A safe and effective protocol for postdilution hemofiltration with regional citrate anticoagulation.

BACKGROUND: Regional citrate anticoagulation (RCA) is recommended during continuous renal replacement therapy. Compared to systemic anticoagulation, RCA provides a longer filter lifespan with the risk of metabolic alkalosis and impaired calcium homeostasis. Surprisingly, most RCA protocols are designed for continuous veno-venous hemodialysis or hemodiafiltration. Effective protocols for continuous veno-venous hemofiltration (CVVH) are rare, although CVVH is a standard treatment for high-molecular-weight clearance. Therefore, we evaluated a new RCA protocol for postdilution CVVH. METHODS: This is a monocentric prospective interventional study to evaluate a new RCA protocol for postdilution CVVH. We recruited surgical patients with stage III acute kidney injury who needed renal replacement therapy. We recorded dialysis and RCA data and hemodynamic and laboratory parameters during treatment sessions of 72 h. The primary endpoint was filter patency at 72 h. The major safety parameters were metabolic alkalosis and severe hypocalcemia at any time. RESULTS: We included 38 patients who underwent 66 treatment sessions. The mean filter lifespan was 66 ± 12 h, and 44 of 66 (66%) filters were patent at 72 h. After censoring for non-CVVH-related cessation of treatment, 83% of all filters were patent at 72 h. The delivered dialysis dose was 28 ± 5 ml/kgBW/h. The serum levels of creatinine, urea and beta2-microglobulin decreased significantly from day 0 to day 3. Metabolic alkalosis occurred in one patient. An iCa++ below 1.0 mmol/L occurred in four patients. Citrate accumulation did not occur. CONCLUSIONS: We describe a safe, effective, and easy-to-use RCA protocol for postdilution CVVH. This protocol provides a long and sustained filter lifespan without serious adverse effects. The risk of metabolic alkalosis and hypocalcemia is low. Using this protocol, a recommended dialysis dose can be safely administered with effective clearance of low- and middle-molecular-weight molecules. TRIAL REGISTRATION: The study was approved by the medical ethics committee of Heinrich-Heine University Duesseldorf (No. 2018-82KFogU). The trial was registered in the local study register of the university (No: 2018044660) on 07/04/2018 and was retrospectively registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03969966) on 31/05/2019.

Natural Fe-bearing aluminous bridgmanite in the Katol L6 chondrite.

Bridgmanite, the most abundant mineral of the Earth's lower mantle, has been reported in only a few shocked chondritic meteorites; however, the compositions of these instances differ from that expected in the terrestrial bridgmanite. Here, we report the first natural occurrence of Fe-bearing aluminous bridgmanite in shock-induced melt veins within the Katol L6 chondrite with a composition that closely matches those synthesized in high-pressure and temperature experiments over the last three decades. The Katol bridgmanite coexists with majorite and metal-sulfide intergrowths. We found that the natural Fe-bearing aluminous bridgmanite in the Katol L6 chondrite has a significantly higher Fe3+/ΣFe ratio (0.69 ± 0.08) than coexisting majorite (0.37 ± 0.10), which agrees with experimental studies. The Katol bridgmanite is arguably the closest natural analog for the bridgmanite composition expected to be present in the Earth's lower mantle. Textural observations and comparison with laboratory experiments suggest that the Katol bridgmanite formed at pressures of ∼23 to 25 gigapascals directly from the chondritic melt generated by the shock event. Thus, the Katol L6 sample may also serve as a unique analog for crystallization of bridgmanite during the final stages of magma ocean crystallization during Earth's formation.

Pravastatin Improves Colonic and Hepatic Microcirculatory Oxygenation during Sepsis without Affecting Mitochondrial Function and ROS Production in Rats.

