Wharton’s jelly or bone marrow mesenchymal stromal cells improve cardiac function following myocardial infarction for more than 32 weeks in a rat model: a preliminary report

The therapeutic effect of mesenchymal stromal cells (MSCs) following myocardial infarction (MI) is small. This may be due to differences in cellular sources and donor age, route of administration, in vitro cellular manipulations and the short time course of follow up in many animal studies. Here, we compared MSCs from two different sources (adult bone marrow or Wharton’s jelly from umbilical cord) for their long-term therapeutic effect following MI in a rat model to evaluate the effect of donor age. MSCs (or control infusions) were given intravenously 24-48 hr after myocardial ischemia (MI) induced by coronary artery ligation. Cardiac function was assessed by ultrasound at time points starting from before MSC infusion through 68 weeks after MI. A significant improvement in ejection fraction was seen in animals that received MSCs in time points 25 to 31 wks after treatment (p <0.01). These results support previous work that show that MSCs can cause improvement in cardiac function and extend that work by showing that the beneficial effects are durable. To investigate MSCs’ cardiac differentiation potential, Wharton’s jelly MSCs were co-cultured with fetal or adult bone-derived marrow MSCs. When Wharton’s jelly MSCs were co-cultured with fetal MSCs, and not with adult MSCs, myotube structures were observed in two-three days and spontaneous contractions (beating) cells were observed in fiveseven days. The beating structures formed a functional syncytium indicated by coordinated contractions (beating) of independent nodes. Taken together, these results suggest that MSCs given 24-48 hr after MI have a significant and durable beneficial effect more than 25 weeks after MI and that MSC treatment can home to damaged tissue and improve heart function after intravenous infusion 24-48 hrs after MI, and that WJCs may be a useful source for off-the-shelf cellular therapy for MI

Thermal Dose Inactivation of Escherichia coli by Magnetic Induced Hyperthermia

Background: Apoptosis of mutated cells via magnetic hyperthermia has gained advocacy as technology capable of being used in lieu of chemotherapy for targeting cancer tumors. Progress of nanotechnology offers effective remote heating of magnetic fluid via hyperthermia. The heating and specific power absorption of these nanoparticles use in the magnetic fluid are dependent on particle properties and treatment locations. Methods: Nanoparticles were fabricated using microfluidic system by interaction of two solutions containing 2Fe(NO3)3+FeSO4 and NaOH+2%Dextran to create nanostructured media with a biocompatible dextran coating and a Fe3O4 core. The nanoparticles, of a concentration of 5mg/ml, were placed in a vile containing Luria-Bertani (LB) media with approximately 2.0x108 cells. The vile was inserted into a DM100 Series Magnetic Hyperthermia Device that provides an alternating magnetic field of 300 Gauss with a frequency of 604KHz. Results: Magnetite produced via the microfluidic systems at flow rate of 0.04mL/s showed uniform particle size distribution with average size 10nm and saturation magnetization up to 60emu/g as well as pure-phase of Fe3O4 with high crystallinity. Zero-Field-Cooled and Field-Cooled measurements indicated a superparamagnetic nature of as synthesized particles with a low blocking temperature that varies by the amount of dextran introduced in the mixture. Conclusions: The superparamagnetic nanoparticles were heated up to 60°C, inciting a heat shock effect that led to the destruction of the E.coli bacteria. The specific power absorption value obtained was 130 W/g, showing that magnetite–dextran nanostructured fluid appears to be a promising active media for the local magnetic hyperthermia for cancer therapy

