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We introduce Implied Volatility Duration (IVD) as a new measure for the timing of uncertainty resolution, with a high IVD corresponding to late resolution. Portfolio sorts on a large cross-section of stocks indicate that investors demand on average about seven percent return per year as a compensation for a late resolution of uncertainty. In a general equilibrium model, we show that `late' stocks can only have higher expected returns than `early' stocks if the investor exhibits a preference for early resolution of uncertainty. Our empirical analysis thus provides a purely market-based assessment of the timing preferences of the marginal investor.
Relja, Borna ; Weber, Roxane ; Maraslioglu, Miriam ; Wagner, Nils ; Borsello, Tiziana ; Jobin, Christian ; Marzi, Ingo ; Lehnert, Mark
Background: Chronic ethanol (EtOH) abuse worsens pathophysiological derangements after hemorrhagic shock and resuscitation (H/R) that induce hepatic injury and strong inflammatory changes via JNK and NF-κB activation. Inhibiting JNK with a cell-penetrating, protease-resistant peptide D-JNKI-1 after H/R in mice with healthy livers ameliorated these effects. Here, we studied if JNK inhibition by D-JNKI-1 in chronically EtOH-fed mice after hemorrhagic shock prior to the onset of resuscitation also confers protection.
Methods: Male mice were fed a Lieber-DeCarli diet containing EtOH or an isocaloric control (ctrl) diet for 4 weeks. Animals were hemorrhaged for 90 min (32 ± 2 mm Hg) and randomly received either D-JNKI-1 (11 mg/kg, intraperitoneally, i. p.) or sterile saline as vehicle (veh) immediately before the onset of resuscitation. Sham animals underwent surgical procedures without H/R and were either D-JNKI-1 or veh treated. Two hours after resuscitation, blood samples and liver tissue were harvested.
Results: H/R induced hepatic injury with increased systemic interleukin (IL)-6 levels, and enhanced local gene expression of NF-κB-controlled genes such as intercellular adhesion molecule (ICAM)-1 and matrix metallopeptidase (MMP)9. c-Jun and NF-κB phosphorylation were increased after H/R. These effects were further increased in EtOH-fed mice after H/R. D-JNKI-1 application inhibited the proinflammatory changes and reduced significantly hepatic injury after H/R in ctrl-fed mice. Moreover, D-JNKI-1 reduces in ctrl-fed mice the H/R-induced c-Jun and NF-κB phosphorylation. However, in chronically EtOH-fed mice, JNK inhibition did not prevent the H/R-induced hepatic damage and proinflammatory changes nor c-Jun and NF-κB phosphorylation after H/R.
Conclusions: These results indicate, that JNK inhibition is protective only in not pre-harmed liver after H/R. In contrast, the pronounced H/R-induced liver damage in mice being chronically fed with ethanol cannot be prevented by JNK inhibition after H/R and seems to be under the control of NF-κB.
