Effects of prone positioning on lung mechanical power components in patients with acute respiratory distress syndrome: a physiologic study.

BACKGROUND: Prone positioning (PP) homogenizes ventilation distribution and may limit ventilator-induced lung injury (VILI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The static and dynamic components of ventilation that may cause VILI have been aggregated in mechanical power, considered a unifying driver of VILI. PP may affect mechanical power components differently due to changes in respiratory mechanics; however, the effects of PP on lung mechanical power components are unclear. This study aimed to compare the following parameters during supine positioning (SP) and PP: lung total elastic power and its components (elastic static power and elastic dynamic power) and these variables normalized to end-expiratory lung volume (EELV). METHODS: This prospective physiologic study included 55 patients with moderate to severe ARDS. Lung total elastic power and its static and dynamic components were compared during SP and PP using an esophageal pressure-guided ventilation strategy. In SP, the esophageal pressure-guided ventilation strategy was further compared with an oxygenation-guided ventilation strategy defined as baseline SP. The primary endpoint was the effect of PP on lung total elastic power non-normalized and normalized to EELV. Secondary endpoints were the effects of PP and ventilation strategies on lung elastic static and dynamic power components non-normalized and normalized to EELV, respiratory mechanics, gas exchange, and hemodynamic parameters. RESULTS: Lung total elastic power (median [interquartile range]) was lower during PP compared with SP (6.7 [4.9-10.6] versus 11.0 [6.6-14.8] J/min; P < 0.001) non-normalized and normalized to EELV (3.2 [2.1-5.0] versus 5.3 [3.3-7.5] J/min/L; P < 0.001). Comparing PP with SP, transpulmonary pressures and EELV did not significantly differ despite lower positive end-expiratory pressure and plateau airway pressure, thereby reducing non-normalized and normalized lung elastic static power in PP. PP improved gas exchange, cardiac output, and increased oxygen delivery compared with SP. CONCLUSIONS: In patients with moderate to severe ARDS, PP reduced lung total elastic and elastic static power compared with SP regardless of EELV normalization because comparable transpulmonary pressures and EELV were achieved at lower airway pressures. This resulted in improved gas exchange, hemodynamics, and oxygen delivery. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00017449). Registered June 27, 2019. https://drks.de/search/en/trial/DRKS00017449.

[Prehospital treatment of tension pneumothorax in children-which decisions do we make? : Results of a survey among German emergency physicians]. / Die prähospitale Therapie eines Spannungspneumothorax bei Kindern ­ welche Entscheidungen treffen wir? : Ergebnisse einer Umfrage unter deutschen Notärzten.

BACKGROUND: The preclinical treatment of a traumatic or spontaneous tension pneumothorax remains a particular challenge in pediatric patients. Currently recommended interventions for decompression are either finger thoracostomy or needle decompression. Due to the tiny intercostal spaces, finger thoracostomy may not be feasible in small children and surgical preparation may be necessary. In needle decompression, the risk of injuring underlying vital structures is increased because of the smaller anatomic structures. As most emergency physicians do not regularly work in pediatric trauma care, decompression of tension pneumothorax is associated with significant uncertainty; however, in this rare emergency situation, consistent and goal-oriented action is mandatory and lifesaving. An assessment of pre-existing experience and commonly used techniques therefore seems necessary to deduce the need for future education and training. OBJECTIVE: In this study an online survey was created to evaluate the experience and the favored prehospital treatment of tension pneumothorax in children among German emergency physicians. MATERIAL AND METHODS: An online survey was conducted with 43 questions on previous experience with tension pneumothorax in children, favored decompression technique and anatomical structures in different age groups. Surveyed were the emergency physicians of the ground-based emergency medical service of the University Medical Center Mannheim, the German Air Rescue Service (DRF) and the pediatric emergency medical service of the City of Munich. RESULTS: More than half of all respondents stated that there was uncertainty about the procedure of choice. Needle decompression was favored in smaller children and mini-thoracostomy in older children. In comparison with the literature, the thickness of the chest wall was mostly estimated correctly by the emergency medical physicians. The depth of the vital structures was underestimated at most of the possible insertion sites in all age groups. At the lateral insertion sites on the left hemithorax, however, the distance to the left ventricle was overestimated. The caliber of the needle selected for decompression tended to be too large, especially in younger children. CONCLUSION: Even though having interviewed an experienced group of prehospital emergency physicians, the experience in decompression of tension pneumothorax in children is relatively scant. Knowledge of chest wall thickness and depth to vital structures is sufficient, the choice of needle calibers tends to be too large but still reasonable. For many providers a large amount of uncertainty about the right choice of technique and equipment arises from the challenge of decompressing a tension pneumothorax in children and therefore further theoretical education and regular training are required for safe performance of the procedure.

