Solubility and aging of lead magnesium niobate in water

Lead magnesium niobate (PMN) is an important relaxor ferroelectric material commonly employed in multilayer capacitor and actuator manufacturing owing to its high dielectric constant and superior electrostrictive properties. However, stability of this material in water is not very well known and there is need for a detailed investigation. In this research, solubility of lead magnesium niobate powders in water was determined as a function of solids concentration. The obtained results showed that the amount of cation leaching from the PMN surface depends on the pH value of the suspension and the solids concentration. The Pb2+ and Mg2+ ion dissolution was very high especially in the acidic pH range. Nevertheless, neither the dissolution mechanism nor the effects of dissolved ions on the stability were the same for those ions. The study provides new aspects on the solubility of perovskite materials which possess more than one soluble cation in their structure.TUBITAK and DP

Suprachiasmatic Nucleus Interaction with the Arcuate Nucleus; Essential for Organizing Physiological Rhythms

The suprachiasmatic nucleus (SCN) is generally considered the master clock, independently driving all circadian rhythms. We recently demonstrated the SCN receives metabolic and cardiovascular feedback adeptly altering its neuronal activity. In the present study, we show that microcuts effectively removing SCN-arcuate nucleus (ARC) interconnectivity in Wistar rats result in a loss of rhythmicity in locomotor activity, corticosterone levels, and body temperature in constant dark (DD) conditions. Elimination of these reciprocal connections did not affect SCN clock gene rhythmicity but did cause the ARC to desynchronize. Moreover, unilateral SCN lesions with contralateral retrochiasmatic microcuts resulted in identical arrhythmicity, proving that for the expression of physiological rhythms this reciprocal SCN-ARC interaction is essential. The unaltered SCN c-Fos expression following glucose administration in disconnected animals as compared to a significant decrease in controls demonstrates the importance of the ARC as metabolic modulator of SCN neuronal activity. Together, these results indicate that the SCN is more than an autonomous clock, and forms an essential component of a larger network controlling homeostasis. The present novel findings illustrate how an imbalance between SCN and ARC communication through circadian disruption could be involved in the etiology of metabolic disorders

MRI and CT in the follow-up after irreversible electroporation of small renal masses

PURPOSE Ablation plays a growing role in the treatment of small renal masses (SRMs) due to its nephron sparing properties and low invasiveness. Irreversible electroporation (IRE) has the potential, although still experimental, to overcome current limitations of thermal ablation. No prospective imaging studies exist of the ablation zone in the follow-up after renal IRE in humans. Objectives are to assess the use of computed tomography (CT) and magnetic resonance imaging (MRI) to determine the ablation zone volume (AZV), enhancement and imaging characteristics after renal IRE. METHODS This was a prospective phase 2 study of IRE in 9 patients with 10 SRMs. MRI was performed pre-IRE, 1 week, 3 months, 6 months, and 12 months after IRE. CT was performed pre-IRE, perioperatively (direct after ablation), 3 months, 6 months, and 12 months after IRE. AZVs were assessed by two independent observers. Observer variation was analyzed. Evolution of AZVs, and their relation with the needle configuration volume (NCV; indicating planned AZV) were evaluated based on CT and MRI measurements. RESULTS Eight SRMs were clear cell renal cell carcinomas, one SRM was a papillary renal cell carcinoma and one patient had a nondiagnostic biopsy. On CT, median AZV increased perioperatively until 3 months post-IRE (16.8 cm(3) and 6.2 cm(3), respectively) compared with the NCV (4.8 cm(3)). On MRI, median AZV increased 1 week post-IRE until 3 months post-IRE (14.5 cm(3) and 4.6 cm(3), respectively) compared with the NCV (4.8 cm3). At 6 months the AZV starts decreasing (CT 4.8 cm(3); MRI 3.0 cm(3)), continuing at 12 months (CT 4.2 cm(3), MRI 1.1 cm(3)). Strong correlation was demonstrated between the planned and the post-treatment volumes. Inter-observer agreement was excellent (CT: 95% CI 0.82-0.95; MRI: 95% CI 0.86-0.96). All SRMs appeared non-enhanced immediately after ablation, except for one residual tumor. Subtraction images confirmed non-enhancement on MRI in cases with unclear enhancement (3/9). Directly after IRE, gas bubbles, perinephric stranding, and edema were observed in all cases. CONCLUSION Both CT and MRI findings indicate increase of AZV until 3 months post-IRE, followed by gradual decrease in AZV from 6 to 12 months post-IRE. Enhancement is absent in cases with complete ablation. Gas bubbles, perinephric stranding, and edema are normal findings directly post-IRE.Netherlands Organization for Health Research and Developmen

Feasibility and safety of irreversible electroporation (IRE) in patients with small renal masses: Results of a prospective study

