Two-dimensional van der Waals (vdW) heterojunctions have been regarded as promising candidates for photocatalytic water splitting and solar energy conversion. Here, we propose a two-dimensional GeC/GaN vdW heterostructure, where the GaN monolayer and the GeC monolayer are stacked. The binding energy, phonon spectrum, and elastic constants demonstrate this material's high dynamic and mechanical stability. Most notably, the GW band structure, GW + Bethe-Salpeter equation (BSE) optical absorption spectrum, and the band alignment of the density functional theory (DFT) scheme and empirical formula reveal that the GeC/GaN vdW heterostructures have a dramatically high optical absorption coefficient (∼105 cm-1) in the visible region and a suitable band edge with sufficiently large kinetic overpotentials of the hydrogen evolution reaction (ΔEc ≥ 1.945 eV) and the oxygen evolution reaction (ΔEv ≥ 1.244 eV). https://www.selleckchem.com/products/sivelestat-sodium.html Photogenerated electrons and holes aggregate on the GeC monolayer and GaN monolayer surfaces, respectively, which could make this heterojunction a promising candidate for photocatalytic water splitting and solar energy conversion.Electrocatalysts with high activities toward multiple electrode reactions are scarce and therefore highly sought. Here, we investigate the electrocatalytic performance of the two-dimensional (2D) Pt5Se4 monolayer toward hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR). Our density functional theory calculations show that the Pt5Se4 monolayer can serve as a low-Pt-loading trifunctional electrocatalyst with good kinetic and thermal stabilities. Specifically, the HER performance of the Pt5Se4 basal plane is predicted to be superior to that of 2D layered Pd or Pt dichalcogenides. Even considering the solvent effect, the catalytic OER performance of the Pt5Se4 monolayer is predicted to be comparable to the prevalent OER catalyst-IrO2, while the catalytic ORR performance of the Pt5Se4 monolayer is even higher than the predominating Pt(111) surface. Overall, the Pt5Se4 monolayer can be a promising trifunctional catalyst that exhibits high activities toward all hydrogen and oxygen electrode reactions.Recent findings of an unexpected slowdown in the decline of CFC-11 mixing ratios in the atmosphere have led to the conclusion that global CFC-11 emissions have increased over the past decade and have been attributed in part to eastern China. This study independently assesses these findings by evaluating enhancements of CFC-11 mixing ratios in air samples collected in Taiwan between 2014 and 2018. Using the NAME (Numerical Atmospheric Modeling Environment) particle dispersion model, we find the likely source of the enhanced CFC-11 observed in Taiwan to be East China. Other halogenated trace gases were also measured, and there were positive interspecies correlations between CFC-11 and CHCl3, CCl4, HCFC-141b, HCFC-142b, CH2Cl2, and HCFC-22, indicating co-location of the emissions of these compounds. These correlations in combination with published emission estimates of CH2Cl2 and HCFC-22 from China, and of CHCl3 and CCl4 from eastern China, are used to estimate CFC-11 emissions. Within the uncertainties, these estimates do not differ for eastern China and the whole of China, so we combine them to derive a mean estimate that we term as being from "(eastern) China". For 2014-2018, we estimate an emission of 19 ± 5 Gg year-1 (gigagrams per year) of CFC-11 from (eastern) China, approximately one-quarter of global emissions. Comparing this to previously reported CFC-11 emissions estimated for earlier years, we estimate CFC-11 emissions from (eastern) China to have increased by 7 ± 5 Gg year-1 from the 2008-2011 average to the 2014-2018 average, which is 50 ± 40% of the estimated increase in global CFC-11 emissions and is consistent with the emission increases attributed to this region in an earlier study.Driven by global warming and eutrophication, outbreaks of cyanobacterial blooms have severely impacted ecosystem stability and water safety. Of the organisms used to control cyanobacteria, protozoa can highly resist cyanotoxins, efficiently control cyanobacterial populations, and show considerably different feeding strategies from those of metazoans. Thus, protozoa have great potential to control harmful cyanobacteria and improve phytoplankton composition in eutrophic waters. To evaluate the actual effects of protozoa in controlling cyanobacteria and improving the phytoplankton community structure in the field, an in situ microcosm study was performed using a flagellate Ochromonas gloeopara that ingests Microcystis. Results showed that adding Ochromonas reduced the cyanobacterial populations and increased the chlorophyte and diatom proportions. Furthermore, the species richness and diversity of the phytoplankton community were enhanced in microcosms with Ochromonas. Additionally, there was a gradual increase in the chlorophyte population in the unicellular Microcystis control, while Ochromonas addition significantly accelerated the replacement of dominant species. This study was the first to show the practical effects of protozoa on controlling cyanobacteria in the field, highlighting that a reduction in in situ cyanobacteria via protozoa can improve the phytoplankton community structure, dredge the toxic cyanobacteria-dominated microbial food web, and mitigate harmful cyanobacteria risks in fresh waters.Various two-dimension (2D) side-chain substituted benzo(1,2-b4,5-b')dithiophene (BDT) block have been used to construct donor polymers, while the size effect of side-chains on photovoltaic performance was overlooked in past few years. This work, three size varied conjugated space (benzene, naphthalene and biphenyl) were introduced into corresponding polymers PBDB-Ph, PBDB-Na and PBDB-BPh. This space engineering has significant impact on the extent of phase separation in active layer which blended with polymer and acceptor ITCPTC and preserved the desired morphology. Varied space size in side-chains leading to distinct balance mobility ratios of hole to electron (benzene is 0.21, and for naphthalene is 0.75, biphenyl is 0.57). Finally, PBDB-Na-based polymer solar cells (PSCs) deliver the highest power conversion efficiency (PCE) 12.52% when compared to the PSCs performance of PBDB-Ph (8.48%) and PBDB-BPh (11.35%). The mothed of tailoring the side-chains structures for fabricating balance between phase separation and charge transport would provide enlightenment for the development of photovoltaic device.

