Mapping of mobile charges on insulator surfaces with the electrostatic force microscope

Journal ArticleMigration of surface ions in lateral fields on insulator surfaces may modify the electrical characteristics of underlying semiconductor structures causing device instabilities. A high sensitivity electrostatic force microscope is used to image the movement and spatial distribution of surface ions on Si3N4. Mobile surface ions are distributed by the fringing fields of a p-n junction and an open-gate field-effect transistor. The surface charge distribution and topography are imaged simultaneously on a micrometer scale

Результаты использования миопластики для закрытия дефекта тазового дна после экстралеваторной брюшно-промежностной экстирпации прямой кишки

Background. Extralevator abdominoperineal excision is associated with a high incidence of perineal wound complications. There is no uniform standard for choosing the method for pelvic floor reconstruction after extralevator abdominoperineal excision.The purpose of the study was to compare the results of extralevator abdominoperineal excisions of the rectum using various methods of perineal wound closure.Materials and Methods. Between 2014 and 2018, 120 patients underwent extralevator abdominoperineal excisions of the rectum using various options for closure of the pelvic floor. The patients were divided into 3 groups. Group I patients (n=64) underwent simple plasty of the peritoneal wound. Group II patients (n=43) underwent myoplasty using the gluteus maximus muscle. Group III patients (n=13) underwent myoplasty using the rectus abdominis muscle. The incidence of perineal wound complications in the early postoperative period was assessed.Results. The total number of perineal wound complications in Group I, II and III was 33 (51.5 %), 13 (30.2 %), and 6 (46.1 %), respectively. Grade IIIA-IIIB complications according to the Clavien-Dindo classification were observed in 25 % of Group I patients, in 18.6 % of Group II patients and in 7.7 % of Group II patients. Postoperative perineal wound complications occurred more often in Group I patients after simple plasty than in Group II and III patients after myoplasty (51.5 % versus 30.2 %). However, perineal wound complications were observed more often in Group III than in Group II (46.1 % versus 30.2 %, respectively). No significant differences in the frequency of complications between 3 groups were found.Conclusion. Using various options for closure of the pelvic floor after extralevator abdominoperineal excisions of the rectum, there was a tendency to reduction in the incidence of grade IIIA-IIIB perineal wound complications.Введение. Экстралеваторная брюшно-промежностная экстирпация связана с большой частотой послеоперационных осложнений со стороны промежностной раны. В литературе нет единых стандартных рекомендаций по выбору метода пластики дефекта тазового дна.Целью исследования является сравнение результатов использования простой пластики, пластики лоскутом ягодичной мышцы и лоскутом прямой мышцы живота при закрытии промежностной раны после экстралеваторной брюшнопромежностной экстирпации прямой кишки.Материал и методы. Проведен анализ результатов лечения 120 больных, которым в период с 2014 по 2018 г. выполнена экстралеваторная брюшнопромежностная экстирпация с использованием различных методов закрытия дефекта тазового дна. В зависимости от способа промежностной пластики больные были разделены на три группы. В I группе (n=64) пациентам выполнена простая пластика промежностной раны, во II группе (n=43) - миопластика с использованием большой ягодичной мышцы, в III группе (n=13) - миопластика с использованием прямой мышцы живота. Оценивались частота и характер осложнений со стороны промежностной раны в раннем послеоперационном периоде.Результаты. Общее количество осложнений со стороны промежности в первой группе составило 33 (51,5 %), во второй - 13 (30,2 %), в третьей группе - 6 (46,1 %) случаев. «Большие» осложнения (NIA-ШВ степени по классификации Clavien-Dindo) в I группе возникли у 25 %, во II группе - у 18,6 %, в III группе - у 7,7 % больных. Независимо от методики миопластики (II и III группы) при этих операциях послеоперационные осложнения промежностной раны наблюдались реже - 30,2 %, чем после простой пластики (I группа), - 51,5 % случаев. Однако в третьей группе осложнения встречались чаще, чем во второй, - 46,1 и 30,2 % соответственно. Значимых различий в частоте осложнений во всех трех группах не выявлено.Заключение. При использовании различных вариантов миопластики после экстралеваторной брюшно-промежностной экстирпации прямой кишки наблюдается тенденция к уменьшению частоты «больших» осложнений со стороны промежностной раны

Integrated Proteomic and Transcriptomic Investigation of the Acetaminophen Toxicity in Liver Microfluidic Biochip