Effect of sex and reproductive status on the immunity of the temperate bat Myotis daubentonii.

Studies of immunity in bat species are rare. However, it is important to determine immunological variations to identify factors influencing the health status of these endangered mammals from an evolutionary, ecological, conservation, and public health point of view. Immunity is highly variable and can be influenced by both internal (e.g. hormone levels, energy demand) and external factors (e.g. pathogens, climate). As bats have some peculiar ecological, energetic, and putative immunological characteristics, they are outstanding study organisms for ecoimmunological studies. We tested if (i) female bats have a higher immunity than males similar to most other mammalian species and (ii) individuals differ according to their energy demand (e.g. reproductive status). To study these questions, we sampled female and male Myotis daubentonii with different reproductive states and estimated their bacterial killing activity, hemolysis/hemagglutination titer, immunoglobulin G (IgG) concentration, and total and differential white blood cell counts. These methods characterize the cellular and humoral branches of both the adaptive and the innate immune responses of these individuals. Reproductively active males had lower cellular immunity compared to non-reproductive individuals. Pregnant females had increased IgG concentrations while hemolysis was enhanced during lactation. No clear trade-off between immunity and reproduction was found; instead immunity of males and female bats seems to be modulated differently due to varying hormonal and energetic states. Our data suggest that both adaptive and innate immunity as well as individual differences (i.e. sex and reproductive state) need to be considered to get a comprehensive overall picture of immunity in wild mammals.

Structural Characterization of Acidic Compounds in Pyrolysis Liquids Using Collision-Induced Dissociation and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

In this study, a novel approach to characterize and identify acidic oil compounds utilizing the fragmentational behavior of their corresponding precursor ions is presented. Precursor ions of seven analyzed pyrolysis oils that were generated from pyrolysis educts of different origins and degrees of coalification were produced by electrospray ionization in the negative ion mode (ESI(-)). Following a fragmentation of all ions in the ion cloud by collision-induced dissociation (CID), the precursor and product ions were subsequently detected by ultrahigh resolving Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The ESI(-)-CID data sets were evaluated by applying either a targeted classification or untargeted clustering approach. In the case of the targeted classification, 10% of the ionized precursor ions of the analyzed pyrolysis liquid samples could be classified into one of 11 compound classes utilizing theoretical fragmentation pathways of these classes. In contrast, theoretical fragmentation pathways were not necessary for the untargeted clustering approach, making it the more transmittable method. Results from both approaches were verified by analyzing standard compounds of known structure. The analysis and data evaluation methods presented in this work can be used to characterize complex organic mixtures, such as pyrolysis oils, and their compounds in-depth on a structural level.

Estimating population heat exposure and impacts on working people in conjunction with climate change.