Background: Irreversible electroporation (IRE) has the potential to overcome limitations of thermal ablation, enabling small renal mass (SRM) ablation near vital structures. Purpose: To assess feasibility and safety of percutaneous IRE for the treatment of SRMs. Materials and methods: This prospective study is a phase 2 trial (NCT02828709) of IRE for patients with SRMs. Primary endpoints are feasibility and safety. Device- and procedural-adverse events were assessed by Clavien-Dindo and Common Terminology Criteria for Adverse Events version 4.0 grading systems. Technical feasibility was assessed by recording the technical success of the procedures. Technical success was evaluated by performing a CT immediately after ablation where complete tumor coverage and nonenhancement were evaluated. Tumor charcateristics and patient characteristics, procedural and anesthesia details, postprocedural events, and perioperative complications were recorded. Results: Ten SRMs were included with a mean tumor size of 2.2 cm (range 1.1–3.9 cm) were treated with IRE. Renal mass biopsies revealed 7 clear cell and 1 papillary renal cell carcinoma. Two renal mass biopsies were nondiagnostic. The median follow-up was 6 months (range 3–12 months). Technical success was achieved in 9 out of 10 cases. One patient had a grade 3 Clavien-Dindo complication (1/10, 95% Confidence interval (CI) 0.0179–0.4041). Mean anesthesia time was 3.7 hours (range 3–5 hours), mean procedural time was 2.1 hours (range 1 hour 45 minutes–2 hours 30 minutes) and mean ablation time was 50 minutes (range 20 minutes–1 hour 45 minutes). The creatinine preoperative and postoperative (1 week, 3 months, 6 months, and 12 months) did not significantly differ. In total, 8 out of 10 cases did not experience postoperative pain. Conclusion: IRE in SRMs is safe and feasible. Renal function is not affected by IRE and postoperative pain is rare. Anesthesia time and procedural time are a potential concern

MRI and CT in the follow-up after irreversible electroporation of small renal masses

PURPOSE Ablation plays a growing role in the treatment of small renal masses (SRMs) due to its neph-ron sparing properties and low invasiveness. Irreversible electroporation (IRE) has the po-tential, although still experimental, to overcome current limitations of thermal ablation. No prospective imaging studies exist of the ablation zone in the follow-up after renal IRE in humans. Objectives are to assess the use of computed tomography (CT) and magnetic resonance imaging (MRI) to determine the ablation zone volume (AZV), enhancement and imaging characteristics after renal IRE. METHODS This was a prospective phase 2 study of IRE in 9 patients with 10 SRMs. MRI was performed pre-IRE, 1 week, 3 months, 6 months, and 12 months after IRE. CT was performed pre-IRE, perioperatively (direct after ablation), 3 months, 6 months, and 12 months after IRE. AZVs were assessed by two independent observers. Observer variation was analyzed. Evolution of AZVs, and their relation with the needle configuration volume (NCV; indicating planned AZV) were evaluated based on CT and MRI measurements. RESULTS Eight SRMs were clear cell renal cell carcinomas, one SRM was a papillary renal cell carcinoma and one patient had a nondiagnostic biopsy. On CT, median AZV increased perioperatively until 3 months post-IRE (16.8 cm3 and 6.2 cm3, respectively) compared with the NCV (4.8 cm3). On MRI, median AZV increased 1 week post-IRE until 3 months post-IRE (14.5 cm3 and 4.6 cm3, respectively) compared with the NCV (4.8 cm3). At 6 months the AZV starts decreasing (CT 4.8 cm3; MRI 3.0 cm3), continuing at 12 months (CT 4.2 cm3, MRI 1.1 cm3). Strong correlation was demonstrated between the planned and the post-treatment volumes. Inter-observer agreement was excellent (CT: 95% CI 0.82–0.95; MRI: 95% CI 0.86–0.96). All SRMs appeared non-enhanced immediately after ablation, except for one residual tumor. Subtraction images confirmed non-enhancement on MRI in cases with unclear enhancement (3/9). Directly after IRE, gas bubbles, perinephric stranding, and edema were observed in all cases. CONCLUSION Both CT and MRI findings indicate increase of AZV until 3 months post-IRE, followed by grad-ual decrease in AZV from 6 to 12 months post-IRE. Enhancement is absent in cases with com-plete ablation. Gas bubbles, perinephric stranding, and edema are normal findings directly post-IRE

Minor Changes in Daily Rhythms Induced by a Skeleton Photoperiod Are Associated with Increased Adiposity and Glucose Intolerance

Eating during the rest phase is associated with metabolic syndrome, proposed to result from a conflict between food consumption and the energy-saving state imposed by the circadian system. However, in nocturnal rodents, eating during the rest phase (day-feeding, DF) also implies food intake during light exposure. To investigate whether light exposure contributes to DF-induced metabolic impairments, animals receive food during the subjective day without light. A skeleton photoperiod (SP) is used to entrain rats to a 12:12 cycle with two short light pulses framing the subjective day. DF-induced adiposity is prevented by SP, suggesting that the conflict between light and feeding stimulates fat accumulation. However, all animals under SP conditions develop glucose intolerance regardless of their feeding schedule. Moreover, animals under SP with ad libitum or night-feeding have increased adiposity. SP animals show a delayed onset of the daily rise in body temperature and energy expenditure and shorter duration of nighttime activity, which may contribute to the metabolic disturbances. These data emphasize that metabolic homeostasis can only be achieved when all daily cycling variables are synchronized. Even small shifts in the alignment of different metabolic rhythms, such as those induced by SP, may predispose individuals to metabolic disease

