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Research into and applications of phthalocyanines (Pc) are mostly connected to their intriguing electronic properties. Here, messenger-type UV-vis spectroscopy of two metal-free ions from the phthalocyanine family, cationic H 2 Pc + and H 2 PcD + , along with their hydrates is performed. They show that the electronic properties of both ions can be traced to those in the conjugate base, Pc 2- , however, they are affected by state splitting due to the reduced symmetry; in the H 2 Pc + radical cation, a new band appears due to excitations into the singly-occupied molecular orbital. Quantum chemical spectra modeling reproduces all important features of the measured spectra and provides insight into the nature of electronic transitions. Hydration of the ions has only a mild effect on the electronic spectra, showing the stability of the electronic structure with respect to solvation effects., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Accidental hypothermia with severe frostbite is a rare combination of injuries with a high risk for long-term sequelae. There are widely accepted recommendations for the management of avalanche victims and for frostbite treatment, but no recommendation exists for the treatment of frostbite in severe hypothermic patients, specifically for the management of hypothermic avalanche victims presenting with frostbite., Case Presentation: We present a case of a previously healthy, 53-year-old male skier who was critically buried by an avalanche at 2300 m of altitude at an ambient temperature of - 8 °C for nearly 23 h. The victim was found with the right hand out of the snow and an air connection to outside. He was somnolent with Glasgow Coma Scale 11 (Eye 4, Verbal 2, Motor 5) and spontaneously breathing, in a severely hypothermic state with an initial core temperature of 23.1 °C and signs of cold injuries in all four extremities. After rescue and active external forced air rewarming in the intensive care unit, the clinical signs of first-degree frostbite on both feet and the left hand vanished, while third- to fourth-degree frostbite injuries became apparent on all fingers of the right hand. After reaching a core body temperature of approximately 36 °C, aggressive frostbite treatment was started with peripheral arterial catheter-directed thrombolysis with alteplase, intravenous iloprost, ibuprofen, dexamethasone and regional sympathicolysis with a right-sided continuous axillary block. After ten months, the patient had no tissue loss but needed neuropathic pain treatment with pregabalin., Conclusion: The combination of severe accidental hypothermia and severe frostbite is rare and challenging, as drug metabolism is unpredictable in a hypothermic patient and no recommendations for combined treatment exist. There is general agreement to give hypothermia treatment the priority and to begin frostbite treatment as early as possible after full rewarming of the patient. More evidence is needed to identify the optimal dosage and time point to initiate treatment of frostbite in severely hypothermic patients. This should be taken into consideration by future treatment recommendations., (© 2024. The Author(s).)

Infrared spectra of C60+ and C120+, obtained via helium messenger spectroscopy, are reported. For C60+, new absorption features have been found just above the discrete vibrational spectrum of the ion. The absorption profile, which is broad and contains little structure, is assigned to one or more electronic absorption transitions and is in good agreement with predictions from time-dependent density functional theory. It seems likely that the transitions observed correspond to excitation from the 2A1u electronic ground state to one or both of the low-lying 2E1u and 2E2u electronic states previously identified as dark states of C60+. These states presumably become optically bright through vibronic coupling and specifically the Jahn-Teller effect. In the case of C120+, the simplest positively charged oligomer of C60, we present the first vibrational spectrum of this ion. Through a comparison with theory, vibrational features are best explained by a peanut-shaped structure for C120+, maintained by covalent bonding between the two C60 units. We have also discovered electronic transitions for C120+, which, similar to C60+, lie just above the vibrational spectrum., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

In this contribution, we present an efficient and alternative method to the commonly used RF-multipole trap technique to produce He-tagged molecular ions at cryogenic temperatures, which are perfectly suitable for messenger spectroscopy. The seeding of dopant ions in multiply charged helium nanodroplets, in combination with a gentle extraction of the latter from the helium matrix, enables the efficient production of He-tagged ion species. With a quadrupole mass filter, a specific ion of interest is selected, merged with a laser beam, and the photoproducts are measured in a time-of-flight mass-spectrometer. The detection of the photofragment signal from a basically zero background is much more sensitive than the depletion of the same amount of signal from precursor ions, delivering high quality spectra at reduced data acquisition times. Proof-of-principle measurements of bare and He-tagged Ar-cluster ions, as well as of He-tagged C60 ions, are presented., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

In this Letter, we report the experimental detection of likely the largest ordered structure of helium atoms surrounding a monatomic impurity observed to date using a recently developed technique. The mass spectrometry investigation of He N Ca 2+ clusters, formed in multiply charged helium nanodroplets, reveals magic numbers at N = 12, 32, 44, and 74. Classical optimization and path integral Monte Carlo calculations suggest the existence of up to four shells surrounding the calcium dication which are closed with well-ordered Mozartkugel-like structures: He 12 Ca 2+ with an icosahedron, the second at He 32 Ca 2+ with a dodecahedron, the third at He 44 Ca 2+ with a larger icosahedron, and finally for He 74 Ca 2+ , we find that the outermost He atoms form an icosidodecahedron which contains the other inner shells. We analyze the reasons for the formation of such ordered shells in order to guide the selection of possible candidates to exhibit a similar behavior.

