contributes to breast cancer progression and endocrine resistance. We reported that although tamoxifen stimulated miR-29b-1/a transcription in tamoxifen (TAM)-resistant breast cancer cells, ectopic expression of miR-29b-1/a did not drive TAM-resistance in MCF-7 breast cancer cells. However, miR-29b-1/a overexpression significantly repressed TAM-resistant LCC9 cell proliferation, suggesting that miR-29b-1/a is not mediating TAM resistance but acts as a tumor suppressor in TAM-resistant cells. The target genes mediating this tumor suppressor activity were unknown. Here, we identify miR-29b-1 and miR-29a target transcripts in both MCF-7 and LCC9 cells. We find that miR-29b-1 and miR-29a regulate common and unique transcripts in each cell line. The cell-specific and common downregulated genes were characterized using the MetaCore Gene Ontology (GO) enrichment analysis algorithm. LCC9-sepecific miR-29b-1/a-regulated GO processes include oxidative phosphorylation, ATP metabolism, and apoptosis. Extracellular flux analysis of cells transfected with anti- or pre- miR-29a confirmed that miR-29a inhibits mitochondrial bioenergetics in LCC9 cells. qPCR,luciferase reporter assays, and western blot also verified the ATP synthase subunit genes ATP5G1 and ATPIF1 as bone fide miR29b-1/a targets. Our results suggest that miR-29 repression of TAM-resistant breast cancer cell proliferation is mediated in part through repression of genes important in mitochondrial bioenergetics.
The Effect of Clinical Experience on the Learning Curve of Pediatric Intensive Care Unit Residents for the Central Venous Catheter Placement Procedure
Authors: Abe Michiko , Matsumoto Shotaro , Nishimura Nao , Nakagawa Satoshi , Tsuboi Norihiko 
Published: July 2017

AbstractThe objective of this study is to ascertain the effect of clinical experience on pediatric intensive care unit (PICU) residents' learning curve for central venous catheter placement in critically ill children. It was a 58-month retrospective observational study. The setting was multivalent PICU with 20 beds at a tertiary children's hospital. The subjects were PICU residents undergoing training in central venous catheter placement. During the study period, 22 residents were enrolled in the study, and 1,157 catheter placement procedures (485 central venous, 605 peripherally inserted central venous, 57 hemodialysis, and 10 “other” types of catheter placement procedures) were analyzed. The total success rate was 82.7%. After ultrasound-guided training simulation in catheter placement, the residents' learning curve for the procedure rose from 71% in the clinical setting at the first trial to 75% at the fourth trial and 80% by the 24th trial. Significant positive correlation was found between procedure success and number of trials with a Spearman coefficient (p  <  0.019). Adequate clinical experiences were necessary for PICU residents to achieve competency in central venous catheter placement in critically ill children.
C1-C4 Dorsal Column Stimulation for Refractory Occipital Neuralgia Treatment. Case Report
Authors: Malheiros José , Cancado Sergio , Oliveira Célia , Santos Wancler 
Published: July 2017

Introduction Refractory occipital neuralgia is a difficult medical condition, especially when the patient has already been submitted to occipital nerve neurectomy and radiofrequency rhizotomy. There is no case report of spinal cord stimulation in the C1-C4 cervical segments for this condition.
Objective To evaluate if C1-C4 dorsal spinal cord stimulation is effective in a patient with refractory occipital neuralgia who was already submitted to neurectomy and rhizotomy.
Methods After obtaining the approval from the Ethics Committee of one of our institutions, a unilateral laminectomy was performed between C3 and C4, and a neurostimulator lead was conducted until the posterior portion of the C1 arc was in full view. Then we performed an intraoperative test to evaluate the correspondence between pain location and stimulation-induced paresthesias. We could not put the subcutaneous lead for such condition because of the scar tissue of the area and the previous neurectomy.
Results After one year of follow up, we noticed a dramatic improvement in pain control, as well as medication withdrawal. The score of the visual analogue scale was 9 before the surgery, and it dropped to 2 after 1 year of follow-up.
Conclusion Spinal cord stimulation between the C1 and C4 cervical segments can be an option for selected cases of refractory occipital neuralgia, including those patients who have already been submitted to neurectomy or rhizotomy.
Netzwerk 40+: Vernetzung von Sucht- und Altenhilfe zur Versorgung älterer Drogengebraucher
Authors: Schäffler Florian , Thym Monika , Stubican Davor , Bolz Manuela , Braasch Sylvia , Körner Ulrich , Kolb Gudrun , Fuhrmann Klaus 
Published: July 2017

