Current Status of Angiogenic Cell Therapy and Related Strategies Applied in Critical Limb Ischemia

Critical limb ischemia (CLI) constitutes the most severe form of peripheral arterial disease (PAD), it is characterized by progressive blockade of arterial vessels, commonly correlated to atherosclerosis. Currently, revascularization strategies (bypass grafting, angioplasty) remain the first option for CLI patients, although less than 45% of them are eligible for surgical intervention mainly due to associated comorbidities. Moreover, patients usually require amputation in the short-term. Angiogenic cell therapy has arisen as a promising alternative for these “no-option” patients, with many studies demonstrating the potential of stem cells to enhance revascularization by promoting vessel formation and blood flow recovery in ischemic tissues. Herein, we provide an overview of studies focused on the use of angiogenic cell therapies in CLI in the last years, from approaches testing different cell types in animal/pre-clinical models of CLI, to the clinical trials currently under evaluation. Furthermore, recent alternatives related to stem cell therapies such as the use of secretomes, exosomes, or even microRNA, will be also described.     

Indoor heterogeneous photochemistry of furfural drives emissions of nitrous acid

People spend approximately 80% of their time indoor, making the understanding of the indoor chemistry an important task for safety. The high surface-area-to-volume ratio characteristic of indoor environments leads the semi-volatile organic compounds (sVOCs) to deposit on the surfaces. Using a long path absorption photometer (LOPAP), this work investigates the formation of nitrous acid (HONO) through the photochemistry of adsorbed nitrate anions and its enhancement by the presence of furfural. Using a high-resolution proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF-MS), this work also investigates the surface emissions of VOCs from irradiated films of furfural and a mix of furfural and nitrate anions. Among the emitted VOCs, 2(5H)-furanone/2-Butenedial was observed at high concentrations, leading to maleic anhydride formation after UV irradiation. Moreover, the addition of potassium nitrate to the film formed NO_x and HONO concentrations up to 10 ppb, which scales to ca. 4 ppb for realistic indoor conditions. This work helps to understand the high levels of HONO and NO_x measured indoors.     

Biological evaluation of two anomeric glucose analogues iodinated in position 6

Two anomeric analogues of glucose labelled with 123 iodine in position 6, proposed as tracers of glucose transport in vivo, have been synthesized: alpha- and beta-methyl-6-deoxy-6-iodo-D-glucopyranoside (alpha MDIG and beta MDIG). The aim of this study was to determine whether these molecules interact with the glucose transporter and whether they could be used as tracers of glucose transport in vivo. The biodistribution of alpha MDIG and beta MDIG was studied in the mouse in vivo. To determine if these two anomers enter the cell via the glucose transporter, their uptake was measured in isolated perfused rat hearts, in human erythrocytes in suspension, and in cardiomyocytes of neonatal rat in culture. Both alpha MDIG and beta MDIG had similar repartitions in the mouse: myocardial uptake averaged 7% of the injected dose/g of organ at 2 min postinjection and alpha MDIG competed with D-glucose to enter the cells. Insulin produced a 123% increase of its uptake in isolated perfused rat hearts and a 100% increase in cardiomyocytes of neonatal rat in culture. alpha MDIG uptake was lowered in the presence of glucose transport inhibitors in each experimental model. An interaction between beta MDIG and glucose transporters was observed only in human erythrocytes in suspension. Only alpha MDIG interacts with the glucose transporter, and thus could be used to estimate glucose transport in vivo.     

Macroscopic and crystallographic density of solid-state extruded polyethylene

Summary The influence of draw ratio on macroscopic and crystallographic density of polyethylene with different initial morphologies, has been investigated by solid-state extrusion. An initial drop followed by an increase in macroscopic density as a function of draw ratio has been observed. Since precision X-ray measurements of unit cell parameters showed no variation of crystallographic density, it was concluded that plastic deformation of polyethylene upon drawing proceeds with a decrease of the degree of crystallinity. This was confirmed by differential scanning calorimetry.     

Assessing continuous bivariate effects among different groups through nonparametric regression models: An application to breast cancer detection

In many applications, the joint effect of two continuous covariates on the target binary response may vary across groups defined by levels of a given factor. A testing procedure that would enable this type of surface-by-factor interactions to be detected has been designed. To accomplish this goal, a logistic generalized additive model (GAM) with bivariate continuous interactions varying across groups defined by levels of a factor is considered. A local scoring algorithm based on local linear kernel smoothers was implemented to estimate the proposed logistic GAM. Bootstrap resampling techniques were used for the purpose of testing for factor-by-surface interactions. Given the high computational cost involved, binning techniques were used to speed up computation in the estimation and testing processes. The adequacy of the bootstrap-based test was assessed by means of a simulation study. If a factor-by-surface interaction is detected in the model, it is then established that the use of the odds-ratio curves is very useful in obtaining a direct interpretation of the fitted model. The benefits of using this methodology when analyzing real data are illustrated by applying the technique to the outputs produced by a computerized system dedicated to the early detection of breast cancer.     

