Withdrawal Notice: Drug Repurposing for Prospective Anti-Cancer Agents Along with the Clinical Status of the Repurposed Drug

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The weekend effect for stroke patients admitted to intensive care: A retrospective cohort analysis.

OBJECTIVES: To examine the effect of weekend admission on short and long-term morbidity and mortality, for patients admitted to intensive care after suffering a cerebrovascular accident (stroke). DESIGN, SETTING, AND PARTICIPANTS: A hospital-wide, retrospective cohort study of 3,729 adult stroke patients admitted to the Beth Israel Deaconess Medical Centre (BIDMC) intensive care unit (ICU) between 2001 and 2012, using the Medical Information Mart for Intensive Care III (MIMIC-III) database. PRIMARY OUTCOME MEASURES: Primary outcome measures were ICU length-of-stay and mortality, hospital length-of-stay and mortality, proportions of patients discharged home after admission, and 6-month mortality. RESULTS: Overall, 23% of BIDMC ICU stroke admissions occurred over the weekend. Those admitted over the weekend were likelier to have suffered haemorrhagic stroke than those admitted during the week (60.6% vs 47.9%). Those admitted on the weekend were younger, and likelier to be male and unmarried, with similar ethnic representation. The OASIS severity of illness (32.5 vs. 32) and lowest day-one GCS (12.6 vs. 12.9) were similar between groups. Unadjusted ICU-mortality was significantly higher for patients admitted over the weekend (OR 1.32, CI 1.08-1.61), but when adjusted for type of stroke, became non-significant (OR 1.17, CI 0.95-1.44). In-hospital mortality was significantly higher for patients admitted to ICU over the weekend in both unadjusted (OR 1.45, CI 1.22-1.73) and adjusted (OR 1.31, CI 1.09-1.58) analyses. There was no significant difference in ICU or hospital length of stay. While patients admitted on the weekend appeared less likely to be discharged back to home and more at risk of 6-month mortality compared to weekday admissions, results were non-significant. CONCLUSIONS: The effect of weekend ICU-admission for stroke patients appears to be significant for in-hospital mortality. There were no significant differences in adjusted ICU-mortality, ICU or hospital length-of-stay, or longer-term morbidity and mortality measures.

Mitochondrial membrane studies using impedance spectroscopy with parallel pH monitoring.

A biological microelectromechanical system (BioMEMS) device was designed to study complementary mitochondrial parameters important in mitochondrial dysfunction studies. Mitochondrial dysfunction has been linked to many diseases, including diabetes, obesity, heart failure and aging, as these organelles play a critical role in energy generation, cell signaling and apoptosis. The synthesis of ATP is driven by the electrical potential across the inner mitochondrial membrane and by the pH difference due to proton flux across it. We have developed a tool to study the ionic activity of the mitochondria in parallel with dielectric measurements (impedance spectroscopy) to gain a better understanding of the properties of the mitochondrial membrane. This BioMEMS chip includes: 1) electrodes for impedance studies of mitochondria designed as two- and four-probe structures for optimized operation over a wide frequency range and 2) ion-sensitive field effect transistors for proton studies of the electron transport chain and for possible monitoring other ions such as sodium, potassium and calcium. We have used uncouplers to depolarize the mitochondrial membrane and disrupt the ionic balance. Dielectric spectroscopy responded with a corresponding increase in impedance values pointing at changes in mitochondrial membrane potential. An electrical model was used to describe mitochondrial sample's complex impedance frequency dependencies and the contribution of the membrane to overall impedance changes. The results prove that dielectric spectroscopy can be used as a tool for membrane potential studies. It can be concluded that studies of the electrochemical parameters associated with mitochondrial bioenergetics may render significant information on various abnormalities attributable to these organelles.

Protein adsorption enhanced radio-frequency heating of silica nanoparticles.

Measurements of specific-absorption-rate (SAR) of silica 30, 50, and 100 nm nanoparticles (NP) suspended in water were carried out at 30 MHz in 7 kV/m radio-frequency (rf) electric field. Size dependent, NP-suspension interface related heating of silica NP was observed. To investigate a possible mechanism of heating, bovine serum albumin was adsorbed on the surface of silica NPs in suspension. It resulted in significant enhancement of SAR when compared to bare silica NPs. A calorimetric and rf loss model was used to calculate effective conductivity of silica NP with/without adsorbed albumin as a function of silica size and albumin concentration.

Design maps for the hyperthermic treatment of tumors with superparamagnetic nanoparticles.

A plethora of magnetic nanoparticles has been developed and investigated under different alternating magnetic fields (AMF) for the hyperthermic treatment of malignant tissues. Yet, clinical applications of magnetic hyperthermia are sporadic, mostly due to the low energy conversion efficiency of the metallic nanoparticles and the high tissue concentrations required. Here, we study the hyperthermic performance of commercially available formulations of superparamagnetic iron oxide nanoparticles (SPIOs), with core diameter of 5, 7 and 14 nm, in terms of absolute temperature increase ΔT and specific absorption rate (SAR). These nanoparticles are operated under a broad range of AMF conditions, with frequency f varying between 0.2 and 30 MHz; field strength H ranging from 4 to 10 kA m(-1); and concentration cMNP varying from 0.02 to 3.5 mg ml(-1). At high frequency field (∼30 MHz), non specific heating dominates and ΔT correlates with the electrical conductivity of the medium. At low frequency field (<1 MHz), non specific heating is negligible and the relaxation of the SPIO within the AMF is the sole energy source. We show that the ΔT of the medium grows linearly with cMNP , whereas the SARMNP of the magnetic nanoparticles is independent of cMNP and varies linearly with f and H(2) . Using a computational model for heat transport in a biological tissue, the minimum requirements for local hyperthermia (Ttissue >42°C) and thermal ablation (Ttissue >50°C) are derived in terms of cMNP , operating AMF conditions and blood perfusion. The resulting maps can be used to rationally design hyperthermic treatments and identifying the proper route of administration - systemic versus intratumor injection - depending on the magnetic and biodistribution properties of the nanoparticles.

A method to measure specific absorption rate of nanoparticles in colloidal suspension using different configurations of radio-frequency fields.

We report a method for characterization of the efficiency of radio-frequency (rf) heating of nanoparticles (NPs) suspended in an aqueous medium. Measurements were carried out for water suspended 5 nm superparamagnetic iron-oxide NPs with 30 nm dextran matrix for three different configurations of rf electric and magnetic fields. A 30 MHz high-Q resonator was designed to measure samples placed inside a parallel plate capacitor and solenoid coil with or without an rf electric field shield. All components of rf losses were analyzed and rf electric and magnetic field induced heating of NPs and the dispersion medium was determined and discussed.

Use of the radiofrequency-intermodulation distortion technique to investigate intrinsic nonlinearity at the electrode-electrolyte interface.

We report on investigations of nonlinear radiofrequency responses of electrolytes with Na(+) and Cl(-) ions placed within gold electrodes of a capacitor. The sample was part of a frequency-adjustable inductance-capacitance-resistance (LCR) parallel resonant circuit, and measurements were carried out using the two frequencies intermodulation distortion technique. We employed double layer model to analyze the observed nonlinearities and their dependence on ionic concentration. Electrode-electrolyte interface polarization was found to be a predominant cause of this intrinsic nonlinearity and to be dependent on electrolytic ion concentration. We also measured and calculated coefficients of resistive and capacitive components of the observed nonlinearity.