scholarly journals Time-Dependent Impact of Irreversible Electroporation on Pathology and Ablation Size in the Porcine Liver: A 24-Hour Experimental Study

2019 ◽  
Vol 18 ◽  
pp. 153303381987689 ◽  
Author(s):  
Jantien A. Vogel ◽  
Eran van Veldhuisen ◽  
Lindy K. Alles ◽  
Olivier R. Busch ◽  
Frederike Dijk ◽  
...  

Irreversible electroporation causes cell death through low frequency, high voltage electrical pulses and is increasingly used to treat non-resectable cancers. A recent systematic review revealed that tissue damage through irreversible electroporation is time-dependent, but the impact of time on the ablation zone size remains unknown. Irreversible electroporation ablations were performed hourly during 24 consecutive hours in the peripheral liver of 2 anaesthetized domestic pigs using clinical treatment settings. Immediately after the 24th ablation, the livers were harvested and examined for tissue response in time based on macroscopic and microscopic pathology. The impact of time on these outcomes was assessed with Spearman rank correlation test. Ablation zones were sharply demarcated as early as 1 hour after treatment. During 24 hours, the ablation zones showed a significant increase in diameter (rs = 0.493, P = .014) and total surface (rs = 0.499, P = .013), whereas the impact of time on the homogeneous ablated area was not significant (rs = 0.172, P = .421). Therefore, the increase in size could mainly be attributed to an increase in the transition zone. Microscopically, the ablation zones showed progression in cell death and inflammation. This study assessed the dynamics of irreversible electroporation on the porcine liver during 24 consecutive hours and found that the pathological response (ie, cell death/inflammation), and ablation size continue to develop for at least 24 hours. Consequently, future studies on irreversible electroporation should prolong their observation period.

Author(s):  
Paulo A. Garcia ◽  
Christopher B. Arena ◽  
Robert E. Neal ◽  
S. Nahum Goldberg ◽  
Eliel Ben-David ◽  
...  

Irreversible electroporation (IRE) is a new minimally invasive non-thermal focal ablation technique that has been used for the treatment of spontaneous tumors in canine and human patients [1, 2]. The procedure typically involves placing two electrodes into or around a tumor and delivering a series of low energy electric pulses to kill tumor tissue with sub-millimeter resolution. The pulses generate an electric field that alters the resting transmembrane potential (TMP) of the cells. Depending on the magnitude of the induced TMP, the electric pulses can have no effect, reversibly increase membrane permeability, or cause cell death in the case of IRE.


Author(s):  
Chunlan Jiang ◽  
Zhenpeng Qin ◽  
Gary Long ◽  
John C. Bischof

Recently, irreversible electroporation (IRE) has emerged as a promising tumor ablation technique. IRE induces cell death by irreversibly compromising membrane integrity with a series of short, high voltage electrical pulses [1]. IRE offers many advantages over surgery and thermal ablations including that it 1) is fast and minimally invasive, 2) destroys the tumor while preserving adjacent connective tissues [2], and 3) can be delivered with negligible thermal injury [3]. Here we hypothesize that the thresholds necessary to successfully electroporate cancer cell membranes, and therefore more effectively destroy an entire tumor, can be dramatically improved by careful choice of 1) electroporation parameter, and 2) chemical adjuvants that specifically impact the cell membrane.


Author(s):  
Guilherme Borzacchiello ◽  
Carl Albrecht ◽  
Fabricio N Correa ◽  
Breno Jacob ◽  
Guilherme da Silva Leal

2020 ◽  
Vol 133 (1) ◽  
pp. 182-189
Author(s):  
Tae-Jin Song ◽  
Seung-Hun Oh ◽  
Jinkwon Kim