Although offshore freshened groundwater (OFG) systems have been documented in numerous continental margins worldwide, their geometry, controls and emplacement dynamics remain poorly constrained. Here we integrate controlled-source electromagnetic, seismic reflection and borehole data with hydrological modelling to quantitatively characterise a previously unknown OFG system near Canterbury, New Zealand. The OFG system consists of one main, and two smaller, low salinity groundwater bodies. The main body extends up to 60 km from the coast and a seawater depth of 110 m. We attribute along-shelf variability in salinity to permeability heterogeneity due to permeable conduits and normal faults, and to recharge from rivers during sea level lowstands. A meteoric origin of the OFG and active groundwater migration from onshore are inferred. However, modelling results suggest that the majority of the OFG was emplaced via topographically-driven flow during sea level lowstands in the last 300 ka. Global volumetric estimates of OFG will be significantly revised if active margins, with steep coastal topographies like the Canterbury margin, are considered.Geospatial techniques are mediating in decision making, diversified data management and critical analysis. Jatropha Curcas. https://www.selleckchem.com/products/pd-1-pd-l1-inhibitor-1.html is a biodiesel crop and friendly to the regions of saline water environment. This study focuses to map the suitable plantation sites for biodiesel energy crop by using meteorological parameters and satellite imageries of ASTER GDEM and Landsat 8. The thematic layers of soil adjacent to existing vegetation, topographical elevation, slope, land surface temperature, and humidity are created and analyzed with soil types, bareness index and stream orders. Suitability of sites for plantation is a function of these variables which are found to be favorable in the study area. It should be taken into consideration that Jatropha Curcas plantation in Karachi which may contribute in local economic prosperity and support in maintaining heat-sink for the industrialized city.The amphipathic α-helical antimicrobial peptide MSI-103 (aka KIA21) can form stable transmembrane pores when the bilayer takes on a positive spontaneous curvature, e.g. by the addition of lyso-lipids. Solid-state 31P- and 15N-NMR demonstrated an enrichment of lyso-lipids in these toroidal wormholes. Anionic lyso-lipids provided additional stabilization by electrostatic interactions with the cationic peptides. The remaining lipid matrix did not affect the nature of the pore, as peptides maintained the same orientation independent of lipid charge, and a change in membrane thickness did not considerably affect their tilt angle. Under optimized conditions (i.e. in the presence of lyso-lipids and appropriate bilayer thickness), stable and well-aligned pores could be obtained for solid-state 2H-NMR analysis. These data revealed for the first time the complete 3D alignment of this representative amphiphilic peptide in fluid membranes, which is compatible with either monomeric helices as constituents, or left-handed supercoiled dimers as building blocks from which the overall toroidal wormhole is assembled.Bioinspired manufacturing, in the sense of replicating the way nature fabricates, may hold great potential for supporting a socioeconomic transformation towards a sustainable society. Use of unmodified ubiquitous biological components suggests for a fundamentally sustainable manufacturing paradigm where materials are produced, transformed into products and degraded in closed regional systems with limited requirements for transport. However, adoption is currently limited by the fact that despite their ubiquitous nature, these biopolymers are predominantly harvested as industrial and agricultural products. In this study, we overcome this limitation by developing a link between bioinspired manufacturing and urban waste bioconversion. This result is paramount for the development of circular economic models, effectively connecting the organic by-products of civilization to locally decentralized, general-purpose manufacturing.Due to the very limited quantity of associated tetradymite, both mineralogical and geochemical research on tetradymite is scarce and incomplete. By taking advantage of the discovery of the Dashuigou tellurium deposit in Tibet Plateau, the authors conducted mineralogical studies on tetradymite. The authors present new mineralogical data including reflectance, micro-pressure hardness, chemical compositions focusing on its chemical formula Bi2.00Te1.89S0.95~1.00, unit cell parameters (a = 4.239 Å, c = 29.595 Å) and lattice parameters (a = 10.172 Å, v = 154.391 Å3), pyroelectricity (N type), and stable isotopes including sulfur and lead. The authors find that δ34S‰ of tetradymite varies between -0.5~2.1 with a 15-sample average of 0.56, similar to that of meteorites and rocks from the mantle, indicating that the sulfur is from the mantle; lead isotopes of the tetradymite formed in the late metallogenic epoch is different from that of both pyrite and pyrrhotite formed in the early metallogenic epoch, further indicating that the three minerals formed in different metallogenic epochs; lead isotope compositions reveal that tellurium ore bodies emplaced in a quick process mainly in the form of ore magma; lead of the deposit is primarily from the mantle with some captured from the Earth's crust. These findings help fill in large gaps of information for the mineral tetradymite.Depth of invasion (DOI) can be calculated preoperatively by MRI, and whether MRI-determined DOI can predict prognosis as well as whether it can be used as an indicator of neck dissection in cT1N0 tongue squamous cell carcinoma (SCC) remains unknown. The main goal of the current study was to answer these unknowns. A total of 151 patients with surgically treated cT1N0 tongue SCC were retrospectively enrolled, and MRI-determined DOI was measured based on T1-weighted layers with a 3.0T scan. The Chi-square test was used to evaluate the association between clinical pathologic variables and neck lymph node metastasis, and the factors that were significant in the Chi-square test were then analyzed in a multivariate logistic regression analysis model to determine the independent predictors. The main study endpoints were locoregional control (LRC) and disease-specific survival (DSS), and the Kaplan-Meier method (log-rank test) was used to calculate the LRC and DSS rates. The factors that were significant in univariate analysis were then analyzed in the Cox model to determine the independent prognostic factors.

