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PURPOSE OF REVIEW: To fully exploit the concept of hemodynamic coherence in resuscitating critically ill one should preferably take into account information about the state of parenchymal cells. Monitoring of mitochondrial oxygen tension (mitoPO2) has emerged as a clinical means to assess information of oxygen delivery and oxygen utilization at the mitochondrial level. This review will outline the basics of the technique, summarize its development and describe the rationale of measuring oxygen at the mitochondrial level. RECENT FINDINGS: Mitochondrial oxygen tension can be measured by means of the protoporphyrin IX-Triplet State Lifetime Technique (PpIX-TSLT). After validation and use in preclinical animal models, the technique has recently become commercially available in the form of a clinical measuring system. This system has now been used in a number of healthy volunteer studies and is currently being evaluated in studies in perioperative and intensive care patients in several European university hospitals. SUMMARY: PpIX-TSLT is a noninvasive and well tolerated method to assess aspects of mitochondrial function

Inertial microfluidics is an active field of research that deals with crossflow positioning of the suspended entities in microflows. Until now, the majority of the studies have focused on the behavior of rigid particles in order to provide guidelines for microfluidic applications such as sorting and filtering. Deformable entities such as bubbles and droplets are considered in fewer studies despite their importance in multiphase microflows. In this paper, we show that the trajectory of bubbles flowing in rectangular and square microchannels can be controlled by tuning the balance of forces acting on them. A T-junction geometry is employed to introduce bubbles into a microchannel and analyze their lateral equilibrium position in a range of Reynolds (1 < Re < 40) and capillary numbers (0.1 < Ca < 1). We find that the Reynolds number (Re), the capillary number (Ca), the diameter of the bubble (D), and the aspect ratio of the channel are the influential parameters in this phenomenon. For instance, at high Re, the flow pushes the bubble towards the wall while large Ca or D moves the bubble towards the center. Moreover, in the shallow channels, having aspect ratios higher than one, the bubble moves towards the narrower sidewalls. One important outcome of this study is that the equilibrium position of bubbles in rectangular channels is different from that of solid particles. The experimental observations are in good agreement with the performed numerical simulations and provide insights into the dynamics of bubbles in laminar flows which can be utilized in the design of flow based multiphase flow reactors., QC 20180411

The aim of this study is to derive accurate models for quantities characterizing the dynamics of droplets of non-vanishing viscosity in capillaries. In particular, we propose models for the uniform-film thickness separating the droplet from the tube walls, for the droplet front and rear curvatures and pressure jumps, and for the droplet velocity in a range of capillary numbers, Ca, from 10 - 4 to 1 and inner-to-outer viscosity ratios, λ, from 0, i.e. a bubble, to high-viscosity droplets. Theoretical asymptotic results obtained in the limit of small capillary number are combined with accurate numerical simulations at larger Ca. With these models at hand, we can compute the pressure drop induced by the droplet. The film thickness at low capillary numbers (Ca< 10 - 3) agrees well with Bretherton’s scaling for bubbles as long as λ< 1. For larger viscosity ratios, the film thickness increases monotonically, before saturating for λ> 10 3 to a value 2 2 / 3 times larger than the film thickness of a bubble. At larger capillary numbers, the film thickness follows the rational function proposed by Aussillous and Quéré (Phys Fluids 12(10):2367–2371, 2000) for bubbles, with a fitting coefficient which is viscosity-ratio dependent. This coefficient modifies the value to which the film thickness saturates at large capillary numbers. The velocity of the droplet is found to be strongly dependent on the capillary number and viscosity ratio. We also show that the normal viscous stresses at the front and rear caps of the droplets cannot be neglected when calculating the pressure drop for Ca> 10 - 3., QC 20180702

Various manufacturing techniques exist to produce double-curvature shells, including injection, rotational and blow molding, as well as dip coating. However, these industrial processes are typically geared for mass production and are not directly applicable to laboratory research settings, where adaptable, inexpensive and predictable prototyping tools are desirable. Here, we study the rapid fabrication of hemispherical elastic shells by coating a curved surface with a polymer solution that yields a nearly uniform shell, upon polymerization of the resulting thin film. We experimentally characterize how the curing of the polymer affects its drainage dynamics and eventually selects the shell thickness. The coating process is then rationalized through a theoretical analysis that predicts the final thickness, in quantitative agreement with experiments and numerical simulations of the lubrication flow field. This robust fabrication framework should be invaluable for future studies on the mechanics of thin elastic shells and their intrinsic geometric nonlinearities., European Research Council (ERC-2011-StG), European Research Council (PE8 SIMCOMICS), National Science Foundation (U.S.) (CAREER CMMI-1351449)