Microfluidic bioartificial organs allow the reproduction of in vivo-like properties such as cell culture in a 3D dynamical micro environment. In this work, we established a method and a protocol for performing a toxicogenomic analysis of HepG2/C3A cultivated in a microfluidic biochip. Transcriptomic and proteomic analyses have shown the induction of the NRF2 pathway and the related drug metabolism pathways when the HepG2/C3A cells were cultivated in the biochip. The induction of those pathways in the biochip enhanced the metabolism of the N-acetyl-p-aminophenol drug (acetaminophen-APAP) when compared to Petri cultures. Thus, we observed 50% growth inhibition of cell proliferation at 1 mM in the biochip, which appeared similar to human plasmatic toxic concentrations reported at 2 mM. The metabolic signature of APAP toxicity in the biochip showed similar biomarkers as those reported in vivo, such as the calcium homeostasis, lipid metabolism and reorganization of the cytoskeleton, at the transcriptome and proteome levels (which was not the case in Petri dishes). These results demonstrate a specific molecular signature for acetaminophen at transcriptomic and proteomic levels closed to situations found in vivo. Interestingly, a common component of the signature of the APAP molecule was identified in Petri and biochip cultures via the perturbations of the DNA replication and cell cycle. These findings provide an important insight into the use of microfluidic biochips as new tools in biomarker research in pharmaceutical drug studies and predictive toxicity investigations

Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity

Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFNγ, IL-1α, and IL-6. Using this assay, we observed drug–cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug–cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1α, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug–cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.Pfizer Inc.Institute for Collaborative BiotechnologiesMIT Center for Cell Decision ProcessesNational Institute of Mental Health (U.S.) (grant P50-GM68762)National Institute of Mental Health (U.S.) (grant T32-GM008334)Massachusetts Institute of Technology. Biotechnology Process Engineering CenterMassachusetts Institute of Technology. Center for Environmental Health SciencesNational Institute of Mental Health (U.S.) (grant U19ES011399)Whitaker Foundatio

Ensemble Analysis of Angiogenic Growth in Three-Dimensional Microfluidic Cell Cultures

We demonstrate ensemble three-dimensional cell cultures and quantitative analysis of angiogenic growth from uniform endothelial monolayers. Our approach combines two key elements: a micro-fluidic assay that enables parallelized angiogenic growth instances subject to common extracellular conditions, and an automated image acquisition and processing scheme enabling high-throughput, unbiased quantification of angiogenic growth. Because of the increased throughput of the assay in comparison to existing three-dimensional morphogenic assays, statistical properties of angiogenic growth can be reliably estimated. We used the assay to evaluate the combined effects of vascular endothelial growth factor (VEGF) and the signaling lipid sphingoshine-1-phosphate (S1P). Our results show the importance of S1P in amplifying the angiogenic response in the presence of VEGF gradients. Furthermore, the application of S1P with VEGF gradients resulted in angiogenic sprouts with higher aspect ratio than S1P with background levels of VEGF, despite reduced total migratory activity. This implies a synergistic effect between the growth factors in promoting angiogenic activity. Finally, the variance in the computed angiogenic metrics (as measured by ensemble standard deviation) was found to increase linearly with the ensemble mean. This finding is consistent with stochastic agent-based mathematical models of angiogenesis that represent angiogenic growth as a series of independent stochastic cell-level decisions

The results of use of myoplasty for closure of the pelvic floor defect after extralevator abdominoperineal excision of the rectum

Background. Extralevator abdominoperineal excision is associated with a high incidence of perineal wound complications. There is no uniform standard for choosing the method for pelvic floor reconstruction after extralevator abdominoperineal excision.The purpose of the study was to compare the results of extralevator abdominoperineal excisions of the rectum using various methods of perineal wound closure.Materials and Methods. Between 2014 and 2018, 120 patients underwent extralevator abdominoperineal excisions of the rectum using various options for closure of the pelvic floor. The patients were divided into 3 groups. Group I patients (n=64) underwent simple plasty of the peritoneal wound. Group II patients (n=43) underwent myoplasty using the gluteus maximus muscle. Group III patients (n=13) underwent myoplasty using the rectus abdominis muscle. The incidence of perineal wound complications in the early postoperative period was assessed.Results. The total number of perineal wound complications in Group I, II and III was 33 (51.5 %), 13 (30.2 %), and 6 (46.1 %), respectively. Grade IIIA-IIIB complications according to the Clavien-Dindo classification were observed in 25 % of Group I patients, in 18.6 % of Group II patients and in 7.7 % of Group II patients. Postoperative perineal wound complications occurred more often in Group I patients after simple plasty than in Group II and III patients after myoplasty (51.5 % versus 30.2 %). However, perineal wound complications were observed more often in Group III than in Group II (46.1 % versus 30.2 %, respectively). No significant differences in the frequency of complications between 3 groups were found.Conclusion. Using various options for closure of the pelvic floor after extralevator abdominoperineal excisions of the rectum, there was a tendency to reduction in the incidence of grade IIIA-IIIB perineal wound complications