Arthroscopic lysis in knee arthrofibrosis

OBJECTIVE: To compare the efficacy and toxicity of three patient-controlled analgesia (PCA) morphine regimens. DESIGN: A prospective, randomized, pilot study of three PCA morphine regimens: (1) 1 mg with 6-minute lockout (n = 10), (2) 2 mg with 12-minute lockout (n = 12), and (3) 2 mg with 20-minute lockout (n = 12). SETTING: Large teaching institution. PARTICIPANTS: Thirty-four patients undergoing cholecystectomy or hysterectomy. MAIN OUTCOME MEASURES: Pain scores (0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = severe pain), sedation scores, analgesic consumption, and patient attempts (patient activation of PCA device) and injections (doses actually delivered) were evaluated using analysis of covariance. Distribution of pain and sedation scores and adverse effects were assessed using Fisher's exact test. RESULTS: Data on 24 patients were evaluable. Six patients withdrew for poor pain control (2 in group 1, 1 in group 2, and 3 in group 3). Three other patients withdrew because of adverse effects and 1 withdrew because of pump problems. Mean morphine consumption did not differ significantly among the groups. Distribution of pain and sedation scores and the number of patients with nausea were similar across treatment groups. The mean injection to attempt ratio was significantly smaller in group 3 (0.71 +/- 0.11) compared with groups 1 and 2 (0.9 +/- 0.06 and 0.83 +/- 0.09, respectively; p = 0.001). Adverse events occurred similarly among treatment groups. CONCLUSIONS: No significant differences in the efficacy or toxicity of the three morphine PCA regimens were identified.     

VRCTC-310--a novel compound of purified animal toxins separates antitumor efficacy from neurotoxicity

Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to produce a unique natural product (VRCTC-310) currently under investigation as an antitumor agent by the National Cancer Institute. In vitro, it has demonstrated cytotoxic disease specificity and a unique mechanism of action when submitted to COMPARE analysis. In vivo, tolerance was developed to the neurotoxic properties of crotoxin which allowed comparison of several schedules of fixed and escalating daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites of i.m. injection was noted, animal weight loss was negligible and there were no other signs of adverse toxicity. This natural product represents a new, membrane interactive anticancer agent which produces a unique spectrum of cytotoxicity in vitro and which has demonstrated interesting in vivo antitumor efficacy.     

Standardizing formats of corporate source data

This paper describe an approach for improving the data quality of corporate sources when databases are used for bibliometric purposes. Research management relies on bibliographic databases and citation index systems as analytical tools, yet the raw resources for bibliometric studies are plagued by a lack of consistency in fied formatting for institution data. The present contribution puts forth a Natural Language Processing (NLP)-oriented method for the identification of the structures guiding corporate data and their mapping into a standardized format. The proposed unification process is based on the definition of address patterns and the ensuing application of Enhanced Finite-State Transducers (E-FST). Our procedure was tested on address formats downloaded from the INSPEC, MEDLINE and CAB Abstracts. The results demonstrate the helpfulness of the method as long as close control of errors is exercised as far as the formats to be unified. The computational efficacy of the model is noteworthy, due to the fact that it is firmly guided by the definition of data in the application domain.     

Effect of Crude Oil Composition and Blending on Flowing Properties

The effect of crude oil n-paraffin molecular weight distribution on wax crystallization risk was studied. Sixteen highly paraffinic crude oils from Eastern Venezuela were characterized, in terms of hydrocarbon family distribution, by High Temperature Simulate Distillation (HTSD), Gel Permeation Chromatography (GPC), and wax content. n-Paraffin chain length was correlated with crude oil cloud point and pour point. It was demonstrated that high molecular weight linear paraffins are responsible for crude oil wax precipitation. A quantitative correlation between molecular weight distribution and crude oil flowing properties was also obtained. It was found that the wider the molecular weight distribution, the lower is the wax crystallization risk. Blends of different paraffinic crude oils were prepared and their flowing properties were evaluated in comparison with the original crudes. Cloud points below the mean value were obtained. In some cases, a synergistic effect was observed (cloud points below the minimum of the two crude oils). Blends of some of these crudes with condensates afforded improvements on crude oil flow and a reduction of wax crystallization tendency (cloud point). This phenomenon can be attributed to a combination of two factors: I. increases in C24-n-paraffins, and II. a wider molecular weight distribution.