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About 10% of Europe's surface area is prone to rapid flooding of rivers confined in valleys. The devastating potential of such floods is exacerbated by the deficits of existing gauging networks, including low station densities and recording frequencies, and lack of information beyond stage height. Here, we use seismic data of the July 2021 Ahrtal flood, Germany, to extract information to complement sparse hydrometric data, and to reconstruct the rapid evolution of this fatal event. We show that a seismic station can deliver essential flood metrics such as magnitude, propagation velocity and debris transport rate. These seismic products provide high resolution insight to the non‐linear flood behavior. We argue that an approach combining distributed low‐cost seismometers with existing seismic stations, can provide important real time data on future catastrophic floods and associated hazards in upland catchments, offering precious response time also in currently ungauged landscapes. Plain Language Summary: Rapidly evolving floods are a major hazard for 10% of European landscapes. They are hard to adequately detect and describe by the classic gauge station scheme, but seismic sensors provide a valuable alternative to this difficulty. A seismometer can sense a flood like the devastating one that hit the Ahr valley, Germany, in July 2021 up to 1.5 km away. The seismic footprint of the flood allows to provide information on flood magnitude, velocity and trajectory at sub‐minute resolution and at near real time. We show how this new approach can be utilized for future flood protection. Key Points: Seismic sensing of valley confined floods improves classic detection approachesNear‐real time information on flood magnitude, trajectory, and velocityGate keeper seismometer networks can improve flood risk management in Europe [ABSTRACT FROM AUTHOR]

Background: Tooth extractions lead to morphological changes of the alveolar ridge. For oral rehabilitation sufficient bone volume of the alveolar ridge is required. This clinical study compared the ability of Bio-Oss® Collagen to autogenous bone to preserve bone volume after tooth extraction.Methods: A total of 17 patients with 20 extraction sites were examined. After extraction, 10 sockets were each filled with either autogenous bone or Bio-Oss® Collagen and covered with a resorbable membrane. The width of the alveolar ridge was measured postoperatively, and after 4 and 6 months respectively. Prior to implant insertion, a bone biopsy was taken from the grafted sites and evaluated histologically.Results: The width of the alveolar ridge in the Bio-Oss® Collagen group decreased about 5.33 ± 6.62% after 4 months and 9.45 ± 10.51% after 6 months. The reduction in the group augmented with autogenous bone was 14.31 ± 21.41% after 4 months and 19.17 ± 8.38% after 6 months. No statistically significant differences were observed. The histological examination showed comparable area fractions of total bone in both groups (Bio-Oss® Collagen: 59.99 ± 24.23%; autogenous bone: 61.55 ± 25.13%; p = 1.0).Conclusions: The present study demonstrated that autogenous bone and Bio-Oss® Collagen are suitable for ridge preservation. However, both techniques could not entirely prevent tissue volume loss. [ABSTRACT FROM AUTHOR]

At 18 months, children engage in a variety of social behaviors that reflect their nascent ability to understand the intentions of other people (e.g. joint attention, empathy, cooperation and self-recognition). Although numerous contextual factors have been shown to predict social cognition in young children, the genetic underpinnings of social-cognitive traits has been understudied in this age group. Owing to the known effects of oxytocin on adult social cognition and psychopathology, this study hypothesized that variability in the oxytocin receptor gene ( OXTR) would be associated with social cognition in children at 18 months. Participants consisted of 350 children (182 males; 168 females) who were part of an ongoing longitudinal study that aimed to assess environmental and genetic contributions to children's cognitive and socio-emotional functioning. At 18 months, social cognition was measured using previously validated and developmentally sensitive tasks assessing children's joint attention, empathy, cooperation and self-recognition. Five potentially functional OXTR variants were genotyped: rs1042778, rs2254298, rs11131149, rs237897 and rs237899. A family-based association design was used to control for population admixture and stratification, and additional non-genomic covariates were controlled. Results showed that variability in rs11131149 was significantly associated with social cognition ( P = 0.009), with more copies of the major allele related to higher social cognition, and more copies of the minor (risk) allele associated with lower social cognition. A haplotype consisting of rs11131149-rs2254298 was also associated with social cognition ( P = 0.020). Implications for normative and pathological development are discussed, and key areas for future research are proposed. [ABSTRACT FROM AUTHOR]

