Stable, covalent attachment of laminin to microposts improves the contractility of mouse neonatal cardiomyocytes.

The mechanical output of contracting cardiomyocytes, the muscle cells of the heart, relates to healthy and disease states of the heart. Culturing cardiomyocytes on arrays of elastomeric microposts can enable inexpensive and high-throughput studies of heart disease at the single-cell level. However, cardiomyocytes weakly adhere to these microposts, which limits the possibility of using biomechanical assays of single cardiomyocytes to study heart disease. We hypothesized that a stable covalent attachment of laminin to the surface of microposts improves cardiomyocyte contractility. We cultured cells on polydimethylsiloxane microposts with laminin covalently bonded with the organosilanes 3-glycidoxypropyltrimethoxysilane and 3-aminopropyltriethoxysilane with glutaraldehyde. We measured displacement of microposts induced by the contractility of mouse neonatal cardiomyocytes, which attach better than mature cardiomyocytes to substrates. We observed time-dependent changes in contractile parameters such as micropost deformation, contractility rates, contraction and relaxation speeds, and the times of contractions. These parameters were affected by the density of laminin on microposts and by the stability of laminin binding to micropost surfaces. Organosilane-mediated binding resulted in higher laminin surface density and laminin binding stability. 3-glycidoxypropyltrimethoxysilane provided the highest laminin density but did not provide stable protein binding with time. Higher surface protein binding stability and strength were observed with 3-aminopropyltriethoxysilane with glutaraldehyde. In cultured cardiomyocytes, contractility rate, contraction speeds, and contraction time increased with higher laminin stability. Given these variations in contractile function, we conclude that binding of laminin to microposts via 3-aminopropyltriethoxysilane with glutaraldehyde improves contractility observed by an increase in beating rate and contraction speed as it occurs during the postnatal maturation of cardiomyocytes. This approach is promising for future studies to mimic in vivo tissue environments

Damage function for historic paper. Part I: Fitness for use

Background In heritage science literature and in preventive conservation practice, damage functions are used to model material behaviour and specifically damage (unacceptable change), as a result of the presence of a stressor over time. For such functions to be of use in the context of collection management, it is important to define a range of parameters, such as who the stakeholders are (e.g. the public, curators, researchers), the mode of use (e.g. display, storage, manual handling), the long-term planning horizon (i.e. when in the future it is deemed acceptable for an item to become damaged or unfit for use), and what the threshold of damage is, i.e. extent of physical change assessed as damage. Results In this paper, we explore the threshold of fitness for use for archival and library paper documents used for display or reading in the context of access in reading rooms by the general public. Change is considered in the context of discolouration and mechanical deterioration such as tears and missing pieces: forms of physical deterioration that accumulate with time in libraries and archives. We also explore whether the threshold fitness for use is defined differently for objects perceived to be of different value, and for different modes of use. The data were collected in a series of fitness-for-use workshops carried out with readers/visitors in heritage institutions using principles of Design of Experiments. Conclusions The results show that when no particular value is pre-assigned to an archival or library document, missing pieces influenced readers/visitors’ subjective judgements of fitness-for-use to a greater extent than did discolouration and tears (which had little or no influence). This finding was most apparent in the display context in comparison to the reading room context. The finding also best applied when readers/visitors were not given a value scenario (in comparison to when they were asked to think about the document having personal or historic value). It can be estimated that, in general, items become unfit when text is evidently missing. However, if the visitor/reader is prompted to think of a document in terms of its historic value, then change in a document has little impact on fitness for use

Anesthesia of Epinephelus marginatus with essential oil of Aloysia polystachya: an approach on blood parameters

This study investigated the anesthetic potential of the essential oil (EO) of Aloysia polystachya in juveniles of dusky grouper (Epinephelus marginatus). Fish were exposed to different concentrations of EO of A. polystachya to evaluate time of induction and recovery from anesthesia. In the second experiment, fish were divided into four groups: control, ethanol and 50 or 300 mu L L-1 EO of A. polystachya, and each group was submitted to induction for 3.5 min and recovery for 5 or 10 min. The blood gases and glucose levels showed alterations as a function of the recovery times, but Na+ and K+ levels did not show any alteration. In conclusion, the EO from leaves of A. polystachya is an effective anesthetic for dusky grouper, because anesthesia was reached within the recommended time at EO concentrations of 300 and 400 mu L L-1. However, most evaluated blood parameters showed compensatory responses due to EO exposure.Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul/Programa de Apoio a Nucleos de Excelencia (FAPERGS/PRONEX) [10/0016-8]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [470964/2009-0]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (CAPES)info:eu-repo/semantics/publishedVersio

