An electrically conducting 3D coronene-based metal-organic framework.

A novel cubic mesoporous metal-organic framework (MOF), consisting of hexahydroxy-cata-hexabenzocoronene (c-HBC) and FeIII ions is presented. The highly crystalline and porous MOF features broad optical absorption over the whole visible and near infrared spectral regions. An electrical conductivity of 10-4 S cm-1 was measured on a pressed pellet.

Dynamic two-dimensional covalent organic frameworks.

Porous covalent organic frameworks (COFs) enable the realization of functional materials with molecular precision. Past research has typically focused on generating rigid frameworks where structural and optoelectronic properties are static. Here we report dynamic two-dimensional (2D) COFs that can open and close their pores upon uptake or removal of guests while retaining their crystalline long-range order. Constructing dynamic, yet crystalline and robust frameworks requires a well-controlled degree of flexibility. We have achieved this through a 'wine rack' design where rigid π-stacked columns of perylene diimides are interconnected by non-stacked, flexible bridges. The resulting COFs show stepwise phase transformations between their respective contracted-pore and open-pore conformations with up to 40% increase in unit-cell volume. This variable geometry provides a handle for introducing stimuli-responsive optoelectronic properties. We illustrate this by demonstrating switchable optical absorption and emission characteristics, which approximate 'null-aggregates' with monomer-like behaviour in the contracted COFs. This work provides a design strategy for dynamic 2D COFs that are potentially useful for realizing stimuli-responsive materials.

Imaging built-in electric fields and light matter by Fourier-precession TEM.

We report the precise measurement of electric fields in nanostructures, and high-contrast imaging of soft matter at ultralow electron doses by transmission electron microscopy (TEM). In particular, a versatile method based on the theorem of reciprocity is introduced to enable differential phase contrast imaging and ptychography in conventional, plane-wave illumination TEM. This is realised by a series of TEM images acquired under different tilts, thereby introducing the sampling rate in reciprocal space as a tuneable parameter, in contrast to momentum-resolved scanning techniques. First, the electric field of a p-n junction in GaAs is imaged. Second, low-dose, in-focus ptychographic and DPC characterisation of Kagome pores in weakly scattering covalent organic frameworks is demonstrated by using a precessing electron beam in combination with a direct electron detector. The approach offers utmost flexibility to record relevant spatial frequencies selectively, while acquisition times and dose requirements are significantly reduced compared to the 4D-STEM counterpart.

Alloying Effects on Charge-Carrier Transport in Silver-Bismuth Double Perovskites.

Alloying is widely adopted for tuning the properties of emergent semiconductors for optoelectronic and photovoltaic applications. So far, alloying strategies have primarily focused on engineering bandgaps rather than optimizing charge-carrier transport. Here, we demonstrate that alloying may severely limit charge-carrier transport in the presence of localized charge carriers (e.g., small polarons). By combining reflection-transmission and optical pump-terahertz probe spectroscopy with first-principles calculations, we investigate the interplay between alloying and charge-carrier localization in Cs2AgSbxBi1-xBr6 double perovskite thin films. We show that the charge-carrier transport regime strongly determines the impact of alloying on the transport properties. While initially delocalized charge carriers probe electronic bands formed upon alloying, subsequently self-localized charge carriers probe the energetic landscape more locally, thus turning an alloy's low-energy sites (e.g., Sb sites) into traps, which dramatically deteriorates transport properties. These findings highlight the inherent limitations of alloying strategies and provide design tools for newly emerging and highly efficient semiconductors.

[Pathophysiology and management of heat illness]. / Pathophysiologie und Management der Hitzeerkrankung.

BACKGROUND: The frequency and intensity of heat waves are currently increasing due to climate change. Hence more cases of heat illness are being observed, a potentially life-threatening disease, which requires rapid and expert management. OBJECTIVES: An overview of the pathophysiology and acute management of heat illness is presented. MATERIALS AND METHODS: Analysis and evaluation of important, recently published contributions, studies, and reviews regarding heat illness without claim for completeness or fulfilling the criteria for a 'systematic meta-analysis'. Presentation of a recommended clinical-practical classification and management of heat illness in emergency departments or intensive care units. RESULTS: The manifestation of heat illness arising from prolonged exposure to heat prevaries (heat cramps, heat edema, heat exhaustion, heat stroke). The main pathophysiologic mechanisms are disruption of thermoregulation, peripheral vasodilation of the skin surface, hypoperfusion of visceral organs, and brain, and cardiac stress. Uncompensated heat stress can result in multiorgan dysfunction/failure syndrome due to the initiation of cytokine pathways, specifically in at-risk and/or chronically ill patients. The manifestation of uncompensated heat stroke is associated with a hospital mortality > 50%. Rapid identification, classification and targeted management are crucial for the outcome, in particular the initiation of adequate cooling measures. CONCLUSION: In the future, increasing numbers of patients suffering from prolonged heat exposure will require treatment in emergency departments and intensive care units. Sufficient professional knowledge regarding pathophysiology and management are decisive for successful therapy. Hence, the topic heat illness should be implemented in training and education.