Microcirculatory and mitochondrial dysfunction are considered the main mechanisms of septic shock. Studies suggest that statins modulate inflammatory response, microcirculation, and mitochondrial function, possibly through their action on peroxisome proliferator-activated receptor alpha (PPAR-α). The aim of this study was to examine the effects of pravastatin on microcirculation and mitochondrial function in the liver and colon and the role of PPAR-α under septic conditions. This study was performed with the approval of the local animal care and use committee. Forty Wistar rats were randomly divided into 4 groups: sepsis (colon ascendens stent peritonitis, CASP) without treatment as control, sepsis + pravastatin, sepsis + PPAR-α-blocker GW6471, and sepsis + pravastatin + GW6471. Pravastatin (200 µg/kg s.c.) and GW6471 (1 mg/kg) were applied 18 h before CASP-operation. 24 h after initial surgery, a relaparotomy was performed, followed by a 90 min observation period for assessment of microcirculatory oxygenation (µHbO2) of the liver and colon. At the end of the experiments, animals were euthanized, and the colon and liver were harvested. Mitochondrial function was measured in tissue homogenates using oximetry. The ADP/O ratio and respiratory control index (RCI) for complexes I and II were calculated. Reactive oxygen species (ROS) production was assessed using the malondialdehyde (MDA)-Assay. Statistics: two-way analysis of variance (ANOVA) + Tukey's/Dunnett's post hoc test for microcirculatory data, Kruskal-Wallis test + Dunn's post hoc test for all other data. In control septic animals µHbO2 in liver and colon deteriorated over time (µHbO2: -9.8 ± 7.5%* and -7.6 ± 3.3%* vs. baseline, respectively), whereas after pravastatin and pravastatin + GW6471 treatment µHbO2 remained constant (liver: µHbO2 pravastatin: -4.21 ± 11.7%, pravastatin + GW6471: -0.08 ± 10.3%; colon: µHbO2 pravastatin: -0.13 ± 7.6%, pravastatin + GW6471: -3.00 ± 11.24%). In both organs, RCI and ADP/O were similar across all groups. The MDA concentration remained unchanged in all groups. Therefore, we conclude that under septic conditions pravastatin improves microcirculation in the colon and liver, and this seems independent of PPAR-α and without affecting mitochondrial function.

Gemfibrozil Improves Microcirculatory Oxygenation of Colon and Liver without Affecting Mitochondrial Function in a Model of Abdominal Sepsis in Rats.

Recent studies observed, despite an anti-hyperlipidaemic effect, a positive impact of fibrates on septic conditions. This study evaluates the effects of gemfibrozil on microcirculatory variables, mitochondrial function, and lipid peroxidation levels with regard to its potential role as an indicator for oxidative stress in the colon and liver under control and septic conditions and dependencies on PPARα-mediated mechanisms of action. With the approval of the local ethics committee, 120 Wistar rats were randomly divided into 12 groups. Sham and septic animals were treated with a vehicle, gemfibrozil (30 and 100 mg/kg BW), GW 6471 (1 mg/kg BW, PPARα inhibitor), or a combination of both drugs. Sepsis was induced via the colon ascendens stent peritonitis (CASP) model. Then, 24 h post sham or CASP surgery, a re-laparotomy was performed. Measures of vital parameters (heart rate (HR), mean arterial pressure (MAP), and microcirculation (µHbO2)) were recorded for 90 min. Mitochondrial respirometry and assessment of lipid peroxidation via a malondialdehyde (MDA) assay were performed on colon and liver tissues. In the untreated sham animals, microcirculation remained stable, while pre-treatment with gemfibrozil showed significant decreases in the microcirculatory oxygenation of the colon. In the CASP animals, µHbO2 levels in the colon and the liver were significantly decreased 90 min after laparotomy. Pre-treatment with gemfibrozil prevented the microcirculatory aberrations in both organs. Gemfibrozil did not affect mitochondrial function and lipid peroxidation levels in the sham or CASP animals. Gemfibrozil treatment influences microcirculation depending on the underlying condition. Gemfibrozil prevents sepsis-induced microcirculatory aberrances in the colon and liver PPARα-independently. In non-septic animals, gemfibrozil impairs the microcirculatory variables in the colon without affecting those in the liver.