Hypoxia is a condition in which the whole body or a region of the body is deprived of oxygen supply. The brain is very sensitive to the lack of oxygen and cerebral hypoxia can rapidly cause severe brain damage. Astrocytes are essential for the survival and function of neurons. Therefore, protecting astrocytes against cell death is one of the main therapeutic strategies for treating hypoxia. Hence, the mechanism of hypoxia-induced astrocytic cell death should be fully elucidated. In this study, astrocytes were exposed to hypoxic conditions using a hypoxia work station or the hypoxia mimetic agent cobalt chloride (CoCl2 ). Both the hypoxic gas mixture (1% O2 ) and chemical hypoxia-induced apoptotic cell death in T98G glioblastoma cells and mouse primary astrocytes. Reactive oxygen species were generated in response to the hypoxia-mediated activation of caspase-1. Active caspase-1 induced the classical caspase-dependent apoptosis of astrocytes. In addition, the microRNA processing enzyme Dicer was cleaved by caspase-3 during hypoxia. Knockdown of Dicer using antisense oligonucleotides induced apoptosis of T98G cells. Taken together, these results suggest that astrocytic cell death during hypoxia is mediated by the reactive oxygen species/caspase-1/classical caspase-dependent apoptotic pathway. In addition, the decrease in Dicer levels by active caspase-3 amplifies this apoptotic pathway via a positive feedback loop. These findings may provide a new target for therapeutic interventions in cerebral hypoxia. © 2020 International Federation for Cell Biology.Elevated 1-hour plasma glucose (1h-PG) (≥155 mg/dL) during an oral glucose tolerance test (OGTT) is a risk factor for type 2 diabetes. However, the metabolic characteristics of nonobese Asians with elevated 1h-PG are unknown. Thus, we studied 59 nonobese Japanese men with normal glucose tolerance. We divided study participants into the Low 1h-PG group ( less then 155 mg/dL) and the High 1h-PG group (≥155 mg/dL). We compared the metabolic characteristics of the groups, including tissue-specific insulin sensitivity measured using a two-step hyperinsulinemic-euglycemic clamp. Insulinogenic index and adiponectin levels were significantly lower in the High 1h-PG group than in the Low 1h-PG group. Other characteristics, including insulin sensitivity, adiposity, and ectopic fat accumulation, were similar between the groups. In conclusion, nonobese Japanese men with high 1h-PG have impaired early-phase insulin secretion and lower adiponectin levels. Insulin resistance and abnormal fat distribution were not evident in this population. This article is protected by copyright. All rights reserved.Effective conservation and management of animal populations requires knowledge of abundance and trends. For many species, these quantities are estimated using systematic visual surveys. Additional individual-level data are available for some species. Integrated population modelling (IPM) offers a mechanism for leveraging these datasets into a single estimation framework. IPMs that incorporate both population- and individual-level data have previously been developed for birds, but have rarely been applied to cetaceans. Here, we explore how IPMs can be used to improve the assessment of cetacean populations. We combined three types of data that are typically available for cetaceans of conservation concern population-level visual survey data, individual-level capture-recapture data, and data on anthropogenic mortality. We used this IPM to estimate the population dynamics of the Cook Inlet population of beluga whales (CIBW; Delphinapterus leucas) as a case study. Our state-space IPM included a population process mrotected by copyright. All rights reserved.BACKGROUND Little is known on the phenotypic characteristics of stem cells after they are transplanted to the myocardium, in part due to lack of non-invasive platforms to study stem cells directly in the living subject. Reporter gene imaging has played a valuable role in the non-invasive assessment of cell fate in vivo. In this study, we validated a pathway-specific reporter gene that can be used to non-invasively image the phenotype of stem cells transplanted to the myocardium. METHODS AND RESULTS Rat mesenchymal stem cells (MSCs) were studied for phenotypic evidence of myogenic characteristics under in vitro conditions. After markers of myogenic characteristics were identified, we constructed a reporter gene sensor, comprising the firefly luciferase (Fluc) reporter gene driven by the TroponinT promoter (cardio MSCs had 3-fold PCR expression compared to control MSCs) using a two-step signal amplification strategy. MSCs transfected with TroponinT-Fluc were studied and validated under in vitro conditions, showy. In this report, we extend these studies and report the development and validation of a pathway-specific reporter gene to study the changing phenotype of mesenchymal stromal cells after transplantation to the ischemic myocardium. In addition, we propose an algorithm for the development of these monitoring strategies for the entire scientific community to adopt. © 2020 AlphaMed Press.Wings are essential for insect fitness. A number of proteins and enzymes have been identified to be involved in wing terminal differentiation, which is characterized by the formation of the wing cuticle. Here, we addressed the question whether Chitinase 10 (Cht10) may play an important role in chitin organization in the wings of the fruit fly Drosophila melanogaster. Initially, we first found that Cht10 expression coincides with the expression of the chitin synthase coding gene kkv. This suggests that the respective proteins may cooperate during wing differentiation. In tissue-specific RNA interference experiments, we demonstrate that suppression of Cht10 causes an excess in chitin amounts in the wing cuticle. https://www.selleckchem.com/products/gsk805.html Chitin organization is severely disrupted in these wings. Based on these data, we hypothesize that Cht10 restricts chitin amounts produced by Kkv in order to ensure normal chitin organization and wing cuticle formation. In addition, we found by scanning electron microscopy that Cht10 suppression also affects the cuticle surface.