Micro- and nanoplastics (MNPs) are recognized as emerging contaminants, especially in food, with unknown health significance. MNPs passing through the gastrointestinal tract have been brought in context with disruption of the gut microbiome. Several molecular mechanisms have been described to facilitate tissue uptake of MNPs, which then are involved in local inflammatory and immune responses. Furthermore, MNPs can act as potential transporters ("vectors") of contaminants and as chemosensitizers for toxic substances ("Trojan Horse effect"). In this review, we summarize current multidisciplinary knowledge of ingested MNPs and their potential adverse health effects. We discuss new insights into analytical and molecular modeling tools to help us better understand the local deposition and uptake of MNPs that might drive carcinogenic signaling. We present bioethical insights to basically re-consider the "culture of consumerism." Finally, we map out prominent research questions in accordance with the Sustainable Development Goals of the United Nations., Competing Interests: Conflict of interestThe authors have not disclosed any competing interests., (© The Author(s) 2022.)

The adsorption of helium on charged hexabenzocoronene (Hbc, C 42 H 18 ), a planar polycyclic aromatic hydrocarbon (PAH) molecule of D 6 h symmetry, was investigated by a combination of high-resolution mass spectrometry and classical and quantum computational methods. The ion abundance of He n Hbc + complexes versus size n features prominent local anomalies at n = 14, 38, 68, 82, and a weak one at 26, indicating that for these "magic" sizes, the helium evaporation energies are relatively large. Surprisingly, the mass spectra of anionic He n Hbc - complexes feature a different set of anomalies, namely at n = 14, 26, 60, and 62, suggesting that the preferred arrangement of the adsorbate atoms depends on the charge of the substrate. The results of our quantum calculations show that the adsorbate layer grows by successive filling of concentric rings that surround the central benzene ring, which is occupied by one helium atom each on either side of the substrate. The helium atoms are fairly localized in filled rings and they approximately preserve the D 6 h symmetry of the substrate, but helium atoms in partially filled rings are rather delocalized. The first three rings contain six atoms each; they account for magic numbers at n = 14, 26, and 38. The size of the first ring shrinks as atoms are filled into the second ring, and the position of atoms in the second ring changes from hollow sites to bridge sites as atoms are filled into the third ring. Beyond n = 38, however, the arrangement of helium atoms in the first three rings remains essentially frozen. Presumably, another ring is filled at n = 68 for cations and n = 62 for anions. The calculated structures and energies do not account for the difference between charge states, although they agree with the measurements for the cations and show that the first solvation shell of Hbc ± is complete at n = 68. Beyond that size, the adsorbate layer becomes three-dimensional, and the circular arrangement of helium changes to hexagonal.

The adsorption of helium or hydrogen on cationic triphenylene (TPL, C 18 H 12 ), a planar polycyclic aromatic hydrocarbon (PAH) molecule, and of helium on cationic 1,3,5-triphenylbenzene (TPB, C 24 H 18 ), a propeller-shaped PAH, is studied by a combination of high-resolution mass spectrometry and classical and quantum computational methods. Mass spectra indicate that He n TPL + complexes are particularly stable if n = 2 or 6, in good agreement with the quantum calculations that show that for these sizes, the helium atoms are strongly localized on either side of the central carbon ring for n = 2 and on either side of the three outer rings for n = 6. Theory suggests that He 14 TPL + is also particularly stable, with the helium atoms strongly localized on either side of the central and outer rings plus the vacancies between the outer rings. For He n TPB + , the mass spectra hint at enhanced stability for n = 2, 4 and, possibly, 11. Here, the agreement with theory is less satisfactory, probably because TPB + is a highly fluxional molecule. In the global energy minimum, the phenyl groups are rotated in the same direction, but when the zero-point harmonic correction is included, a structure with one phenyl group being rotated opposite to the other two becomes lower in energy. The energy barrier between the two isomers is very small, and TPB + could be in a mixture of symmetric and antisymmetric states, or possibly even vibrationally delocalized.