ZusammenfassungZiel des Projekts war es, den Anteil von Klientel mit Doppelbelastung (altersassoziierte Problemlagen in der Suchthilfe, Sucht in der Altenhilfe) zu ermitteln sowie die Bedarfe von Mitarbeitenden beider Hilfesysteme zu eruieren.Hierzu sind zunächst 7 explorative Experteninterviews geführt worden, deren Ergebnisse sodann Grundlage für die Entwicklung zweier elektronischer Erhebungsinstrumente waren. Die so konstruierten Fragebögen wurden im Rahmen einer quantitativen Querschnittsstudie an einem Stichtag per Email an die Mitarbeitenden der Münchner Sucht- und Altenhilfe versendet.Im Rahmen beider Untersuchungsschritte wurde insbesondere deutlich, dass das Thema Alter bzw. Pflegebedürftigkeit und der Konsum illegaler Drogen bislang in der Suchthilfe eine deutlich größere Bedeutung erfährt als in der Altenhilfe. Im Rahmen der Fragebogenerhebung zeigte sich zudem ein in beiden Hilfesystemen bestehender Bedarf an gegenseitigem Austausch und wechselseitiger Unterstützung sowie Interesse an Informationen und Fortbildungen. Das bisherige Regularium der Substitutionsbehandlung wurde in beiden Hilfesystemen als Problem benannt.Aufgrund geringer Fallzahlen von Drogenkonsumenten im Altenhilfesystem ist derzeit (noch) davon auszugehen, dass die Thematik „Abhängigkeit von illegalen Substanzen“ dort nicht explizit, sondern höchstens im Kontext legaler Drogen aufgegriffen wird. Nachdem die Zielgruppe somit auch weiterhin schwerpunktmäßig in der Suchthilfe betreut werden wird, sind Fortbildungsangebote zu alters- und pflegerelevanten Themen, sowie der Ausbau bedarfsgerechter Versorgungskonzepte (z. B. Betreute Wohnangebote für ältere Süchtige) überfällig.
Akupressur in der Palliativmedizin
Authors: Wellens-Mücher Dorothee 
Published: July 2017

SummaryDie Akupressur ist eine einfach erlernbare Methode, die auch von Nichtmedizinern ausgeführt werden kann. Daher kann sie häufiger und unproblematischer eingesetzt werden als die Akupunktur. Die Wirkung der Stimulation von Reizpunkten auf die unterschiedlichsten Krankheitssymptome wird mit der Regulation des Qi erklärt.Der Beitrag stellt einfache Punktkombinationen vor, die häufige Symptome bei Patienten in palliativen Situation lindern können. Fälle aus der Praxis exemplifizieren die Anwendungsmöglichkeiten.
Bestens ausgerüstet
Authors: Büchi Katharina , Tyndall Rahel , Weibel Lukas , Imhof Romy Mahrer 
Published: July 2017

Zusammenfassung
APN in der Intensivpflege Die komplexe Versorgung und die häufige Multimorbidität von intensivpflichtigen Patienten erfordern hohe
Kompetenz und ausgezeichnete Zusammenarbeit im interprofessionellen Team. Advanced Practice Nurses (APN), die über einen Abschluss als
Master of Science verfügen, haben vertiefte und erweiterte Kompetenzen erlangt, um eine hohe Pflege- und Versorgungsqualität am
Patientenbett zu leisten und gleichzeitig die Zusammenarbeit in interprofessionellen Teams zu unterstützen und zu fördern.
Lesen hilft
Authors: Hähnel Valentin 
Published: July 2017

Zusammenfassung
Psychotherapeutische Komponente in der Intensivtherapie Bietet ein Intensivtagebuch die Möglichkeit zur Aufarbeitung einer nicht
gelebten Zeit? Dieser Frage ist Valentin Hähnel nachgegangen und hat dazu nicht nur die Effekte eines Intensivtagebuchs auf die betroffenen
Patienten untersucht. Auch die Bedeutung für Pflegende und Angehörige ist bemerkenswert – und das noch weit nach der Entlassung des
Patienten aus der Klinik.
Notfallkeratoplastik mit porcinen Xenotransplantaten bei nekrotisierender Keratitis
Authors: Drozhzhyna Galyna , Gaidamaka Tetiana , Cursiefen Claus , Bachmann Björn , Ivanovska Olena , Ostashevsky Viktor , Kogan Boris , Usov Volodymyr , Pasyechnikova Natalija 
Published: July 2017

