Micro-solvated DMABN: Excited state quantum dynamics and dual fluorescence spectra

In this work, we report a complete analysis by theoretical and spectroscopic methods of the short-time behaviour of 4-(dimethylamino)benzonitrile (DMABN) in the gas phase as well as in cyclohexane, tetrahydrofuran, acetonitrile, and water solution, after excitation to the La state. The spectroscopic properties of DMABN were investigated experimentally using UV absorption and fluorescence emission spectroscopy. The computational study was developed at different electronic structure levels and using the Polarisable Continuum Model (PCM) and explicit solvent molecules to reproduce the solvent environment. Additionally, excited state quantum dynamics simulations in the diabatic picture using the direct dynamics variational multiconfigurational Gaussian (DD-vMCG) method were performed, the largest quantum dynamics “on-the-fly” simulations performed with this method until now. The comparison with fully converged multilayer multiconfigurational time-dependent Hartree (ML-MCTDH) dynamics on parametrised linear vibronic coupling (LVC) potentials show very similar population decays and evolution of the nuclear wavepacket. The ring C=C stretching and three methyl tilting modes are identified as the responsible motions for the internal conversion from the La to the Lb states. No major differences are observed in the ultrafast initial decay in different solvents, but we show that this effect depends strongly on the level of electronic structure used

The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer

Programmed death 1 (PD-1) is a co-inhibitory receptor in the CD28/CTL-4 family, and functions as a negative regulator of the immune system. Tumor-infiltrating lymphocytes (TIL) in many epithelial cancers express PD-1, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway, and promising results from two recent clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 confirm the clinical relevance of this pathway in human cancer. To explore the role of PD-1+ TIL in human breast cancer, we performed immunohistochemistry studies on a tissue microarray encompassing 660 breast cancer cases with detailed clinical annotation and outcomes data. PD-1+ TIL were present in 104 (15.8%) of the 660 breast cancer cases. Their presence was associated with tumor size, grade, and lymph node status, and was differentially associated with the intrinsic subtypes of breast cancer. In univariate survival analyses, the presence of PD-1+ TIL was associated with a significantly worse overall survival (HR=2.736, p<0.001). In subset analyses, the presence of PD-1+ TIL was associated with significantly worse overall survival in the luminal B HER2− subtype (HR=2.678, p<0.001), the luminal B HER2+ subtype (HR=3.689, p<0.001), and the basal-like subtype (HR=3.140, p<0.001). This is the first study to demonstrate that the presence of PD-1+ TIL is associated with poor prognosis in human breast cancer, with important implications for the potential application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this diseas

PTP1B expression is an independent positive prognostic factor in human breast cancer

Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine phosphatase that has come into focus as a critical regulator of multiple signaling pathways. The role of PTP1B in breast cancer remains unclear with evidence suggesting that PTP1B can exert both tumor-suppressing and tumor-promoting effects. To better define the role of PTP1B in human breast cancer, and its relationship with HER2, we performed immunohistochemical studies on a large cohort of functionally annotated primary breast cancer specimens. 683 of 1,402 (49%) evaluable primary breast cancers are positive for PTP1B. There is no statistically significant association between PTP1B expression and age, tumor size, T stage, histologic grade, lymph node status, or histological subtype. Of note, there is no significant association between PTP1B expression and HER2 expression (PTP1B expression53.1% in HER2+ cancers vs. 47.5% in HER2− cancers, p=0.0985). However, PTP1B expression is significantly associated with estrogen receptor expression (PTP1B expression50.7% in ER+ cancers vs. 43.1% in ER− cancers, p=0.0137) and intrinsic molecular subtype (PTP1B expression53.9% in the luminal B HER2+ subtype and 37.9% in the basal-like subtype). Of note, multivariate analyses demonstrate that PTP1B is an independent predictor of improved survival in breast cancer (HR 0.779, p=0.006). Taken together, we demonstrate in the largest study to date that (1) PTP1B is commonly expressed in breast cancer, (2) there is no association or functional impact of PTP1B expression in HER2+ breast cancer, and (3) PTP1B expression in breast cancer is associated with significantly improved clinical outcome. Until additional studies are performed, caution should be exercised in using PTP1B inhibitors in human breast cance

A promising new device for the prevention of parastomal hernia.

