Pharmacokinetics and Toxicity of Sodium Selenite in the Treatment of Patients with Carcinoma in a Phase I Clinical Trial: The SECAR Study.

Background: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients' refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits.

Asymmetric Flow-Field Flow Fractionation Hyphenated ICP-MS as an Alternative to Cloud Point Extraction for Quantification of Silver Nanoparticles and Silver Speciation: Application for Nanoparticles with a Protein Corona.

Production and application of nanoparticles in consumer products is at an all-time high due to the emerging field of nanotechnology. Direct detection and quantification of trace levels of nanoparticles within consumer products is very challenging and problematic. Although multiple methodologies are available for this purpose, each method has its own set of limitations.

A framework for evaluating the cost-effectiveness of patient decision aids: A case study using colorectal cancer screening.

Objective: Patient decision aids are important tools for facilitating balanced, evidence-based decision making. However, the potential of decision aids to lower health care utilization and costs is uncertain; few studies have investigated the cost-effectiveness of decision aids that change patient behavior. Using an example of a decision aid for colorectal cancer screening, we provide a framework for analyzing the cost-effectiveness of decision aids.

Three-Dimensional Cell Culture-Based Screening Identifies the Anthelmintic Drug Nitazoxanide as a Candidate for Treatment of Colorectal Cancer.

Because dormant cancer cells in hypoxic and nutrient-deprived regions of solid tumors provide a major obstacle to treatment, compounds targeting those cells might have clinical benefits. Here, we describe a high-throughput drug screening approach, using glucose-deprived multicellular tumor spheroids (MCTS) with inner hypoxia, to identify compounds that specifically target this cell population. We used a concept of drug repositioning-using known molecules for new indications.

Consistency of response to sumatriptan/naproxen sodium in a randomized placebo-controlled, cross-over study for the acute treatment of migraine in adolescence.

A multi-centered, randomized, placebo-controlled, early intervention, cross-over study was conducted to evaluate the consistency of response of sumatriptan/naproxen sodium 85/500 mg (S/NS) over 4 attacks in the acute treatment of migraine in adolescents. Inclusion of subjects was dependent on their age of 12-17 years, frequency, and history of migraine headaches (1-8 per month) over the previous 6 months prior to screening and generally healthy males and females of non-childbearing potential that were not on excluded medications. Subjects were instructed to treat within 1 hour of pain onset, including when the pain was still mild.

Synthesis and evaluation of derivatives of the proteasome deubiquitinase inhibitor b-AP15.

The ubiquitin-proteasome system (UPS) is increasingly recognized as a therapeutic target for the development of anticancer therapies. The success of the 20S proteasome core particle (20S CP) inhibitor bortezomib in the clinical management of multiple myeloma has raised the possibility of identifying other UPS components for therapeutic intervention. We previously identified the small molecule b-AP15 as an inhibitor of 19S proteasome deubiquitinase (DUB) activity.

Using Accelerometer and Gyroscopic Measures to Quantify Postural Stability.

Context: Force platforms and 3-dimensional motion-capture systems provide an accurate method of quantifying postural stability. Substantial cost, space, time to administer, and need for trained personnel limit widespread use of biomechanical techniques in the assessment of postural stability in clinical or field environments.

Objective: To determine whether accelerometer and gyroscope data sampled from a consumer electronics device (iPad2) provide sufficient resolution of center-of-gravity (COG) movements to accurately quantify postural stability in healthy young people.

The HAAPI (Home Arm Assistance Progression Initiative) Trial: A Novel Robotics Delivery Approach in Stroke Rehabilitation.

Background: Geographical location, socioeconomic status, and logistics surrounding transportation impede access of poststroke individuals to comprehensive rehabilitative services. Robotic therapy may enhance telerehabilitation by delivering consistent and state-of-the art therapy while allowing remote monitoring and adjusting therapy for underserved populations. The Hand Mentor Pro (HMP) was incorporated within a home exercise program (HEP) to improve upper-extremity (UE) functional capabilities poststroke.

Arsenic speciation in rice by capillary electrophoresis/inductively coupled plasma mass spectrometry: enzyme-assisted water-phase microwave digestion.

We report an analytical methodology for the quantification of common arsenic species in rice and rice cereal using capillary electrophoresis coupled with inductively coupled plasma mass spectrometry (CE-ICPMS). An enzyme (i.e.

Interactions with successional stage and nutrient status determines the life-form-specific effects of increased soil temperature on boreal forest floor vegetation.

