Diphenyl ether offers competing docking sites for methanol: the ether oxygen acts as a common hydrogen‐bond acceptor and the π system of each phenyl ring allows for OH–π interactions driven by ...electrostatic, induction, and dispersion forces. Based on investigations in the electronic ground state (S0), we present a detailed study of the electronically excited state (S1) and the ionic ground state (D0), in which an impact on the structural preference is expected compared with the S0 state. Dispersion forces in the electronically excited state were analyzed by comparing the computed binding energies at the coupled‐cluster‐singles (CCS) and approximate coupled‐cluster‐singles‐doubles levels of theory (CC2 approximation). By applying UV/IR/UV spectroscopy, we found a more strongly bound OH–π structure in the S1 state compared with the S0 state, in agreement with spin‐component‐scaled CC2 calculations. A structural rearrangement into a non‐hydrogen‐bonded structure takes places upon ionization in the D0 state, which was revealed by using IR photodissociation spectroscopy and confirmed by theory.
A walk through electronic states: A combined IR/UV and theoretical study reveals that the OH–π contact in the diphenyl ether (DPE)–MeOH complex is initially strengthened upon electronic excitation, and then broken during the following photoionization.
Human hepatocellular carcinoma (HCC) is among the most lethal and common cancers in the human population, and new molecular targets for therapeutic intervention are urgently needed. Deleted in liver ...cancer 1 (DLC1) was originally identified as a tumor suppressor gene in human HCC. DLC1 is a Rho-GTPase-activating protein (RhoGAP) which accelerates the return of RhoGTPases to an inactive state. We recently described that the restoration of DLC1 expression induces cellular senescence. However, this principle is not amenable to direct therapeutic targeting. We therefore performed gene expression profiling for HepG2 cells depleted of DLC1 to identify druggable gene targets mediating the effects of DLC1 on senescence induction. This approach revealed that versican (VCAN), tetraspanin 5 (TSPAN5) and N-cadherin (CDH2) were strongly upregulated upon DLC1 depletion in HCC cells, but only TSPAN5 affected the proliferation of HCC cells and human HCC. The depletion of TSPAN5 induced oncogene-induced senescence (OIS), mediated by the p16INK4a/pRb pathways. Mechanistically, silencing TSPAN5 reduced actin polymerization and thereby myocardin-related transcription factor A- filamin A (MRTF-A-FLNA) complex formation, resulting in decreased expression of MRTF/SRF-dependent target genes and senescence induction in vitro and in vivo. Our results identify TSPAN5 as a novel druggable target for HCC.
Bleeding is a major adverse effect of veno-venous extracorporeal membrane oxygenation (vvECMO) therapy in surgical patients. This study retrospectively describes the amount of transfused packed red ...blood cells (PRBC) and coagulation parameters of patients requiring surgery during vvECMO therapy.
We included patients who underwent at least one surgical procedure during vvECMO therapy and analyzed hemoglobin levels, coagulation parameters, blood gas parameters and transfused blood products. Patients with perioperative transfusion of less than two PRBC during the perioperative period (group A) were compared to those who were given two or more PRBCs (group B).
Seventy-three patients (group A: 42 patients, group B: 31 patients) were included. Activated PTT (54.7 vs. 56.2 sec), Quick test (61.5% vs. 60.0%), Platelet count (91 vs 72 / nL, P=0.322) and mortality (40.5 vs. 45.2%; P=0.689) were not different between both groups. Fibrinogen was significantly decreased in group B (245 mg/dL) compared to group A (353 mg/dL; P=0.004).
In patients requiring surgery during vvECMO therapy with perioperative transfusion of two or more PRBCs preoperative fibrinogen levels were significantly reduced compared to patients with transfusion of less than two PRBCs. No other analyzed lab value showed any predictive qualities in terms of bleeding.
Plasma concentrations of many cardiovascular and inflammatory proteins are altered after ST-elevation myocardial infarction (STEMI) and may provide prognostic information. We conducted a large-scale ...proteomic analysis in patients with STEMI, correlating protein levels to infarct size and left ventricular ejection fraction (LVEF) determined with cardiac magnetic resonance imaging. We analysed 131 cardiovascular and inflammatory proteins using a multiplex proximity extension assay and blood samples obtained at baseline, 6, 24, and 96 h from the randomised clinical trial CHILL-MI. Cardiac magnetic resonance imaging data at 4 ± 2 days and 6 months were available as per trial protocol. Using a linear regression model with bootstrap resampling and false discovery rate adjustment we identified five proteins (ST2, interleukin-6, pentraxin-3, interleukin-10, renin, and myoglobin) with elevated values corresponding to larger infarct size or worse LVEF and four proteins (TNF-related apoptosis-inducing ligand, TNF-related activation induced cytokine, interleukin-16, and cystatin B) with values inversely related to LVEF and infarct size, concluding that among 131 circulating inflammatory and cardiovascular proteins in the acute and sub-acute phase of STEMI, nine showed a relationship with infarct size and LVEF post-STEMI, with IL-6 and ST2 exhibiting the strongest association.
Introduction
Sacral nerve stimulation is a widely accepted therapeutic option for neurogenic fecal incontinence. More recently, case reports showed a positive effect of sacral nerve stimulation in ...patients with fecal incontinence following low anterior resection. The purpose of this study was to gain more information for this selected indication for sacral nerve stimulation through a nationwide survey.