Gender does not make the difference: interest in STEM by gender is fully mediated by technical socialization and degree program.

In Germany, there is a shortage of skilled workers in the fields of science, technology, engineering, and mathematics (STEM) and especially in technology with declining interest in technology and with supposedly fewer teachers in technology education in the next 20 years. The present study examined whether students' interest in STEM is dependent on their career choices (i.e., their degree program), their technical socialization, their personality, and gender. A survey in Germany, Baden-Wuerttemberg (N = 350) examined gender-specific differences in teacher training students with and without technology and engineering students via structural equation modelling with the mediators personality, technical socialization, and degree program. Results show that interest in STEM by gender is fully mediated by technical socialization and degree program. Solutions for the reduction of the staff shortage and gender gap in the technical domain are discussed and it is suggested that an integration of technology lessons in the school curriculum and a reduction of gender normatives may help.

Exogenous vasopressin dose-dependently modulates gastric microcirculatory oxygenation in dogs via V1A receptor.

BACKGROUND: Hypercapnia improves gastric microcirculatory oxygenation (µHbO2) and increases vasopressin plasma levels, whereas V1A receptor blockade abolishes the increase of µHbO2. The aim of this study was to evaluate the effect of exogenous vasopressin (AVP) in increasing doses on microcirculatory perfusion and oxygenation and systemic hemodynamic variables. Furthermore, we evaluated the role of the vasopressin V1A receptor in mediating the effects. METHODS: In repetitive experiments, six anesthetized dogs received a selective vasopressin V1A receptor inhibitor ([Pmp1, Tyr (Me)2]-Arg8-Vasopressin) or sodium chloride (control groups). Thereafter, a continuous infusion of AVP was started with dose escalation every 30 min (0.001 ng/kg/min-1 ng/kg/min). Microcirculatory variables of the oral and gastric mucosa were measured with reflectance spectrometry, laser Doppler flowmetry, and incident dark field imaging. Transpulmonary thermodilution was used to measure systemic hemodynamic variables. AVP plasma concentrations were measured during baseline conditions and 30 min after each dose escalation. RESULTS: During control conditions, gastric µHbO2 did not change during the course of experiments. Infusion of 0.001 ng/kg/min and 0.01 ng/kg/min AVP increased gastric µHbO2 to 87 ± 4% and 87 ± 6%, respectively, compared to baseline values (80 ± 7%), whereas application of 1 ng/kg/min AVP strongly reduced gastric µHbO2 (59 ± 16%). V1A receptor blockade prior to AVP treatment abolished these effects on µHbO2. AVP dose-dependently enhanced systemic vascular resistance (SVR) and decreased cardiac output (CO). After prior V1A receptor blockade, SVR was reduced and CO increased (0.1 ng/kg/min + 1 ng/kg/min AVP). CONCLUSIONS: Exogenous AVP dose-dependently modulates gastric µHbO2, with an increased µHbO2 with ultra-low dose AVP. The effects of AVP on µHbO2 are abolished by V1A receptor inhibition. These effects are independent of a modulation of systemic hemodynamic variables.

Weak Associations of Morningness-Eveningness and Stability with Skin Temperature and Cortisol Levels.

Differences in daytime preferences can be described on the dimension of morningness-eveningness (continuous) or circadian typology (categorical) and are associated with our physiological functioning, which is reflected in body temperature and cortisol levels in the morning. The purpose of the present study was to explore the relationship between morningness-eveningness, stability and physiological markers (body temperature and cortisol) based on a three-dimensional conceptualization of morningness-eveningness using the Morningness-Eveningness-Stability Scale improved (MESSi). In contrast to previously used unidimensional measures, the MESSi determines circadian typology and its amplitude in three dimensions: Morning affect (MA), Eveningness (EV) and Stability/Distinctness (DI). Furthermore, the differences of the cortisol levels between weekday and weekend were examined. The sample (N = 42) consisted of extreme chronotypes (age 18-54 years; M = 24.8 years, SD = 5.83; 22 morning types [5 men and 17 women] and 20 evening types [8 men and 12 women]). The participants were asked to measure their skin temperature for one week and sample four saliva probes for cortisol determination. Morning types showed a better fit in the actual temperature data to the approximating data as compared to Evening types and showed a higher overall temperature. The Stability/Distinctness (DI) component of the MESSi was negatively correlated with the nadir. Morning types also showed higher cortisol levels than Evening types immediately after awakening. The cortisol levels were higher on a weekday compared to the weekend. To conclude, the present findings demonstrate that the skin temperature is weakly associated with morningness-eveningness and the stability of the circadian phase.

