Motion sickness, stress and the endocannabinoid system

A substantial number of individuals are at risk for the development of motion sickness induced nausea and vomiting (N&V) during road, air or sea travel. Motion sickness can be extremely stressful but the neurobiologic mechanisms leading to motion sickness are not clear. The endocannabinoid system (ECS) represents an important neuromodulator of stress and N&V. Inhibitory effects of the ECS on N&V are mediated by endocannabinoid-receptor activation

A comparison of polymineral and K-feldspar post-infrared infrared stimulated luminescence ages of loess from Franconia, southern Germany

Loess-paleosol sequences (LPSs) are essential records for reconstructing Quaternary paleoenvironments. No previous study has provided numerical chronologies of loess in Lower Franconia, southern Germany; their chronostratigraphic assumptions have relied mainly on German (pedo)stratigraphic schemes. In this study, we provide for the first time a chronology for LPSs in Lower Franconia based on optically stimulated luminescence (OSL) dating using quartz and a comparison of K-feldspar (63–100 µm) and the polymineral fraction (4–11 µm). Our results show that all obtained ages are in stratigraphic order, ranging from Holocene to late Pleistocene, and in general confirm the former stratigraphical interpretations. A good agreement of the obtained ages is observed between both feldspar grain size fractions; they also agree well with the quartz OSL ages up to ∼50 ka. However, a marked difference between the growth pattern of the dose response curves and consequently different saturation characteristics of fine and coarse grains is found. Even though in our samples the discrepancy in ages is not very significant, we suggest the use of coarse-grained K-feldspar whenever possible in order to not be confronted with unknowns such as the mineral composition of the polymineral fraction.Löss-Paläoboden-Sequenzen sind wichtige Archive zur Rekonstruktion der quartären Umwelt. Bisher hat sich noch keine Arbeit mit der numerischen Chronologie mainfränkischer Lösse befasst; die bisherigen chronostratigraphischen Einordnungen haben ihren Ursprung in deutschen (pedo)stratigraphischen Schemata. In der vorliegenden Arbeit stellen wir erstmals eine auf optisch stimulierter Lumineszenz (OSL) basierende Chronologie für Löss-Paläoboden-Sequenzen in Mainfranken vor. Hierzu wurden Quarz und in vergleichender Weise sowohl K-Feldspat (63–100 µm) als auch die polymineralische Feinkornfraktion (4–11 µm) verwendet. Unsere Ergebnisse zeigen, dass alle gewonnenen Alter in stratigraphischer Reihenfolge sind, vom Holozän bis zum Spätpleistozän, und generell die früher angenommenen stratigraphischen Interpretationen stützen. Eine gute Altersübereinstimmung liegt für die beiden Feldspatfraktionen vor; die Alter stimmen weiterhin mit den Quarz-OSL-Altern bis 50 ka überein. Im Vergleich von Feldspat-Grobkorn und Feinkorn (polymineralische Fraktion) zeigt sich bei jedoch ein stark voneinander abweichendes Verhalten in den Wachstumsverläufen der Dose Response Curves und ein sich daraus ergebendes unterschiedliches Sättigungsverhalten. Auch wenn die Unterschiede für die hier vorliegenden Proben nicht übermäßig groß sind, so empfehlen wir, wenn immer möglich, die Verwendung von grobkörnigem K-Feldspat für die Datierung, um nicht mit möglichen Unbekannten, wie der Mineralzusammensetzung von polymineralischen Extrakten konfrontiert zu sein

Pleistocene loess deposits and mollusc assemblages in the Eastern Pre-Alps

Die Lössablagerungen im nördlichen Wienerwald sind im Vergleich mit anderen Mittelgebirgsregionen aufgrund ihrer Mächtigkeit sehr eindrucksvoll. Charakterista in der Korngrößenverteilung zeigen deutlich, dass die Lösse im Hagenbachtal sich von denen anderer Lösssgebiete unterscheiden. Ein Vergleich mit Lössprofilen in Krems und Stillfried hat ergeben, dass der Löss im Hagenbachtal einen erhöhten Sandanteil aufweist und damit den Einfluss der Flysch-Sandsteine widerspiegelt. Das spricht für einen lokalen Sedimenteintrag und kurze äolische Transportstrecken. Zudem wurde der Löss unter kühl-humiden Paläoklimabedingungen zum Teil als Schwemmlöss abgelagert. Die malakologischen Ergebnisse stimmen mit den geomorphodynamischen Bedingungen überein. Die Umlagerungsprozesse haben zu einer intensiven Fragmentierung der Schalenreste geführt. Die malakologischen Untersuchungen belegen insgesamt 28 unterschiedliche Arten von terrestrischen Gastropoden mit 3283 Individuen. Die paläoökologische Auswertung spricht für sehr humide, kühle Klimabedingungen mit einer schwach ausgeprägten, klimatisch etwas günstigeren Phase.researc