Background: The leading cause of mortality due to pulmonary arterial hypertension (PAH) is failure of the cardiac right ventricle. It has long been hypothesized that during the development of chronic cardiac failure the heart becomes energy deprived, possibly due to shortage of oxygen at the level of cardiomyocyte mitochondria. However, direct evaluation of oxygen tension levels within the in vivo right ventricle during PAH is currently lacking. Here we directly evaluated this hypothesis by using a recently reported technique of oxygen-dependent quenching of delayed fluorescence of mitochondrial protoprophyrin IX, to determine the distribution of mitochondrial oxygen tension (mitoPO2) within the right ventricle (RV) subjected to progressive PAH.Methods: PAH was induced through a single injection of monocrotaline (MCT). Control (saline-injected), compensated RV hypertrophy (30 mg/kg MCT; MCT30), and RV failure (60 mg/kg MCT; MCT60) rats were compared 4 wk after treatment. The distribution of mitoPO2 within the RV was determined in mechanically-ventilated, anaesthetized animals, applying different inspired oxygen (FiO2) levels and two increment dosages of dobutamine.Results: MCT60 resulted in RV failure (increased mortality, weight loss, increased lung weight), MCT30 resulted in compensated RV hypertrophy. At 30% or 40% FiO2, necessary to obtain physiological arterial PO2 in the diseased animals, RV failure rats had significantly less mitochondria (15% of total mitochondria) in the 0-20 mmHg mitoPO2 range than hypertrophied RV rats (48%) or control rats (54%). Only when oxygen supply was reduced to 21% FiO2, resulting in low arterial PO2 for the MCT60 animals, or when oxygen demand increased with high dose dobutamine, the number of failing RV mitochondria with low oxygen became similar to control RV. In addition, metabolic enzyme analysis revealed similar mitochondrial mass, increa

Objective: Since 2011, the new national final examination in human medicine has been implemented in Switzerland, with a structured clinical-practical part in the OSCE format. From the perspective of the national Working Group, the current article describes the essential steps in the development, implementation and evaluation of the Federal Licensing Examination Clinical Skills (FLE CS) as well as the applied quality assurance measures. Finally, central insights gained from the last years are presented. Methods: Based on the principles of action research, the FLE CS is in a constant state of further development. On the foundation of systematically documented experiences from previous years, in the Working Group, unresolved questions are discussed and resulting solution approaches are substantiated (planning), implemented in the examination (implementation) and subsequently evaluated (reflection). The presented results are the product of this iterative procedure.Results: The FLE CS is created by experts from all faculties and subject areas in a multistage process. The examination is administered in German and French on a decentralised basis and consists of twelve interdisciplinary stations per candidate. As important quality assurance measures, the national Review Board (content validation) and the meetings of the standardised patient trainers (standardisation) have proven worthwhile. The statistical analyses show good measurement reliability and support the construct validity of the examination. Among the central insights of the past years, it has been established that the consistent implementation of the principles of action research contributes to the successful further development of the examination.Conclusion: The centrally coordinated, collaborative-iterative process, incorporating experts from all faculties, makes a fundamental contribution to the quality of the FLE CS. The processes and insights presented here can be useful for others planning a similar undert, Zielsetzung: Seit 2011 wird in der Schweiz eine neue nationale Schlussprüfung in Humanmedizin mit einem strukturierten klinisch-praktischen Teil im OSCE Format durchgeführt. Der vorliegende Beitrag beschreibt, aus Sicht der nationalen Arbeitsgruppe, die essentiellen Schritte der Erstellung, Durchführung und Auswertung der Eidgenössischen Prüfung Clinical Skills (EP CS) sowie der jeweils eingesetzten Qualitätssicherungsmassnahmen. Schliesslich werden zentrale Erkenntnisse der vergangenen Jahre vorgestellt. Methodik: Basierend auf den Prinzipien der Aktionsforschung wird die EP CS kontinuierlich weiter entwickelt. Auf der Grundlage systematisch dokumentierter Erfahrungen aus den Vorjahren werden in der Arbeitsgruppe anstehende Fragen diskutiert, daraus resultierende Lösungsansätze konkretisiert (Planung), in der Prüfung umgesetzt (Implementation) und anschliessend evaluiert (Reflexion). Die vorgestellten Ergebnisse sind das Produkt dieses iterativen Vorgehens. Ergebnisse: Die EP CS wird durch Fachexperten aller Fakultäten und Fachrichtungen in einem mehrstufigen Prozess erstellt. Die Prüfung wird dezentral in Deutsch und Französisch durchgeführt und besteht aus zwölf interdisziplinären Stationen pro Kandidat. Als wichtige Qualitätssicherungsmassnahmen haben sich das nationale Review Board (inhaltliche Validierung) und die Treffen der Schauspielpatienten-Trainer (Standardisierung) erwiesen. Die statistischen Auswertungen zeigen eine gute Messzuverlässigkeit und weisen auf die Konstruktvalidität der Prüfung hin. Zu den zentralen Erkenntnissen der vergangenen Jahre gehört, dass die konsequente Umsetzung der Prinzipien der Aktionsforschung zur erfolgreichen Weiterentwicklung der Prüfung beiträgt.Schlussfolgerung: Der zentral koordinierte, kollaborativ-iterative Prozess mit Einbindung von Fachexperten aus allen Fakultäten trägt wesentlich zur Qualität der EP CS bei. Die hier vorgestellten Prozesse und Erkenntnisse können für andere nützlich sein, welche Ähnliches vorhaben.