Caudillo-Plath, Lucía ; Rörup, Birte ; Heinritzi, Martin ; Marie, Guillaume ; Simon, Mario ; Wagner, Andrea C. ; Müller, Tatjana ; Granzin, Manuel ; Amorim, António ; Ataei, Farnoush ; Baalbaki, Rima ; Bertozzi, Barbara ; Brasseur, Zoé ; Chiu, Randall ; Chu, Biwu ; Dada, Lubna ; Duplissy, Jonathan ; Finkenzeller, Henning ; Gonzalez Carracedo, Loïc ; He, Xu-Cheng ; Hofbauer, Victoria ; Kong, Weimeng ; Lamkaddam, Houssni ; Lee, Chuan P. ; Lopez, Brandon ; Mahfouz, Naser G. A. ; Makhmutov, Vladimir ; Manninen, Hanna E. ; Marten, Ruby ; Massabò, Dario ; Mauldin, Roy L. ; Mentler, Bernhard ; Molteni, Ugo ; Onnela, Antti ; Pfeifer, Joschka ; Philippov, Maxim ; Piedehierro, Ana A. ; Schervish, Meredith ; Scholz, Wiebke ; Schulze, Benjamin ; Shen, Jiali ; Stolzenburg, Dominik ; Stožkov, Ju. I. ; Surdu, Mihnea ; Tauber, Christian ; Tham, Yee Jun ; Tian, Ping ; Tomé, António ; Vogt, Steffen ; Wang, Mingyi ; Wang, Dongyu S. ; Weber, Stefan K. ; Welti, André ; Yonghong, Wang ; Yusheng, Wu ; Zauner-Wieczorek, Marcel ; Baltensperger, Urs ; El Haddad, Imad ; Flagan, Richard C. ; Hansel, Armin ; Höhler, Kristina ; Kirkby, Jasper ; Kulmala, Markku ; Lehtipalo, Katrianne ; Möhler, Ottmar ; Saathoff, Harald ; Volkamer, Rainer ; Winkler, Paul M. ; Donahue, Neil M. ; Kürten, Christoph Andreas ; Curtius, Joachim
Biogenic organic precursors play an important role in atmospheric new particle formation (NPF). One of the major precursor species is α-pinene, which upon oxidation can form a suite of products covering a wide range of volatilities. Highly oxygenated organic molecules (HOMs) comprise a fraction of the oxidation products formed. While it is known that HOMs contribute to secondary organic aerosol (SOA) formation, including NPF, they have not been well studied in newly formed particles due to their very low mass concentrations. Here we present gas- and particle-phase chemical composition data from experimental studies of α-pinene oxidation, including in the presence of isoprene, at temperatures (−50 and −30 ∘C) and relative humidities (20 % and 60 %) relevant in the upper free troposphere. The measurements took place at the CERN Cosmics Leaving Outdoor Droplets (CLOUD) chamber. The particle chemical composition was analyzed by a thermal desorption differential mobility analyzer (TD-DMA) coupled to a nitrate chemical ionization–atmospheric pressure interface–time-of-flight (CI-APi-TOF) mass spectrometer. CI-APi-TOF was used for particle- and gas-phase measurements, applying the same ionization and detection scheme. Our measurements revealed the presence of C8−10 monomers and C18−20 dimers as the major compounds in the particles (diameter up to ∼ 100 nm). Particularly, for the system with isoprene added, C5 (C5H10O5−7) and C15 compounds (C15H24O5−10) were detected. This observation is consistent with the previously observed formation of such compounds in the gas phase. However, although the C5 and C15 compounds do not easily nucleate, our measurements indicate that they can still contribute to the particle growth at free tropospheric conditions. For the experiments reported here, most likely isoprene oxidation products enhance the growth of particles larger than 15 nm. Additionally, we report on the nucleation rates measured at 1.7 nm (J1.7 nm) and compared with previous studies, we found lower J1.7 nm values, very likely due to the higher α-pinene and ozone mixing ratios used in the present study.
