Incident Chronic Spinal Pain and Depressive Disorders: Data From the National Comorbidity Survey

This study examined pre-existing depression as a risk factor for the development of chronic spinal pain, and pre-existing chronic spinal pain as a risk factor for the development of depression. Data from the National Comorbidity Survey, a stratified sample of 5,001 participants evaluated in 1990 to 1992 (NCS-1) and again in 2000 to 2001 (NCS-2) were used to address these associations. Cox regression was used to estimate hazard ratios and time-to-incidence after NCS-1. Participants with antecedent acute or chronic depressive disorders at NCS-1 were more likely to develop chronic spinal pain in the ensuing 10 years compared with participants without depressive disorders. Those with antecedent chronic spinal pain at NCS-1 were more likely to develop dysthymic disorder than subjects without chronic spinal pain at NCS-1; however, antecedent chronic spinal pain was not associated the subsequent development of major depressive disorder. These results suggest that both pain and depression are associated with the development of the other condition. In particular, chronic depression is more strongly linked to chronic spinal pain than is acute depression. The results are discussed in terms of the need to assess the presence of both disorders given the presence of one. PERSPECTIVE: Chronic spinal pain and depressive disorders, especially chronic depression, increase the likelihood for the subsequent development of the other condition. The results underscore the need to routinely assess for the presence of both disorders given the presence of one to mitigate the effects of developing comorbid conditions

Control of a Power Generation System Based on a Dual Star Induction Generator

International audienceThis paper presents a control scheme of a power generation system based on a dual star squirrel-cage induction machine operating as an induction generator. The operating mode based on an excitation control scheme is chosen to ensure a controlled magnitude and frequency of the generator output voltage. Some preliminary simulation and experimental test results, carried out on a prototype of dual star induction machine operating as generator and supplying various loads under different conditions, are presented and discussed

Anti-cancer Antibody Trastuzumab- Melanotransferrin Conjugate (BT2111) for the Treatment of Metastatic HER2+ Breast Cancer Tumors in the Brain: an In-Vivo Study

Purpose—The ability of human melanotransferrin (hMTf) to carry a therapeutic concentration of trastuzumab (BTA) in the brain after conjugation (in the form of trastuzumab-melanotransferrin conjugate, BT2111 conjugate) was investigated by measuring the reduction of the number and size of metastatic human HER2+ breast cancer tumors in a preclinical model of brain metastases of breast cancer. Methods—Human metastatic brain seeking breast cancer cells were injected in NuNu mice (n=6–12 per group) which then developed experimental brain metastases. Drug uptake was analyzed in relation to metastasis size and blood-tumor barrier permeability. To investigate in-vivo activity against brain metastases, equimolar doses of the conjugate, and relevant controls (hMTF and BTA) in separate groups were administered biweekly after intracardiac injection of the metastatic cancer cells. Results—The trastuzumab-melanotransferrin conjugate (BT2111) reduced the number of preclinical human HER2+ breast cancer metastases in the brain by 68% compared to control groups. Tumors which remained after treatment were 46% smaller than the control groups. In contrast, BTA alone had no effect on reducing number of metastases, and was associated with only a minimal reduction in metastasis size. Conclusions—The results suggest the novel trastuzumab-melanotransferrin conjugate (BT2111) may have utility in treating brain metastasis and validate hMTf as a potential vector for antibody transport across the Blood Brain Barrier (BBB)

A novel preclinical method to quantitatively evaluate early-stage metastatic events at the murine blood-brain barrier

The observation that approximately 15% of women with disseminated breast cancer will develop symptomatic brain metastases combined with treatment guidelines discouraging single-agent chemotherapeutic strategies facilitates the desire for novel strategies aimed at outright brain metastasis prevention. Effective and robust preclinical methods to evaluate early stage metastatic processes, brain metastases burden, and overall mean survival are lacking. Here, we develop a novel method to quantitate early metastatic events (arresting and extravasation) in addition to traditional end time-point parameters such as tumor burden and survival in an experimental mouse model of brain metastases of breast cancer. Using this method, a reduced number of viable brain seeking metastatic cells (from 3331 ± 263 cells/brain to 1079 ± 495 cells/brain) arrested in brain one week post injection after TGFβ knockdown. Treatment with a TGFβ receptor inhibitor, galunisertib, reduced the number of arrested cells in brain to 808 ± 82 cells/brain. Further, we observed a reduction in the percent of extravasated cells (from 63% to 30%) compared to cells remaining intralumenal when TGFβ is knocked down or inhibited with galunisertib (40%). The observed reduction of extravasated metastatic cells in brain translated to smaller and fewer brain metastases and resulted in prolonged mean survival (from 36 days to 62 days). This method opens up potentially new avenues of metastases prevention research by providing critical data important to early brain metastasis of breast cancer events

