Identification of MS-specific serum miRNAs in an international multicenter study.

ObjectiveTo identify circulating microRNAs (miRNAs) linked to disease, disease stage, and disability in MS across cohorts.MethodsSamples were obtained from the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB, Boston, MA), EPIC (San Francisco, CA), AMIR (Beirut, Lebanon) as part of the SUMMIT consortium, and Stockholm Prospective Assessment of Multiple Sclerosis (Stockholm, Sweden) cohorts. Serum miRNA expression was measured using locked nucleic acid-based quantitative PCR. Four groups were compared: (1) MS vs healthy control (HC), (2) relapsing-remitting (RR) vs HC, (3) secondary progressive (SP) vs HC, and (4) RR vs SP. A Wilcoxon rank-sum test was used for the comparisons. The association between each miRNA and the Expanded Disability Status Scale (EDSS) score was assessed using the Spearman correlation coefficient. For each comparison, the p values were corrected for multiple comparisons using the approach of Benjamini and Hochberg to control the false discovery rate.ResultsIn the CLIMB cohort, 5 miRNAs (hsa-miR-484, hsa-miR-140-5p, hsa-miR-320a, hsa-miR-486-5p, and hsa-miR-320c) showed a significant difference between patients with MS and healthy individuals; among these, miR-484 remained significant after accounting for multiple comparisons (p = 0.01). When comparing RRMS with HCs, hsa-miR-484 showed a significant difference (p = 0.004) between the groups after accounting for multiple group comparisons. When SP and HC were compared, 6 miRNAs (hsa-miR-484, hsa-miR-140-5p, hsa-miR-142-5p, hsa-miR-320a, hsa-miR-320b, and hsa-miR-320c) remained significantly different after accounting for multiple comparisons. Disability correlation analysis with miRNA provided 4 miRNAs (hsa-miR-320a, hsa-miR-337-3p, hsa-miR-199a-5p, and hsa-miR-142-5p) that correlated with the EDSS during the internal reproducibility phase. Among these, hsa-miR-337-3p was the most statistically significant miRNA that negatively correlated with the EDSS in three of the MS cohorts tested.ConclusionsThese findings further confirm the use of circulating serum miRNAs as biomarkers to diagnose and monitor disease status in MS.Classification of evidenceThis study provides Class III evidence that levels of circulating miRNAs identify patients with MS

Stability of Diluted Adenosine Solutions in Polyolefin Infusion Bags

Background Intravenous or intracoronary adenosine is used in the cardiac catherization lab to achieve maximal coronary blood flow and determine fractional flow reserve. Objective To determine the stability of adenosine 10 and 50 µg/mL in either 0.9% sodium chloride injection or 5% dextrose injection in polyolefin infusion bags stored at 2 temperatures, refrigeration (2°C-8°C) or controlled room temperature (20°C-25°C). Methods Adenosine 10 µg/mL and 50 µg/mL solutions were prepared in 50 mL polyolefin infusion bags containing 0.9% sodium chloride injection or 5% dextrose injection and stored at controlled room temperature or under refrigeration. Each combination of concentration, diluent, and storage was prepared in triplicate. Samples were assayed using stability-indicating, reversed-phase high-performance liquid chromatography immediately at time 0 and at 24 hours, 48 hours, 7 days, and 14 days. Stability was defined as retaining 90% to 110% of the initial adenosine concentration. The samples were also visually inspected against a light background for clarity, color, and the presence of particulate matter. Results After 14 days, all samples retained 99% to 101% of the initial adenosine concentration. No considerable change in pH or visual appearance was noted. The stability data indicated no significant loss of drug due to chemical degradation or physical interactions during storage. Conclusion Adenosine solutions of 10 and 50 µg/mL were stable for at least 14 days in 50 mL polyolefin infusion bags of 0.9% sodium chloride injection or 5% dextrose injection stored at controlled room temperature and refrigerated conditions

The role of acidity in solid tumour growth and invasion

Acidic pH is a common characteristic of human tumours. It has a significant impact on tumour progression and response to therapies. In this paper, we develop a simple model of three-dimensional tumour growth to examine the role of acidosis in the interaction between normal and tumour cell populations. Both vascular and avascular tumour dynamics are investigated, and a number of different behaviours are observed. Whilst an avascular tumour always proceeds to a benign steady state, a vascular tumour may display either benign or invasive dynamics, depending on the value of a critical parameter. Analysis of the model allows us to assess novel therapies directed towards changing the level of acidity within the tumour

Index to Library Trends Volume 38

published or submitted for publicatio

Optimization of cell disruption in Raphidocelis subcapitata and Chlorella vulgaris for biomarker evaluation