Caudillo-Plath, Lucı́a ; Rörup, Birte ; Heinritzi, Martin ; Marie, Guillaume ; Simon, Mario ; Wagner, Andrea C. ; Müller, Tatjana ; Granzin, Manuel ; Amorim, Antonio ; Ataei, Farnoush ; Baalbaki, Rima ; Bertozzi, Barbara ; Brasseur, Zoé ; Chiu, Randall ; Chu, Biwu ; Dada, Lubna ; Duplissy, Jonathan ; Finkenzeller, Henning ; Gonzalez Carracedo, Loïc ; He, Xu-Cheng ; Hofbauer, Victoria ; Kong, Weimeng ; Lamkaddam, Houssni ; Lee, Chuan P ; Lopez, Brandon ; Mahfouz, Naser G. A. ; Makhmutov, Vladimir ; Manninen, Hanna E. ; Marten, Ruby ; Massabò, Dario ; Mauldin, Roy L. ; Mentler, Bernhard ; Molteni, Ugo ; Onnela, Antti ; Pfeifer, Joschka ; Philippov, Maxim ; Piedehierro, Ana A. ; Schervish, Meredith ; Scholz, Wiebke ; Schulze, Benjamin ; Shen, Jiali ; Stolzenburg, Dominik ; Stožkov, Ju. I. ; Surdu, Mihnea ; Tauber, Christian ; Tham, Yee Jun ; Tian, Ping ; Tomé, António ; Vogt, Steffen ; Wang, Mingyi ; Wang, Dongyu S. ; Weber, Stefan K. ; Welti, André ; Yonghong, Wang ; Yusheng, Wu ; Zauner-Wieczorek, Marcel ; Baltensperger, Urs ; El Haddad, Imad ; Flagan, Richard C. ; Hansel, Armin ; Höhler, Kristina ; Kirkby, Jasper ; Kulmala, Markku ; Lehtipalo, Katrianne ; Möhler, Ottmar ; Saathoff, Harald ; Volkamer, Rainer ; Winkler, Paul M. ; Donahue, Neil M. ; Kürten, Christoph Andreas ; Curtius, Joachim
Biogenic organic precursors play an important role in atmospheric new particle formation (NPF). One of the major precursor species is α-pinene, which upon oxidation can form a suite of products covering a wide range of volatilities. Highly oxygenated organic molecules (HOMs) comprise a fraction of the oxidation products formed. While it is known that HOMs contribute to secondary organic aerosol (SOA) formation, including NPF, they have not been well studied in newly formed particles due to their very low mass concentrations. Here we present gas- and particle-phase chemical composition data from experimental studies of α-pinene oxidation, including in the presence of isoprene, at temperatures (−50 and −30 ∘C) and relative humidities (20 % and 60 %) relevant in the upper free troposphere. The measurements took place at the CERN Cosmics Leaving Outdoor Droplets (CLOUD) chamber. The particle chemical composition was analyzed by a thermal desorption differential mobility analyzer (TD-DMA) coupled to a nitrate chemical ionization–atmospheric pressure interface–time-of-flight (CI-APi-TOF) mass spectrometer. CI-APi-TOF was used for particle- and gas-phase measurements, applying the same ionization and detection scheme. Our measurements revealed the presence of C8−10 monomers and C18−20 dimers as the major compounds in the particles (diameter up to ∼ 100 nm). Particularly, for the system with isoprene added, C5 (C5H10O5−7) and C15 compounds (C15H24O5−10) were detected. This observation is consistent with the previously observed formation of such compounds in the gas phase. However, although the C5 and C15 compounds do not easily nucleate, our measurements indicate that they can still contribute to the particle growth at free tropospheric conditions. For the experiments reported here, most likely isoprene oxidation products enhance the growth of particles larger than 15 nm. Additionally, we report on the nucleation rates measured at 1.7 nm (J1.7 nm) and compared with previous studies, we found lower J1.7 nm values, very likely due to the higher α-pinene and ozone mixing ratios used in the present study.
Clees, Ada-Sophia ; Stolp, Verena ; Häupl, Björn ; Fuhrmann, Dominik Christian ; Wempe, Frank ; Seibert, Marcel ; Weber, Sarah ; Banning, Antje ; Tikkanen, Ritva ; Williams, Richard ; Brüne, Bernhard ; Serve, Hubert ; Schnütgen, Frank ; Metzler, Ivana von ; Kurrle, Nina Susanne
Multiple myeloma (MM) is the second most common hematologic malignancy, which is characterized by clonal proliferation of neoplastic plasma cells in the bone marrow. This microenvironment is characterized by low oxygen levels (1–6% O2), known as hypoxia. For MM cells, hypoxia is a physiologic feature that has been described to promote an aggressive phenotype and to confer drug resistance. However, studies on hypoxia are scarce and show little conformity. Here, we analyzed the mRNA expression of previously determined hypoxia markers to define the temporal adaptation of MM cells to chronic hypoxia. Subsequent analyses of the global proteome in MM cells and the stromal cell line HS-5 revealed hypoxia-dependent regulation of proteins, which directly or indirectly upregulate glycolysis. In addition, chronic hypoxia led to MM-specific regulation of nine distinct proteins. One of these proteins is the cysteine protease legumain (LGMN), the depletion of which led to a significant growth disadvantage of MM cell lines that is enhanced under hypoxia. Thus, herein, we report a methodologic strategy to examine MM cells under physiologic hypoxic conditions in vitro and to decipher and study previously masked hypoxia-specific therapeutic targets such as the cysteine protease LGMN.