Increased environmental heat levels as a result of climate change present a major challenge to the health, wellbeing and sustainability of human communities in already hot parts of this planet. This challenge has many facets from direct clinical health effects of daily heat exposure to indirect effects related to poor air quality, poor access to safe drinking water, poor access to nutritious and safe food and inadequate protection from disease vectors and environmental toxic chemicals. The increasing environmental heat is a threat to environmental sustainability. In addition, social conditions can be undermined by the negative effects of increased heat on daily work and life activities and on local cultural practices. The methodology we describe can be used to produce quantitative estimates of the impacts of climate change on work activities in countries and local communities. We show in maps the increasing heat exposures in the shade expressed as the occupational heat stress index Wet Bulb Globe Temperature. Some tropical and sub-tropical areas already experience serious heat stress, and the continuing heating will substantially reduce work capacity and labour productivity in widening parts of the world. Southern parts of Europe and the USA will also be affected. Even the lowest target for climate change (average global temperature change = 1.5 °C at representative concentration pathway (RCP2.6) will increase the loss of daylight work hour output due to heat in many tropical areas from less than 2% now up to more than 6% at the end of the century. A global temperature change of 2.7 °C (at RCP6.0) will double this annual heat impact on work in such areas. Calculations of this type of heat impact at country level show that in the USA, the loss of work capacity in moderate level work in the shade will increase from 0.17% now to more than 1.3% at the end of the century based on the 2.7 °C temperature change. The impact is naturally mainly occurring in the southern hotter areas. In China, the heat impact will increase from 0.3 to 2%, and in India, from 2 to 8%. Especially affected countries, such as Cambodia, may have losses going beyond 10%, while countries with most of the population at high cooler altitude, such as Ethiopia, may experience much lower losses.

Heat, Human Performance, and Occupational Health: A Key Issue for the Assessment of Global Climate Change Impacts.

Ambient heat exposure is a well-known health hazard, which reduces human performance and work capacity at heat levels already common in tropical and subtropical areas. Various health problems have been reported. Increasing heat exposure during the hottest seasons of each year is a key feature of global climate change. Heat exhaustion and reduced human performance are often overlooked in climate change health impact analysis. Later this century, many among the four billion people who live in hot areas worldwide will experience significantly reduced work capacity owing to climate change. In some areas, 30-40% of annual daylight hours will become too hot for work to be carried out. The social and economic impacts will be considerable, with global gross domestic product (GDP) losses greater than 20% by 2100. The analysis to date is piecemeal. More analysis of climate change-related occupational health impact assessments is greatly needed.

Solid-Sampling Electrothermal Vaporization Inductively Coupled Plasma Optical Emission Spectrometry for Direct Determination of Total Oxygen in Coal.

A new analytical method for direct determination of total oxygen contents in eight coal samples of the Argonne Premium Coal (APC) series and in the NIST SRM 1632d is presented. The development of a suitable calibration procedure, optimization of measurement conditions, and the application of a tailored data processing for handling of plasma effects and high blanks enable the quantification of oxygen simultaneously with other trace, minor, or major elements in whole coal samples by means of electrothermal vaporization inductively coupled plasma optical emission spectrometry (ETV-ICP OES). For comparison, the oxygen contents were determined by a direct oxygen analyzer. The obtained oxygen values of the APC and the reference material NIST SRM 1632d were compared to data in the literature. The precision of the ETV-ICP OES was within ±3.5%, and the recovery better than 92%. With this good accuracy, the developed direct solid sampling method ETV-ICP OES is well suited for the fast determination of oxygen in coals, varying in rank from lignite to semianthracite, in a content range of about 100 ppm up to 27% using 1.5 mg sample weight. This direct analysis method represents an accurate, advantageous alternative to currently used methods for estimation of total oxygen contents in coals.

Comparative Study of Graphite-Supported LDI- and ESI-FT-ICR-MS of a Pyrolysis Liquid from a German Brown Coal.