Pathologic Risk Factors for Higher Clinical Stage in Testicular Seminomas

Introduction Testicular seminomas require accurate staging for effective management. 20% are metastatic at presentation while 80% are clinical stage I, requiring only orchiectomy and surveillance. Tumor size, rete testis invasion, hilar soft tissue invasion, and lymphovascular invasion have been shown to incur a higher risk of metastasis and recurrence in clinical stage I seminomas, with little congruence between studies. Materials and Methods We reviewed 211 cases of testicular seminomas and recorded patient age, tumor size, lymphovascular invasion and rete testis, hilar soft tissue, epididymis, spermatic cord, tunica albuginea, and tunica vaginalis involvement. A univariate and multivariate analysis was performed comparing clinical stage I to advanced clinical stage patients (stages II and III) in reference to these factors. Results We found that tumor size (p=0.02), vascular invasion (p=0.02), and invasion of rete testis stroma (p=0.01), epididymis (p=0.02), spermatic cord (p=0.047), and hilar soft tissue (p=0.04) were predictors of higher clinical stage at the univariate level. However, multivariate analysis showed that only tumor size and vascular invasion remained significant (p=0.008 and 0.032, respectively). A tumor size of 4 cm was the size cutoff found to be significant. Discussion Tumor size and vascular invasion are the strongest predictors of higher clinical stage in testicular seminomas. Our univariate data suggests that rete testis and hilar soft tissue invasion relate to higher clinical stage. However, neither of these factors were found to be independent risk factors at multivariate analysis. Therefore, this study supports tumor upstaging based only upon size and vascular invasion

The Application of Electrosprayed Minocycline-Loaded PLGA For The Treatment Of Glioblastoma

Background: Glioblastoma multiforme (GBM) is one of the most common and aggressive forms of cancer with unfavorable prognosis due to high levels of reoccurrence with around 10,000 patients in the U.S. diagnosed each year. Despite treatment with surgery, radiotherapy, and chemotherapy, survival rate for this disease is around 21 months after diagnosis. Minocycline, a tetracycline-derivative used as an antibiotic, has also demonstrated the ability to inhibit angiogenesis or tumor growth and, presents a possible treatment option for GBM. Methods: Microparticles were fabricated by electrospraying by varying solvent type, distance, flow rate, voltage, and polymer concentration as parameters. The cytotoxicity of endothelial and glioblastoma cells was determined by an MTT assay by determining the absorbance using a spectrophotometer at a wavelength of 350 nm. Scanning electron microscopy (SEM) imaging was used to image the samples to determine microparticle surface morphology and size via an electron beam due to microparticles being sputter coated with gold to generate an electrical conduction. Results: The electrospraying process consists of numerous parameters which directly affect the creation of microparticles. The use of the solvent methanol aids in dissolving minocycline, while the use of DCM is important for the process of electrospraying, due to its higher vapor pressure and ability to dissolve PLGA. Conclusion: In conclusion, electrospraying is a promising method to fabricate drug loaded PLGA microparticles. However, optimization is needed whenever there is a new drug of interest as it can modify the properties of the electrospray solution and result in different effects on the fabrication parameters and particles produced

Carbon combustion synthesis of Janus-like particles of magnetoelectric cobalt ferrite and barium titanate

Carbon combustion synthesis of oxides was applied for quick and energy efficient production of multiferroic composite of cobalt ferrite and barium titanate to form Janus-like particles matrix structure. The exothermic oxidation of carbon nanoparticles with an average size of 5 nm and a specific surface area of 110 m2/g generates a self-propagating thermal wave with peak temperature of up to 1000 °C. The thermal front rapidly propagates through the mixture of solid reactants (magnetic- CoFe2O4 and ferroelectric-BaTiO3) and results in localized hot-spot sintering of magneto-electric phases to form a nanocomposite structure. Carbon is not incorporated in the product and is emitted as a gaseous CO2. Existence of discrete CoFe2O4 and BaTiO3phases in the composites nanostructures was confirmed using X-ray powder diffraction along with SEM and TEM analysis. We estimated the activation energy for the combustion synthesis of Janus-like particles to be 112 ± 3.3 kJ/mol, indicating that the barium titanate and cobalt ferrite presence decrease the activation energy barrier of carbon oxidation and facilitate the ignition process of the combustion synthesis. We observe that the as-synthesized samples show magnetoelectric coupling on multiferroic cobalt ferrite–barium titanate ceramic composites

DACC Resting State Functional Connectivity as a Predictor of Pain Symptoms Following Motor Vehicle Crash: A Preliminary Investigation