Melatonin pretreatment improves gastric mucosal blood flow and maintains intestinal barrier function during hemorrhagic shock in dogs.

OBJECTIVE: Melatonin improves hepatic perfusion after hemorrhagic shock and may reduce stress-induced gastric lesions. This study was designed to investigate whether pretreatment with melatonin may influence gastric mucosal microcirculatory perfusion (µflow), oxygenation (µHbO2 ), or intestinal barrier function during physiological and hemorrhagic conditions in dogs. METHODS: In a randomized crossover study, five anesthetized foxhounds received melatonin 100 µg kg-1 or vehicle (ethanol 5%) intravenously in the absence or presence of hemorrhagic shock (60 minutes, -20% blood volume). Systemic hemodynamic variables, gastric mucosal perfusion, and oxygenation were recorded continuously; intestinal barrier function was assessed intermittently via xylose absorption. RESULTS: During hemorrhagic shock, melatonin significantly attenuated the decrease in µflow, compared with vehicle (-19±9 vs -43±10 aU, P<.05), without influence on µHbO2 . A significant increase in xylose absorption was detected during hemorrhage in vehicle-treated dogs, compared with sham-operated animals (13±2 vs 8±1 relative amounts, P<.05); this was absent in melatonin-treated animals (6±1 relative amounts). Melatonin did not influence macrocirculation. CONCLUSIONS: Melatonin improves regional blood flow suggesting improved oxygen delivery in gastric mucosa during hemorrhagic shock. This could provide a mechanism for the observed protection of intestinal barrier function in dogs.

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs.

BACKGROUND: Topical drug application is used to avoid systemic side effects. The aim of this study was to analyze whether locally applied iloprost or nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier function during physiological and hemorrhagic conditions. METHODS: In repeated experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro- and microcirculatory variables were recorded continuously. Gastric barrier function was assessed via translocation of sucrose into the blood. RESULTS: During hemorrhage, gastric mucosal oxygenation decreased from 77 ± 4 to 37 ± 7%. This effect was attenuated by nitroglycerin (78 ± 6 to 47 ± 13%) and iloprost (82 ± 4 to 54 ± 9%). Sucrose plasma levels increased during hemorrhage from 7 ± 4 to 55 ± 15 relative amounts. This was alleviated by nitroglycerin (5 ± 8 to 29 ± 38 relative amounts). These effects were independent of systemic hemodynamic variables. CONCLUSIONS: During hemorrhage, topical nitroglycerin and iloprost improve regional gastric oxygenation without affecting perfusion. Nitroglycerin attenuated the shock-induced impairment of the mucosal barrier integrity. Thus, local drug application improves gastric microcirculation without compromising systemic hemodynamic variables, and it may also protect mucosal barrier function.

Fluid-induced organic synthesis in the solar nebula recorded in extraterrestrial dust from meteorites.