Current quark mass dependence of nucleon magnetic moments and radii

A calculation of the current-quark-mass-dependence of nucleon static electromagnetic properties is necessary in order to use observational data as a means to place constraints on the variation of Nature's fundamental parameters. A Poincare' covariant Faddeev equation, which describes baryons as composites of confined-quarks and -nonpointlike-diquarks, is used to calculate this dependence The results indicate that, like observables dependent on the nucleons' magnetic moments, quantities sensitive to their magnetic and charge radii, such as the energy levels and transition frequencies in Hydrogen and Deuterium, might also provide a tool with which to place limits on the allowed variation in Nature's constants.Comment: 23 pages, 2 figures, 4 tables, 4 appendice

Preliminary study: Treatment with intramuscular interferon beta-1a results in increased levels of IL-12Rβ2+ and decreased levels of IL23R+ CD4+ T - Lymphocytes in multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>There are a lack of biomarkers which can be used to predict clinical outcomes for multiple sclerosis (MS) patients receiving interferon beta (IFN-β). Thus the objective of this study was to characterize changes in CD4+ T-lymphocyte expression in an unbiased manner following initiation of intramuscular (IM) IFN-β-1a treatment, and then to verify those findings using marker-specific assays.</p> <p>Methods</p> <p>Peripheral blood specimens were collected from twenty MS patients before and after treatment with intramuscular (IM) IFN-β-1a and were used for isolation of mononuclear cells (PBMCs). mRNA expression patterns of negatively-selected CD4+ T-cells from the PBMCs were analyzed using microarray gene expression technology. IL-12 and IL-23 receptor levels on PBMC-derived CD4+ T-cells were analyzed by flow cytometry. The phosphorylation status of Stat4 was measured by performing densitometry on western blots.</p> <p>Results</p> <p>Microarray analyses demonstrated that mRNA expression of the IL-12Rβ2 gene was uniformly up-regulated in response to IFN-β-1a treatment and was associated with an increased number of IL-12Rβ2⁺CD4⁺T-cells by flow cytometry in 4 of 6 patients. This finding was substantiated by demonstrating that Stat4 phosphorylation, a transcription factor for IL-12, was increased after treatment. Conversely, the number of IL-23R⁺CD4⁺T-cells was decreased following treatment.</p> <p>Conclusions</p> <p>The IL-12 receptor shares a common subunit, the IL-12Rβ2, with the IL-23 receptor. Both of these receptors have a probable role in regulating IL-17 and TH-17 cells, important mediators of inflammation in multiple sclerosis (MS). Thus, the changes in the numbers of CD4⁺T-cells expressing these receptors in response to IFN-β-1a treatment may point to an important mechanism of action for this drug, but further large scale studies are needed to confirm these preliminary observations.</p

Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry.

BACKGROUND: The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children. METHODS: Data from patients with HCM in the international, multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed. LVSD was defined as left ventricular ejection fraction <50% on echocardiographic reports. Prognosis was assessed by a composite of death, cardiac transplantation, and left ventricular assist device implantation. Predictors of developing incident LVSD and subsequent prognosis with LVSD were assessed using Cox proportional hazards models. RESULTS: We studied 1010 patients diagnosed with HCM during childhood (<18 years of age) and compared them with 6741 patients with HCM diagnosed as adults. In the pediatric HCM cohort, median age at HCM diagnosis was 12.7 years (interquartile range, 8.0-15.3), and 393 (36%) patients were female. At initial SHaRe site evaluation, 56 (5.5%) patients with childhood-diagnosed HCM had prevalent LVSD, and 92 (9.1%) developed incident LVSD during a median follow-up of 5.5 years. Overall LVSD prevalence was 14.7% compared with 8.7% in patients with adult-diagnosed HCM. Median age at incident LVSD was 32.6 years (interquartile range, 21.3-41.6) for the pediatric cohort and 57.2 years (interquartile range, 47.3-66.5) for the adult cohort. Predictors of developing incident LVSD in childhood-diagnosed HCM included age <12 years at HCM diagnosis (hazard ratio [HR], 1.72 [CI, 1.13-2.62), male sex (HR, 3.1 [CI, 1.88-5.2), carrying a pathogenic sarcomere variant (HR, 2.19 [CI, 1.08-4.4]), previous septal reduction therapy (HR, 2.34 [CI, 1.42-3.9]), and lower initial left ventricular ejection fraction (HR, 1.53 [CI, 1.38-1.69] per 5% decrease). Forty percent of patients with LVSD and HCM diagnosed during childhood met the composite outcome, with higher rates in female participants (HR, 2.60 [CI, 1.41-4.78]) and patients with a left ventricular ejection fraction <35% (HR, 3.76 [2.16-6.52]). CONCLUSIONS: Patients with childhood-diagnosed HCM have a significantly higher lifetime risk of developing LVSD, and LVSD emerges earlier than for patients with adult-diagnosed HCM. Regardless of age at diagnosis with HCM or LVSD, the prognosis with LVSD is poor, warranting careful surveillance for LVSD, especially as children with HCM transition to adult care