Tumor hypoxia and the tissue penetration limitation of excitation light hamper the widespread clinical use of photodynamic therapy. The development of new therapeutic strategies that can generate oxygen-independent free radicals without penetration depth limitation is of great demand. Herein, a novel magnetothermodynamic strategy for deep-seated tumor therapy is reported. In this system, a radical initiator (AIPH) was loaded into porous hollow iron oxide nanoparticles (PHIONs). Under the induction of an alternating magnetic field (AMF), PHIONs can generate heat to trigger the release and decomposition of AIPH, resulting in the generation of oxygen-independent alkyl radicals. The resulting alkyl radicals can effectively kill cancer cells under hypoxic conditions. More importantly, this magnetothermally triggered free-radical generator exhibits significant therapeutic efficacy for orthotopic liver tumors in a rat model. This magnetothermodynamic therapy strategy with the advantages of oxygen independence and no limitation of penetration depth holds great promise in deep-seated solid tumor treatment.The introduction of thiophene rings to the helical structure of carbohelicenes has electronic effects that may be used advantageously in organic electronics. The performance of these devices is highly dependent on the sulfur atom topology, so a precise knowledge of the synthetic routes that may afford isomeric structures is necessary. We have studied the photocyclization pathway of both 2- and 3-styrylthiophenes on their way to thiahelicenes by experiment and theory. To begin with, the synthesis of stereochemically well-defined 2- and 3-styrylthiophenes allowed us to register first, and simulate later, the UV-vis electronic spectra of these precursors. https://www.selleckchem.com/products/trimethoprim.html This information gave us access through time-dependent density functional theory calculations to the very nature of the excited states involved in the photocyclization step and from there to the regio- and stereochemical outcome of the reaction. For the widely known case of a 2-styrylthiophene derivative, the expected naphtho[2,1-b]thiophene type of ring fusion was predicted and experimentally observed by synthesis. On the contrary, 3-styrylthiophene derivatives have been seldom used in synthetic photocyclizations. Among the two possible structural outcomes, only the naphtho[1,2-b]thiophene type of ring fusion was found to be mechanistically sound, and this was actually the only compound observed by synthesis.Several investigations have suggested that ultrasound triggers the release of drugs encapsulated into liposomes at acoustic pressures low enough to avoid cavitation or high hyperthermia. However, the mechanism leading to this triggered release as well as the adequate composition of the liposome membrane remains unknown. Here, we investigate the ultrasound-triggered release of fluorescein disodium salt encapsulated into liposomes made of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-distearoylphosphatidyl-ethanolamine (DSPC) lipids with various concentrations of cholesterol (from 0 to 44 mol %). The passive release of encapsulated fluorescein was first characterized. It was observed to be higher when the membrane is in a fluid phase and increased with temperature but decreased upon addition of cholesterol. Next, the release of fluorescein was measured at different acoustic frequencies (0.8, 1.1, and 3.3 MHz) and peak-to-peak pressures (0, 2, 2.5, 5, and 8 MPa). Measurements were performed at temperatu lipids.We examine the theoretical underpinnings of the seminal discoveries by Reiner Sustmann about the ambiphilic nature of Huisgen's phenyl azide cycloadditions. Density functional calculations with ωB97X-D and B2PLYP-D3 reproduce the experimental data and provide insights into ambiphilic control of reactivity. Distortion/interaction-activation strain and energy decomposition analyses show why Sustmann's use of dipolarophile ionization potential is such a powerful predictor of reactivity. We add to Sustmann's data set several modern distortion-accelerated dipolarophiles used in bioorthogonal chemistry to show how these fit into the orbital energy criteria that are often used to understand cycloaddition reactivity. We show why such a simple indicator of reactivity is a powerful predictor of reaction rates that are actually controlled by a combination of distortion energies, charge transfer, closed-shell repulsion, polarization, and electrostatic effects.ZnZrO ternary oxide represents a prominent catalytic system, identified recently for syngas conversion and CO2 reduction via OX-ZEO technology. One intriguing observation of the ZnZrO catalyst is the very low amount of Zn required for achieving high activity, which challenges the current views on the active site of binary oxide catalysts. Herein, we demonstrate, via machine-learning-based atomic simulation, that the structure evolution of the ZnZrO system in synthesis can be traced from bulk to surface, which leads to the identification of the active site of the ZnZrO catalyst. Theory shows that an unprecedented single-layer Zn-O structure can adhere strongly to the monoclinic ZrO2 minority (001) surface, forming a stable oxide-on-oxide interface Zn-O/M(001). The single-layer Zn-O can convert syngas to methanol with a high turnover frequency (7.38 s-1) from microkinetics simulation. Electron structure analyses reveal that the pentahedron [ZnO4] in Zn-O/M(001) enhances the surface electron donation to promote the catalytic activity.Milk is a complex biological fluid composed mainly of water, carbohydrates, lipids, proteins, and diverse bioactive factors. Human milk represents a unique tailored source of nutrients that adapts during lactation to the specific needs of the developing infant. Proteins in milk have been studied for decades, and proteomics, peptidomics, and glycoproteomics are the main approaches previously deployed to decipher the proteome of human milk. In the present work, we aimed at implementing a highly automated pipeline for the proteomic analysis of human milk with liquid chromatography mass spectrometry (MS). Commercial human milk samples were used to evaluate and optimize workflows. Centrifugation for defatting milk samples was assessed before and after reduction, alkylation, and enzymatic digestion of proteins, without and with presence of surfactants. Skimmed milk samples were analyzed using isobaric labeling-based quantitative MS on an Orbitrap Tribrid mass spectrometer. Sample fractionation using isoelectric focusing was also evaluated to more deeply profile the human milk proteome.