BACKGROUND: A broad range of gemcitabine dosages have been used in dogs. HYPOTHESIS/OBJECTIVES: To determine maximally tolerated dose (MTD), dose-limiting toxicity (DLT), and preliminary antitumor activity of intravenous administration of gemcitabine in dogs with advanced solid tumors. ANIMALS: Twenty-two client-owned dogs. METHODS: Dogs with advanced cancer were prospectively enrolled in an open-label Phase 1 study of gemcitabine. Gemcitabine was administered as a 30-minute intravenous bolus starting at 800 mg/m(2), using escalation of 50 mg/m(2) increments with 3 dogs per dose level. MTD was established based on the number of dogs experiencing DLT assessed after 1 cycle. Treatment continued until disease progression or unacceptable toxicosis. Additional dogs were enrolled at MTD to better characterize tolerability, and to assess the extent and duration of gemcitabine excretion. RESULTS: Twenty-two dogs were treated at 4 dose levels, ranging from 800 to 950 mg/m(2). Neutropenia was identified as DLT. MTD was 900 mg/m(2). DLT consisting of grade 4 febrile neutropenia was observed at 950 mg/m(2) in 2 dogs. There were no nonhematologic DLTs. Twenty dogs received multiple doses, and none had evidence of severe toxicosis from any of their subsequent treatments. At 900 mg/m(2), 2 complete and 5 partial responses were observed in dogs with measurable tumors. The amount of gemcitabine excreted in urine decreased over time, and was undetectable after the first 24 hours. CONCLUSIONS AND CLINICAL IMPORTANCE: The recommended dose of gemcitabine for future Phase 2 studies is weekly 900 mg/m(2). In chemotherapy-naïve dogs with advanced solid tumor this dose level merits further evaluation.

La questione che si pone con maggior urgenza al reduce di Auschwitz è quello della memoria: paradossalmente, è la stessa enormità dei crimini commessi a mettere a repentaglio la possibilità di ricordare. Tuttavia nel corso degli anni la riflessione di Primo Levi si rivolge in maniera via via sempre più esplicita verso temi connessi alla dimensione della giustizia, tant’è che I sommersi e i salvati del 1986 mette a fuoco con esemplare lucidità i fenomeni della “zona grigia” e della vergogna di essere sopravvissuti. Non meno significativi sono però anche altri aspetti, che trovano la loro espressione meno reticente in opere collaterali o minori, come il tema del perdono, trattato con incisiva sintesi in un commento al Girasole di Simon Wiesenthal. Ma è soprattutto nelle poesie che affiorano, in tutta la loro controversa drammaticità, i sentimenti connessi al bisogno di giudicare: dal senso di colpa dei superstiti, così straziante da risultare a tratti incontrollabile, a un desiderio di ottenere giustizia che riesce a esprimersi in tutta la sua veemenza solo nella forma della traduzione o della citazione

Background: The resuscitation strategy for hemorrhagic shock remains controversial, with the kidney being especially prone to hypoxia. Methods: The authors used a three-phase hemorrhagic shock model to investigate the effects of fluid resuscitation on renal oxygenation. After a 1-h shock phase, rats were randomized into four groups to receive either normal saline or hypertonic saline targeting a mean arterial pressure (MAP) of either 40 or 80 mmHg. After such resuscitation, rats were transfused with the shed blood. Renal macro-and microcirculation were monitored with cortical and outer-medullary microvascular oxygen pressure, renal oxygen delivery, and renal oxygen consumption measured using oxygen-dependent quenching of phosphorescence. Results: Hemorrhagic shock was characterized by a drop of aortic blood flow, MAP, renal blood flow, renal oxygen delivery, renal oxygen consumption, and renal microvascular PO2. During the fluid resuscitation phase, normal saline targeting a MAP = 80 mmHg was the sole strategy able to restore aortic blood flow, renal blood flow, and renal oxygen consumption, although without improving renal oxygen delivery. However, none of the strategies using either normal saline or hypertonic saline or targeting a high MAP could restore the renal microvascular Po2. Blood transfusion increased microvascular Po2 but was unable to totally restore renal microvascular oxygenation to baseline values. Conclusions: This experimental rat study shows that (1) high MAP-directed fluid resuscitation (80 mmHg) does not lead to higher renal microvascular Po2 compared with fluid resuscitation targeted to MAP (40 mmHg); (2) hypertonic saline is not superior to normal saline regarding renal oxygenation; and (3) decreased renal oxygenation persists after blood transfusion.