Zusammenfassung
Hintergrund Der große Mangel an Spendermaterial in der Ukraine macht es notwendig, zusätzliche Quellen von Transplantationsmaterial zu finden. Ein möglicherweise geeignetes Material ist die Hornhaut von Schweinen, weil sie in ihrer Struktur und ihren biomechanischen Parametern der menschlichen Hornhaut ähnlich ist. Das Ziel unserer Studie war, die Ergebnisse der therapeutischen Keratoplastik (KP) mit Keratoxenotransplantaten aus gefriergetrockneten porcinen Xenotransplantaten bei Patienten mit schwerer nekrotisierender Keratitis zu analysieren.
Material und Methoden Retrospektive Analyse von 32 Xenotransplantationen (32 Patienten) mit schwerer nekrotisierender Keratitis (17 lamelläre, 6 gestufte perforierende, 4 perforierende, 5 „biologische Deckungen“ nach Puchkovskaya).
Ergebnisse Alle Augen konnten erhalten werden, das Transplantat wurde jedoch in allen Augen abgestoßen. Ein semitransparentes Xenotransplantat (XT) wurde bei 9 Patienten (33,3%) erreicht. Die besten Ergebnisse wurden nach lamellärer XKP (Xenokeratoplastik) mit einem (XT) Durchmesser von 3,5 – 6,5 mm erreicht. Lamelläre XT mit größerem Durchmesser (7,0 – 10,0 mm) waren trüb. Postoperativ war die Intensität der entzündlichen Reaktion nach gestufter XKP etwas niedriger als nach der klassischen perforierenden XKP. Im Verlauf musste bei 5 Patienten eine erneute KP mit humaner Hornhaut durchgeführt werden, in einem Fall gleichzeitig mit einer antiglaukomatösen Operation und in einem anderen Fall mit Kataraktextraktion. Antiglaukomatöse Operationen mussten bei 5 Patienten durchgeführt werden (15,6%).
Schlussfolgerung Bei Abwesenheit von humanen Spenderhornhäuten kann im Notfall ein porcines Keratoxenoimplantat als temporäre therapeutische Keratoplastik verwendet werden, um den Entzündungsprozess zu stoppen und das Auge zu retten.
A randomized trial comparing winged versus conventional plastic stents for malignant bile duct strictures
Authors: Ayres Lachlan , Cheriyan Danny , Scott Ryan , Kim Edward , Lee Terry , Singer Joel , Donnellan Fergal , Byrne Michael , Weiss Alan , Enns Robert , Amar Jack , Lam Eric , Telford Jennifer 
Published: July 2017

Abstract
Background and study aims Stent insertion at endoscopic retrograde cholangiopancreatography (ERCP) is an established therapy for managing malignant biliary obstruction. Conventional plastic stents with a tubular design are most commonly used despite limited patency. Plastic stents with a winged design may theoretically increase the duration of stent patency. The aim of this study was to compare stent patency of the winged versus conventional plastic stents in patients with malignant biliary obstruction.
Patients and methods A prospective, randomized subject-blinded trial was conducted. Patients with malignant biliary obstruction were randomized (1:1) to either a 10 French winged stent or 7 or 10 French conventional plastic stent. Strictures greater than 1 cm distal to the hilum were included. Patients were followed clinically to determine the frequency of stent failure until surgery, death or study closure.
Results Fifty-eight patients were enrolled. Following 9 exclusions, 49 patients were randomized to a winged (n = 23) or conventional stent (n = 26). Median time to stent failure was 89 (95 % CI 26-NA) vs 143 (95 % CI 33 – 266) days (P = 0.963) for the winged and conventional group, respectively. Stent failure for the winged group occurred in 11 (48 %) compared to 14 (54 %) in the conventional group. Median survival was 123 (95 % CI 81 – 189) vs 342 days (95 % CI 123 – 704) (p = 0.084) in the winged and conventional group respectively. There were no procedure related adverse events.
Conclusions Improvement in stent patency was not seen with the winged stent when compared to the conventional plastic stent. Clinical trials number NCT01514214.
Bedeutung der intraoperativen indirekten Kanalografie bei der Glaukomstentimplantation
Authors: Wirbelauer Christopher , Mertens Charlotte 
Published: July 2017