Trajectories of quality of life, return to work, psychopathology, and disability in survivors of the acute respiratory distress syndrome (ARDS): A three-year prospective cohort study (DACAPO).

PURPOSE: Describe the long-term development of outcomes for survivors of the Acute Respiratory Distress Syndrome (ARDS). MATERIAL AND METHODS: A cohort study with N = 877 ARDS survivors was conducted. Health related quality of life (HRQoL, Physical and Mental Component Scale: PCS, MCS of the SF-12), return to work (RtW), panic disorder, depressive symptoms (PHQD), and post-traumatic-stress-disorder (PTSD, PTSS-14) were assessed at 3, 6, 12, 24, and 36 months after discharge from ICU. RESULTS: PCS, MCS, and RtW increased during the first 12 months [e.g. PCS: Md = 36 (IQR 31-43) at 3 months, Md = 42 (IQR 34-52) at 12 months; MCS: Md = 44 (IQR 32-54) at 3 months, Md = 47 (IQR 33-57) at 12 months, RtW = 23.2% at 3 months, 54.5% at 12 months], and remained relatively stable afterwards. Proportion of major depressive syndrome decreased from 3 (14.2%) to 36 months (8.9%). Proportions of panic disorder (5.3% to 7.4%) and PTSD (27.1% to 32.6%) varied only slightly. CONCLUSIONS: Most of recovery in HRQoL and RtW occur during the first 12 months, after which a plateau is reached, indicating a chronification for many patients. Contrary to this, however, psychopathological symptoms remain stable, except for depressive symptoms. [200 words].

Electrically Conductive Carbazole and Thienoisoindigo-Based COFs Showing Fast and Stable Electrochromism.

Thienothiophene thienoisoindigo (ttTII)-based covalent organic frameworks (COFs) have been shown to offer low band gaps and intriguing optical and electrochromic properties. So far, only one tetragonal thienothiophene thienoisoindigo-based COF has been reported showing stable and fast electrochromism and good coloration efficiencies. We have developed two novel COFs using this versatile and nearly linear ttTII building block in a tetragonal and a hexagonal framework geometry to demonstrate their attractive features for optoelectronic applications of thienoisoindigo-based COFs. Both COFs exhibit good electrical conductivities, show promising optical absorption features, are redox-active, and exhibit a strong electrochromic behavior when applying an external electrical stimulus, shifting the optical absorption even farther into the NIR region of the electromagnetic spectrum and achieving absorbance changes of up to 2.5 OD. Cycle-stable cyclic voltammograms with distinct oxidation and reduction waves reveal excellent reversibility and electrochromic switching over 200 cycles and confirm the high stability of the frameworks. Furthermore, high coloration efficiencies in the NIR region and fast switching speeds for coloration/decoloration as fast as 0.75 s/0.37 s for the Cz-ttTII COF and 0.61 s/0.29 s for the TAPB-ttTII COF at 550 nm excitation were observed, outperforming many known electrochromic materials, and offering options for a great variety of applications, such as stimuli-responsive coatings, optical information processing, or thermal control.

[The CO2 footprint of intensive care medicine-let's go green]. / CO2-Fußabdruck der Intensivmedizin ­ "let's go green".

Climate change and global warming are facts, and actually they are a hot topic for politics, economics, and societies. Global healthcare contributes approximately 5% of worldwide anthropogenic emissions, and this fact might produce an ethical dilemma between the Hippocratic principles of 'beneficence' (promotion of health) and of 'non-maleficence' (avoiding reinforcement of the climate crisis). Intensive care medicine has continuous high staff activity, resource use, and energy demands, and it is clear that intensive care medicine must become green to commence with practical measures to reduce their intensive care unit (ICU) carbon footprint. In this article several strategies are introduced, beginning with the creation of green teams on the ICUs from the bottom. Furthermore, systematic recycle programs, and the assessment and control of energy use are required to make ICUs more sustainable. Strategies for avoiding futile treatment combined with a choose wisely philosophy might contribute to such projects. Immediate engagement of all healthcare staff, particularly those who work in the ICU, is necessary to join the 'race to zero carbon emissions'.

Covalent Organic Framework Thin-Film Photodetectors from Solution-Processable Porous Nanospheres.

