Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation.

PURPOSE: Currently, tumor-treating field (TTField) therapy utilizes a single "optimal" frequency of electric fields to achieve maximal cell death in a targeted population of cells. However, because of differences in cell size, shape, and ploidy during mitosis, optimal electric field characteristics for universal maximal cell death may not exist. This study investigated the anti-mitotic effects of modulating electric field frequency as opposed to utilizing uniform electric fields. METHODS: We developed and validated a custom device that delivers a wide variety of electric field and treatment parameters including frequency modulation. We investigated the efficacy of frequency modulating tumor-treating fields on triple-negative breast cancer cells compared to human breast epithelial cells. RESULTS: We show that frequency-modulated (FM) TTFields are as selective at treating triple-negative breast cancer (TNBC) as uniform TTFields while having a greater efficacy for combating TNBC cell growth. TTField treatment at a mean frequency of 150 kHz with a frequency range of ± 10 kHz induced apoptosis in a greater number of TNBC cells after 24 h as compared to unmodulated treatment which led to further decreased cell viability after 48 h. Furthermore, all TNBC cells died after 72 h of FM treatment while cells that received unmodulated treatment were able to recover to cell number equivalent to the control. CONCLUSION: TTFields were highly efficacious against TNBC growth, FM TTFields showed minimal effects on epithelial cells similar to unmodulated treatment.

Efficacy and selectivity of tumor-treating field therapy for triple-negative breast cancer cells via in-house delivery device.

PURPOSE: Triple-negative breast cancer continues to be one of the leading causes of death in women, making up 7% of all cancer deaths. Tumor-treating electric fields are low-energy, low-frequency oscillating electric fields that induce an anti-proliferative effect on mitotic cells in glioblastoma multiforme, non-small cell lung cancer, and ovarian cancer. Little is known about effects of tumor-treating fields on triple-negative breast cancer and known research for tumor-treating fields only utilizes low (< 3 V/cm) electric field intensities. METHODS: We have developed an in-house field delivery device capable of high levels of customization to explore a much wider variety of electric field and treatment parameters. Furthermore, we investigated the selectivity of tumor-treating field treatment between triple-negative breast cancer and human breast epithelial cells. RESULTS: Tumor-treating fields show greatest efficacy against triple-negative breast cancer cell lines between 1 and 3 V/cm electric field intensities while having little effect on epithelial cells. CONCLUSION: These results provide a clear therapeutic window for tumor-treating field delivery to triple-negative breast cancer.

The efficacy of written exposure therapy versus imaginal exposure delivered online for posttraumatic stress disorder: Design of a randomized controlled trial in Veterans.

Adapting evidence-based treatments for online delivery has potential to significantly increase the reach of effective care to Veterans with posttraumatic stress disorder (PTSD). This paper describes the rationale for and methods of a randomized controlled trial comparing the efficacy and efficiency of written exposure therapy versus imaginal exposure for PTSD delivered in a novel online and variable length format. Participants will be 300 Veterans seeking treatment for clinically significant symptoms of PTSD. Participants will be randomly assigned to either written exposure or imaginal exposure via verbal recounting and will complete between 4 and 8 online therapy sessions facilitated by trained peer support specialists. Treatment is terminated before session 8 if the PTSD symptom improvement criterion is met. Assessments will be conducted at baseline, post-treatment, and at 3-month follow-up. The primary hypotheses are that written exposure therapy will be noninferior to imaginal exposure with respect to treatment efficacy and efficiency. Secondary hypotheses relate to identifying and comparing potential mediators of PTSD treatment outcome, including trauma-related cognitions and emotion regulation.

Effects of Different Athletic Playing Surfaces on Jump Height, Force, and Power.

Hatfield, DL, Murphy, KM, Nicoll, JX, Sullivan, WM, and Henderson, J. Effects of different athletic playing surfaces on jump height, force, and power. J Strength Cond Res 33(4): 965-973, 2019-Artificial turfs (ATs) have become more commonplace. Some aspects of performance such as speed seem to be better on ATs, but there are few published studies on the effects of playing surfaces on performance. Furthermore, there is no research that compares performance on ATs, hard surfaces (HSs), and different composite natural surfaces. Forty-three subjects, 21 men (age: 20 ± 1.82 years; height: 177.53 ± 5.87 cm; body mass: 78.44 ± 11.59 kg; and body fat: 11.17 ± 4.45%) and 22 women (age: 25 ± 1.32 years; height: 161.37 ± 6.47 cm; body mass: 60.94 ± 10.24 kg; and body fat: 27.16 ± 7.08%) performed a single countermovement jump (SCMJ), repeated CMJs (RCMJs), and single depth jump (SDJ) on 4 different playing surfaces (peat soil composition turf [NT1], sandy loam composition turf [NT2], 1 AT, and 1 HS. Repeated-measures analysis of variance with Bonferroni post hoc was used to calculate differences in performance across playing surfaces. Statistical significance was set at p ≤ 0.05. Force and jump height were not different across different surfaces. Men had significantly higher force, power, and jump height on all surfaces. Only SCMJ power was lower on NT1 compared with all other surfaces. The difference in power between surfaces was not reproduced when RCMJ and SDJ were performed, and may be due to the increased reactiveness of the stretch-shortening cycle during those jumps. Because of marginal differences between athletic performance and playing surface type, future research comparing playing surface type and other aspects of athletic success such as rate of injury should be considered.

DiPyMe in SDS Micelles: Artifacts and Their Implications in the Interpretation of Micellar Properties.

This study provides experimental evidence that di(1-pyrenylmethyl) ether or DiPyMe, a well-known fluorescent probe employed to determine the microviscosity of surfactant or polymeric micelles, is being hydrolyzed in the presence of water upon UV irradiation. This effect was established from a careful analysis of the fluorescence spectra and decays acquired with aqueous solutions of DiPyMe dissolved in micelles of sodium dodecyl sulfate (SDS). The size of the SDS micelles could be adjusted from an aggregation number (N(agg)) of 70 to 172 by increasing the ionic strength of the aqueous solution from 0.0 to 0.5 M NaCl. The hydrolysis of DiPyMe was much reduced in the larger SDS micelles. While the degradation of DiPyMe in aqueous solutions of SDS micelles affected the analysis of the fluorescence spectra, model-free analysis (MFA) of the fluorescence decays of DiPyMe could reliably retrieve the rate constant ⟨k⟩ of excimer formation for DiPyMe. After calibration with mixtures of organic solvents of known macroscopic viscosity, the ⟨k⟩ values obtained for DiPyMe yielded the microviscosity (µÎ·) of the SDS micelles as a function of salt concentration. The µÎ· was found to increase from 4.0 to 8.8 mPa·s as the salt concentration increased from 0.0 to 0.5 M. This study demonstrated that, regardless of the problem of its hydrolysis that jeopardizes its use in steady-state fluorescence experiments, DiPyMe remains an extremely valuable probe for describing the microviscosity of hydrophobic domains in aqueous solution as long as its decays are analyzed with a model that accounts for the presence of degradation products as the MFA does.

Synthesis of neutral nickel catalysts for ethylene polymerization--the influence of ligand size on catalyst stability.

A facile synthesis of nickel salicylaldimine complexes with labile dissociating ligands is described. In addition to producing highly active ethylene polymerization catalysts, important insights into the effect of ligand size on catalyst stability and information on the mechanism of polymerization are provided.