Material and methods
In the period 2002 to 2005, three Austrian departments reported data of patients who underwent SNS for fecal incontinence following rectal resection. Data were available of seven patients (two female, five male) with a median age of 57 years (min 42; max 79). Six patients had undergone rectal resection as a treatment for low rectal cancer. One patient had undergone rectal resection for Crohn’s disease, one patient subtotal colectomy and ileorectostomy for slow colon transit constipation.
Results
Test stimulation was performed in the foramen S3 unilaterally over a median period of 14 days (2–21 days). Seven patients reported a marked reduction of episodes of incontinence during the observation period and received a permanent stimulation system. After a median follow-up of 32 months (17–46), five patients reported a marked improvement of their continence situation.
Conclusion
Despite a nationwide survey experiences with SNS as a treatment for fecal incontinence following rectal resection is still limited. Our observations show an improvement of the continence function following SNS. However, the promising results of our series as well as others need further research and more clinical data by a larger number of patients in a prospective trial.
Stressors are especially widespread in urban agglomerations. Common themes of built environment interventions that support health and well-being are blue and green infrastructure, indoor and outdoor ...air quality, thermal comfort, access to natural lighting, and acoustics. Given the current megatrends of increasing summer temperatures and the high popularity of home offices, we aimed at modeling thermal comfort changes of people working at home in three Austrian cities (Vienna, Innsbruck, and Graz) during the next decades until 2090. We present findings based on (I) an inter-disciplinary literature search and (II) indoor and outdoor climate simulations for actual and future climate scenarios. Based on the results, we discuss the potential impacts for work and human health and well-being, and we suggest a framework for the home office in “post-COVID-19 Austria” that integrates social, ecological, and economic aspects. The results of our study indicate that, in future climate scenarios, overheating of the interior can no longer be prevented without active cooling measures and nature-based solutions. Recommendations on the adjustment of behavior under climate change, including greening, adequate ventilation, and cooling techniques, are thus urgently needed for employees who are working from home in order to maintain physical and mental health and wellbeing.
Despite primary PCI (PPCI), ST-elevation myocardial infarction (STEMI) can still result in large infarct size (IS). New technology with rapid intravascular cooling showed positive signals for ...reduction in IS in anterior STEMI.
We investigated the effectiveness and safety of rapid systemic intravascular hypothermia as an adjunct to PPCI in conscious patients, with anterior STEMI, without cardiac arrest.
Hypothermia was induced using the ZOLL® Proteus™ intravascular cooling system. After randomisation of 111 patients, 58 to hypothermia and 53 to control groups, the study was prematurely discontinued by the sponsor due to inconsistent patient logistics between the groups resulting in significantly longer total ischaemic delay in the hypothermia group (232 vs 188 minutes; p<0.001).
There were no differences in angiographic features and PPCI result between the groups. Intravascular temperature at wire crossing was 33.3+0.9°C. Infarct size/left ventricular (IS/LV) mass by cardiac magnetic resonance (CMR) at day 4-6 was 21.3% in the hypothermia group and 20.0% in the control group (p=0.540). Major adverse cardiac events at 30 days increased non-significantly in the hypothermia group (8.6% vs 1.9%; p=0.117) while cardiogenic shock (10.3% vs 0%; p=0.028) and paroxysmal atrial fibrillation (43.1% vs 3.8%; p<0.001) were significantly more frequent in the hypothermia group.
The ZOLL Proteus intravascular cooling system reduced temperature to 33.3°C before PPCI in patients with anterior STEMI. Due to inconsistent patient logistics between the groups, this hypothermia protocol resulted in a longer ischaemic delay, did not reduce IS/LV mass and was associated with increased adverse events.
Patients with glioblastoma multiforme (GBM) suffer from an increased incidence of vascular thrombotic events. However, key influencing factors of the primary hemostasis have not been characterized in ...GBM patients to date. Thus, the present study determines the activation level of circulating platelets in GBM patients,
reactivity to agonist-induced platelet stimulation and the formation of circulating platelet-leucocyte conjugates as well as the plasma levels of the proinflammatory lipid mediator sphingosine-1-phosphate (S1P). The endogenous thrombin potential (ETP) was determined as global marker for hemostasis. The 21 GBM patients and 21 gender and age matched healthy individuals enrolled in this study did not differ in mean total platelet count. Basal surface expression of platelet CD63 determined by flow cytometry was significantly increased in GBM patients compared to controls as was observed for the concentration of soluble P-selectin in the plasma of GBM patients. While the ETP was not affected, the immunomodulatory lipid S1P was significantly decreased in peripheral blood in GBM. Interestingly, monocyte expression of PSGL-1 (CD162) was decreased in GBM patient blood, possibly explaining the rather decreased formation of platelet-monocyte conjugates. Our study reveals an increased CD63 expression and P-selectin expression/ secretion of circulating platelets in GBM patients. In parallel a down-modulated PSGL-1 expression in circulating monocytes and a trend towards a decreased formation of heterotypic platelet-monocyte conjugates in GBM patients was seen. Whether this and the observed decreased plasma level of the immunomodulatory S1P reflects a systemic anti-inflammatory status needs to be addressed in future studies.
Summary
The pandemic from the SARS-CoV‑2 virus is currently challenging healthcare systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to ...guarantee a safe working environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develop respiratory or circulatory failure that is refractory to conventional treatment, it is of utmost importance to clearly define criteria for the use of ECMO in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.
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