The boreal forest is one of the largest terrestrial biomes and plays a key role for the global carbon balance and climate. The forest floor vegetation has a strong influence on the carbon and nitrogen cycles of the forests and is sensitive to changes in temperature conditions and nutrient availability. Additionally, the effects of climate warming on forest floor vegetation have been suggested to be moderated by the tree layer.

Detection and characterization of SiO2 and TiO2 nanostructures in dietary supplements.

Nanomaterials are beginning to enter our daily lives through various consumer products as the result of technology commercialization. The development of methodologies to detect the presence of nanomaterials in consumer products is an essential element in understanding our exposure. In this study, we have developed methods for the separation and characterization of silicon dioxide (SiO2) and titanium dioxide (TiO2) nanostructures in dietary supplements marketed in products specifically targeted for women.

Houston's Novel Strategy to Control Hazardous Air Pollutants: A Case Study in Policy Innovation and Political Stalemate.

Although ambient concentrations have declined steadily over the past 30 years, Houston has recorded some of the highest levels of hazardous air pollutants in the United States. Nevertheless, federal and state regulatory efforts historically have emphasized compliance with the National Ambient Air Quality Standard for ozone, treating "air toxics" in Houston as a residual problem to be solved through application of technology-based standards. Between 2004 and 2009, Mayor Bill White and his administration challenged the well-established hierarchy of air quality management spelled out in the Clean Air Act, whereby federal and state authorities are assigned primacy over local municipalities for the purpose of designing and implementing air pollution control strategies.

Targeted inhibition of the deubiquitinating enzymes, USP14 and UCHL5, induces proteotoxic stress and apoptosis in Waldenström macroglobulinaemia tumour cells.

Deubiquitinase enzymes (DUBs) of the proteasomal 19S regulatory particle are emerging as important therapeutic targets in several malignancies. Here we demonstrate that inhibition of two proteasome-associated DUBs (USP14 and UCHL5) with the small molecule DUB inhibitor b-AP15, results in apoptosis of human Waldenström macroglobulinaemia (WM) cell lines and primary patient-derived WM tumour cells. Importantly, b-AP15 produced proteotoxic stress and apoptosis in WM cells that have acquired resistance to the proteasome inhibitor bortezomib.

The risk paradox: use of elective cholecystectomy in older patients is independent of their risk of developing complications.

Background: We recently developed and validated a prognostic model that accurately predicts the 2-year risk of emergent gallstone-related hospitalization in older patients presenting with symptomatic gallstones.

Study Design: We used 100% Texas Medicare data (2000 to 2011) to identify patients aged 66 years and older with an initial episode of symptomatic gallstones not requiring emergency hospitalization. At presentation, we calculated each patient's risk of 2-year gallstone-related emergent hospitalization using the previously validated model.

Simple functionalization strategies for enhancing nanoparticle separation and recovery with asymmetric flow field flow fractionation.

Due to the increasing use of engineered nanomaterials in consumer products, regulatory agencies and other research organizations have determined that the development of robust, reliable, and accurate methodologies to characterize nanoparticles in complex matrices is a top priority. Of particular interest are methods that can separate and determine the size of nanomaterials in samples that contain polydisperse and/or multimodal nanoparticle populations. Asymmetric-flow field flow fractionation (AF4) has shown promise for the separation of nanoparticles with wide size range distributions; however, low analyte recoveries and decreased membrane lifetimes, due to membrane fouling, have limited its application.

Citation searches are more sensitive than keyword searches to identify studies using specific measurement instruments.

Objectives: To compare the effectiveness of two search methods in identifying studies that used the Control Preferences Scale (CPS), a health care decision-making instrument commonly used in clinical settings.

Study Design And Setting: We searched the literature using two methods: (1) keyword searching using variations of "Control Preferences Scale" and (2) cited reference searching using two seminal CPS publications. We searched three bibliographic databases [PubMed, Scopus, and Web of Science (WOS)] and one full-text database (Google Scholar).

Predictors of Serious Psychological Distress in an Urban Population.

While there are state and national estimates of serious psychological distress (SPD), these are not useful for targeting local mental health interventions or for addressing the needs of sub-populations at increased risk for SPD. This cross-sectional study uses data from the population-based 2010 Health of Houston Survey (n = 5,116) to examine (1) the prevalence of SPD and its determinants in Houston area and (2) predictors of the utilization of mental health services among people with SPD. The prevalence of SPD among the Houston area adult population was 7 %, more than twice the national average.

Deubiquitinase inhibition as a cancer therapeutic strategy.