Helium droplets represent a cold inert matrix, free of walls with outstanding properties to grow complexes and clusters at conditions that are perfect to simulate cold and dense regions of the interstellar medium. At sub-Kelvin temperatures, barrierless reactions triggered by radicals or ions have been observed and studied by optical spectroscopy and mass spectrometry. The present review summarizes developments of experimental techniques and methods and recent results they enabled., (© 2021 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd.)

Latinx women face a myriad of unique pressures to meet unrealistic standards of beauty that are not captured in the dominant, Eurocentric framework of beauty and body image in the U.S. The majority of the extant body image literature represents the experiences of White women and overlooks salient body areas that women of color may experience dissatisfaction with. The present researchers employed a convergent-parallel mixed methods design to examine demographic differences as well as the lived experiences of Latinx women's relationship with beauty and their bodies. Quantitative results from 118 participants revealed that Latinx women with an annual income< 60k (54.2%) reported a higher discrepancy between their actual and ideal buttock size compared to Latinx women with an annual income> 60k (45.8%). Furthermore, a thematic analysis revealed four emergent themes that reflected the unique perceptions and lived experiences of 98 Latinx women's experiences with body image. Findings may assist clinicians working with Latinx women, as they will be able to better understand and integrate relevant cultural aspects of body dissatisfaction when working with Latinx clients., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

It has been debated for years if the polycyclic aromatic hydrocarbon phenanthrene exists in its anionic form, or, in other words, if its electron affinity (EA) is positive or negative. In this contribution we confirm that the bare phenanthrene anion Ph - created in a binary collision with an electron at room temperature has a lifetime shorter than microseconds. However, the embedding of neutral phenanthrene molecules in negatively charged helium nanodroplets enables the formation of phenanthrene anions by charge transfer processes and the stabilization of the latter in the ultracold environment. Gentle shrinking of the helium matrix of phenanthrene-doped HNDs by collisions with helium gas makes the bare Ph - visible by high-resolution mass spectrometry. From these and previous measurements we conclude, that the EA of phenanthrene is positive and smaller than 24.55 meV.

Objective: Molecular taxonomy of tumours is the foundation of personalised medicine and is becoming of paramount importance for therapeutic purposes. Four transcriptomics-based classification systems of pancreatic ductal adenocarcinoma (PDAC) exist, which consistently identified a subtype of highly aggressive PDACs with basal-like features, including ΔNp63 expression and loss of the epithelial master regulator GATA6. We investigated the precise molecular events driving PDAC progression and the emergence of the basal programme., Design: We combined the analysis of patient-derived transcriptomics datasets and tissue samples with mechanistic experiments using a novel dual-recombinase mouse model for Gata6 deletion at late stages of KRas G12D -driven pancreatic tumorigenesis (Gata6 LateKO )., Results: This comprehensive human-to-mouse approach showed that GATA6 loss is necessary, but not sufficient, for the expression of ΔNp63 and the basal programme in patients and in mice. The concomitant loss of HNF1A and HNF4A, likely through epigenetic silencing, is required for the full phenotype switch. Moreover, Gata6 deletion in mice dramatically increased the metastatic rate, with a propensity for lung metastases. Through RNA-Seq analysis of primary cells isolated from mouse tumours, we show that Gata6 inhibits tumour cell plasticity and immune evasion, consistent with patient-derived data, suggesting that GATA6 works as a barrier for acquiring the fully developed basal and metastatic phenotype., Conclusions: Our work provides both a mechanistic molecular link between the basal phenotype and metastasis and a valuable preclinical tool to investigate the most aggressive subtype of PDAC. These data, therefore, are important for understanding the pathobiological features underlying the heterogeneity of pancreatic cancer in both mice and human., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Quite a few molecules do not form stable anions that survive the time needed for their detection; their electron affinities (EA) are either very small or negative. How does one measure the EA if the anion cannot be observed? Or, at least, can one establish lower and upper bounds to their EA? We propose two approaches that provide lower and upper bounds. We choose the phenanthrene (Ph) molecule whose EA is controversial. Through competition between helium evaporation and electron detachment in He n Ph - clusters, formed in helium nanodroplets, we estimate the lower bound of the vertical detachment energy (VDE) of Ph - as about -3 meV. In the second step, Ph is complexed with calcium whose electron affinity is just 24.55 meV. When CaPh - ions are collided with a thermal gas of argon, one observes Ca - product ions but no Ph - , suggesting that the EA of Ph is below that of Ca.