Background and Purpose: Clinical results of osanetant and talnetant (selective-NK₃ antagonists) indicate that blocking the NK₃ receptor could be beneficial for the treatment of schizophrenia. The objective of this study was to characterize the in vitro and in vivo properties of a novel dual NK₁/NK₃ antagonist, RO4583298 (2-phenyl-N-(pyridin-3-yl)-N-methylisobutyramide derivative).Experimental Approach: RO4583298 in vitro pharmacology was investigated using radioligand binding ([³H]-SP, [³H]-osanetant, [³H]-senktide), [³H]-inositol-phosphate accumulation Schild analysis (SP- or [MePhe⁷]-NKB-induced) and electrophysiological studies in guinea-pig substantia nigra pars compacta (SNpc). The in vivo activity of RO4583298 was assessed using reversal of GR73632-induced foot tapping in gerbils (GFT; NK₁) and senktide-induced tail whips in mice (MTW; NK₃).Key Results: RO4583298 has a high-affinity for NK₁ (human and gerbil) and NK₃ (human, cynomolgus monkey, gerbil and guinea-pig) receptors and behaves as a pseudo-irreversible antagonist. Unusually it binds with high-affinity to mouse and rat NK₃, yet with a partial non-competitive mode of antagonism. In guinea-pig SNpc, RO4583298 inhibited the senktide-induced potentiation of spontaneous activity of dopaminergic neurones with an apparent non-competitive mechanism of action. RO4583298 (p.o.) robustly blocked the GFT response, and inhibited the MTW.Conclusions and Implications: RO4583298 is a high-affinity, non-competitive, long-acting in vivo NK₁/NK₃ antagonist; hence providing a useful in vitro and in vivo pharmacological tool to investigate the roles of NK₁ and NK₃ receptors in psychiatric disorders. [ABSTRACT FROM AUTHOR]

This study was designed to identify new factors which may contribute to angiotensin-converting-enzyme-inhibitor (ACEI)-induced angioedema.In a retrospective cohort study we examined 25 patients who used an ACEI and presented at our emergency room with acute angioedema as well as 18 patients with unknown cause of angioedema and a total of 21 patients on ACEI-therapy without previous angioedema. We measured markers of inflammation such as acute-phase proteins (C-reactive protein, fibrinogen), leukocyte count and body temperature.The mean interval between initiation of ACEI treatment and first manifestation of angioedema was 35.8 ± 5.3 months. During symptomatic angioedema, mean plasma levels of C-reactive protein and fibrinogen were significantly increased by 7.3-fold and 1.5-fold, respectively, while leukocyte count and body temperature were normal. These changes disappeared after successful treatment of angioedema and were not found in patients with angioedema of unknown cause and those receiving ACEI without having experienced angioedema.Our findings demonstrate for the first time that ACEI-induced angioedema is associated with strongly increased plasma levels of CRP. We suggest that CRP is involved in the pathophysiology of ACEI-induced angioedema. [ABSTRACT FROM AUTHOR]

The article presents a study on emission of volatile organic compounds (VOC) from ozone exposed plants. It mentions that the ozone-induced reactions of the ozone-sensitive Bel W3 plants look like the hypersensitive response found after pathogen attack. It highlights that feedback mechanisms in photooxidant formation may be caused by an increased VOC emission as a consequence of elevated ozone concentrations in the troposphere.