Pyrolysis liquids from coal are complex mixtures of organic compounds with low to high molecular mass and low to high polarity. Compared to low-molecular-weight compounds, little information is available regarding high-molecular-weight compounds in pyrolysis liquids, although their characterization is important for the elucidation of degradation pathways. In this study, laser desorption ionization (LDI) using graphite powder as the support material has been used in conjunction with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) for the analysis of a pyrolysis liquid from brown coal. The acquired data is compared to previous results of the same sample using electrospray ionization (ESI). Using LDI, compounds with masses between 300 and 900 Da were detected by LDI. An evaluation of the spectra was based on the frequency of molecular formulas with a different number of heteroatoms. Hydrocarbon compounds and heteroatomic compounds containing oxygen and sulfur were found. A comparison to ESI results shows that the numbers of observed molecular formulas are virtually the same, but a higher quantity of molecular formulas with a low number of oxygen can be detected by LDI. The observation of molecular formulas without oxygen is a unique feature of the LDI spectra. A more detailed investigation was possible by the utilization of double bond equivalent plots versus carbon number, which revealed a prevalence of LDI for the ionization of compounds with higher DBE.

Metabolic Effect Level Index Links Multivariate Metabolic Fingerprints to Ecotoxicological Effect Assessment.

A major goal of ecotoxicology is the prediction of adverse outcomes for populations from sensitive and early physiological responses. A snapshot of the physiological state of an organism can be provided by metabolic fingerprints. However, to inform chemical risk assessment, multivariate metabolic fingerprints need to be converted to readable end points suitable for effect estimation and comparison. The concentration- and time-dependent responsiveness of metabolic fingerprints to the PS-II inhibitor isoproturon was investigated by use of a Myriophyllum spicatum bioassay. Hydrophilic and lipophilic leaf extracts were analyzed with gas chromatography-mass spectrometry (GC-MS) and preprocessed with XCMS. Metabolic changes were aggregated in the quantitative metabolic effect level index (MELI), allowing effect estimation from Hill-based concentration-response models. Hereby, the most sensitive response on the concentration scale was revealed by the hydrophilic MELI, followed by photosynthetic efficiency and, 1 order of magnitude higher, by the lipophilic MELI and shoot length change. In the hydrophilic MELI, 50% change compares to 30% inhibition of photosynthetic efficiency and 10% inhibition of dry weight change, indicating effect development on different response levels. In conclusion, aggregated metabolic fingerprints provide quantitative estimates and span a broad response spectrum, potentially valuable for establishing adverse outcome pathways of chemicals in environmental risk assessment.

Stage of pregnancy dictates heterothermy in temperate forest-dwelling bats.

Bats face high energetic requirements, as powered flight is costly and they have a disadvantageous surface-to-volume-ratio. To deal with those requirements energy saving mechanisms, such as heterothermy (torpor), have evolved. Torpor during pregnancy, however, reduces rates of foetal development and consequently prolongs pregnancy. Therefore, heterothermy has a great effect on reproduction, as an unhindered parturition can only be assured by high body temperatures. Regardless of these adverse affects of torpor the energetic requirements of bats during reproduction urge for energy savings and bats are known to enter torpor during pregnancy. The species in the current study differ in their torpor patterns and thus their heterothermic strategy. However, we hypothesized, that species-specific heterothermic behaviour should be revoked at the end of pregnancy. We analyzed skin temperatures of Myotis bechsteinii, Myotis nattereri and Plecotus auritus during pregnancy and found no differences in torpor depth between species during the last phase of pregnancy. Furthermore, we could show that individuals entered torpor frequently during pregnancy and only minimized torpor during the last stage of pregnancy. This suggests that close to the end of pregnancy, heterothermy is restricted but not species-specific and the required energy is allocated otherwise.

Direct determination of sulfur species in coals from the Argonne premium sample program by solid sampling electrothermal vaporization inductively coupled plasma optical emission spectrometry.