Théry, Clotilde ; Witwer, Kenneth W. ; Aikawa, Elena ; Alcaraz, Maria Jose ; Anderson, Johnathon D. ; Andriantsitohaina, Ramaroson ; Antoniou, Anna ; Arab, Tanina ; Archer, Fabienne ; Atkin-Smith, Georgia K. ; Ayre, D. Craig ; Bach, Jean-Marie ; Bachurski, Daniel ; Baharvand, Hossein ; Balaj, Leonora ; Baldacchino, Shawn ; Bauer, Natalie N. ; Baxter, Amy A. ; Bebawy, Mary ; Beckham, Carla ; Zavec, Apolonija Bedina ; Benmoussa, Abderrahim ; Berardi, Anna C. ; Bergese, Paolo ; Bielska, Ewa ; Blenkiron, Cherie ; Bobis-Wozowicz, Sylwia ; Boilard, Eric ; Boireau, Wilfrid ; Bongiovanni, Antonella ; Borràs, Francesc E. ; Bosch, Steffi ; Boulanger, Chantal M. ; Breakefield, Xandra ; Breglio, Andrew M. ; Brennan, Meadhbh Aín ; Brigstock, David R. ; Brisson, Alain ; Broekman, Marike L. D. ; Bromberg, Jacqueline F. ; Bryl-Gorecka, Paulina ; Buch, Shilpa ; Buck, Amy H. ; Burger, Dylan ; Busatto, Sara ; Buschmann, Dominik ; Bussolati, Benedetta ; Buzás, Edit I. ; Byrd, James Bryan ; Camussi, Giovanni ; Carter, David R. F. ; Caruso, Sarah ; Chamley, Lawrence W. ; Chang, Yu-Ting ; Chen, Chihchen ; Chen, Shuai ; Cheng, Lesley ; Chin, Andrew R. ; Clayton, Aled ; Clerici, Stefano P. ; Cocks, Alex ; Cocucci, Emanuele ; Coffey, Robert J. ; Cordeiro-da-Silva, Anabela ; Couch, Yvonne ; Coumans, Frank A. W. ; Coyle, Beth ; Crescitelli, Rossella ; Criado, Miria Ferreira ; D’Souza-Schorey, Crislyn ; Das, Saumya ; Chaudhuri, Amrita Datta ; de-Candia, Paola ; De Santana, Eliezer F. ; De Wever, Olivier ; del Portillo, Hernando A. ; Demaret, Tanguy ; Deville, Sarah ; Devitt, Andrew ; Dhondt, Bert ; Di Vizio, Dolores ; Dieterich, Lothar C. ; Dolo, Vincenza ; Dominguez Rubio, Ana Paula ; Dominici, Massimo ; Dourado, Mauricio R. ; Driedonks, Tom A. P. ; Duarte, Filipe V. ; Duncan, Heather M. ; Eichenberger, Ramon Marc ; Ekström, Karin ; El Andaloussi, Samir ; Elie-Caille, Celine ; Erdbrügger, Uta ; Falcón-Pérez, Juan M. ; Fatima, Farah ; Fish, Jason E. ; Flores-Bellver, Miguel ; Försönits, András ; Frelet-Barrand, Annie ; Fricke, Fabia ; Fuhrmann, Gregor ; Gabrielsson, Susanne ; Gámez-Valero, Ana ; Gardiner, Chris ; Gärtner, Kathrin ; Gaudin, Raphael ; Gho, Yong Song ; Giebel, Bernd ; Gilbert, Caroline ; Gimona, Mario ; Giusti, Ilaria ; Goberdhan, Deborah C. I. ; Görgens, André ; Gorski, Sharon M. ; Greening, David W. ; Groß, Julia Christina ; Gualerzi, Alice ; Gupta, Gopal N. ; Gustafson, Dakota ; Handberg, Aase ; Haraszti, Réka Ágnes ; Harrison, Paul ; Hegyesi, Hargita ; Hendrix, An ; Hill, Andrew F. ; Hochberg, Fred H. ; Hoffmann, Karl F. ; Holder, Beth ; Holthofer, Harry ; Hosseinkhani, Baharak ; Hu, Guoku ; Huang, Yiyao ; Huber, Veronica ; Hunt, Stuart ; Ibrahim, Ahmed Gamal-Eldin ; Ikezu, Tsuneya ; Inal, Jameel M. ; Isin, Mustafa ; Ivanova, Alena ; Jackson, Hannah K. ; Jacobsen, Soren ; Jay, Steven M. ; Jayachandran, Muthuvel ; Jenster, Guido ; Jiang, Lanzhou ; Johnson, Suzanne M. ; Jones, Jennifer C. ; Jong, Ambrose ; Jovanovic-Talisman, Tijana ; Jung, Stephanie ; Kalluri, Raghu ; Kano, Shin-ichi ; Kaur, Sukhbir ; Kawamura, Yumi ; Keller, Evan T. ; Khamari, Delaram ; Khomyakova, Elena ; Khvorova, Anastasia ; Kierulf, Peter ; Kim, Kwang Pyo ; Kislinger, Thomas ; Klingeborn, Mikael ; Klinke, David J. ; Kornek, Miroslaw ; Kosanović, Maja M. ; Kovács, Árpád Ferenc ; Krämer-Albers, Eva-Maria ; Krasemann, Susanne ; Krause, Mirja ; Kurochkin, Igor V. ; Kusuma, Gina D. ; Kuypers, Sören ; Laitinen, Saara ; Langevin, Scott M. ; Languino, Lucia R. ; Lannigan, Joanne ; Lässer, Cecilia ; Laurent, Louise C. ; Lavieu, Gregory ; Lázaro-Ibáñez, Elisa ; Le Lay, Soazig ; Lee, Myung-Shin ; Lee, Yi Xin Fiona ; Lemos, Debora S. ; Lenassi, Metka ; Leszczynska, Aleksandra ; Li, Isaac T. S. ; Liao, Ke ; Libregts, Sten F. ; Ligeti, Erzsebet ; Lim, Rebecca ; Lim, Sai Kiang ; Linē, Aija ; Linnemannstöns, Karen ; Llorente, Alicia ; Lombard, Catherine Ann ; Lorenowicz, Magdalena J. ; Lörincz, Ákos M. ; Lötvall, Jan ; Lovett, Jason ; Lowry, Michelle C. ; Loyer, Xavier ; Lu, Quan ; Lukomska, Barbara ; Lunavat, Taral Rameshchand ; Maas, Sybren L. N. ; Malhi, Harmeet ; Marcilla, Antonio ; Mariani, Jacopo ; Mariscal, Javier ; Martens-Uzunova, Elena S. ; Martin-Jaular, Lorena ; Martinez, M. Carmen ; Martins, Vilma Regina ; Mathieu, Mathilde ; Mathivanan, Suresh ; Maugeri, Marco ; McGinnis, Lynda K. ; McVey, Mark J. ; Meckes, David G. ; Meehan, Katie ; Mertens, Inge ; Minciacchi, Valentina R. ; Möller, Andreas ; Møller Jørgensen, Malene ; Morales-Kastresana, Aizea ; Morhayim, Jess ; Mullier, François ; Muraca, Maurizio ; Musante, Luca ; Mussack, Veronika ; Muth, Dillon C. ; Myburgh, Kathryn H. ; Najrana, Tanbir ; Nawaz, Muhammad ; Nazarenko, Irina ; Nejsum, Peter ; Neri, Christian ; Neri, Tommaso ; Nieuwland, Rienk ; Nimrichter, Leonardo ; Nolan, John P. ; Nolte-’t Hoen, Esther N. M. ; Hooten, Nicole Noren ; O’Driscoll, Lorraine ; O’Grady, Tina ; O’Loghlen, Ana ; Ochiya, Takahiro ; Olivier, Martin ; Ortiz, Alberto ; Ortiz, Luis A. ; Osteikoetxea, Xabier ; Østergaard, Ole ; Ostrowski, Matias ; Park, Jaesung ; Pegtel, Dirk Michiel ; Peinado, Hector ; Perut, Francesca ; Pfaffl, Michael ; Phinney, Donald G. ; Pieters, Bartijn C. H. ; Pink, Ryan Charles ; Pisetsky, David S. ; Pogge von Strandmann, Elke ; Polakovicova, Iva ; Poon, Ivan K. H. ; Powell, Bonita H. ; Prada, Ilaria ; Pulliam, Lynn ; Quesenberry, Peter ; Radeghieri, Annalisa ; Raffai, Robert L. ; Raimondo, Stefania ; Rak, Janusz ; Ramirez, Marcel I. ; Raposo, Graça ; Rayyan, Morsi S. ; Regev-Rudzki, Neta ; Ricklefs, Franz Lennard ; Robbins, Paul D. ; Roberts, David D. ; Rodrigues, Silvia C. ; Rohde, Eva ; Rome, Sophie ; Rouschop, Kasper M. ; Rughetti, Aurelia ; Russell, Ashley E. ; Saá, Paula ; Sahoo, Susmita ; Salas-Huenuleo, Edison ; Sánchez, Catherine ; Saugstad, Julie A. ; Saul, Meike J. ; Schiffelers, Raymond M. ; Schneider, Raphael ; Schøyen, Tine Hiorth ; Scott, Aaron ; Shahaj, Eriomina ; Sharma, Shivani ; Shatnyeva, Olga ; Shekari, Faezeh ; Shelke, Ganesh Vilas ; Shetty, Ashok K. ; Shiba, Kiyotaka ; Siljander, Pia R.-M. ; Silva, Andreia M. ; Skowronek, Agata ; Snyder, Orman L. ; Soares, Rodrigo Pedro ; Sódar, Barbara W. ; Soekmadji, Carolina ; Sotillo, Javier ; Stahl, Philip D. ; Stoorvogel, Willem ; Stott, Shannon L. ; Strasser, Erwin F. ; Swift, Simon ; Tahara, Hidetoshi ; Tewari, Muneesh ; Timms, Kate ; Tiwari, Swasti ; Tixeira, Rochelle ; Tkach, Mercedes ; Toh, Wei Seong ; Tomasini, Richard ; Torrecilhas, Ana Claudia ; Tosar, Juan Pablo ; Toxavidis, Vasilis ; Urbanelli, Lorena ; Vader, Pieter ; Balkom, Bastiaan Wilhelmus Maria van ; Grein, Susanne G. van der ; Van Deun, Jan ; Herwijnen, Martijn J. C. van ; Van Keuren-Jensen, Kendall R. ; Niel, Guillaume van ; Royen, Martin E. van ; Wijnen, Andre J. van ; Vasconcelos, M. Helena ; Vechetti, Ivan J. ; Veit, Tiago D. ; Vella, Laura J. ; Velot, Émilie ; Verweij, Frederik ; Vestad, Beate ; Viñas, Jose Luis ; Visnovitz, Tamás ; Vukman, Krisztina V. ; Wahlgren, Jessica ; Watson, Dionysios C. ; Wauben, Marca H. M. ; Weaver, Alissa ; Webber, Jason P. ; Weber, Viktoria ; Wehman, Ann M. ; Weiss, Daniel J. ; Welsh, Joshua