Irreversible electroporation: state of the art

The field of focal ablative therapy for the treatment of cancer is characterized by abundance of thermal ablative techniques that provide a minimally invasive treatment option in selected tumors. However, the unselective destruction inflicted by thermal ablation modalities cats result in damage to vital structures its the vicinity- of the tumor. Furthermore, the efficacy of thermal ablation intensity can be impaired due to thermal sink caused by large blood vessels in the proximity of the tumor. Irreversible electroporation (IRE) is a novel ablation modality based on the principle of electroporation or electropenneabilization, in which electric pulses are used to create nanoscale defects in the cell membrane. In theory, IRE has the potential of overcoming the aforementioned limitations of thermal ablation techniques. This review provides a description of the principle of IRE, combined with an overview of in vivo research performed to date in the liver, pancreas, kidney, and prostat

Irreversible electroporation for the treatment of localized prostate cancer: a summary of imaging findings and treatment feedback

PURPOSE Imaging plays a crucial role in ablative therapies for prostate cancer (PCa). Irreversible electro-poration (IRE) is a new treatment modality used for focal treatment of PCa. We aimed to demonstrate what imaging modalities can be used by descriptively reporting contrast-enhanced ultrasonography (CEUS), multiparametric magnetic resonance imaging (mpMRI), and grey-scale transrectal ultrasound (TRUS) results. Furthermore, we aimed to correlate quantitatively the ablation zone seen on mpMRI and CEUS with treatment planning to provide therapy feedback. METHODS Imaging data was obtained from two prospective multicenter trials on IRE for localized low-to intermediate-risk PCa. The ablation zone volume (AZV) seen on mpMRI and CEUS was 3D reconstructed to correlate with the planned AZV. RESULTS Descriptive examples are provided using mpMRI, TRUS, and CEUS for treatment planning and follow-up after IRE. The mean AZV on T2-weighted imaging 4 weeks following IRE was 12.9 cm(3) (standard deviation [SD]=7.0), 5.3 times larger than the planned AZV. Linear regression showed a positive correlation (r=0.76, P = 0.002). For CEUS the mean AZV was 20.7 cm(3) (SD=8.7), 8.5 times larger than the planned AZV with a strong positive correlation (r=0.93, P = 0.001). Prostate volume is reduced over time (mean= -27.5%, SD=11.9%) due to ablation zone fibrosis and deformation, illustrated by 3D reconstruction. CONCLUSION The role of imaging in conjunction with IRE is of crucial importance to guide clinicians throughout the treatment protocol. CEUS and mpMRI may provide essential treatment feedback by visualizing the ablation zone dimensions and volum

Irreversible Electroporation for the Ablation of Renal Cell Carcinoma: A Prospective, Human, In Vivo Study Protocol (IDEAL Phase 2b)

Background: Irreversible electroporation (IRE) is an emerging technique delivering electrical pulses to ablate tissue, with the theoretical advantage to overcome the main shortcomings of conventional thermal ablation. Recent short-term research showed that IRE for the ablation of renal masses is a safe and feasible treatment option. In an ablate and resect design, histopathological analysis 4 weeks after radical nephrectomy demonstrated that IRE-targeted renal tumors were completely covered by ablation zone. In order to develop a validated long-term IRE follow-up study, it is essential to obtain clinical confirmation of the efficacy of this novel technology. Additionally, follow-up after IRE ablation obliges verification of a suitable imaging modality. Objective: The objectives of this study are the clinical efficacy and safety of IRE ablation of renal masses and to evaluate the use of cross-sectional imaging modalities in the follow-up after IRE in renal tumors. This study conforms to the recommendations of the IDEAL Collaboration and can be categorized as a phase 2B exploration trial. Methods: In this prospective clinical trial, IRE will be performed in 20 patients aged 18 years and older presenting with a solid enhancing small renal mass (SRM) ( <= 4 cm) who are candidates for ablation. Magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) will be performed at 1 day pre-IRE, and 1 week post-IRE. Computed tomography (CT), CEUS, and MRI will be performed at 3 months, 6 months, and 12 months post-IRE. Results: Presently, recruitment of patients has started and the first inclusions are completed. Preliminary results and outcomes are expected in 2018. Conclusions: To establish the position of IRE ablation for treating renal tumors, a structured stepwise assessment in clinical practice is required. This study will offer fundamental knowledge on the clinical efficacy of IRE ablation for SRMs, potentially positioning IRE as ablative modality for renal tumors and accrediting future research with long-term follow-u