Survival trends for small intestinal cancer in England and Wales, 1971–1990: national population-based study

This population-based study examines prognostic factors and survival trends among adults (15–99 years) diagnosed with small intestinal cancer in England and Wales during 1971–1990 and followed up to 1995. During this period, the 1- and 5-year age-standardised relative survival rates for small intestinal cancers combined were 42% and 23%, respectively. Duodenal tumours, adenocarcinomas, men, patients with advanced age and the most deprived patients had the poorest prognosis. For all small bowel tumours combined, the excess risk of death fell significantly by 6–9% every 4 years over the 20-year period (adjusted excess hazard ratio (EHR) 0.91 at 1 year after diagnosis, 0.94 at 5 years). For duodenal tumours, the EHR fell by about 14% (95% CI 5–22%) every 4 years between 1979 and 1990, and a similar trend for jejunal tumours was of borderline significance. Further population-based investigations linking survival data to individual data on diagnostic methods and types of treatment are needed

Herpes simplex virus infections among rural residents in eastern China

<p>Abstract</p> <p>Background</p> <p>Herpes simplex virus (HSV) has two types: HSV-1 and HSV-2. Both infect epithelial cells and establish latent infections in neurons causing an infection that persists for life. Information on age- and gender-specific seroprevalence of HSV-1 and HSV-2 is valuable for understanding HSV transmission dynamics and designing population-based prevention and intervention programs for HSV. However, such information is not available for China.</p> <p>Methods</p> <p>Cryopreserved serum samples of all subjects aged 5 to 60 years from two randomly selected rural villages in Zhejiang province in Eastern China who had participated in the China national seroepidemiological survey of hepatitis B virus (HBV) infection conducted in 2006 were tested. Seroprevalence of HSV-1 and HSV-2 infections were determined by type-specific IgG antibody tests using an ELISA technique. Their 95% confidence intervals adjusted for the sampling fraction were calculated according to the Clopper-Pearson method.</p> <p>Results</p> <p>A total of 2,141 residents participated in the survey, with a response rate of 82.3%. HSV-1 seroprevalence was 92.0% overall, 89.1% for males and 94.2% for females. HSV-1 seroprevalence was 61.6% among children aged 5-9 years, 90.3% among 25-29 years, and nearly 100% among those aged > = 40 years. HSV-2 seroprevalence was 13.2% overall, 10.5% for males and 15.3% for females. No children aged 5-14 years were HSV-2 positive, and HSV-2 seroprevalence was 7.1% among 15-19 years and peaked at 24.3% among those aged 45-49 years. Neither HSV-1 nor HSV-2 infections were significantly different by gender. About 11.8% of study subjects were co-infected with both types of HSV. Among 549 participating couples, 8.6% were HSV-1 serodiscordant and 11.8% were HSV-2 serodiscordant. No one tested positive for HIV. The overall prevalence of HBsAg was 16.2%, 16.9% for males and 15.4% for females.</p> <p>Conclusions</p> <p>HSV-1 was highly prevalent among all rural residents aged between 5-60 years in Eastern China, whereas HSV-2 was prevalent among sexually active people. HSV-1 and HSV-2 have different transmission modes and dynamics. Future HSV prevention and control programs in China should be type specific.</p