The diagnosis of and criteria for gestational diabetes mellitus (GDM) continue to divide the scientific and medical community, both between and within countries. Many argue for universal adoption of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria and feel that further clinical trials are unjustified and even unethical. However, there are concerns about the large increase in number of women who would be diagnosed with GDM using these criteria and the subsequent impact on health care resources and the individual. This Perspective reviews the origins of the IADPSG consensus and points out some of its less well-known limitations, particularly with respect to identifying women at risk for an adverse pregnancy outcome. https://www.selleckchem.com/products/namodenoson-cf-102.html It also questions the clinical and cost-effectiveness data often cited to support the IADPSG glycemic thresholds. We present the argument that adoption of diagnostic criteria defining GDM should be based on response to treatment at different diagnostic thresholds of maternal glycemia. This will likely require an international multicenter trial of treatment.Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δβ) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization. SIGNIFICANCE This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers. GRAPHICAL ABSTRACT http//cancerres.aacrjournals.org/content/canres/81/10/2612/F1.large.jpg.Intestinal crypts are composed of heterogeneous and highly plastic cell populations. Lgr5high-stem cells (SC) are responsible for homeostatic renewal, but other cells can revert to an SC-like phenotype to maintain epithelial integrity. Despite their distinct roles in orchestrating homeostasis, both populations have been designated as the putative "cell-of-origin" of colorectal cancer. However, their respective involvement in the emergence of drug-resistant cancer SCs (CSC), responsible for tumor relapse and associated with poor outcome of colorectal cancer, remains elusive. In this context, the intestinal SC/progenitor-marker Musashi1 (MSI1) is interesting as it plays important functions in intestinal homeostasis and is frequently overexpressed in human colorectal cancer. Therefore, our aims were (i) to study the impact of chemotherapy on Lgr5-expressing and MSI1-expressing cell populations, (ii) to explore the effect of increased MSI1 levels in response to treatment, and (iii) to evaluate the relevance in human colorectal cancer. Engineered mouse models treated with the therapeutic agent 5-fluorouracil showed that upon increased MSI1 levels, Lgr5high SCs remain sensitive while Lgr5low progenitors reprogram to a drug-resistant phenotype. This resulted in the expansion of an MSI1-expressing cell subpopulation with improved resistance to DNA damage and increased detoxification, typical properties of dormant-CSCs that can reactivate after chemotherapy. Analysis in patients with colorectal cancer revealed a correlation between MSI1 levels and tumor grading, CSC phenotype, and chemoresistance. Altogether, these results shed new light on the biology and plasticity of normal crypt and cancer cell populations and also open new perspectives to target MSI1 to improve chemotherapy outcome. SIGNIFICANCE This study unveils paradoxical roles for MSI1, underlining its importance in facilitating intestinal regeneration upon injury but also unraveling its new function in drug-resistant colorectal cancer stem cells.Label-free nonlinear microscopy enables nonperturbative visualization of structural and metabolic contrast within living cells in their native tissue microenvironment. Here a computational pipeline was developed to provide a quantitative view of the microenvironmental architecture within cancerous tissue from label-free nonlinear microscopy images. To enable single-cell and single-extracellular vesicle (EV) analysis, individual cells, including tumor cells and various types of stromal cells, and EVs were segmented by a multiclass pixelwise segmentation neural network and subsequently analyzed for their metabolic status and molecular structure in the context of the local cellular neighborhood. By comparing cancer tissue with normal tissue, extensive tissue reorganization and formation of a patterned cell-EV neighborhood was observed in the tumor microenvironment. The proposed analytic pipeline is expected to be useful in a wide range of biomedical tasks that benefit from single-cell, single-EV, and cell-to-EV analysis.

3%) and lung cancers (15.3%). Among the first-line drugs recommended in NeuPSIG for CRNP, pregabalin (78.7%) was the most common drug prescribed followed by amitriptyline (67%). The most common co-prescribed drugs were acid suppressants drugs (50.7%). Tapentadol, which is not part of the NeuPSIG guidelines, was prescribed on 51 occasions for neuropathic pain. Underdosing was observed in 272 prescriptions. Only 12 prescriptions completely adhered, while 275 had partial, and 13 prescriptions had poor adherence to NeuPSIG guidelines. Conclusion The most commonly used drugs in the treatment of CRNP were pregabalin and amitriptyline. Most physician partially or did not adhere to the NeuPSIG guideline in the management of CRNP. Copyright © 2020 Indian Journal of Palliative Care.Background Insomnia and poor sleep quality are common problems in patients with cancer. It interferes with the coping ability, symptoms, and treatment outcomes. The Pittsburgh Sleep Quality Index (PSQI) is a reliable, valid instrument to assess the quality of sleep in patients with cancer. Patients and Methods The study was conducted at the department of medical oncology of a tertiary cancer care center. Consecutive eligible participants were recruited and evaluated for sleep quality using PSQI questionnaire. The questionnaire was administered only once with the questions evaluating to the quality of sleep over the last 1 month. A PSQI total score of ≤5 was suggestive of good quality of sleep and a score of >5 was indicative of poor quality of sleep. Results Ninety-two consecutive consenting cancer patients admitted for chemotherapy participated in the study. Thirty-one (33.7%) patients had early cancer and 35 (38%) patients had Stage IV metastatic disease. Thirty-six (39.1%) patients reported sleep of less then 6 h and 30 (32.6%) patients had impaired functioning during day due to sleepiness. Fifty-three (57.6%) patients had poor total PSQI score, of which 39 (73.5%) were female and 14 (26.5%) were male. The study showed no correlation of the PSQI scores with the stage of the disease, and the prior treatment received. Conclusions The study showed that Indian cancer patients have short sleep duration and poor quality of sleep. A higher prevalence of sleep disturbances was seen among female cancer patients. PSQI questionnaire can be a cost-effective way of screening cancer patients for poor quality of sleep. Copyright © 2020 Indian Journal of Palliative Care.Injection calcitonin is a natural hormone inhibiting osteoclastic bone resorption have been used as an analgesic to control bone metastasis pain or pain due to osteoporosis or fracture. This randomized double blind placebo controlled trial was undertaken to determine the role of injection Salmon Calcitonin therapy to control refractory pain caused due to bone metastasis arising from cancer breast, lung, prostate or kidney. All patients had received palliative radiotherapy and were suffering unsatisfactory pain relief on NSAIDs and tab morphine. Fourteen days inj. calcitonin or placebo injections were administered in 23 patients initially as high dose induction dose (800 IU per day SC) followed 200 IU subcutaneous (SC) once a day. Patients were assessed for pain intensity and quality of life on EORTC QLQ-30 questionnaire 6 hourly for 2 days and on 7th and 30th day. Any incidence of hypercalcemia, bone fracture, nerve root and bone marrow compression were also noted. https://www.selleckchem.com/products/GDC-0941.html This study found a significant reduction in pain after SC calcitonin injection therapy at 14 and 30 days' assessment. No patients in the study group required rescue analgesia after 18 hrs. There was a statistically significant difference in rescue analgesics required between the groups during two days hospitalization. Global health as well as physical and social wellbeing was better at 30 and 90 days in the study group as compared to control group, however it could not reach a statistical significance which may be attributed to the small sample size of the study. Copyright © 2020 Indian Journal of Palliative Care.Penalized likelihood approaches are widely used for high-dimensional regression. Although many methods have been proposed and the associated theory is now well developed, the relative efficacy of different approaches in finite-sample settings, as encountered in practice, remains incompletely understood. There is therefore a need for empirical investigations in this area that can offer practical insight and guidance to users. In this paper, we present a large-scale comparison of penalized regression methods. We distinguish between three related goals prediction, variable selection and variable ranking. Our results span more than 2300 data-generating scenarios, including both synthetic and semisynthetic data (real covariates and simulated responses), allowing us to systematically consider the influence of various factors (sample size, dimensionality, sparsity, signal strength and multicollinearity). We consider several widely used approaches (Lasso, Adaptive Lasso, Elastic Net, Ridge Regression, SCAD, the Dantzig Selector and Stability Selection). We find considerable variation in performance between methods. Our results support a "no panacea" view, with no unambiguous winner across all scenarios or goals, even in this restricted setting where all data align well with the assumptions underlying the methods. The study allows us to make some recommendations as to which approaches may be most (or least) suitable given the goal and some data characteristics. Our empirical results complement existing theory and provide a resource to compare methods across a range of scenarios and metrics. © The Author(s) 2019.Approximate Bayesian computation (ABC) has become one of the major tools of likelihood-free statistical inference in complex mathematical models. Simultaneously, stochastic differential equations (SDEs) have developed to an established tool for modelling time-dependent, real-world phenomena with underlying random effects. When applying ABC to stochastic models, two major difficulties arise First, the derivation of effective summary statistics and proper distances is particularly challenging, since simulations from the stochastic process under the same parameter configuration result in different trajectories. Second, exact simulation schemes to generate trajectories from the stochastic model are rarely available, requiring the derivation of suitable numerical methods for the synthetic data generation. To obtain summaries that are less sensitive to the intrinsic stochasticity of the model, we propose to build up the statistical method (e.g. the choice of the summary statistics) on the underlying structural properties of the model.