Helium clusters around the recently experimentally observed sulphur hexafluoride SF 6 + and sulphur pentafluoride SF 5 + ions are investigated using a combined experimental and theoretical effort. Mass spectrometry ion yields are obtained and the energetics and structure of the corresponding He N -SF 6 + and He N -SF 5 + clusters are analyzed using path integral molecular dynamics calculations as a function of N , the number of He atoms, employing a new intermolecular potential describing the interaction between the dopant and the surrounding helium. The new force field is optimized on benchmark potential energy ab initio calculations and represented by improved Lennard-Jonnes analytical expressions. This procedure improves the previous potentials employed in similar simulations for neutral SF 6 attached to helium nanodroplets. The theoretical analysis explains the characteristic features observed in the experimental ion yields which suggest the existence of stable configurations at specific sizes.

Excited-state dynamics plays a key role for light harvesting and energy transport in photosynthetic proteins but it is nontrivial to separate the intrinsic photophysics of the light-absorbers (chlorophylls) from interactions with the protein matrix. Here we study chlorophyll a (4-coordinate complex) and axially ligated chlorophyll a (5-coordinate complex) isolated in vacuo applying mass spectrometry to shed light on the intrinsic dynamics in the absence of nearby chlorophylls, carotenoids, amino acids, and water molecules. The 4-coordinate complexes are tagged by quaternary ammonium ions while the charge is provided by a formate ligand in the case of 5-coordinate complexes. Regardless of excitation to the Soret band or the Q band, a fast ps decay is observed, which is ascribed to the decay of the lowest excited singlet state either by intersystem crossing (ISC) to nearby triplet states or by excited-state relaxation on the excited-state potential-energy surface. The lifetime of the first excited state is 15 ps with Mg 2+ at the chlorophyll center, but only 1.7 ps when formate is attached to Mg 2+ . When the Soret band is excited, an initial sup-ps relaxation is observed which is ascribed to fast internal conversion to the first excited state. With respect to ISC, two factors seem to play a role for the reduced lifetime of the formate-chlorophyll complex: (i) The Mg ion is pulled out of the porphyrin plane thus reducing the symmetry of the chromophore, and (ii) the first excited state (Q band) and T 3 are tuned almost into resonance by the ligand, which increases the singlet-triplet mixing.

The protonated Schiff-base retinal acts as the chromophore in bacteriorhodopsin as well as in rhodopsin. In both cases, photoexcitation initializes fast isomerization which eventually results in storage of chemical energy or signaling. The details of the photophysics for this important chromophore is still not fully understood. In this study, action-absorption spectra and photoisomerization dynamics of three retinal derivatives are measured in the gas phase and compared to that of the protonated Schiff-base retinal. The retinal derivatives include C 9 C 10 trans -locked, C 13 C 14 trans -locked and a retinal derivative without the β-ionone ring. The spectroscopy as well as the isomerization speed of the chromophores are altered significantly as a consequence of the steric constraints.

Complexes of atomic gold with a variety of ligands have been formed by passing helium nanodroplets (HNDs) through two pickup cells containing gold vapor and the vapor of another dopant, namely a rare gas, a diatomic molecule (H 2 , N 2 , O 2 , I 2 , P 2 ), or various polyatomic molecules (H 2 O, CO 2 , SF 6 , C 6 H 6 , adamantane, imidazole, dicyclopentadiene, and fullerene). The doped HNDs were irradiated by electrons; ensuing cations were identified in a high-resolution mass spectrometer. Anions were detected for benzene, dicyclopentadiene, and fullerene. For most ligands L, the abundance distribution of AuL n + &nbsp;versus size n displays a remarkable enhancement at n = 2. The propensity towards bis-ligand formation is attributed to the formation of covalent bonds in Au + L 2 which adopt a dumbbell structure, L-Au + -L, as previously found for L = Xe and C 60 . Another interesting observation is the effect of gold on the degree of ionization-induced intramolecular fragmentation. For most systems gold enhances the fragmentation, i.e., intramolecular fragmentation in AuL n + is larger than in pure L n + . Hydrogen, on the other hand, behaves differently, as intramolecular fragmentation in Au(H 2 ) n + is weaker than in pure (H 2 ) n + by an order of magnitude.

There are myriad ions that are deemed too short-lived to be experimentally accessible. One of them is SF 6 + . It has never been observed, although not for lack of trying. We demonstrate that long-lived SF 6 + can be formed by doping charged helium nanodroplets (HNDs) with sulfur hexafluoride; excess helium is then gently stripped from the doped HNDs by collisions with helium gas. The ion is identified by high-resolution mass spectrometry (resolution m /Δ m = 15000), the close agreement between the expected and observed yield of ions that contain minor sulfur isotopes, and collision-induced dissociation in which mass-selected He n SF 6 + ions collide with helium gas. Under optimized conditions, the yield of SF 6 + exceeds that of SF 5 + . The procedure is versatile and suitable for stabilizing many other transient molecular ions.

