Enhanced endothelial cell density on NiTi surfaces with sub-micron to nanometer roughness

The shape memory effect and superelastic properties of NiTi (or Nitinol, a nickel-titanium alloy) have already attracted much attention for various biomedical applications (such as vascular stents, orthodontic wires, orthopedic implants, etc). However, for vascular stents, conventional approaches have required coating NiTi with anti-thrombogenic or anti-inflammatory drug-eluting polymers which as of late have proven problematic for healing atherosclerotic blood vessels. Instead of focusing on the use of drug-eluting anti-thrombogenic or anti-inflammatory proteins, this study focused on promoting the formation of a natural anti-thrombogenic and anti-inflammatory surface on metallic stents: the endothelium. In this study, we synthesized various NiTi substrates with different micron to nanometer surface roughness by using dissimilar dimensions of constituent NiTi powder. Endothelial cell adhesion on these compacts was compared with conventional commercially pure (cp) titanium (Ti) samples. The results after 5 hrs showed that endothelial cells adhered much better on fine grain (<60 μm) compared with coarse grain NiTi compacts (<100 μm). Coarse grain NiTi compacts and conventional Ti promoted similar levels of endothelial cell adhesion. In addition, cells proliferated more after 5 days on NiTi with greater sub-micron and nanoscale surface roughness compared with coarse grain NiTi. In this manner, this study emphasized the positive pole that NiTi with sub-micron to nanometer surface features can play in promoting a natural anti-thrombogenic and anti-inflammatory surface (the endothelium) on a vascular stent and, thus, suggests that more studies should be conducted on NiTi with sub-micron to nanometer surface features

Ethical and Methodological Challenges of Implementing Social Work Survey Research in Schools: A Perspective from the Suburban United States

Many researchers view schools as the ideal setting to study social and behavioral interventions with youth. As trusted community-based organizations, schools are natural partners for social work researchers who focus on bridging the needs of the most vulnerable populations. Awareness and consideration of critical issues related to conducting research within the school system enables social work researchers to plan and conduct rigorous studies while developing sustainable partnerships with schools. This article outlines key ethical and methodological challenges of conducting school-based survey research, and shares lessons learned and recommendations from the evaluation of a dating violence prevention curriculum implemented in U.S. suburban high schools

Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis

<p>Abstract</p> <p>Background</p> <p>The inbred mouse strain BTBR T+ tf/J (BTBR) exhibits behavioral deficits that mimic the core deficits of autism. Neuroanatomically, the BTBR strain is also characterized by a complete absence of the corpus callosum. The goal of this study was to identify novel molecular and cellular changes in the BTBR mouse, focusing on neuronal, synaptic, glial and plasticity markers in the limbic system as a model for identifying putative molecular and cellular substrates associated with autistic behaviors.</p> <p>Methods</p> <p>Forebrains of 8 to 10-week-old male BTBR and age-matched C57Bl/6J control mice were evaluated by immunohistochemistry using free-floating and paraffin embedded sections. Twenty antibodies directed against antigens specific to neurons, synapses and glia were used. Nissl, Timm and acetylcholinesterase (AchE) stains were performed to assess cytoarchitecture, mossy fibers and cholinergic fiber density, respectively. In the hippocampus, quantitative stereological estimates for the mitotic marker bromodeoxyuridine (BrdU) were performed to determine hippocampal progenitor proliferation, survival and differentiation, and brain-derived neurotrophic factor (BDNF) mRNA was quantified by <it>in situ </it>hybridization. Quantitative image analysis was performed for NG2, doublecortin (DCX), NeuroD, GAD67 and Poly-Sialic Acid Neural Cell Adhesion Molecule (PSA-NCAM).</p> <p>Results</p> <p>In midline structures including the region of the absent corpus callosum of BTBR mice, the myelin markers 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and myelin basic protein (MBP) were reduced, and the oligodendrocyte precursor NG2 was increased. MBP and CNPase were expressed in small ectopic white matter bundles within the cingulate cortex. Microglia and astrocytes showed no evidence of gliosis, yet orientations of glial fibers were altered in specific white-matter areas. In the hippocampus, evidence of reduced neurogenesis included significant reductions in the number of doublecortin, PSA-NCAM and NeuroD immunoreactive cells in the subgranular zone of the dentate gyrus, and a marked reduction in the number of 5-bromo-2'-deoxyuridine (BrdU) positive progenitors. Furthermore, a significant and profound reduction in BDNF mRNA was seen in the BTBR dentate gyrus. No significant differences were seen in the expression of AchE, mossy fiber synapses or immunoreactivities of microtubule-associated protein MAP2, parvalbumin and glutamate decarboxylase GAD65 or GAD67 isoforms.</p> <p>Conclusions</p> <p>We documented modest and selective alterations in glia, neurons and synapses in BTBR forebrain, along with reduced neurogenesis in the adult hippocampus. Of all markers examined, the most distinctive changes were seen in the neurodevelopmental proteins NG2, PSA-NCAM, NeuroD and DCX. Our results are consistent with aberrant development of the nervous system in BTBR mice, and may reveal novel substrates to link callosal abnormalities and autistic behaviors. The changes that we observed in the BTBR mice suggest potential novel therapeutic strategies for intervention in autism spectrum disorders.</p