Overall, due to its ability to degrade many hydrocarbons and withstand high salt and heavy metals, strain Wilcox may prove useful for remediation of produced waters.Emerging evidence has highlighted the connection between exposure to air pollution and the increased risk of obesity, metabolic syndrome, and comorbidities. Given the recent interest in studying the effects of ultrafine particle (UFP) on the health of obese individuals, this study examined the effects of gastrointestinal UFP exposure on gut microbial composition and metabolic function using an in vivo murine model of obesity in both sexes. UFPs generated from light-duty diesel engine combustion of petrodiesel (B0) and a petrodiesel/biodiesel fuel blend (8020 v/v, B20) were administered orally. Multi-omics approaches, including liquid chromatography-mass spectrometry (LC-MS) based targeted metabolomics and 16S rRNA gene sequence analysis, semi-quantitatively compared the effects of 10-day UFP exposures on obese C57B6 mouse gut microbial population, changes in diversity and community function compared to a phosphate buffer solution (PBS) control group. Our results show that sex-specific differences in the gut microbial population in response to UFP exposure can be observed, as UFPs appear to have a differential impact on several bacterial families in males and females. Meanwhile, the alteration of seventy-five metabolites from the gut microbial metabolome varied significantly (ANOVA p  less then  0.05) across the PBS control, B0, and B20 groups. Multivariate analyses revealed that the fuel-type specific disruption to the microbial metabolome was observed in both sexes, with stronger disruptive effects found in females in comparison to male obese mice. Metabolic signatures of bacterial cellular oxidative stress, such as the decreased concentration of nucleotides and lipids and increased concentrations of carbohydrate, energy, and vitamin metabolites were detected. Furthermore, blood metabolites from the obese mice were differentially affected by the fuel types used to generate the UFPs (B0 vs. B20).With the rapid growth and increasing use of brain MRI, there is an interest in automated image classification to aid human interpretation and improve workflow. We aimed to train a deep convolutional neural network and assess its performance in identifying abnormal brain MRIs and critical intracranial findings including acute infarction, acute hemorrhage and mass effect. A total of 13,215 clinical brain MRI studies were categorized to training (74%), validation (9%), internal testing (8%) and external testing (8%) datasets. Up to eight contrasts were included from each brain MRI and each image volume was reformatted to common resolution to accommodate for differences between scanners. Following reviewing the radiology reports, three neuroradiologists assigned each study to abnormal vs normal, and identified three critical findings including acute infarction, acute hemorrhage, and mass effect. A deep convolutional neural network was constructed by a combination of localization feature extraction (LFE) modules an MRIs, while addressing the fact that some MR contrasts might not be available in individual studies.Colorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multiple others, and an enriched extract containing 84% (w/v) artocarpin (determined by HPLC-MS-DAD) was prepared. The enriched extract irreversibly inhibited the activity of human cytochrome P450 CYP2C9, an enzyme previously shown to be overexpressed in CRC models. In vitro evaluations on heterologously expressed microsomes, revealed irreversible inhibitory kinetics with an IC50 value of 0.46 µg/mL. Time- and concentration-dependent cytotoxicity was observed on human cancerous HCT116 cells with an IC50 value of 4.23 mg/L in 72 h. We then employed the azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-induced model in C57BL/6 mice, which revealed that the enriched extract suppressed tumor multiplicity, reduced the protein expression of proliferating cell nuclear antigen, and attenuated the gene expression of proinflammatory cytokines (Il-6 and Ifn-γ) and protumorigenic markers (Pcna, Axin2, Vegf, and Myc). The extract significantly (p = 0.03) attenuated (threefold) the gene expression of murine Cyp2c37, an enzyme homologous to the human CYP2C9 enzyme. These promising chemopreventive, cytotoxic, anticancer and anti-inflammatory responses, combined with an absence of toxicity, validate further evaluation of A. heterophyllus extract as a therapeutic agent.Tendon extracellular matrix (ECM) mechanical unloading results in tissue degradation and breakdown, with niche-dependent cellular stress directing proteolytic degradation of tendon. Here, we show that the extracellular-signal regulated kinase (ERK) pathway is central in tendon degradation of load-deprived tissue explants. We show that ERK 1/2 are highly phosphorylated in mechanically unloaded tendon fascicles in a vascular niche-dependent manner. Pharmacological inhibition of ERK 1/2 abolishes the induction of ECM catabolic gene expression (MMPs) and fully prevents loss of mechanical properties. Moreover, ERK 1/2 inhibition in unloaded tendon fascicles suppresses features of pathological tissue remodeling such as collagen type 3 matrix switch and the induction of the pro-fibrotic cytokine interleukin 11. This work demonstrates ERK signaling as a central checkpoint to trigger tendon matrix degradation and remodeling using load-deprived tissue explants.The formula of a standardized extract of Centella asiatica (ECa 233) was modified to improve its dissolution, with implications for pharmacokinetics and metabolomic profile. This study aimed to understand the resultant changes in disposition kinetics of ECa 233 and alterations to human metabolome after oral administration. https://www.selleckchem.com/products/azd5305.html This study was a two-sequence of dosages (250 and 500 mg), with an open-label phase I clinical trial. The modified formula was administered in single and multiple doses to twelve healthy Thai volunteers. The major parent compounds, madecassoside and asiaticoside, were rarely absorbed, instead undergoing biotransformation into active metabolites, madecassic acid and asiatic acid with possibility to be eliminated via fecal route. Increasing the dose of ECa 233 resulted in significantly greater plasma levels of those active metabolites, with accumulation of asiatic acid after multiple oral administration for seven days. Examining the impacts of accumulation behavior on metabolomics, the study traced changes in levels pre- and post-dose of five relevant human metabolites.