A. ; Wendt, Sebastian ; Wheelock, Åsa M. ; Wiener, Zoltán ; Witte, Leonie ; Wolfram, Joy ; Xagorari, Angeliki ; Xander, Patricia ; Xu, Jing ; Yan, Xiaomei ; Yáñez-Mó, María ; Yin, Hang ; Yuana, Yuana ; Zappulli, Valentina ; Zarubova, Jana ; Žėkas, Vytautas ; Zhang, Jian-ye ; Zhao, Zezhou ; Zheng, Lei ; Zheutlin, Alexander R. ; Zickler, Antje Maria ; Zimmermann, Pascale ; Zivkovic, Angela M. ; Zocco, Davide ; Zuba-Surma, Ewa K.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Bartsch, Detlef K. ; Dotzenrath, Cornelia ; Vorländer, Christian ; Zielke, Andreas ; Weber, Theresia ; Buhr, Heinz J. ; Klinger, Carsten ; Lorenz, Kerstin
Background: To evaluate the current indications, resection strategies and short-term outcomes of surgery for benign goitre in a country with endemic goitre. Methods: Data of patients who underwent surgery for benign goitre were retrieved from the prospective StuDoQ/Thyroid registry and retrospectively analysed regarding the patient’s demographics, indications for surgery, surgical procedures, histology, and perioperative outcomes. Results: In a 15-month period, 12,888 patients from 83 departments underwent thyroid resections for benign conditions. Main indications for surgery were exclusion of malignancy (68%), compression symptoms (20.7%) and hyperthyroidism (9.7%). Preoperative fine needle aspiration cytology was performed in only 12.2% of patients with the indication "exclusion of malignancy". Thyroidectomy (49.8%) or hemithyroidectomy (36.9%) were performed in 86.7% of patients. Minimally invasive or alternative surgical techniques were applied in only 2.2%. Intraoperative neuromonitoring was used in 98.4% of procedures, in 97.5% of patients at least one parathyroid gland was visualized, and in 15.3% of patients parathyroid tissue was autografted, respectively. The rates of unilateral and bilateral transient recurrent nerve palsy were 3.6% and 0.07% of nerves at risk, the rate of transitory hypoparathyroidism was 15.3%. The rates of postoperative bleeding and wound infections requiring reoperation were 1.4% and 0.07%, respectively. Conclusions: The indication "exclusion of malignancy" is made too liberally, and there is a strong attitude to perform complete thyroid resections. Postoperative hypoparathyroidism is the major complication after surgery for benign thyroid disease, thus requiring more awareness.