Thin Polymer Brush Decouples Biomaterial's Micro-/Nano-Topology and Stem Cell Adhesion

Surface morphology and chemistry of polymers used as biomaterials, such as tissue engineering scaffolds, have a strong influence on the adhesion and behavior of human mesenchymal stem cells. Here we studied semicrystalline poly(ε-caprolactone) (PCL) substrate scaffolds, which exhibited a variation of surface morphologies and roughness originating from different spherulitic superstructures. Different substrates were obtained by varying the parameters of the thermal processing, i.e. crystallization conditions. The cells attached to these polymer substrates adopted different morphologies responding to variations in spherulite density and size. In order to decouple substrate topology effects on the cells, sub-100 nm bio-adhesive polymer brush coatings of oligo(ethylene glycol) methacrylates were grafted from PCL and functionalized with fibronectin. On surfaces featuring different surface textures, dense and sub-100 nm thick brush coatings determined the response of cells, irrespective to the underlying topology. Thus, polymer brushes decouple substrate micro-/nano-topology and the adhesion of stem cells

Significant Association of Estrogen Receptor Binding Site Variation with Bipolar Disorder in Females

Major depression is nearly twice as prevalent in women compared to men. In bipolar disorder, depressive episodes have been reported to be more common amongst female patients. Furthermore, periods of depression often correlate with periods of hormonal fluctuations. A link between hormone signaling and these mood disorders has, therefore, been suggested to exist in many studies. Estrogen, one of the primary female sex hormones, mediates its effect mostly by binding to estrogen receptors (ERs). Nuclear ERs function as transcription factors and regulate gene transcription by binding to specific DNA sequences. A nucleotide change in the binding sequence might alter the binding efficiency, which could affect transcription levels of nearby genes. In order to investigate if variation in ER DNA-binding sequences may be involved in mood disorders, we conducted a genome-wide study of ER DNA-binding in patients diagnosed with major depression or bipolar disorder. Association studies were performed within each gender separately and the results were corrected for multiple testing by the Bonferroni method. In the female bipolar disorder material a significant association result was found for rs6023059 (corrected p-value = 0.023; odds ratio (OR) 0.681, 95% confidence interval (CI) 0.570–0.814), a single nucleotide polymorphism (SNP) placed downstream of the gene coding for transglutaminase 2 (TGM2). Thus, females with a specific genotype at this SNP may be more vulnerable to fluctuating estrogen levels, which may then act as a triggering factor for bipolar disorder

Ethical and Methodological Challenges of Implementing Social Work Survey Research in Schools: A Perspective from the Suburban United States

Many researchers view schools as the ideal setting to study social and behavioral interventions with youth. As trusted community-based organizations, schools are natural partners for social work researchers who focus on bridging the needs of the most vulnerable populations. Awareness and consideration of critical issues related to conducting research within the school system enables social work researchers to plan and conduct rigorous studies while developing sustainable partnerships with schools. This article outlines key ethical and methodological challenges of conducting school-based survey research, and shares lessons learned and recommendations from the evaluation of a dating violence prevention curriculum implemented in U.S. suburban high schools

Novel Immune Response to Gluten in Individuals with Schizophrenia.

A link between celiac disease and schizophrenia has been postulated for several years, based primarily on reports of elevated levels of antibody to gliadin in patients. We sought to examine the proposed connection between schizophrenia and celiac disease by characterizing the molecular specificity and mechanism of the anti-gliadin immune response in a subset of individuals with schizophrenia. Blood samples from individuals with schizophrenia and elevated anti-gliadin antibody titer were examined for celiac disease-associated biomarkers, including antibodies to transglutaminase 2 (TG2) enzyme and deamidated gliadin peptides, as well as the HLA-DQ2 and -DQ8 MHC genes. The anti-gliadin antibody response was further characterized through examination of reactivity towards chromatographically separated gluten proteins. Target proteins of interest were identified by peptide mass mapping. In contrast to celiac disease patients, an association between the anti-gliadin immune response and anti-TG2 antibody or HLA-DQ2 and -DQ8 markers was not found in individuals with schizophrenia. In addition, the majority of individuals with schizophrenia and anti-gliadin antibody did not exhibit antibody reactivity to deamidated gliadin peptides. Further characterization of the antibody specificity revealed preferential reactivity towards different gluten proteins in the schizophrenia and celiac disease groups. These findings indicate that the anti-gliadin immune response in schizophrenia has a different antigenic specificity from that in celiac disease and is independent of the action of transglutaminase enzyme and HLA-DQ2/DQ8. Meanwhile, the presence of elevated levels of antibodies to specific gluten proteins points to shared immunologic abnormalities in a subset of schizophrenia patients. Further characterization and understanding of the immune response to gluten in schizophrenia may provide novel insights into the etiopathogenesis of specific disease phenotypes