Each functional annotation was assigned one point, and those genes with a score ≥2 were designated "biological CRC risk genes". Using this method, we revealed 82 biological CRC risk genes, which were mapped to 128 genes in an expanded PPI network. https://www.selleckchem.com/products/BEZ235.html Further utilizing DrugBank and the Therapeutic Target Database, we found 21 genes in our list that are targeted by 166 candidate drugs. Based on data from ClinicalTrials.gov and literature review, we found four known target genes with six drugs for clinical treatment in CRC, and three target genes with nine drugs supported by previous preclinical results in CRC. Additionally, 12 genes are targeted by 32 drugs approved for other indications, which can possibly be repurposed for CRC treatment. Finally, analysis from Connectivity Map (CMap) showed that 18 drugs have a high potential for CRC.Resistance to antimicrobials is a challenging issue that complicates the treatment of infections caused by bacteria and fungi, thus requiring new therapeutic options. Oncocalyxone A, a benzoquinone obtained from Auxemma oncocalyx (Allem) Taub has several biological effects; however, there is no data on its antimicrobial action. In this study, its antimicrobial and antibiofilm activities were evaluated against bacteria and fungi of clinical interest. Strains of Gram-positive and Gram-negative bacteria, and filamentous fungi and yeasts were selected to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of oncocalyxone A. The antibacterial effect of oncocalyxone A was studied using survival curves, atomic force microscopy (AFM), and the involvement of oxidative stress. We examined the inhibitory action of the molecule on biofilm formation and its hemolytic activity against human erythrocytes. Our results showed that among the strains tested, Staphylococcus epidermidis was highly sensitive to the action of oncocalyxone A, with an MIC of 9.43 μg/mL. In most bacterial strains analyzed, a bacteriostatic effect was observed, though the molecule showed no antifungal activity. Antibiofilm activity was observed against the methicillin-resistant S. aureus bacteria. Additionally, results from atomic force microscopy imaging showed that oncocalyxone A significantly altered bacterial morphology. Further, oncocalyxone A showed no hemolytic activity at concentrations ≥151 μg/mL. Together, our results demonstrate the antibacterial and antibiofilm potential of oncocalyxone A, indicating its therapeutic potential against bacterial resistance.Bacteroides fragilis is a most frequent anaerobic pathogen isolated from human infections, particularly found in the abdominal cavity. Different factors contribute to the pathogenesis and persistence of B. fragilis at infection sites. The knowledge of the virulence factors can provide applicable information for finding alternative options for the antibiotic therapy and treatment of B. fragilis caused infections. Herein, a comprehensive review of the important B. fragilis virulence factors was prepared. In addition to B. fragilis toxin (BFT) and its potential role in the diarrhea and cancer development, some other important virulence factors and characteristics of B. fragilis are described including capsular polysaccharides, iron acquisition, resistance to antimicrobial agents, and survival during the prolonged oxidative stress, quorum sensing, and secretion systems.Retrospective diagnosis of a bacterial collection (n = 31) originated from five farms reportedly affected by early mortality syndrome (EMS) in Southeast Asia in 2016 revealed that 9/31 isolates from two farms tested positive for V. parahaemolyticus causing acute hepatopancreatic necrosis disease (VPAHPND). Molecular analysis of the 22 remaining isolates showed that 21 isolates belong to Vibrio species including VPnon-AHPND, V. vulnificus, V. cholerae, V. owensii and V. alginolyticus. One isolate from an AHPND farm was preliminarily identified as Aeromonas schubertii based on 99.43% nucleotide identity of 16S rRNA to the reference strain ATCC 43700 (X60416). Diseases caused by Vibrio bacteria have been well-studied in shrimp while pathogenic potential of non-Vibrio species has been relatively overlooked. Since the description of A. schubertii present in shrimp farms is rare, this study therefore focused on species identification and its pathogenic potential to shrimp based on a combination of multiple approachas, active surveillance of this pathogen, therefore, should not be overlooked.Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) has been increasingly reported and is now recognized as a public health concern. The aim of this study was to investigate the molecular epidemiology of CR-hvKp strains that were isolated from an Iranian hospital. A total of 74 non-duplicated carbapenem-resistant K. pneumoniae (CR-Kp) were collected from patients' clinical or surveillance cultures. Resistance/virulence genes were identified by PCR and sequencing. String test, capsular genotyping, conjugation assays, PCR-based replicon typing, pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and were performed. All 74 CR-Kp isolates were carbapenemase producers, which co-carried multiple resistance genes such as blaCTX-M-15, blaTEM-1, blaSHV-type, qnrB1, and qnrS1. The most common carbapenemase gene was blaOXA-48 (67/74 90.5%), followed by blaNDM-1 (18/74 24.3%), and blaNDM-7 (3/74 4%). The blaOXA-48 and blaNDM-1 were found on IncL/M and IncFII conjugative plasmids, respectively. Of 74 CR-Kp isolates, 49 were positive for string test. Capsular genotyping revealed that 34 and 10 CR-Kp strains belonged to the K1 and K2 serotypes, respectively. rmpA was the most prevalent virulence gene detected in 64.8% of the isolates. Fifty two strains were identified as CR-hvKp. PFGE typing showed 5 different clusters with two major clusters B (39 isolates, 52.7%) associated with sequence type 11 (ST11), and A (21 isolates, 28.4%) associated with ST893. Furthermore, ST147, ST392, and ST15 carbapenemase producers have also been sporadically identified. One isolate belonging to ST11 was resistant to colistin and were negative for mcr-1-2-3 genes. Insertional inactivation of mgrB due to IS elements was observed in the colistin-resistant isolate. Our findings suggest that ST11 CR-hvKP strain has a clonal distribution in our hospital. Therefore, immediate implementation of infection-control measures may be the best way to prevent the spread of these clones.