The synthesis of homogeneous covalent organic framework (COF) thin films on a desired substrate with decent crystallinity, porosity, and uniform thickness has great potential for optoelectronic applications. We have used a solution-processable sphere transmutation process to synthesize 300 ± 20 nm uniform COF thin films on a 2 × 2 cm2 TiO2-coated fluorine-doped tin oxide (FTO) surface. This process controls the nucleation of COF crystallites and molecular morphology that helps the nanospheres to arrange periodically to form homogeneous COF thin films. We have synthesized four COF thin films (TpDPP, TpEtBt, TpTab, and TpTta) with different functional backbones. In a close agreement between the experiment and density functional theory, the TpEtBr COF film showed the lowest optical band gap (2.26 eV) and highest excited-state lifetime (8.52 ns) among all four COF films. Hence, the TpEtBr COF film can participate in efficient charge generation and separation. We constructed optoelectronic devices having a glass/FTO/TiO2/COF-film/Au architecture, which serves as a model system to study the optoelectronic charge transport properties of COF thin films under dark and illuminated conditions. Visible light with a calibrated intensity of 100 mW cm-2 was used for the excitation of COF thin films. All of the COF thin films exhibit significant photocurrent after illumination with visible light in comparison to the dark. Hence, all of the COF films behave as good photoactive substrates with minimal pinhole defects. The fabricated out-of-plane photodetector device based on the TpEtBr COF thin film exhibits high photocurrent density (2.65 ± 0.24 mA cm-2 at 0.5 V) and hole mobility (8.15 ± 0.64 ×10-3 cm2 V-1 S-1) compared to other as-synthesized films, indicating the best photoactive characteristics.

A reduced glycine-to-taurine ratio of conjugated serum bile acids signifies an adaptive mechanism and is an early marker of outcome in acute respiratory distress syndrome.

The accumulation of Bile Acids (BA) in serum is a common finding in critically ill patients and has been found in patients with Acute Respiratory Distress Syndrome (ARDS), where liver and biliary function could be essentially affected by the underlying disease process and subsequent therapeutic measures. We hypothesized that the glycine-to-taurine conjugation ratio (G/T-ratio) is predictive of outcome in ARDS patients and would support our previously published hypothesis that the BA profile reflects a (mal-) adaptive response of bile acid production when suffering from a disease or syndrome such as ARDS. In 70 patients with ARDS, we determined conjugated BA fractions from protein precipitated serum samples using a LC-MS/MS method and calculated the G/T-ratios, which were then compared with a healthy control group. In patients with ARDS, the G/T-ratio was markedly lower compared to the control group, due to an increase in taurine-conjugated BA. The G/T ratio was lowest on the day of diagnosis and increased steadily during the following days (control = 3.80 (2.28-4.44); day 0 = 1.79 (1.31-3.86); day 3 = 2.91 (1.71-5.68); day 5 = 2.28 (1.25-7.85), significant increases were found between day 0 and day 3 (p = 0.019) and between day 0 and day 5 (p = 0.031). G/T-ratio was significantly correlated with SAPS II score on day 0 (p = 0.009) and day 3 (p = 0.036) and with survival (p = 0.006). Regarding survival, the receiver-operator characteristic revealed an area-under-the-curve of 0.713 (CI 0.578-0.848), the Youden index revealed a G/T-ratio cut-off level of 2.835 (sensitivity 78.4%, specificity 63.2%). Our findings further support our previously published hypothesis that alterations in BA profiles represent adaptive mechanisms in states of severe disease. Our current study adds the finding of an increase in taurine-conjugated BA expressed by a decrease in the G/T-ratio of conjugated BA in serum. The G/T-ratio on day 3 using a threshold G/T-ratio of 2.8 was even associated with survival (p = 0.006); these results are yet to be confirmed by subsequent studies.

Inhibition of IL-1ß release from macrophages targeted with necrosulfonamide-loaded porous nanoparticles.

Inflammation is required for protective responses against pathogens and is thus essential for survival, but sustained inflammation can lead to diseases, such as atherosclerosis and cancer. Two important mediators of inflammation are the cytokines IL-1ß and IL-18, which are produced by myeloid cells of the immune system, including macrophages. These cytokines are released into the extracellular space through pores formed in the plasma membrane by the oligomerized protein gasdermin D (GSDMD). Necrosulfonamide (NSA) was recently identified as an effective GSDMD inhibitor and represents a promising therapeutic agent in GSDMD-dependent inflammatory diseases. Here, we targeted NSA to both mouse and human macrophages by using three different types of porous nanoparticles (NP), i.e. mesoporous silica (MSN), porous crosslinked cyclodextrin carriers (CD-NP), and a mesoporous magnesium-phosphate carrier (MPC-NP), all displaying high loading capacities for this hydrophobic drug. Cellular uptake and intracellular NSA delivery were tracked in time-lapse experiments by live-cell, high-throughput fluorescence microscopy, demonstrating rapid nanoparticle uptake and effective targeted delivery of NSA to phagocytic cells. Notably, a strong cytostatic effect was observed when a macrophage cell line was exposed to free NSA. In contrast, cell growth was much less affected when NSA was delivered via the nanoparticle carriers. Utilizing NSA-loaded nanoparticles, a successful concentration-dependent suppression of IL-1ß secretion from freshly differentiated primary murine and human macrophages was observed. Functional assays showed the strongest suppressive effect on human macrophages when using CD-NP for NSA delivery, followed by MSN-NP. In contrast, MPC-NP completely blocked the metabolic activity in macrophages when loaded with NSA. This study demonstrates the potential of porous nanoparticles for the effective delivery of hydrophobic drugs to macrophages in order to suppress inflammatory responses.