Parastomal hernia (PSH) is the most frequent long-term stoma complication with serious negative effects on quality of life. Surgical revision is often required and has a substantial morbidity and recurrence rate. The development of PSH requires revisional surgery with a substantial perioperative morbidity and high failure rate in the long-term follow-up. Prophylactic parastomal mesh insertion during stoma creation has the potential to reduce the rate of PSH, but carries the risk of early and late mesh-related complications such as infection, fibrosis, mesh shrinkage, and/or bowel erosion. We developed a new stomaplasty ring (KORING), which is easy to implant, avoids potential mesh-related complications, and has a high potential of long-term prevention of PSH. Here we describe the technique and the first use

Embolisation von Katheterbeschichtung in das Myokard

Zusammenfassung: Interventionelle kardiovaskuläre Eingriffe nehmen stetig zu. Die verwendeten Führungskatheter sind mit hydrophilem Material beschichtet, das Einführen wie Kontrolle der Katheter erleichtert und gleichzeitig vaskuläre Spasmen verhindert. Wir berichten von 2Fällen, bei denen die Verwendung eines ChoICE®-PT-Führungskatheters bei Koronarangiographie zu einer Embolisation dieser hydrophilen Beschichtung mit nachfolgendem Verschluss kleiner intramyokardialer Arterien führt

The Ethnic 'Other' in Ukrainian History Textbooks: The Case of Russia and the Russians

This paper examines portrayals of Russia and the Russians in two generations of Ukrainian history textbooks. It observes that the textbooks are highly condemning of Ukraine's main ethnic other in the guise of foreign ruler: the tsarist authorities and the Soviet regime are always attributed dubious and malicious intentions even if there is appreciation for some of their policies. By contrast, the books, certainly those of the second generation, refrain from presenting highly biased accounts of the ethnic other as a national group (i.e. Russians). Instances where negative judgements do fall onto Russians are counterbalanced by excerpts criticizing ethnic Ukrainians or highlighting conflicting interests within the Ukrainian ethnic group. The negative appraisal of the ethnic other as foreign ruler is clearly instrumental for the nation-building project as it sustains a discourse legitimating the existence of Ukraine as independent state. However, recent trends in history education, the paper concludes, suggest that the importance of nurturing patriotism as a national policy objective is diminishing

Dynapenic abdominal obesity and susceptibility to fall: a prospective analysis of the Osteoarthritis Initiative

Background: The prediction of the risk of falling remains a challenge in geriatric medicine and the identification of new potential reversible risk factors is a public health priority. In this study, we aim to investigate the association between DAO (dynapenic abdominal obesity) and incident falls in a large sample of people with knee OA (osteoarthritis) or at high risk for this condition, over 8 years of follow-up. Methods: DAO was defined using a waist circumference more than 102 cm in men and 88 cm in women and a concomitant presence of dynapenia, defined as a time over 15 s in the five times chair stands time. Falls, during follow-up, were recorded using self-reported information in the previous year. A logistic binary regression analysis was run, adjusted for potential confounders at the baseline, reporting the data as odds ratios (ORs) with their 95% confidence intervals (CIs). Results: Overall, 3,844 subjects were included, majority of whom had abdominal obesity. Across the 8 years of follow-up, 2,695 participants fell vs. 1,149 not reporting any fall. Taking those without DAO as reference, the presence of only dynapenia was not associated with risk of falls (OR = 1.18;95%CI: 0.73–1.91; p = 0.50), whilst the presence of abdominal obesity (OR = 1.30; 95%CI: 1.09–1.56; p = 0.004) and DAO (OR = 1.31; 95%CI:1.01–1.73; p = 0.04) were significantly associated with a higher risk of incident falls. Conclusion: DAO significantly increased risk of falls as well as the presence of abdominal obesity