Bacillus subtilis, in its natural habitat, is regularly exposed to rapid changes in the osmolarity of its surrounding. As its primary survival strategy, it accumulates large amounts of the compatible solute proline by activating the de novo proline biosynthesis pathway and exploiting the glutamate pools. This osmotically-induced biosynthesis requires activation of a SigA-type promoter that drives the expression of the proHJ operon. Population-wide studies have shown that the activity of the proHJ promoter correlates with the increased osmotic pressure of the environment. Therefore, the activation of the proHJ transcription should be an adequate measure of the adaptation to osmotic stress through proline synthesis in the absence of other osmoprotectants. In this study, we investigate the kinetics of the proHJ promoter activation and the early adaptation to mild osmotic upshift at the single-cell level. Under these conditions, we observed a switching point and heterogeneous proline biosynthesis gene expression, where the subpopulation of cells showing active proHJ transcription is able to continuously divide, and those unresponsive to osmotic stress remain dormant. Additionally, we demonstrate that bactericidal antibiotics significantly upregulate proHJ transcription in the absence of externally imposed osmotic pressure, suggesting that the osmotically-controlled proline biosynthesis pathway is also involved in the antibiotic-mediated stress response., (© 2022 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

In most patients with chronic myeloid leukemia (CML) clonal cells can be kept under control by BCR::ABL1 tyrosine kinase inhibitors (TKI). However, overt resistance or intolerance against these TKI may occur. We identified the epigenetic reader BRD4 and its downstream-effector MYC as growth regulators and therapeutic targets in CML cells. BRD4 and MYC were found to be expressed in primary CML cells, CD34 + /CD38 - leukemic stem cells (LSC), and in the CML cell lines KU812, K562, KCL22, and KCL22 T315I . The BRD4-targeting drug JQ1 was found to suppress proliferation in KU812 cells and primary leukemic cells in the majority of patients with chronic phase CML. In the blast phase of CML, JQ1 was less effective. However, the BRD4 degrader dBET6 was found to block proliferation and/or survival of primary CML cells in all patients tested, including blast phase CML and CML cells exhibiting the T315I variant of BCR::ABL1. Moreover, dBET6 was found to block MYC expression and to synergize with BCR::ABL1 TKI in inhibiting the proliferation in the JQ1-resistant cell line K562. Furthermore, BRD4 degradation was found to overcome osteoblast-induced TKI resistance of CML LSC in a co-culture system and to block interferon-gamma-induced upregulation of the checkpoint antigen PD-L1 in LSC. Finally, dBET6 was found to suppress the in vitro survival of CML LSC and their engraftment in NSG mice. Together, targeting of BRD4 and MYC through BET degradation sensitizes CML cells against BCR::ABL1 TKI and is a potent approach to overcome multiple forms of drug resistance in CML LSC., (© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Background Long QT has been associated with ventricular dysrhythmias, cardiovascular disease (CVD) mortality, and sudden cardiac death. However, no studies to date have investigated the dynamics of within-person QT change over time in relation to risk of incident CVD and all-cause mortality in a real-world setting. Methods and Results A cohort study among members of an integrated health care delivery system in Northern California including 61 455 people (mean age, 62 years; 60% women, 42% non-White) with 3 or more ECGs (baseline in 2005-2009; mean±SD follow-up time, 7.6±2.6 years). In fully adjusted models, tertile 3 versus tertile 1 of average QT corrected (using the Fridericia correction) was associated with cardiac arrest (hazard ratio [HR], 1.66), heart failure (HR, 1.62), ventricular dysrhythmias (HR, 1.56), all CVD (HR, 1.31), ischemic heart disease (HR, 1.28), total stroke (HR, 1.18), and all-cause mortality (HR, 1.24). Tertile 3 versus tertile 2 of the QT corrected linear slope was associated with cardiac arrest (HR, 1.22), ventricular dysrhythmias (HR, 1.12), and all-cause mortality (HR, 1.09). Tertile 3 versus tertile 1 of the QT corrected root mean squared error was associated with ventricular dysrhythmias (HR, 1.34), heart failure (HR, 1.28), all-cause mortality (HR, 1.20), all CVD (HR, 1.14), total stroke (HR, 1.08), and ischemic heart disease (HR, 1.07). Conclusions Our results demonstrate improved predictive ability for CVD outcomes using longitudinal information from serial ECGs. Long-term average QT corrected was more strongly associated with CVD outcomes than the linear slope or the root mean squared error. This new evidence is clinically relevant because ECGs are frequently used, noninvasive, and inexpensive.