The front cover artwork is provided by the groups of Assoc. Prof. Anastasia V. Bochenkova (Lomonosov Moscow State University) and Prof. Lars H. Andersen (Aarhus University). The image shows the quantum nature of wavelength-dependent excited-state proton transfer in gas-phase H-bonded complexes of the GFP chromophore with an anionic proton acceptor. Read the full text of the Article at 10.1002/cphc.202100068., (© 2021 Wiley-VCH GmbH.)

Cardiopulmonary resuscitation (CPR) is considered an aerosol-generating procedure. Consequently, COVID-19 resuscitation guidelines recommend the use of personal protective equipment (PPE) during resuscitation. In this simulation of randomised crossover trials, we investigated the influence of PPE on the quality of chest compressions (CCs). Thirty-four emergency medical service BLS-providers performed two 20 min CPR sequences (five 2 min cycles alternated by 2 min of rest) on manikins, once with and once without PPE, in a randomised order. The PPE was composed of a filtering facepiece 3 FFP3 mask, safety glasses, gloves and a long-sleeved gown. The primary outcome was defined as the difference between compression depth with and without PPE; secondary outcomes were defined as differences in CC rate, release and the number of effective CCs. The participants graded fatigue and performance, while generalised estimating equations (GEE) were used to analyse data. There was no significant difference in CC quality between sequences without and with PPE regarding depth (mean depth 54 ± 5 vs. 54 ± 6 mm respectively), rate (mean rate 119 ± 9 and 118 ± 6 compressions per minute), release (mean release 2 ± 2 vs. 2 ± 2 mm) and the number of effective CCs (43 ± 18 vs. 45 ± 17). The participants appraised higher fatigue when equipped with PPE in comparison to when equipped without PPE ( p < 0.001), and lower performance was appraised when equipped with PPE in comparison to when equipped without PPE ( p = 0.031). There is no negative effect of wearing PPE on the quality of CCs during CPR in comparison to not wearing PPE.

Chlorophyll (Chl) pigments are responsible for vital mechanisms in photosynthetic proteins: light harvesting, energy transfer and charge separation. A complex interplay between the Chl molecule and its microenvironment determines its transition energy. Interactions such as excitonic coupling with one or more pigments (Chls or carotenoids), axial ligation to the magnesium center, or electrostatic interactions between Chl and nearby amino-acid residues all influence the photophysical properties. Here we use time-resolved photodissociation action spectroscopy to determine transition energies of Chla/b complexes in vacuo to directly compare the impact of a negatively charged axial ligand (formate) to that of exciton coupling between two Chls. Experiments carried out at the electrostatic ion storage ring ELISA allow dissociation to be sampled on hundreds of milliseconds time scale. Absorption-band maxima of Chla-formate complexes are found at 433 ± 4 nm/2.86 ± 0.03 eV (Soret band) and in the region 654-675 nm/1.84-1.90 eV (Q band) and those of Chla dimers tagged by a quaternary ammonium ion at 419 ± 5 nm/2.96 ± 0.04 eV (Soret band) and 647 nm/1.92 eV (Q band). The axial ligand strongly affects the Chla transition energies causing redshifts of 0.21 eV of the Soret band and 0.04-0.1 eV of the Q band compared to Chla tagged by a quaternary ammonium. Slightly smaller shifts were found in case of Chlb. The redshifts are approximately twice that induced by excitonic coupling between two Chlas, also tagged by a quaternary ammonium ion. Axial ligation brings the absorption by isolated Chls very close to that of photosynthetic proteins.

Background: Cancer-related inflammation is associated with tumour proliferation, maintenance and dissemination. It therefore impacts pancreatic cancer survival. The goal of this study was to examine the Prognostic Index (PI) as a prognostic biomarker for survival in patients with pancreatic ductal adenocarcinoma (PDAC). In addition, we explored factors known to interact with the immune and inflammation cascade that might interfere with the PI's strength for prognostication., Methods: Patients with PDAC undergoing resection were analysed retrospectively. The PI was calculated from preoperatively derived C-reactive protein levels and white blood count. Data were subject to correlation and survival analysis., Results: Of 357 patients, 235 (65.8%) patients had a PI 0, 108 (30.3%) PI 1, and 14 (3.9%) PI 2. Median (quartiles) survival with a high PI (group 1 + 2) was 13.2 months (7.7-27.0), compared with 18.7 months (10.2-35.4) with a low PI (group 0; p = 0.012). The PI proved to be an independent prognostic factor for cancer-specific survival (p = 0.003) adjusted for conventional prognostic factors. Prognostic strength was influenced by the presence of a bile stent (p = 0.032)., Conclusions: The PI is a strong and solid independent prognostic tool for survival in patients with PDAC undergoing resection. Preoperative survey of inflammatory activity as provided by the use of a biomarker like the PI may help to identify those patients at risk of a poor prognosis.