The ubiquitin proteasome system (UPS) is the main system for controlled protein degradation and a key regulator of fundamental cellular processes. The dependency of cancer cells on a functioning UPS has made this an attractive target for development of drugs that show selectivity for tumor cells. Deubiquitinases (DUBs, ubiquitin isopeptidases) are components of the UPS that catalyze the removal of ubiquitin moieties from target proteins or polyubiquitin chains, resulting in altered signaling or changes in protein stability.

Development and pilot testing of an online case-based approach to shared decision making skills training for clinicians.

Background: Although research suggests that patients prefer a shared decision making (SDM) experience when making healthcare decisions, clinicians do not routinely implement SDM into their practice and training programs are needed. Using a novel case-based strategy, we developed and pilot tested an online educational program to promote shared decision making (SDM) by primary care clinicians.

Methods: A three-phased approach was used: 1) development of a conceptual model of the SDM process; 2) development of an online teaching case utilizing the Design A Case (DAC) authoring template, a well-tested process used to create peer-reviewed web-based clinical cases across all levels of healthcare training; and 3) pilot testing of the case.

Capillary electrophoresis/inductively-coupled plasma-mass spectrometry: development and optimization of a high resolution analytical tool for the size-based characterization of nanomaterials in dietary supplements.

We report the development and optimization of a system consisting of capillary electrophoresis (CE) interfaced with inductively coupled plasma mass spectrometry (ICPMS) for rapid and high resolution speciation and characterization of metallic (e.g., gold, platinum, and palladium) nanoparticles in a dietary supplement.

Nitinol versus steel partially covered self-expandable metal stent for malignant distal biliary obstruction: a randomized trial.

Background And Study Aims: Covered nitinol alloy self-expandable metal stents (SEMSs) have been developed to overcome the shortcomings of steel SEMS in patients with malignant biliary obstruction. In a randomized, multicenter trial, we compared stent patency, patient survival, and adverse events in patients with partly covered stents made from steel or nitinol.

Patients And Methods: A total of 400 patients with unresectable distal malignant biliary obstruction were randomized at endoscopic retrograde cholangiopancreatography (ERCP) to insertion of a steel or nitinol partially covered SEMS, with 200 patients in each group.

Tools of the trade: podosomes as multipurpose organelles of monocytic cells.

Podosomes are adhesion and invasion structures that are particularly prominent in cells of the monocytic lineage such as macrophages, dendritic cells, and osteoclasts. They are multifunctional organelles that combine several key abilities required for cell migration and invasion. The podosome repertoire includes well-established functions such as cell-substrate adhesion, and extracellular matrix degradation, recently discovered abilities such as rigidity and topology sensing as well as antigen sampling, and also more speculative functions such as cell protrusion stabilization and transmigration.

Elevation of proteasomal substrate levels sensitizes cells to apoptosis induced by inhibition of proteasomal deubiquitinases.

Inhibitors of the catalytic activity of the 20S proteasome are cytotoxic to tumor cells and are currently in clinical use for treatment of multiple myeloma, whilst the deubiquitinase activity associated with the 19S regulatory subunit of the proteasome is also a valid target for anti-cancer drugs. The mechanisms underlying the therapeutic efficacy of these drugs and their selective toxicity towards cancer cells are not known. Here, we show that increasing the cellular levels of proteasome substrates using an inhibitor of Sec61-mediated protein translocation significantly increases the extent of apoptosis that is induced by inhibition of proteasomal deubiquitinase activity in both cancer derived and non-transformed cell lines.

Cell crowding induces interferon regulatory factor 9, which confers resistance to chemotherapeutic drugs.

The mechanism of multicellular drug resistance, defined as the reduced efficacy of chemotherapeutic drugs in solid tumors is incompletely understood. Here we report that colon carcinoma cells cultured as 3D microtissues (spheroids) display dramatic increases in the expression of a subset of type I interferon-(IFN)-stimulated genes (ISGs). A similar gene signature was associated previously with resistance to radiation and chemotherapy, prompting us to examine the underlying biological mechanisms.

Microtubule acetylation regulates dynamics of KIF1C-powered vesicles and contact of microtubule plus ends with podosomes.

Microtubule dynamics are important for a variety of key cellular functions such as intracellular trafficking, adjustment of the cell surface proteome, or adhesion structure turnover. In the current study, we investigate the effects of altered microtubule acetylation levels on the subcellular distribution of kinesins and actin cytoskeletal architecture in primary human macrophages. Microtubule acetylation was altered by overexpression or siRNA-induced depletion of the acetylase MEC-17, or by blocking α-tubulin deacetylation by addition of the inhibitor tubacin.