Isotopically anomalous carbonaceous grains in extraterrestrial samples represent the most pristine organics that were delivered to the early Earth. Here we report on gentle aberration-corrected scanning transmission electron microscopy investigations of eight (15)N-rich or D-rich organic grains within two carbonaceous Renazzo-type (CR) chondrites and two interplanetary dust particles (IDPs) originating from comets. Organic matter in the IDP samples is less aromatic than that in the CR chondrites, and its functional group chemistry is mainly characterized by C-O bonding and aliphatic C. Organic grains in CR chondrites are associated with carbonates and elemental Ca, which originate either from aqueous fluids or possibly an indigenous organic source. One distinct grain from the CR chondrite NWA 852 exhibits a rim structure only visible in chemical maps. The outer part is nanoglobular in shape, highly aromatic, and enriched in anomalous nitrogen. Functional group chemistry of the inner part is similar to spectra from IDP organic grains and less aromatic with nitrogen below the detection limit. The boundary between these two areas is very sharp. The direct association of both IDP-like organic matter with dominant C-O bonding environments and nanoglobular organics with dominant aromatic and C-N functionality within one unique grain provides for the first time to our knowledge strong evidence for organic synthesis in the early solar system activated by an anomalous nitrogen-containing parent body fluid.

Trachyandesitic volcanism in the early Solar System.

Volcanism is a substantial process during crustal growth on planetary bodies and well documented to have occurred in the early Solar System from the recognition of numerous basaltic meteorites. Considering the ureilite parent body (UPB), the compositions of magmas that formed a potential UPB crust and were complementary to the ultramafic ureilite mantle rocks are poorly constrained. Among the Almahata Sitta meteorites, a unique trachyandesite lava (with an oxygen isotope composition identical to that of common ureilites) documents the presence of volatile- and SiO2-rich magmas on the UPB. The magma was extracted at low degrees of disequilibrium partial melting of the UPB mantle. This trachyandesite extends the range of known ancient volcanic, crust-forming rocks and documents that volcanic rocks, similar in composition to trachyandesites on Earth, also formed on small planetary bodies ∼ 4.56 billion years ago. It also extends the volcanic activity on the UPB by ∼ 1 million years (Ma) and thus constrains the time of disruption of the body to later than 6.5 Ma after the formation of Ca-Al-rich inclusions.

Vasopressin V1A receptors mediate the stabilization of intestinal mucosal oxygenation during hypercapnia in septic rats.

BACKGROUND: Microvascular oxygen saturation (µHBO2) plays an essential role in the development and outcome of sepsis. Hypercapnia (HC) improves the microvascular oxygenation of the mucosa in both healthy and septic animals. Vasopressin V1A receptor blockade prevents this positive effect under otherwise physiological conditions. The aim of this study was to investigate the effects and mechanisms of the vasopressin system during hypercapnia under septic conditions. METHODS: 80 rats were randomized into 8 groups (N=10). Colon ascendens stent peritonitis (CASP) or sham surgery was performed on 40 animals each to establish a moderate polymicrobial sepsis or sham control, respectively. 24h after sepsis induction the animals were subjected to 120min of volume-controlled and pressure-limited ventilation with either normocapnic (pCO2 35-45mmHg) or moderate hypercapnic (pCO2 of 65-75mmHg) ventilation targets. Animals received either vasopressin V1A receptor blockade (SR 49059, 1mgkg(-1) i.v.) or vehicle solution (dimethyl sulfoxide, 1%). Blood pressure, heart rate, pO2 and pCO2 were measured and microcirculatory oxygenation (µHBO2) and microcirculatory flow (µflow) were recorded using tissue reflectance spectrophotometry. Oxygen supply (µDO2) and consumption (µVO2) were calculated from intermittent blood gas analysis. RESULTS: In septic animals, µHBO2 declined during normocapnia (-11±10.3) but remained unchanged during hypercapnia. µHBO2 declined with vasopressin V1A receptor blockade both during normocapnia (-7.4±10.6) and hypercapnia (-9.2±9.8). Microcirculatory oxygen consumption was significantly reduced by hypercapnia in septic animals (-2.4·10(5) [AU]±2.4·10(5) [AU]). In sham animals, µHBO2 and µVO2 did not change. CONCLUSION: Vasopressin V1A receptors mediate the beneficial effects of hypercapnia on microcirculatory oxygenation during sepsis. The effects of vasopressin on µHBO2 might be related to decreased oxygen consumption during hypercapnia.