Salivary gland malignancies of the head and neck form a heterogeneous group. Adenoid cystic carcinomas are an aggressive entity of salivary gland malignancies characterized by frequent distant metastases and poor response to radio- and chemotherapy. AF1Q is a MLL fusion partner, which can activate Wnt and STAT3 signaling. Recently, overexpression of AF1q has been identified as a poor prognosticator in patients of different malignancies. A total of 46 patients with adenoid cystic carcinoma were immunohistochemically evaluated for expression of AF1q and clinical outcome was analyzed in this context. Additionally, STAT3 and the Wnt downstream target CD44 were investigated and correlated with AF1q. AF1q was overexpressed in 52.2%. Overexpression of AF1q was associated with poorer overall survival (p = 0.03). Additionally, lymph node metastases and solid tumor parts were more frequently observed in AF1qhigh patients (p = 0.07 and 0.05, respectively). AF1q did not influence the occurrence of distant metastases. Expression of AF1q was associated with higher levels of STAT3 and CD44 (p = 0.003 and 0.006, respectively). AF1q is a novel prognostic marker for poor overall survival in adenoid cystic carcinoma patients. The deleterious effects on survival may be a result of promotion of the STAT3 and Wnt pathway.

Background: The systemic immune-inflammation index based on peripheral neutrophil, lymphocyte, and platelet counts has shown a prognostic impact in several malignancies. The aim of this study was to determine the prognostic role of systemic immune-inflammation index in patients with pancreatic ductal adenocarcinoma undergoing resection., Methods: Consecutive patients who underwent surgical resection at the department of surgery at the Medical University of Vienna between 1995 and 2014 were included into this study. The systemic immune-inflammation index was calculated by the formula platelet*neutrophil/lymphocyte. Optimal cutoffs were determined using Youden's index. Uni- and multivariate analyses were calculated by the Cox proportional hazard regression model for overall survival., Results: Three hundred twenty-one patients were included in this study. Clinical data was achieved from a prospective patient database. In univariate survival analysis, elevated systemic immune-inflammation index was found to be significantly associated with shortened patients' overall survival (p = 0.007). In multivariate survival analysis, systemic immune-inflammation index remained an independent prognostic factor for overall survival (p = 0.004). No statistical significance could be found for platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in multivariate analysis. Furthermore, area under the curve analysis showed a higher prognostic significance for systemic immune-inflammation index, compared to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio., Conclusion: A high systemic immune-inflammation index is an independent, preoperative available prognostic factor in patients with resectable pancreatic ductal adenocarcinoma and is superior to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio for predicting overall survival in pancreatic ductal adenocarcinoma patients.

Background: T cell density in colorectal cancer (CRC) has proven to be of high prognostic importance. Here, we evaluated the influence of a hyperfractionated preoperative short-term radiation protocol (25 Gy) on immune cell density in tumor samples of rectal cancer (RC) patients and on patient survival. In addition, we assessed spatial tumor heterogeneity by comparison of analogue T cell quantification on full tissue sections with digital T cell quantification on a virtually established tissue microarray (TMA)., Methods: A total of 75 RC patients (60 irradiated, 15 treatment-naïve) were defined for retrospective analysis. RC samples were processed for immunohistochemistry (CD3, CD8, PD-1, PD-L1). Analogue (score 0-3) as well as digital quantification (TMA: 2 cores vs. 6 cores, mean T cell count) of marker expression in 2 areas (central tumor, CT; invasive margin, IM) was performed. Survival was estimated on the basis of analogue as well as digital marker densities calculated from 2 cores (Immunoscore: CD3/CD8 ratio) and 6 cores per tumor area., Results: Irradiated RC samples showed a significant decrease in CD3 and CD8 positive T cells, independent of quantification mode. T cell densities of 6 virtual cores approximated to T cell densities of full tissue sections, independent of individual core density or location. Survival analysis based on full tissue section quantification demonstrated that CD3 and CD8 positive T cells as well as PD-1 positive tumor infiltrating leucocytes (TILs) in the CT and the IM had a significant impact on disease-free survival (DFS) as well as overall survival (OS). In addition, CD3 and CD8 positive T cells as well as PD-1 positive TILs in the IM proved as independent prognostic factors for DFS and OS; in the CT, PD-1 positive TILs predicted DFS and CD3 and CD8 positive T cells as well as PD-1 positive TILs predicted OS. Survival analysis based on virtual TMA showed no impact on DFS or OS., Conclusion: Spatial tumor heterogeneity might result in inadequate quantification of immune marker expression; however, if using a TMA, 6 cores per tumor area and patient sample represent comparable amounts of T cell densities to those quantified on full tissue sections. Consistently, the tissue area used for immune marker quantification represents a crucial factor for the evaluation of prognostic and predictive biomarker potential.