A new direct solid sampling method for speciation of sulfur in coals by electrothermal vaporization inductively coupled plasma optical emission spectrometry (ETV-ICP OES) is presented. On the basis of the controlled thermal decomposition of coal in an argon atmosphere, it is possible to determine the different sulfur species in addition to elemental sulfur in coals. For the assignment of the obtained peaks from the sulfur transient emission signal, several analytical techniques (reflected light microscopy, scanning electron microscopy with energy dispersive X-ray spectroscopy and X-ray diffraction) were used. The developed direct solid sampling method enables a good accuracy (relative standard deviation ≤ 6%), precision and was applied to determine the sulfur forms in the Argonne premium coals, varying in rank. The generated method is time- and cost-effective and well suited for the fast characterization of sulfur species in coal. It can be automated to a large extent and is applicable for process-accompanying analyses.

[Peripheral extracorporeal membrane oxygenation in perioperative medicine : Principles, indications and challenges]. / Periphere extrakorporale Membranoxygenierung in der perioperativen Medizin : Prinzipien, Indikationen und Herausforderungen.

In recent years the number of patients treated in intensive care units by extracorporeal membrane oxygenation (ECMO) due to severe respiratory failure or cardiogenic shock has steadily increased [1]. Consequently, the number of invasive procedures and operations in these patients has also increased. A fundamental understanding of these systems and the clinical indications is therefore helpful for the practicing (non-cardiac) surgeon. This review article focuses on peripheral ECMO procedures: venovenous (V-V) ECMO for patients with respiratory failure and venoarterial (V-A) ECMO for circulatory support in cardiogenic shock.

Quantification of pulmonary edema using automated lung segmentation on computed tomography in mechanically ventilated patients with acute respiratory distress syndrome.

BACKGROUND: Quantification of pulmonary edema in patients with acute respiratory distress syndrome (ARDS) by chest computed tomography (CT) scan has not been validated in routine diagnostics due to its complexity and time-consuming nature. Therefore, the single-indicator transpulmonary thermodilution (TPTD) technique to measure extravascular lung water (EVLW) has been used in the clinical setting. Advances in artificial intelligence (AI) have now enabled CT images of inhomogeneous lungs to be segmented automatically by an intensive care physician with no prior radiology training within a relatively short time. Nevertheless, there is a paucity of data validating the quantification of pulmonary edema using automated lung segmentation on CT compared with TPTD. METHODS: A retrospective study (January 2016 to December 2021) analyzed patients with ARDS, admitted to the intensive care unit of the Department of Anesthesiology and Critical Care Medicine, University Hospital Mannheim, who underwent a chest CT scan and hemodynamic monitoring using TPTD at the same time. Pulmonary edema was estimated using manually and automated lung segmentation on CT and then compared to the pulmonary edema calculated from EVLW determined using TPTD. RESULTS: 145 comparative measurements of pulmonary edema with TPTD and CT were included in the study. Estimating pulmonary edema using either automated lung segmentation on CT or TPTD showed a low bias overall (- 104 ml) but wide levels of agreement (upper: 936 ml, lower: - 1144 ml). In 13% of the analyzed CT scans, the agreement between the segmentation of the AI algorithm and a dedicated investigator was poor. Manual segmentation and automated segmentation adjusted for contrast agent did not improve the agreement levels. CONCLUSIONS: Automated lung segmentation on CT can be considered an unbiased but imprecise measurement of pulmonary edema in mechanically ventilated patients with ARDS.

Semifluorinated Alkanes as New Drug Carriers-An Overview of Potential Medical and Clinical Applications.

Fluorinated compounds have been used in clinical and biomedical applications for years. The newer class of semifluorinated alkanes (SFAs) has very interesting physicochemical properties including high gas solubility (e.g., for oxygen) and low surface tensions, such as the well-known perfluorocarbons (PFC). Due to their high propensity to assemble to interfaces, they can be used to formulate a variety of multiphase colloidal systems, including direct and reverse fluorocarbon emulsions, microbubbles and nanoemulsions, gels, dispersions, suspensions and aerosols. In addition, SFAs can dissolve lipophilic drugs and thus be used as new drug carriers or in new formulations. In vitreoretinal surgery and as eye drops, SFAs have become part of daily clinical practice. This review provides brief background information on the fluorinated compounds used in medicine and discusses the physicochemical properties and biocompatibility of SFAs. The clinically established use in vitreoretinal surgery and new developments in drug delivery as eye drops are described. The potential clinical applications for oxygen transport by SFAs as pure fluids into the lungs or as intravenous applications of SFA emulsions are presented. Finally, aspects of drug delivery with SFAs as topical, oral, intravenous (systemic) and pulmonary applications as well as protein delivery are covered. This manuscript provides an overview of the (potential) medical applications of semifluorinated alkanes. The databases of PubMed and Medline were searched until January 2023.