The beneficial effects of acute hypercapnia on microcirculatory oxygenation in an animal model of sepsis are independent of K(+)ATP channels.

BACKGROUND: Acute hypercapnia maintains the microcirculatory oxygenation of the splanchnic region during sepsis. The first aim of this study was to characterize the role of K(+)ATP channels on the microcirculatory flow and oxygenation during acute moderate hypercapnia. The second aim was to investigate whether a short period of hypercapnia induces detrimental effects in an otherwise undamaged rodent lung. METHODS: Experiments were performed on 60 male Wistar rats. A moderate polymicrobial sepsis was induced by colon ascendens stent peritonitis (CASP) surgery. 24h after induction of sepsis volume-controlled and pressure-limited ventilation was established for 120 min, with either normocapnic (pCO2 35-45 mmHg) or moderate hypercapnic ventilation targets (pCO2 65-75 mmHg) and with or without non-selective K(+)ATP channel blockade with glibenclamide. Microcirculatory blood flow of the colonic wall as well as oxygen delivery and consumption were assessed with tissue laser Doppler and reflectance spectrophotometry. Hemodynamic variables were recorded and plasma cytokine levels and myeloperoxidase levels of the lungs were analyzed. RESULTS: In septic animals microcirculatory oxygenation deteriorated progressively with normocapnia (-11.7 ± 11.8%) but was maintained (-2.9 ± 5.6%) with hypercapnia. This effect was associated with an increased microcirculatory oxygen consumption in septic animals with normocapnia (+25.7 ± 37.1%) that was decreased in the hypercapnia groups (-7.2 ± 28.1%). The effect of hypercapnia in septic animals was not altered by additional K(+)ATP channel blockade (-5.7 ± 32.7%). Hypercapnia neither induced an inflammatory response in lungs nor altered the systemic cytokine response. CONCLUSIONS: The observed beneficial effect of hypercapnia on microvascular oxygenation of the colon in sepsis does not seem to be mediated via K(+)ATP channels.

Impact of 11C-choline PET/CT on clinical decision making in recurrent prostate cancer: results from a retrospective two-centre trial.

PURPOSE: The aim of this retrospective two-centre study was to investigate the clinical impact of (11)C-choline PET/CT on treatment management decisions in patients with recurrent prostate cancer (rPCa) after radical therapy. METHODS: Enrolled in this retrospective study were 150 patients (95 from Bologna, 55 from Würzburg) with rPCa and biochemical relapse (PSA mean ± SD 4.3 ± 5.5 ng/mL, range 0.2-39.4 ng/mL) after radical therapy. The intended treatment before PET/CT was salvage radiotherapy of the prostatic bed in 95 patients and palliative androgen deprivation therapy (ADT) in 55 patients. The effective clinical impact of (11)C-choline PET/CT was rated as major (change in therapeutic approach), minor (same treatment, but modified therapeutic strategy) or none. Multivariate binary logistic regression analysis included PSA level, PSA kinetics, ongoing ADT, Gleason score, TNM, age and time to relapse. RESULTS: Changes in therapy after (11)C-choline PET/CT were implemented in 70 of the 150 patients (46.7%). A major clinical impact was observed in 27 patients (18%) and a minor clinical impact in 43 (28.7%). (11)C-choline PET/CT was positive in 109 patients (72.7%) detecting local relapse (prostate bed and/or iliac lymph nodes and/or pararectal lymph nodes) in 64 patients (42.7%). Distant relapse (paraaortic and/or retroperitoneal lymph nodes and/or bone lesions) was seen in 31 patients (20.7%), and both local and distant relapse in 14 (9.3%). A significant difference was observed in PSA level and PSA kinetics between PET-positive and PET-negative patients (p < 0.05). In multivariate analysis, PSA level, PSA doubling time and ongoing ADT were significant predictors of a positive scan (p < 0.05). In statistical analysis no significant differences were observed between the Bologna and Würzburg patients (p > 0.05). In both centres the same criteria to validate PET-positive findings were used: in 17.3% of patients by histology and in 82.7% of patients by correlative imaging and/or clinical follow-up (follow-up mean 20.5 months, median 18.3 months, range 6.2-60 months). CONCLUSION: (11)C-Choline PET/CT had a significant impact on therapeutic management in rPCa patients. It led to an overall change in 46.7% of patients, with a major clinical change implemented in 18% of patients. Further prospective studies are needed to evaluate the effect of such treatment changes on patient survival.