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein modulating cell-matrix interactions and was found up-regulated in tumor stroma. To explore the effect of high stromal SPARC on colorectal cancer (CRC) cell behavior and clinical outcome, this study determined SPARC expression in patients suffering from stage II and III CRC using a publicly available mRNA data set and immunohistochemistry of tissue microarray sections. Moreover, in vitro co-culture models using CRC cell lines together with colon-associated fibroblasts were established to determine the effect of fibroblast-derived SPARC on cancer cells. In 466 patient samples, high SPARC mRNA was associated with a shorter disease-free survival. In 99 patients of the tissue microarray cohort, high stromal SPARC in the primary tumor was an independent predictor of shorter survival in patients with relapse (27 cases; HR = 4574, p = 0.004). In CRC cell lines, SPARC suppressed phosphorylation of focal adhesion kinase and stimulated cell migration. Colon-associated fibroblasts increased migration velocity by 30% and doubled track-length in SPARC-dependent manner. In a 3D co-culture system, fibroblast-derived SPARC enhanced tumor cell invasion. Taken together, stromal SPARC had a pro-metastatic impact in vitro and was a characteristic of aggressive tumors with poor prognosis in CRC patients.

Chlorophylls a and b (Chla/b) are responsible for light-harvesting by photosynthetic proteins in plants. They display broad absorption in the visible region with multiple bands, due to the asymmetry of the macrocycle and strong vibronic coupling. Their photophysics relies on the microenvironment, with regard to transition energies as well as quenching of triplet states. Here, we firmly establish the splitting of the Q and Soret bands into x- and y- polarized bands for the isolated molecules in vacuo, and resolve vibronic features. Storage-ring experiments reveal that dissociation of photoexcited charge-tagged complexes occurs over several milliseconds, but with two different time constants. A fast decay is ascribed to dissociation after internal conversion and a slow decay to the population of a triplet state that acts as a bottleneck. Support for the latter is provided by pump-probe experiments, where a second laser pulse probes the long-lived triplet state., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The retinal protonated Schiff-base (RPSB) in its all-trans form is found in bacterial rhodopsins, whereas visual rhodopsin proteins host 11-cis RPSB. In both cases, photoexcitation initiates fast isomerization of the retinal chromophore, leading to proton transport, storage of chemical energy or signaling. It is an unsolved problem, to which degree this is due to protein interactions or intrinsic RPSB quantum properties. Here, we report on time-resolved action-spectroscopy studies, which show, that upon photoexcitation, cis isomers of RPSB have an almost barrierless fast 400 fs decay, whereas all-trans isomers exhibit a barrier-controlled slow 3 ps decay. Moreover, formation of the 11-cis isomer is greatly favored for all-trans RPSB when isolated. The very fast photoresponse of visual photoreceptors is thus directly related to intrinsic retinal properties, whereas bacterial rhodopsins tune the excited state potential-energy surface to lower the barrier for particular double-bond isomerization, thus changing both the timescale and specificity of the photoisomerization.

The absorption of a positively charge-tagged azobenzene molecule is studied in the gas-phase by measuring photoinduced fragmentation of ions as a function of time. This technique provides information on prompt as well as delayed fragmentation, and a single dissociation channel after one-photon absorption is identified. The spectra in solution, as well as in the gas-phase, show a weak S 0 → S 1 , a strong S 0 → S 2 , and a broad absorption band in the UV regime. The bands are assigned through time dependent density functional theory calculations. The ratio of the various absorption bands depends on the trans to cis isomerization fraction and may be tuned by light irradiation. Gas-phase absorption spectra are presented and discussed in terms of trans and cis isomers.