Raphidocelis subcapitata and Chlorella vulgaris are bioassay microalgae with rigid cellulosic cell wall which can hinder the release of intracellular proteins often studied as toxicity biomarkers. Since cell disruption is necessary for recovering intracellular biomolecules in these organisms, this study investigated the efficiency of ultrasonication bath; ultrasonication probe; vortexer; and bead mill in disintegrating the microalgae for anti-oxidative enzyme extraction. The extent of cell disruption was evaluated and quantified using bright field microscopy. Disrupted algae appeared as ghosts. The greatest disintegration of the microalgae (83-99.6 %) was achieved using bead mill with 0.42-0.6 mm glass beads while the other methods induced little or no disruption. The degree of cell disruption using bead mill increased with exposure time, beads-solution ratio and agitation speed while larger beads caused less disruption. Findings revealed that bead milling, with specific parameters optimized, is one of the most effective methods of disintegrating the robust algal cells

Astronomically paced changes in overturning circulation in the Western North Atlantic during the middle Eocene

North Atlantic Deep Water (NADW) currently redistributes heat and salt between Earth’s ocean basins, and plays a vital role in the ocean-atmosphere CO2 exchange. Despite its crucial role in today’s climate system, vigorous debate remains as to when deep-water formation in the North Atlantic started. Here, we present datasets from carbonate-rich middle Eocene sediments from the Newfoundland Ridge, revealing a unique archive of paleoceanographic change from the progressively cooling climate of the middle Eocene. Well-defined lithologic alternations between calcareous ooze and clay-rich intervals occur at the ∼41-kyr beat of axial obliquity. Hence, we identify obliquity as the driver of middle Eocene (43.5–46 Ma) Northern Component Water (NCW, the predecessor of modern NADW) variability. High-resolution benthic foraminiferal δ18O and δ13C suggest that obliquity minima correspond to cold, nutrient-depleted, western North Atlantic deep waters. We thus link stronger NCW formation with obliquity minima. In contrast, during obliquity maxima, Deep Western Boundary Currents were weaker and warmer, while abyssal nutrients were more abundant. These aspects reflect a more sluggish NCW formation. This obliquity-paced paleoceanographic regime is in excellent agreement with results from an Earth system model, in which obliquity minima configurations enhance NCW formation

Evidence for Innate and Adaptive Immune Responses in a Cohort of Intractable Pediatric Epilepsy Surgery Patients.

Brain-infiltrating lymphocytes (BILs) were isolated from resected brain tissue from 10 pediatric epilepsy patients who had undergone surgery for Hemimegalencephaly (HME) (n = 1), Tuberous sclerosis complex (TSC) (n = 2), Focal cortical dysplasia (FCD) (n = 4), and Rasmussen encephalitis (RE) (n = 3). Peripheral blood mononuclear cells (PBMCs) were also isolated from blood collected at the time of the surgery. Cells were immunostained with a panel of 20 antibody markers, and analyzed by mass cytometry. To identify and quantify the immune cell types in the samples, an unbiased clustering method was applied to the entire data set. More than 85 percent of the CD45+ cells isolated from resected RE brain tissue comprised T cells; by contrast NK cells and myeloid cells constituted 80-95 percent of the CD45+ cells isolated from the TSC and the FCD brain specimens. Three populations of myeloid cells made up >50 percent of all of the myeloid cells in all of the samples of which a population of HLA-DR+ CD11b+ CD4- cells comprised the vast majority of myeloid cells in the BIL fractions from the FCD and TSC cases. CD45RA+ HLA-DR- CD11b+ CD16+ NK cells constituted the major population of NK cells in the blood from all of the cases. This subset also comprised the majority of NK cells in BILs from the resected RE and HME brain tissue, whereas NK cells defined as CD45RA- HLA-DR+ CD11b- CD16- cells comprised 86-96 percent of the NK cells isolated from the FCD and TSC brain tissue. Thirteen different subsets of CD4 and CD8 αβ T cells and γδ T cells accounted for over 80% of the CD3+ T cells in all of the BIL and PBMC samples. At least 90 percent of the T cells in the RE BILs, 80 percent of the T cells in the HME BILs and 40-66 percent in the TSC and FCD BILs comprised activated antigen-experienced (CD45RO+ HLA-DR+ CD69+) T cells. We conclude that even in cases where there is no evidence for an infection or an immune disorder, activated peripheral immune cells may be present in epileptogenic areas of the brain, possibly in response to seizure-driven brain inflammation

Aerospace medicine and biology: A continuing bibliography with indexes

This bibliography lists 148 reports, articles and other documents introduced into the NASA scientific and technical information system in December 1984