Background: In the present study we developed, evaluated in volunteers, and clinically validated an image acquisition stabilizer (IAS) for Sidestream Dark Field (SDF) imaging.Methods: The IAS is a stainless steel sterilizable ring which fits around the SDF probe tip. The IAS creates adhesion to the imaged tissue by application of negative pressure. The effects of the IAS on the sublingual microcirculatory flow velocities, the force required to induce pressure artifacts (PA), the time to acquire a stable image, and the duration of stable imaging were assessed in healthy volunteers. To demonstrate the clinical applicability of the SDF setup in combination with the IAS, simultaneous bilateral sublingual imaging of the microcirculation were performed during a lung recruitment maneuver (LRM) in mechanically ventilated critically ill patients. One SDF device was operated handheld; the second was fitted with the IAS and held in position by a mechanic arm. Lateral drift, number of losses of image stability and duration of stable imaging of the two methods were compared.Results: Five healthy volunteers were studied. The IAS did not affect microcirculatory flow velocities. A significantly greater force had to applied onto the tissue to induced PA with compared to without IAS (0.25 ± 0.15 N without vs. 0.62 ± 0.05 N with the IAS, p < 0.001). The IAS ensured an increased duration of a stable image sequence (8 ± 2 s without vs. 42 ± 8 s with the IAS, p < 0.001). The time required to obtain a stable image sequence was similar with and without the IAS. In eight mechanically ventilated patients undergoing a LRM the use of the IAS resulted in a significantly reduced image drifting and enabled the acquisition of significantly longer stable image sequences (24 ± 5 s without vs. 67 ± 14 s with the IAS, p = 0.006).Conclusions: The present study has validated the use of an IAS for improvement of SDF imaging by demonstrating that the IAS did not affect microcirculatory perfusion in the mi

Il contributo contiene un'intervista a Daniele Salvo, regista di "Edipo a Colono" di Sofocle in cartellone nel 2009 per il XLV ciclo di Rappresentazioni Classiche al Teatro greco di Siracusa della Fondazione INDA.

Il contributo propone un'intervista a Giovanni Cerri, traduttore di "Edipo a Colono" di Sofocle per il XLV Ciclo di Spettacoli classici al Teatro greco di Siracusa della Fondazione INDA.

Il contributo si configura come un percorso nella storia della Fondazione INDA, attraverso una panoramica che dalla prima messinscena dell'Orestea di Eschilo al Teatro greco di Siracusa conduce fino a quella del 2008, diretta da Pietro Carriglio con la ripresa della traduzione di P.P. Pasolini.

Mitochondrial oxygen tension (mitoPO2) is a key parameter for cellular function, which is considered to be affected under various pathophysiological circumstances. Although many techniques for assessing in vivo oxygenation are available, no technique for measuring mitoPO2in vivo exists. Here we report in vivo measurement of mitoPO2and the recovery of mitoPO2histograms in rat liver by a novel optical technique under normal and pathological circumstances. The technique is based on oxygen-dependent quenching of the delayed fluorescence lifetime of protoporphyrin IX. Application of 5-aminolevulinic acid enhanced mitochondrial protoporphyrin IX levels and induced oxygen-dependent delayed fluorescence in various tissues, without affecting mitochondrial respiration. Using fluorescence microscopy, we demonstrate in isolated hepatocytes that the signal is of mitochondrial origin. The delayed fluorescence lifetime was calibrated in isolated hepatocytes and isolated perfused livers. Ultimately, the technique was applied to measure mitoPO2in rat liver in vivo. The results demonstrate mitoPO2values of ∼30-40 mmHg. mitoPO2was highly sensitive to small changes in inspired oxygen concentration around atmospheric oxygen level. Ischemia-reperfusion interventions showed altered mitoPO2distribution, which flattened overall compared to baseline conditions. The reported technology is scalable from microscopic to macroscopic applications, and its reliance on an endogenous compound greatly enhances its potential field of applications.

Il contributo costituisce la traduzione di un estratto di O. Taplin, An academic in the rehearsal room edito in John Barsby (ed.) Greek and Roman Drama: Translation and Performance, DRAMA Band 12, Suttgart and Weimar: J.B.Metzler Verlag, 2002. Si tratta di una nota sul metodo relativa alla relazione fra testo e messinscena nella prassi antica e contemporanea.