Inhalationally administered semifluorinated alkanes (SFAs) as drug carriers in an experimental model of acute respiratory distress syndrome

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics

Oxygenation inhibits the physiological tissue-protecting mechanism and thereby exacerbates acute inflammatory lung injury

Acute respiratory distress syndrome (ARDS) usually requires symptomatic supportive therapy by intubation and mechanical ventilation with the supplemental use of high oxygen concentrations. Although oxygen therapy represents a life-saving measure, the recent discovery of a critical tissue-protecting mechanism predicts that administration of oxygen to ARDS patients with uncontrolled pulmonary inflammation also may have dangerous side effects. Oxygenation may weaken the local tissue hypoxia-driven and adenosine A2A receptor (A2AR)-mediated anti-inflammatory mechanism and thereby further exacerbate lung injury. Here we report experiments with wild-type and adenosine A2AR-deficient mice that confirm the predicted effects of oxygen. These results also suggest the possibility of iatrogenic exacerbation of acute lung injury upon oxygen administration due to the oxygenation-associated elimination of A2AR-mediated lung tissue-protecting pathway. We show that this potential complication of clinically widely used oxygenation procedures could be completely prevented by intratracheal injection of a selective A2AR agonist to compensate for the oxygenation-related loss of the lung tissue-protecting endogenous adenosine. The identification of a major iatrogenic complication of oxygen therapy in conditions of acute lung inflammation attracts attention to the need for clinical and epidemiological studies of ARDS patients who require oxygen therapy. It is proposed that oxygen therapy in patients with ARDS and other causes of lung inflammation should be combined with anti-inflammatory measures, e.g., with inhalative application of A2AR agonists. The reported observations may also answer the long-standing question as to why the lungs are the most susceptible to inflammatory injury and why lung failure usually precedes multiple organ failure

The SARS-coronavirus-host interactome

Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock

Is antibacterial treatment intensity lower in elderly patients? A retrospective cohort study in a German surgical intensive care unit

Background: Demographic change concurrent with medical progress leads to an increasing number of elderly patients in intensive care units (ICUs). Antibacterial treatment is an important, often life-saving, aspect of intensive care but burdened by the associated antimicrobial resistance risk. Elderly patients are simultaneously at greater risk of infections and may be more restrictively treated because, generally, treatment intensity declines with age. We therefore described utilization of antibacterials in ICU patients older and younger than 80 years and examined differences in the intensity of antibacterial therapy between both groups. Methods: We analysed 17,464 valid admissions from the electronic patient data management system of our surgical ICU from April 2006 – October 2013. Antibacterial treatment rates were defined as days of treatment (exposed patient days) relative to patient days of ICU stay and calculated for old and young patients. Rates were compared in zero-inflated Poisson regression models adjusted for patients’ sex, mean SAPS II- and TISS-scores, and calendar years yielding adjusted rate ratios (aRRs). Rate ratios exceeding 1 represent higher rates in old patients reflecting greater treatment intensity in old compared to younger patients. Results: Observed antibacterial treatment rates were lower in patients 80 years and older compared to younger patients (30.97 and 39.73 exposed patient days per 100 patient days in the ICU, respectively). No difference in treatment intensity, however, was found from zero-inflated Poisson regression models permitting more adequate consideration of patient days with low treatment probability: for all antibacterials the adjusted rate ratio (aRR) was 1.02 (95%CI: 0.98–1.07). Treatment intensities were higher in elderly patients for penicillins (aRR 1.37 (95%CI: 1.26–1.48)), cephalosporins (aRR 1.20 (95%CI: 1.09–1.31)), carbapenems (aRR 1.35 (95%CI: 1.20–1.50)), fluoroquinolones (aRR 1.17 (95%CI: 1.05–1.30), and imidazoles (aRR 1.34 (95%CI: 1.23–1.46)). Conclusions: Elderly patients were generally less likely to be treated with antibacterials. This observation, however, did not persist in patients with comparable treatment probability. In these, antibacterial treatment intensity did not differ between younger and older ICU patients, for some antibacterial classes treatment intensity was even higher in the latter. Patient-level covariates are instrumental for a nuanced evaluation of age-effects in antibacterial treatment in the ICU