ZusammenfassungInzwischen sind verschiedene Glaukomstents zur operativen Drucksenkung beim primären Offenwinkelglaukom (POWG) entwickelt worden. Die Vorteile dieser mikroinvasiven Glaukomchirurgie (MIGS) gegenüber den bindehauteröffnenden Eingriffen sind das relativ atraumatische Ab-interno-Vorgehen über eine Parazentese, die Schonung der Bindehaut für später notwendige fistulierende Eingriffe und die einfache Kombination mit einer Kataraktoperation. In dieser Übersicht wird die intraoperative indirekte Kanalografie als Entscheidungskriterium für die Glaukomstentimplantation vorgestellt. Hierbei wird eine geringe Hypotonie über eine Parazentese induziert und gonioskopisch die Blutfüllung des Schlemm-Kanals beobachtet. Eine gute retrograde Blutfüllung spricht für ein intaktes Abflusssystem über die Sammelkanäle zu den episkleralen Venen. Bei diesen Patienten ist ein trabekulärer Bypass-Stent im Schlemm-Kanal des Kammerwinkels aussichtsreich. Bei einer negativen intraoperativen indirekten Kanalografie sollte ein alternativer Abflussweg durch andere geeignete Glaukomstents über den supraziliaren oder subkonjunktivalen Abflussweg gewählt werden. Dadurch können mittlere prozentuale Drucksenkungen von 17 – 36% mit einer Reduktion der lokalen antiglaukomatösen Therapie erreicht werden. Schwerwiegende Komplikationen mit Aderhautamotio und Visusabfall durch eine postoperative Hypotonie sind ausgesprochen selten.
Evaluation of endoscopic submucosal dissection using a new endosurgical knife DN-D2718B: a first clinical feasibility study
Authors: Sakaguchi Yoshiki , Tsuji Yosuke , Fujishiro Mitsuhiro , Kataoka Yosuke , Saito Itaru , Shichijo Satoki , Minatsuki Chihiro , Asada-Hirayama Itsuko , Yamaguchi Daisuke , Niimi Keiko , Ono Satoshi , Kodashima Shinya , Yamamichi Nobutake , Koike Kazuhiko 
Published: July 2017

Abstract
Background and study aims Endosurgical devices with injection function have been reported to decrease endoscopic submucosal dissection (ESD) operation times for experts, but the efficacy of these devices for inexperienced endoscopists is unclear. The aim of this study was to evaluate the feasibility of ESD using a novel ESD knife (DN-D2718B).
Patients and methods This is a single-center prospective pilot clinical feasibility study. Patients diagnosed with superficial gastrointestinal neoplasms were enrolled. A pre-specified group of ESD trainees with ESD experience on a porcine gastric model and fewer than 30 cases of ESD in their selected fields performed ESD under expert supervision, using the DN-D2718B. En bloc resection rates, R0 resection rates, procedure times, and incidence of intra-operational/post-operational adverse events were assessed.
Results Between June 2015 and January 2016, 13 esophageal, 27 gastric, and 14 colorectal ESD cases were performed per-protocol with mean resection speeds of 10.2, 12.0, and 15.5 mm2/min, respectively. There were no intra-operational complications.
Conclusion ESD with this novel knife is feasible even when performed by non-experts.
Rituals in gastrointestinal endoscopy at the crossroads of shaman and science
Authors: Sonnenberg Amnon 
Published: July 2017

Abstract
Background and aim Over the last decades, the length of time required for endoscopic procedures has greatly expanded. The aim of the present decision analysis is to study the interactions amongst various factors that have caused such delays and to compare the relative magnitude of their influences.
Methods Performance of gastrointestinal endoscopy is influenced by the interaction of five domains, that is, (1) patient discomfort and fear; (2) injury, disorder, and disruption; (3) rituals to reduce fear, prevent disruption, and maintain order; (4) administrators or various health providers carrying out a ritual; (5) information, knowledge, and science, which influence fear, prevent disruption, and curtail unnecessary ritualistic behavior. A Markov chain model is used to describe the interaction among the five domains.
Results Overall, science exerts the strongest influence, followed by fear and ritual as distant second and third most relevant influences, respectively. Disruption and administrator exert only a minor influence on the system of mutual interactions.
Conclusions Studying patterns of ritualistic behavior during endoscopy and subjecting them to means of scientific research could help eliminate redundancy, cutting unnecessary rituals, and thus making gastrointestinal endoscopy overall more efficient.