Ney, Julia ; Hoffmann, Katleen ; Meybohm, Patrick ; Goetzenich, Andreas ; Kraemer, Sandra ; Benstöm, Carina ; Weber, Nina C. ; Bickenbach, Johannes ; Rossaint, Rolf ; Marx, Gernot ; Zacharowski, Kai ; Bernhagen, Jürgen ; Stoppe, Christian
In contrast to several smaller studies, which demonstrate that remote ischemic preconditioning (RIPC) reduces myocardial injury in patients that undergo cardiovascular surgery, the RIPHeart study failed to demonstrate beneficial effects of troponin release and clinical outcome in propofol-anesthetized cardiac surgery patients. Therefore, we addressed the potential biochemical mechanisms triggered by RIPC. This is a predefined prospective sub-analysis of the randomized and controlled RIPHeart study in cardiac surgery patients (n = 40) that was recently published. Blood samples were drawn from patients prior to surgery, after RIPC of four cycles of 5 min arm ischemia/5 min reperfusion (n = 19) and the sham (n = 21) procedure, after connection to cardiopulmonary bypass (CPB), at the end of surgery, 24 h postoperatively, and 48 h postoperatively for the measurement of troponin T, macrophage migration inhibitory factor (MIF), stromal cell-derived factor 1 (CXCL12), IL-6, CXCL8, and IL-10. After RIPC, right atrial tissue samples were taken for the measurement of extracellular-signal regulated kinase (ERK1/2), protein kinase B (AKT), Glycogen synthase kinase 3 (GSK-3β), protein kinase C (PKCε), and MIF content. RIPC did not significantly reduce the troponin release when compared with the sham procedure. MIF serum levels intraoperatively increased, peaking at intensive care unit (ICU) admission (with an increase of 48.04%, p = 0.164 in RIPC; and 69.64%, p = 0.023 over the baseline in the sham procedure), and decreased back to the baseline 24 h after surgery, with no differences between the groups. In the right atrial tissue, MIF content decreased after RIPC (1.040 ± 1.032 Arbitrary units [au] in RIPC vs. 2.028 ± 1.631 [au] in the sham procedure, p < 0.05). CXCL12 serum levels increased significantly over the baseline at the end of surgery, with no differences between the groups. ERK1/2, AKT, GSK-3β, and PKCɛ phosphorylation in the right atrial samples were no different between the groups. No difference was found in IL-6, CXCL8, and IL10 serum levels between the groups. In this cohort of cardiac surgery patients that received propofol anesthesia, we could not show a release of potential mediators of signaling, nor an effect on the inflammatory response, nor an activation of well-established protein kinases after RIPC. Based on these data, we cannot exclude that confounding factors, such as propofol, may have interfered with RIPC.
DIGITAL CURRENCIES ARE A GLOBALLY SPREADING PHENOMENON THAT IS FREQUENTLY AND PROMINENTLY ADDRESSED BY MEDIA, POLITICS AND ACADEMIA. WE AIM AT GIVING EMPIRICAL INSIGHTS ON WHETHER USERS’ INTEREST REGARDING DIGITAL CURRENCIES IS DRIVEN BY ITS APPEAL AS AN ASSET OR ITS UTILITY AS A CURRENCY. BASED ON OUR EVALUATION, WE FIND STRONG INDICATIONS THAT ESPECIALLY UNINFORMED USERS APPROACHING BITCOIN ARE NOT PRIMARILY INTERESTED IN AN ALTERNATIVE TRANSACTION SYSTEM, BUT SEEK TO PARTICIPATE IN AN ALTERNATIVE INVESTMENT VEHICLE.
The ubiquitous detection of microplastics in aquatic ecosystems promotes the concern for adverse impacts on freshwater ecosystems. The wide variety of material types, sizes, shapes, and physicochemical properties renders interactions with biota via multiple pathways probable.
So far, our knowledge about the uptake and biological effects of microplastics comes from laboratory studies, applying simplified exposure regimes (e.g., one polymer and size, spherical shape, high concentrations) often with limited environmental relevance. However, the available data illustrates species- and material-related interactions and highlights that microplastics represent a multifaceted stressor. Particle-related toxicities will be driven by polymer type, size, and shape. Chemical toxicity is driven by the adsorption-desorption kinetics of additives and pollutants. In addition, microbial colonization, the formation of hetero-aggregates, and the evolutionary adaptations of the biological receptor further increase the complexity of microplastics as stressors. Therefore, the aim of this chapter is to synthesize and critically revisit these aspects based on the state of the science in freshwater research. Where unavailable we supplement this with data on marine biota. This provides an insight into the direction of future research.
In this regard, the challenge is to understand the complex interactions of biota and plastic materials and to identify the toxicologically most relevant characteristics of the plethora of microplastics. Importantly, as the direct biological impacts of natural particles may be similar, future research needs to benchmark synthetic against natural materials. Finally, given the scale of the research question, we need a multidisciplinary approach to understand the role of microplastics in a multiple-particle world.