The Use of an Inspiration-Synchronized Vibrating Mesh Nebulizer for Prolonged Inhalative Iloprost Administration in Mechanically Ventilated Patients-An In Vitro Model.

Mechanically ventilated patients suffering from acute respiratory distress syndrome (ARDS) frequently receive aerosolized iloprost. Because of prostacyclin's short half-life, prolonged inhalative administration might improve its clinical efficacy. But, this is technically challenging. A solution might be the use of inspiration-synchronized vibrating mesh nebulizers (VMNsyn), which achieve high drug deposition rates while showing prolonged nebulization times. However, there are no data comparing prolonged to bolus iloprost nebulization using a continuous vibrating mesh nebulizer (VMNcont) and investigating the effects of different ventilation modes on inspiration-synchronized nebulization. Therefore, in an in vitro model of mechanically ventilated adults, a VMNsyn and a VMNcont were compared in volume-controlled (VC-CMV) and pressure-controlled continuous mandatory ventilation (PC-CMV) regarding iloprost deposition rate and nebulization time. During VC-CMV, the deposition rate of the VMNsyn was comparable to the rate obtained with the VMNcont, but 10.9% lower during PC-CMV. The aerosol output of the VMNsyn during both ventilation modes was significantly lower compared to the VMNcont, leading to a 7.5 times longer nebulization time during VC-CMV and only to a 4.2 times longer nebulization time during PC-CMV. Inspiration-synchronized nebulization during VC-CMV mode therefore seems to be the most suitable for prolonged inhalative iloprost administration in mechanically ventilated patients.

Labour productivity and economic impacts of carbon mitigation: a modelling study and benefit-cost analysis.

BACKGROUND: Despite the emerging carbon neutrality pledges from different countries, it is still unclear how much these pledges would cost and how the costs would compare with the economic benefits. Comparisons at the country level are important for tightening country-specific emissions trajectories to keep the temperature limit targets outlined in the Paris Agreement within reach. We aimed to systematically estimate avoided heat-related labour productivity losses against the costs of climate change mitigation at country and regional levels. METHODS: In this modelling study, to address the above-mentioned research gaps, we first selected two representative climate change scenarios (Representative Concentration Pathway 6.0 [RCP6.0] scenario, a higher warming scenario representing limited mitigation pledges before the Paris Agreement with around 3°C warming by the end of this century; and RCP2.6 scenario, a lower warming scenario assuming global temperature rise is limited to 2°C) and estimated heat-related labour productivity loss using the exposure-response function at country and regional levels. By representing the direct heat-related labour productivity losses in a multiregional global computable general equilibrium model, we then did a benefit-cost analysis to quantify the economic benefits of avoided heat-related labour productivity losses as well as the estimated reduction in gross domestic product (GDP) related to carbon reduction. FINDINGS: By 2100, the overall economic losses due to heat-related labour productivity loss could range from about 1·5% of global GDP under the RCP6.0 scenario to about 0·1% of global GDP under the RCP2.6 scenario. The productivity losses will be highly concentrated in low-latitude regions, especially in southeast Asia, India, and the Middle East, implying the necessity of additional adaptation measures. By 2100, about 51·8% of global climate change mitigation costs could be offset by economic benefits from reduced labour productivity losses. Cumulatively, about 17·0% of climate change mitigation costs could be offset by the economic benefits between 2020 and 2100, when using a 2% social discounting rate. The costs and benefits of climate change mitigation will be distributed highly unevenly across regions due to their varying climate zones and economic structures. Regions with benefits from reduced productivity losses higher than mitigation costs are mainly low-latitude and tropical regions with lower income and lower emissions, such as southeast Asia, Brazil, and Mexico. More than half the climate change mitigation costs could be offset by the economic benefits by 2100 for the world's largest emitters, including the USA, China, the EU, and India. Low benefit-cost ratios are expected in economies that rely on fossil fuels, such as Canada, Russia, and the Middle East. INTERPRETATION: Although pledging carbon neutrality implies radical changes to most economies, substantial health and economic gains can be achieved by reduced heat-related labour productivity loss, even without accounting for other benefits. The benefit-cost analysis in this study shows the potential for choosing more stringent climate change mitigation pathways in some regions. Regions with low benefit-cost ratios need to restructure their economies to reduce mitigation costs as well as losses from declined fossil fuel exports. FUNDING: National Natural Science Foundation of China, Tsinghua-Toyota Joint Research Fund, the Wellcome Trust, Tsinghua University-China Three Gorges Corporation Joint Research Center for Climate Governance Mechanism and Green Low-carbon Transformation Strategy, the National Research Foundation, Prime Minister's Office, Singapore (Campus for Research Excellence and Technological Enterprise [CREATE] programme), and the Global Energy Interconnection Development and Coorperation Organization.