Evening adolescents: the role of family relationships and pubertal development.

Accumulating evidence suggests that evening-type adolescents are exposed to a number of determinants that might have a negative impact on their health condition. Despite the fact that biological and psychosocial factors are interrelated, their impacts on the shift toward eveningness during puberty have been considered only separately. In this study, the effects of frequency of conflicts and functional autonomy on the relationship between pubertal development and Morningness-Eveningness (M-E) were tested together. A sample of 2081 adolescents aged 12-16 completed pubertal development, M-E, family frequency of conflicts and functional autonomy scales. Results indicated that greater functional autonomy and more conflicts in the family were unique predictors of greater eveningness, and they both together were better predictors of M-E than an advanced age and pubertal development. Apart from biological development, family relationship seems an important factor explaining progressive tendency toward eveningness during puberty and adolescence. Some implications to adolescent development were indicated.

Local carbachol application induces oral microvascular recruitment and improves gastric tissue oxygenation during hemorrhagic shock in dogs.

Introduction: Hemorrhagic shock is characterized by derangements of the gastrointestinal microcirculation. Topical therapy with nitroglycerine or iloprost improves gastric tissue oxygenation but not regional perfusion, probably due to precapillary adrenergic innervation. Therefore, this study was designed to investigate the local effect of the parasympathomimetic carbachol alone and in combination with either nitroglycerine or iloprost on gastric and oral microcirculation during hemorrhagic shock. Methods: In a cross-over design five female foxhounds were repeatedly randomized into six experimental groups. Carbachol, or carbachol in combination with either nitroglycerine or iloprost were applied topically to the oral and gastric mucosa. Saline, nitroglycerine, or iloprost application alone served as control groups. Then, a fixed-volume hemorrhage was induced by arterial blood withdrawal followed by blood retransfusion after 1h of shock. Gastric and oral microcirculation was determined using reflectance spectrophotometry and laser Doppler flowmetry. Oral microcirculation was visualized with videomicroscopy. Statistics: 2-way-ANOVA for repeated measurements and Bonferroni post-hoc analysis (mean ± SEM; p < 0.05). Results: The induction of hemorrhage led to a decrease of gastric and oral tissue oxygenation, that was ameliorated by local carbachol and nitroglycerine application at the gastric mucosa. The sole use of local iloprost did not improve gastric tissue oxygenation but could be supplemented by local carbachol treatment. Adding carbachol to nitroglycerine did not further increase gastric tissue oxygenation. Gastric microvascular blood flow remained unchanged in all experimental groups. Oral microvascular blood flow, microvascular flow index and total vessel density decreased during shock. Local carbachol supply improved oral vessel density during shock and oral microvascular flow index in the late course of hemorrhage. Conclusion: The specific effect of shifting the autonomous balance by local carbachol treatment on microcirculatory variables varies between parts of the gastrointestinal tract. Contrary to our expectations, the improvement of gastric tissue oxygenation by local carbachol or nitroglycerine application was not related to increased microvascular perfusion. When carbachol is used in combination with local vasodilators, the additional effect on gastric tissue oxygenation depends on the specific drug combination. Therefore, modulation of tissue oxygen consumption, mitochondrial function or alterations in regional blood flow distribution should be investigated.

Effects of remote ischemic preconditioning on early markers of intestinal injury in experimental hemorrhage in rats.