OBJECTIVECerebral aneurysms represent the most common cause of spontaneous subarachnoid hemorrhage. Statins are lipid-lowering agents that may expert multiple pleiotropic vascular protective effects. The authors hypothesized that statin therapy after coil embolization or surgical clipping of cerebral aneurysms might improve clinical outcomes.METHODSThis was a retrospective cohort study using the National Health Insurance Service–National Sample Cohort Database in Korea. Patients who underwent coil embolization or surgical clipping for cerebral aneurysm between 2002 and 2013 were included. Based on prescription claims, the authors calculated the proportion of days covered (PDC) by statins during follow-up as a marker of statin therapy. The primary outcome was a composite of the development of stroke, myocardial infarction, and all-cause death. Multivariate time-dependent Cox regression analyses were performed.RESULTSA total of 1381 patients who underwent coil embolization (n = 542) or surgical clipping (n = 839) of cerebral aneurysms were included in this study. During the mean (± SD) follow-up period of 3.83 ± 3.35 years, 335 (24.3%) patients experienced the primary outcome. Adjustments were performed for sex, age (as a continuous variable), treatment modality, aneurysm rupture status (ruptured or unruptured aneurysm), hypertension, diabetes mellitus, household income level, and prior history of ischemic stroke or intracerebral hemorrhage as time-independent variables and statin therapy during follow-up as a time-dependent variable. Consistent statin therapy (PDC > 80%) was significantly associated with a lower risk of the primary outcome (adjusted hazard ratio 0.34, 95% CI 0.14–0.85).CONCLUSIONSConsistent statin therapy was significantly associated with better prognosis after coil embolization or surgical clipping of cerebral aneurysms.


2020 ◽  
Author(s):  
Eduardo Atem De Carvalho ◽  
Rogerio Atem De Carvalho

BACKGROUND Since the beginning of the COVID-19 pandemic, researchers and health authorities have sought to identify the different parameters that govern their infection and death cycles, in order to be able to make better decisions. In particular, a series of reproduction number estimation models have been presented, with different practical results. OBJECTIVE This article aims to present an effective and efficient model for estimating the Reproduction Number and to discuss the impacts of sub-notification on these calculations. METHODS The concept of Moving Average Method with Initial value (MAMI) is used, as well as a model for Rt, the Reproduction Number, is derived from experimental data. The models are applied to real data and their performance is presented. RESULTS Analyses on Rt and sub-notification effects for Germany, Italy, Sweden, United Kingdom, South Korea, and the State of New York are presented to show the performance of the methods here introduced. CONCLUSIONS We show that, with relatively simple mathematical tools, it is possible to obtain reliable values for time-dependent, incubation period-independent Reproduction Numbers (Rt). We also demonstrate that the impact of sub-notification is relatively low, after the initial phase of the epidemic cycle has passed.


2021 ◽  
Vol 13 (8) ◽  
pp. 1485
Author(s):  
Naveen Ramachandran ◽  
Sassan Saatchi ◽  
Stefano Tebaldini ◽  
Mauro Mariotti d’Alessandro ◽  
Onkar Dikshit

Low-frequency tomographic synthetic aperture radar (TomoSAR) techniques provide an opportunity for quantifying the dynamics of dense tropical forest vertical structures. Here, we compare the performance of different TomoSAR processing, Back-projection (BP), Capon beamforming (CB), and MUltiple SIgnal Classification (MUSIC), and compensation techniques for estimating forest height (FH) and forest vertical profile from the backscattered echoes. The study also examines how polarimetric measurements in linear, compact, hybrid, and dual circular modes influence parameter estimation. The tomographic analysis was carried out using P-band data acquired over the Paracou study site in French Guiana, and the quantitative evaluation was performed using LiDAR-based canopy height measurements taken during the 2009 TropiSAR campaign. Our results show that the relative root mean squared error (RMSE) of height was less than 10%, with negligible systematic errors across the range, with Capon and MUSIC performing better for height estimates. Radiometric compensation, such as slope correction, does not improve tree height estimation. Further, we compare and analyze the impact of the compensation approach on forest vertical profiles and tomographic metrics and the integrated backscattered power. It is observed that radiometric compensation increases the backscatter values of the vertical profile with a slight shift in local maxima of the canopy layer for both the Capon and the MUSIC estimators. Our results suggest that applying the proper processing and compensation techniques on P-band TomoSAR observations from space will allow the monitoring of forest vertical structure and biomass dynamics.