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.

Toward prediction: using chemometrics for the optimization of sample preparation in MALDI-TOF MS of synthetic polymers.

In recent years, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has become a powerful tool for the study of synthetic polymers although its mechanism is still not understood in detail. Sample preparation plays the key role in obtaining reliable MALDI mass spectra, in particular, the proper choice of matrix, cationization reagent, and solvent. There is still no general sample preparation protocol for MALDI analysis of synthetic polymers. For known synthetic polymers, such as polystyrenes and other frequently investigated polymers, application tables in review articles might be a guide for selecting a MALDI matrix, cationization reagent, and solvent. For unknown polymers (polymers which were not analyzed by MALDI-TOF MS before but whose structures are in part known from the manufacturing process and from NMR analysis as well), the selection of matrix and solvent is based upon the polarity-similarity principle. Chemometric methods provide a useful tool for the investigation of sample preparation because huge data sets can be evaluated in short time, that is, for extracting relevant information and for classification of samples, as well. Furthermore, chemometrics provide a suitable way for the selection of a proper matrix, cationization reagent, and solvent. In this paper, a prediction model is presented using the partial least-squares (PLS) regression. By applying the model, the suitability of appropriate (nontested) combinations (matrix, cationization reagent, solvent) can be predicted for a certain synthetic polymer based upon the investigation of a few combinations. This model may help find suitable combinations in a short time and serve as a starting point for the investigation of unknown polymers. Results are exemplary presented for polystyrene PS2850.

Solvent selection for matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of synthetic polymers employing solubility parameters.

The principle relating to the selection of a proper matrix, cationization reagent, and solvent for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) of synthetic polymers is still a topic of research. In this work we focused on the selection of a suitable MALDI solvent. Polystyrene PS7600 and poly(ethylene glycol) PEG4820 were analyzed by MALDI-TOF MS using various solvents which were selected based on the Hansen solubility parameter system. For polystyrene (PS), dithranol was used as the matrix and silver trifluoroacetate as the cationization reagent whereas, for poly(ethylene glycol) (PEG), the combination of 2,5-dihydroxybenzoic acid and sodium trifluoroacetate was used for all experiments. When employing solvents which dissolve PS and PEG, reliable MALDI mass spectra were obtained while samples in non-solvents (solvents which are not able to dissolve the polymer) failed to provide spectra. It seems that the solubility of the matrix and the cationization reagent are less important than the polymer solubility.