Thus, ILCs may be a sensitive detector of microenvironmental changes, and analysis of their phenotype and function at local sites may enable us to better understand the microenvironment in airway diseases. In this review, we aimed to identify molecules that either positively or negatively influence the function and/or plasticity of ILCs and the sources of the molecules in the airways in order to examine the pathophysiology of airway inflammatory diseases and facilitate the issues to be solved. Copyright © 2020 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.BACKGROUND This study described and analysed the features of powered mobility device (PMD)-related injuries and compared elderly and younger adult injuries. METHODS Data from Korea Emergency Department-based Injury In-depth Surveillance (EDIIS) database involving eight emergency departments in 2011-2016 were analysed. The inclusion criteria were injuries sustained during the use of PMDs. The variables were compared between adults aged ≥ 65 years and younger adults. Primary and secondary outcomes were severe trauma and poor clinical course accordingly. The logistic regression analysis was used to identify risk factors for study outcomes. RESULTS A total of 231 adults were enrolled, of whom 150 were ≥ 65 years of age. The total number of PMD-related injuries and the proportion of elderly injured patients increased annually, and most injuries occurred on the roadway and did not involve crash opponents. By multivariate analysis, patients aged ≥ 65 years had a higher injury severity score (adjusted odds ratio [AOR], 2.78; 95% confidence interval [CI], 1.50-5.40) and had a higher incidence of intensive care unit admissions, surgery, and death (AOR, 2.42; 95% CI, 1.16-5.28). CONCLUSION Given the higher number and severity of injuries sustained among elderly adults ≥ 65 years of age shown in this study, we recommend that safety educations, such as the use of protective equipment and the safe driving on the roadway, are considered for PMD users ≥ 65 years of age. © 2020 The Korean Academy of Medical Sciences.BACKGROUND Long-term administration of ethambutol (EMB) for Mycobacterium avium complex lung disease (MAC-LD) sometimes leads to permanent discontinuation of EMB due to various adverse events. This study aimed to investigate treatment outcomes after discontinuation of EMB. METHODS Among patients diagnosed with MAC-LD between January 2001 and December 2014, 508 patients whose treatment was initiated with standard regimen until May 2018 were enrolled at a tertiary referral center in Korea. Of these 508 patients, 60 (11.8%) discontinued EMB due to various adverse effects. Among these 60 patients, treatment outcomes were analyzed for 44 patients by comparing their outcomes with those of matched subjects who received the standard treatment regimen without EMB discontinuation. https://www.selleckchem.com/products/at-406.html RESULTS The mean age of the 60 patients who discontinued EMB was 64.4 years. Ocular toxicity was the most common cause of discontinuation of EMB (75.0%, 45/60). The mean duration of EMB administration before its discontinuation was 7.0 ± 4.6 months. The treatment failure rate of the 44 patients with EMB discontinuation analyzed for treatment outcome was 29.6%, which was higher than that of the matched patients who received the standard regimen (18.3%), although the difference was not significant (P = 0.095). Of these 44 patients, EMB was substituted with later-generation fluoroquinolone in 23 patients, and the treatment failure rate of these 23 patients was significantly higher than that of the matched patients who received the standard regimen (39.1% vs. 19.3%, P = 0.045). CONCLUSION These findings suggest that treatment outcomes are unsatisfactory in patients with MAC-LD who discontinue EMB owing to adverse events. Notably, there was a statistically significant high failure rate in patients who were prescribed fluoroquinolone to replace EMB. © 2020 The Korean Academy of Medical Sciences.BACKGROUND Sugammadex is a new neuromuscular blockade reversal agent. Recently, it has been used in patients under general anesthesia. However, sugammadex could be toxic to fetuses and pediatric patients under 3 years of age. In this study, we demonstrated the safety of sugammadex in fetuses, using zebrafish larvae. Furthermore, its neurotoxicity was evaluated using neuronal cell lines. METHODS We used SH-SY5Y cells to determine the viability of neuronal cells treated with sugammadex. Zebrafish larvae were used to determine the teratogenic effects of sugammadex. RESULTS Sugammadex showed no adverse effects on neuronal cells and zebrafish larvae. The survival rates of neuronal cells were not different in all concentrations. In addition, the heart formation of zebrafish embryos, which were exposed to various concentrations of sugammadex, were not different. CONCLUSION This study demonstrated the feasibility of using sugammadex during pregnancy. However, further clinical studies will be required to extrapolate these results to humans. © 2020 The Korean Academy of Medical Sciences.BACKGROUND Studies on the efficacy of implantable cardioverter-defibrillator (ICD) therapy for primary prevention in Asian patients are relatively lacking compared to those for secondary prevention. Also, it is important to stratify which patients will benefit from ICD therapy for primary prevention. METHODS Of 483 consecutive patients who received new implantation of ICD in 9 centers in Korea, 305 patients with reduced left ventricular systolic function and/or documented ventricular fibrillation/tachycardia were enrolled and divided into primary (n = 167) and secondary prevention groups (n = 138). RESULTS During mean follow-up duration of 2.6 ± 1.6 years, appropriate ICD therapy occurred in 78 patients (25.6%), and appropriate ICD shock and anti-tachycardia pacing occurred in 15.1% and 15.1% of patients, respectively. Appropriate ICD shock rate was not different between the two groups (primary 12% vs. secondary 18.8%, P = 0.118). However, appropriate ICD therapy rate including shock and anti-tachycardia pacing was significantly higher (primary 18% vs.