There is significant heterogeneity in pain outcomes following motor vehicle crashes (MVCs), such that a sizeable portion of individuals develop symptoms of chronic pain months after injury while others recover. Despite variable outcomes, the pathogenesis of chronic pain is currently unclear. Previous neuroimaging work implicates the dorsal anterior cingulate cortex (dACC) in adaptive control of pain, while prior resting state functional magnetic resonance imaging studies find increased functional connectivity (FC) between the dACC and regions involved in pain processing in those with chronic pain. Hyper-connectivity of the dACC to regions that mediate pain response may therefore relate to pain severity. The present study completed rsfMRI scans on N=22 survivors of MVCs collected within two weeks of the incident to test whole-brain dACC-FC as a predictor of pain severity six months later. At two weeks, pain symptoms were predicted by positive connectivity between the dACC and the premotor cortex. Controlling for pain symptoms at two weeks, pain symptoms at six months were predicted by negative connectivity between the dACC and the precuneus. Previous research implicates the precuneus in the individual subjective awareness of pain. Given a relatively small sample size, approximately half of which did not experience chronic pain at six months, findings warrant replication. Nevertheless, this study provides preliminary evidence of enhanced dACC connectivity with motor regions and decreased connectivity with pain processing regions as immediate and prospective predictors of pain following MVC. Perspective: This article presents evidence of distinct neural vulnerabilities that predict chronic pain in motor vehicle crash survivors based on whole-brain connectivity with the dorsal anterior cingulate cortex

Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia

[[abstract]]Background: Acute leukemias of childhood are a heterogeneous group of malignancies characterized by cytogenetic abnormalities, such as translocations and changes in ploidy. These abnormalities may be influenced by altered DNA repair and cell cycle control processes. Methods: We examined the association between childhood acute lymphoblastic leukemia (ALL) and 32 genes in DNA repair and cell cycle pathways using a haplotype-based approach, among 377 childhood ALL cases and 448 controls enrolled during 1995-2002. Results: We found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total ALL, while haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively. In addition, we observed statistically significant interaction between exposure to 3 or more diagnostic X-rays and haplotypes of XRCC4 on risk of structural abnormality-positive childhood ALL. Conclusions: These results support a role of altered DNA repair and cell cycle processes in the risk of childhood ALL, and show that this genetic susceptibility can differ by cytogenetic subtype and may be modified by exposure to ionizing radiation. To our knowledge, our study is the first to broadly examine the DNA repair and cell cycle pathways using a haplotype approach in conjunction with X-ray exposures in childhood ALL risk. If confirmed, future studies are needed to identify specific functional SNPs in the regions of interest identified in this analysis

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Spillover Effects of Conflict on Economic Growth Along the U.S.-Mexico Border

The violence and insecurity that Mexico has suffered since former President Calderon\u27s war on drugs has come at a grave economic cost to the cities most affected. Businesses and citizens in counties that shared a border with the United States, however, have the ability to move their capital and businesses in search of regaining profits that had been lost due to the insecurity in their cities. These specific counties are considered to be interdependent borderlands, which signify that these borders are in a border region where one nation is symbiotically linked with the border region of an adjoining country. This research seeks to show that increased border violence causes a positive economic spillover in the interdependent borderland by exploring the relationship between violence in one border city and economic growth in the neighboring city for six Mexico-U.S. border counties from 2005 to 2011. This study will be tested with a linear regression with panel-corrected standard errors using lagged dependent variables. The independent variables consist of organized crime related homicides, kidnappings, and extortions. The dependent variables consist of gross total sales, gross retail sales, taxable sales, taxable retail sales, accommodation/food service sales, and total establishments. The study controls for unemployment rates due to the recession the U.S. suffered during the time of the study

PVDF-Fe3O4 nanocomposites: spectroscopic investigations

Nanocomposites have been prepared by melt mixing, loading the polyvinylidene fluoride matrix with various concentrations of magnetite. Wide Angle X-Ray Scattering, Raman, Fourier Transform Infrared, and Electron Paramagnetic Resonance spectroscopy were used to investigate these nanocomposites. Wide Angle X-Ray Scattering revealed that α is the dominant crystalline phase of the polymeric matrix irrespective of the loading with magnetite. Wide Angle X-Ray Scattering investigations on the dependence of the line positions and widths on the loading with magnetite are reported. Raman and Fourier Transform Infrared spectroscopy confirmed that the as-obtained nanocomposites consist of α polyvinylidene fluoride. The main Raman lines were identified, and the dependence of their parameters (line position and widths) on the loading by magnetite was reported. Raman and Wide Angle X-Ray Scattering data demonstrated a strong interaction between the matrix and the nanofiller. Electron Paramagnetic Resonance spectra of these nanocomposites reflect strong anisotropic electron interactions among the nanofiller’s electrons