The maintenance of intestinal integrity and barrier function under conditions of restricted oxygen availability is crucial to avoid bacterial translocation and local inflammation. Both lead to secondary diseases after hemorrhagic shock and might increase morbidity and mortality after surviving the initial event. Monitoring of the intestinal integrity especially in the early course of critical illness remains challenging. Since microcirculation and mitochondrial respiration are main components of the terminal stretch of tissue oxygenation, the evaluation of microcirculatory and mitochondrial variables could identify tissues at risk during hypoxic challenges, indicate an increase of intestinal injury, and improve our understanding of regional pathophysiology during acute hemorrhage. Furthermore, improving intestinal microcirculation or mitochondrial respiration, e.g. by remote ischemic preconditioning (RIPC) that was reported to exert a sufficient tissue protection in various tissues and was linked to mediators with vasoactive properties could maintain intestinal integrity. In this study, postcapillary oxygen saturation (µHbO2), microvascular flow index (MFI) and plasmatic D-lactate concentration revealed to be early markers of intestinal injury in a rodent model of experimental hemorrhagic shock. Mitochondrial function was not impaired in this experimental model of acute hemorrhage. Remote ischemic preconditioning (RIPC) failed to improve intestinal microcirculation and intestinal damage during hemorrhagic shock.

High-spatial resolution functional chemistry of nitrogen compounds in the observed UK meteorite fall Winchcombe.

Organic matter in extraterrestrial samples is a complex material that might have played an important role in the delivery of prebiotic molecules to the early Earth. We report here on the identification of nitrogen-containing compounds such as amino acids and N-heterocycles within the recent observed meteorite fall Winchcombe by high-spatial resolution spectroscopy techniques. Although nitrogen contents of Winchcombe organic matter are low (N/C ~ 1-3%), we were able to detect the presence of these compounds using a low-noise direct electron detector. These biologically relevant molecules have therefore been tentatively found within a fresh, minimally processed meteorite sample by high spatial resolution techniques conserving the overall petrographic context. Carbon functional chemistry investigations show that sizes of aromatic domains are small and that abundances of carboxylic functional groups are low. Our observations demonstrate that Winchcombe represents an important addition to the collection of carbonaceous chondrites and still preserves pristine extraterrestrial organic matter.

Asymmetries in commitment in an avian communication network.

Mobbing of predators occurs within a conspecific and heterospecific context but has not been quantified within the framework of a communication network and analysed with respect to heterospecific reciprocity. Here, we used playbacks of mobbing calls to show that mobbing is unequally distributed within a community of deciduous forest birds. Five species (great tit Parus major, blue tit Cyanistes caeruleus, marsh tit Poecile palustris, nuthatch Sitta europaea and chaffinch Fringilla coelebs) responded to each other's playbacks of mobbing calls. Commitment to mob was measured by minimum distance, response latency and uttering of calls. Commitment was higher when conspecific calls were broadcast. Yet, responses to heterospecific calls were significantly different between the five species. Chaffinches had the lowest commitment, and blue tits tended to have the highest. The communication network is asymmetric. Some species invest more than they receive from other species. As mobbing might incur costs, these are unequally distributed across the community.

Aggression in young adults--a matter of short sleep and social jetlag?

Evening orientation and sleep duration have been linked with aggression and problematic behaviors, but no study has used an explicit aggression questionnaire. The present study used the Buss-Perry Aggression Questionnaire based on physical aggression, verbal aggression, anger, and hostility, as well as questionnaires on the timing of sleep and sleep duration to assess this relationship in young adult men. The Composite Scale of Morningness was used to assess circadian preference; sleep-wake variables (wake time and sleep onset time on weekdays and on weekend days) were used to calculate midpoint of sleep, social jetlag, and sleep duration. Results indicated that sleep duration correlated negatively with verbal aggression, physical aggression, and anger. Short sleepers were more aggressive. Using multivariate analysis of variance, shorter sleep duration was a significant predictor of verbal aggression and anger. Concerning physical aggression, social jetlag also contributed to the model. Morningness-eveningness was associated with the hostility scale with eveningness related to higher hostility. Men scored higher than women in physical and verbal aggression.