Association of analgosedation with psychiatric symptoms and health-related quality of life in ARDS survivors: Post hoc analyses of the DACAPO study.

BACKGROUND: The acute respiratory distress syndrome (ARDS) is a life-threatening condition with the risk of developing hypoxia and thus requires for invasive mechanical ventilation a long-term analgosedation. Yet, prolonged analgosedation may be a reason for declining health-related quality of life (HRQoL) and the development of psychiatric disorders. METHODS: We used data from the prospective observational nation­wide ARDS study across Germany (DACAPO) to investigate the influence of sedation and analgesia on HRQoL and the risk of psychiatric symptoms in ARDS survivors 3, 6 and 12 months after their discharge from the intensive care unit (ICU). HRQoL was measured with the Physical and Mental Component Scale of the Short­Form 12 Questionnaire (PCS­12, MCS­12). The prevalence of psychiatric symptoms (depression and post­traumatic stress disorder [PTSD]) was assessed using the Patient Health Questionnaire­9 and the Post­Traumatic Stress Syndrome­14. The associations of analgosedation with HRQoL and psychiatric symptoms were investigated by means of multivariable linear regression models. RESULTS: The data of 134 ARDS survivors (median age [IQR]: 55 [44-64], 67% men) did not show any significant association between analgosedation and physical or mental HRQoL up to 1 year after ICU discharge. Multivariable linear regression analysis (B [95%­CI]) yielded a significant association between symptoms of psychiatric disorders and increased cumulative doses of ketamine up to 6 months after ICU discharge (after 3 months: depression: 0.15 [0.05, 0.25]; after 6 months: depression: 0.13 [0.03, 0.24] and PTSD: 0.42 [0.04, 0.80)]). CONCLUSIONS: Up to 1 year after ICU discharge, analgosedation did not influence HRQoL of ARDS survivors. Prolonged administration of ketamine during ICU treatment, however, was positively associated with the risk of psychiatric symptoms. The administration of ketamine to ICU patients with ARDS should be with caution. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02637011 (Registered 15 December 2015, retrospectively registered).

Biomimetic Mineralization of Iron-Fumarate Nanoparticles for Protective Encapsulation and Intracellular Delivery of Proteins.

Biomimetic mineralization of proteins and nucleic acids into hybrid metal-organic nanoparticles allows for protection and cellular delivery of these sensitive and generally membrane-impermeable biomolecules. Although the concept is not necessarily restricted to zeolitic imidazolate frameworks (ZIFs), so far reports about intracellular delivery of functional proteins have focused on ZIF structures. Here, we present a green room-temperature synthesis of amorphous iron-fumarate nanoparticles under mildly acidic conditions in water to encapsulate bovine serum albumin (BSA), horseradish peroxidase (HRP), green fluorescent protein (GFP), and Cas9/sgRNA ribonucleoproteins (RNPs). The synthesis conditions preserve the activity of enzymatic model proteins and the resulting nanoparticles deliver functional HRP and Cas9 RNPs into cells. Incorporation into the iron-fumarate nanoparticles preserves and protects the activity of RNPs composed of the acid-sensitive Cas9 protein and hydrolytically labile RNA even during exposure to pH 3.5 and storage for 2 months at 4 °C, which are conditions that strongly impair the functionality of unprotected RNPs. Thus, the biomimetic mineralization into iron-fumarate nanoparticles presents a versatile platform for the delivery of biomolecules and protects them from degradation during storage under challenging conditions.

Extracorporeal carbon dioxide removal for acute respiratory failure: a review of potential indications, clinical practice and open research questions.

Extracorporeal carbon dioxide removal (ECCO2R) is a form of extracorporeal life support (ECLS) largely aimed at removing carbon dioxide in patients with acute hypoxemic or acute hypercapnic respiratory failure, so as to minimize respiratory acidosis, allowing more lung protective ventilatory settings which should decrease ventilator-induced lung injury. ECCO2R is increasingly being used despite the lack of high-quality evidence, while complications associated with the technique remain an issue of concern. This review explains the physiological basis underlying the use of ECCO2R, reviews the evidence regarding indications and contraindications, patient management and complications, and addresses organizational and ethical considerations. The indications and the risk-to-benefit ratio of this technique should now be carefully evaluated using structured national or international registries and large randomized trials.