Tonsillectomy and adenotomy are the most common pediatric surgical procedures, with approximately five millions performed each year worldwide (O'Mathúna, Wiffen & Conlon, 2010). However, this procedure is accompanied by significant postoperative morbidity, which may include postoperative pain, postoperative nausea and vomiting (PONV), poor oral intake with consequent dehydration and postoperative bleeding (Hanasono et al., 2004). If pain is not treated effectively, it can cause avoidance behaviors related to further healthcare. Inadequate pain management has been found to increase morbidity and mortality rates in postoperative patients of all ages (O'Mathúna, Wiffen & Conlon, 2010). In addition, there is an increase in the incidence of PONV: 40% in children with pain compared to 16% in children without pain. PONV also disturbs significantly the wellbeing and patient satisfaction, it can lead to a substantial prolongation of time in the recovery room with increased costs of personal care. In pediatric patients PONV is the most common cause of the approximately 1% to 2% of unplanned hospitalizations following outpatient surgery (Rüsch et al., 2010). The incidence of bleeding after tonsillectomy is approximately 0.5-10%, with deaths occurring in 1 in 20,000 patients (Kim et al., 2011). In recent years, several scientists have explored the effect ofcorticosteroids in the reduction of morbidity after tonsillectomy. In this publication, the question is addressed to what extent perioperatively administered corticosteroids can reduce pain, PONV and postoperative bleeding in the context of tonsillectomy in children and adolescents. For this purpose, a narrative literature analysis of the electronic databases and journals was conducted. There is evidence that corticosteroids can reduce postoperative morbidity. However, no evident and clear recommendation can be drawn from the advices of the various studies.

Objective: Lay rescuers have difficulties acquiring ventilation skills during training. Non-feedback manikins are still widely employed, although skill acquisition is suboptimal. We analysed if a longer training time and verbal feedback, given by an instructor, improved ventilation skill acquisition with non-feedback manikins., Methods: Forty-three high school students without prior medical training participated in this prospective randomised trial. Under one-to-one instructor guidance, 25 volunteers were trained on a manikin with a mouth-to-mask device for 10 min, and 18 volunteers for 20 min. After training, volunteers were assessed and verbal feedback was given: ventilate more if the mean tidal volume <0.5 L, ventilate less if >0.7 L or ventilate the same for 0.5-0.7 L. The volunteers were then reassessed., Results: At the assessment, tidal volume, minute volume, peak airway pressure, ventilation rate and stomach inflation rate were comparable between the 10 and 20 min groups. After verbal feedback, at reassessment both groups increased tidal volume (assessment 0.75+/-0.24 vs reassessment 0.80+/-0.16 l/min; p=0.007), minute volume (9.1+/-3.0 vs 10.0+/-2.4 l/min; p=0.001), peak airway pressure (17.0+/-5.2 vs 18.3+/-3.4 cmH(2)O; p=0.003) and stomach inflation rate (67 vs 88%; p=0.02), while ventilation rate (12.3+/-2.1 vs 12.6+/-2.3 ventilations/min; p=NS) remained comparable., Conclusions: Both 10 and 20 min ventilation training times resulted in comparable skills. Volunteers hyperventilated the manikin and produced excessive stomach inflation in this model. This increased even further after verbal feedback.

Objective and Methods: A prospective randomised study on 70 volunteers without previous first aid education (42 males, 28 females, mean age 17) was performed to compare mouth-to-mouth ventilation (MMV, n = 24) versus mouth-to-pocket-mask ventilation (MPV, n = 25) and mouth-to-face-shield ventilation (MFV, n =21), and to evaluate if an instruction period of 10 min would be sufficient to teach lay persons artificial ventilation. Every volunteer performed three ventilation series using a bench model of an unprotected airway., Results: MMV and MPV show higher mean tidal volume (TV) than MFV (values of series 3: 976 +/- 454 and 868 +/- 459 versus 604 +/- 328 ml, P = 0.002 and P = 0.025, respectively). We found a higher inter-individual variation in TV than in previous studies (P = 0.031). The recommended TV of 700-1000 ml was reached in only 23%, most frequently with MPV (MMV 16.7%, MPV 32%, MFV 19%) but the difference was not significant (P = 0.391). However, we found a significantly higher percentage with a TV below 700 ml with MFV (MMV 33.3%, MPV 36%, MFV 66.7% P = 0.047) and a significantly higher percentage of TV exceeding 1000 ml with MMV (MMV 50%, MPV 32%, MFV 14.3%) (P = 0.039). "Stomach" inflation was highest with MMV (79.2%) followed by MPV (52%) and MFV (42.9%) (P = 0.034). We found further differences between the sexes; males produced a higher TV (P = 0.003) and a higher percentage of stomach inflation (P = 0.029)., Conclusion: MPV showed the best ventilation quality. It resulted in a more adequate TV than MMV and MFV and lower stomach inflation than MMV. Only a relatively low percentage of ventilations were within the recommended range for TV and this may be related to the short training duration. We found different performances between the sexes, a high inter-individual variation and mainly a low ventilation quality. Therefore, further studies have to focus more on teaching duration, sex differences and ventilation quality.