Trastuzumab distribution in an in-vivo and in-vitro model of brain metastases of breast cancer

Background: Drug and antibody delivery to brain metastases has been highly debated in the literature. The blood-tumor barrier (BTB) is more permeable than the blood-brain barrier (BBB), and has shown to have highly functioning efflux transporters and barrier properties, which limits delivery of targeted therapies. Methods: We characterized the permeability of 125I-trastuzumab in an in-vivo, and fluorescent trastuzumab-Rhodamine123 (t-Rho123) in a novel microfluidic in-vitro, BBB and BTB brain metastases of breast cancer model. In-vivo: Human MDA-MB231-HER2+ metastatic breast cancer cells were grown and maintained under static conditions. Cells were harvested at 80% confluency and prepped for intra-cardiac injection into 20 homozygous female Nu/Nu mice. In-vitro: In a microfluidic device (SynVivo), human umbilical vein endothelial cells were grown and maintained under shear stress conditions in the outer compartment and co-cultured with CTX-TNA2 rat brain astrocytes (BBB) or Met-1 metastatic HER2+ murine breast cancer cells (BTB), which were maintained in the central compartment under static conditions. Results: Tissue distribution of 125I-trastuzumab revealed only ~3% of injected dose reached normal brain, with ~5% of injected dose reaching brain tumors. No clear correlation was observed between size of metastases and the amount of 125I-trastuzumab localized in-vivo. This heterogeneity was paralleled in-vitro, where the distribution of t-Rho123 from the outer chamber to the central chamber of the microfluidic device was qualitatively and quantitatively analyzed over time. The rate of t-Rho123 linear uptake in the BBB (0.27 ± 0.33 X 104) and BTB (1.29 ± 0.93 X 104) showed to be significantly greater than 0 (p \u3c 0.05). The BTB devices showed significant heterogenetic tendencies, as seen in in-vivo. Conclusions: This study is one of the first studies to measure antibody movement across the blood-brain and blood-tumor barriers, and demonstrates that, though in small and most likely not efficacious quantities, trastuzumab does cross the bloodbrain and blood-tumor barriers

Preliminary Chelation and Dissolution Effects of Oxalic Acid and Disodium Oxalate on Polymeric 123-Superconductors

The polymeric 123-superconductor material was selectively etched by exposure to aqueous solutions of oxalic acid and disodium oxalate. Superconductivity decreased with time. XPS, AES, FTIR and ATF show that the amount of copper at the surface is decreased, shows the presence of bound oxalate and shows a decrease in peaks associated with superconductivity for the sample treated with oxalat

Optimal Fuzzy Controller Tuned by TV-PSO for Induction Motor Speed Control

This paper reports an automated procedure for the design of an optimal fuzzy logic controller to be used as an induction motor speed controller. The procedure consists of selection of a suitable well known fuzzy logic controller and tuning via particle swarm optimization optimal for the selected criteria. In this way the time required for tuning of the controller is significantly reduced in comparison with trial and error methods. As a benchmark a proportional-integral (PI) controller is used. The PI controller is tuned via the symmetrical optimum procedure, the standard procedure for tuning a speed controller of an induction motor. Simulation results are obtained via a mathematical model developed in Matlab/Simulink. Experimental verification is carried out with a laboratory model based on the DS1104 digital control card. To minimize iron losses and to provide better motor performance for low loads, flux is reduced from nominal and speed is kept below nominal. Results are presented in tables and graphics. The optimal fuzzy logic controller provides a slight practical advantage