Water ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2058 ◽  
Author(s):  
Larissa Rolim ◽  
Francisco de Souza Filho

Improved water resource management relies on accurate analyses of the past dynamics of hydrological variables. The presence of low-frequency structures in hydrologic time series is an important feature. It can modify the probability of extreme events occurring in different time scales, which makes the risk associated with extreme events dynamic, changing from one decade to another. This article proposes a methodology capable of dynamically detecting and predicting low-frequency streamflow (16–32 years), which presented significance in the wavelet power spectrum. The Standardized Runoff Index (SRI), the Pruned Exact Linear Time (PELT) algorithm, the breaks for additive seasonal and trend (BFAST) method, and the hidden Markov model (HMM) were used to identify the shifts in low frequency. The HMM was also used to forecast the low frequency. As part of the results, the regime shifts detected by the BFAST approach are not entirely consistent with results from the other methods. A common shift occurs in the mid-1980s and can be attributed to the construction of the reservoir. Climate variability modulates the streamflow low-frequency variability, and anthropogenic activities and climate change can modify this modulation. The identification of shifts reveals the impact of low frequency in the streamflow time series, showing that the low-frequency variability conditions the flows of a given year.


Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 534
Author(s):  
Sucharat Tungsukruthai ◽  
Onrapak Reamtong ◽  
Sittiruk Roytrakul ◽  
Suchada Sukrong ◽  
Chanida Vinayanwattikun ◽  
...  

Autophagic cell death (ACD) is an alternative death mechanism in resistant malignant cancer cells. In this study, we demonstrated how polyphenol stilbene compound PE5 exhibits potent ACD-promoting activity in lung cancer cells that may offer an opportunity for novel cancer treatment. Cell death caused by PE5 was found to be concomitant with dramatic autophagy induction, as indicated by acidic vesicle staining, autophagosome, and the LC3 conversion. We further confirmed that the main death induction caused by PE5 was via ACD, since the co-treatment with an autophagy inhibitor could reverse PE5-mediated cell death. Furthermore, the defined mechanism of action and upstream regulatory signals were identified using proteomic analysis. Time-dependent proteomic analysis showed that PE5 affected 2142 and 1996 proteins after 12 and 24 h of treatment, respectively. The crosstalk network comprising 128 proteins that control apoptosis and 25 proteins involved in autophagy was identified. Protein–protein interaction analysis further indicated that the induction of ACD was via AKT/mTOR and Bcl-2 suppression. Western blot analysis confirmed that the active forms of AKT, mTOR, and Bcl-2 were decreased in PE5-treated cells. Taken together, we demonstrated the novel mechanism of PE5 in shifting autophagy toward cell death induction by targeting AKT/mTOR and Bcl-2 suppression.


Author(s):  
Mandy Rauschner ◽  
Luisa Lange ◽  
Thea Hüsing ◽  
Sarah Reime ◽  
Alexander Nolze ◽  
...  

Abstract Background The low extracellular pH (pHe) of tumors resulting from glycolytic metabolism is a stress factor for the cells independent from concomitant hypoxia. The aim of the study was to analyze the impact of acidic pHe on gene expression on mRNA and protein level in two experimental tumor lines in vitro and in vivo and were compared to hypoxic conditions as well as combined acidosis+hypoxia. Methods Gene expression was analyzed in AT1 prostate and Walker-256 mammary carcinoma of the rat by Next Generation Sequencing (NGS), qPCR and Western blot. In addition, the impact of acidosis on tumor cell migration, adhesion, proliferation, cell death and mitochondrial activity was analyzed. Results NGS analyses revealed that 147 genes were uniformly regulated in both cell lines (in vitro) and 79 genes in both experimental tumors after 24 h at low pH. A subset of 25 genes was re-evaluated by qPCR and Western blot. Low pH consistently upregulated Aox1, Gls2, Gstp1, Ikbke, Per3, Pink1, Tlr5, Txnip, Ypel3 or downregulated Acat2, Brip1, Clspn, Dnajc25, Ercc6l, Mmd, Rif1, Zmpste24 whereas hypoxia alone led to a downregulation of most of the genes. Direct incubation at low pH reduced tumor cell adhesion whereas acidic pre-incubation increased the adhesive potential. In both tumor lines acidosis induced a G1-arrest (in vivo) of the cell cycle and a strong increase in necrotic cell death (but not in apoptosis). The mitochondrial O2 consumption increased gradually with decreasing pH. Conclusions These data show that acidic pHe in tumors plays an important role for gene expression independently from hypoxia. In parallel, acidosis modulates functional properties of tumors relevant for their malignant potential and which might be the result of pH-dependent gene expression.


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