Synergistic platelet inhibition between Omega-3 and acetylsalicylic acid dose titration; an observational study

Background: Omega-3 and acetylsalicylic acid (ASA) are two widely used “over-the-counter” drugs. Previous researchhas shown multiple electrode aggregometry (MEA) can detect ASA and varying Omega-3 platelet inhibiting effects.Synergistic platelet inhibiting effects of ASA and Omega-3 have been found using other methods than MEA. The aimof this study was to investigate the antiplatelet effects of Omega-3, and ASA synergism with MEA.Methods: Ten healthy male volunteers ingested Omega-3 (1260mg/day) for 5 days. MEA was used to analyse plateletfunction before and after Omega-3 intake. Aggregation was initiated using three different agonists and measured asarea under the curve (AUC): adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) andarachidonic acid (ASPI). Two concentrations of ASA were dose titrated ex vivo to 2 out of 3 ASPI test cells in order tomeasure synergism between Omega-3 and ASA.Results: Following 5 days Omega-3 intake, ADP, TRAP and ASPI AUC did not change significantly. In vitro ASA beforeOmega-3 intake, reduced ASPI AUC < 30 U, indicating a strong platelet inhibiting effect. Below this AUC level, the 5 daysOmega-3 intake increased ASPI-AUC with the ex vivo added low dose ASA (P = 0.02) and high dose ASA (P = 0.04).Conclusions: No synergism between ASA and Omega-3 was found using the MEA ASPI test. The surprising increase inASPI-AUC following Omega-3 intake and ex vivo ASA suggest that there are methodological issuses with the MEA ASPI test

Enhanced differentiation of human embryonic stem cells towards definitive endoderm on ultrahigh aspect ratio nanopillars

Differentiation of human embryonic stem cells is widely studied as a potential unlimited source for cell replacement therapy to treat degenerative diseases such as diabetes. The directed differentiation of human embryonic stem cells relies mainly on soluble factors. Although, some studies have highlighted that the properties of the physical environment, such as substrate stiffness, affect cellular behavior. Here, mass-produced, injection molded polycarbonate nanopillars are presented, where the surface mechanical properties, i.e., stiffness, can be controlled by the geometric design of the ultrahigh aspect ratio nanopillars (stiffness can be reduced by 25.0003). It is found that tall nanopillars, yielding softer surfaces, significantly enhance the induction of definitive endoderm cells from pluripotent human embryonic stem cells, resulting in more consistent differentiation of a pure population compared to planar control. By contrast, further differentiation toward the pancreatic ­endoderm is less successful on “soft” pillars when compared to “stiff” pillars or control, indicating differential cues during the different stages of differentiation. To accompany the mechanical properties of the nanopillars, the concept of surface shear modulus is introduced to describe the characteristics of engineered elastic surfaces through micro or nanopatterning. This provides a framework whereby comparisons can be drawn between such materials and bulk elastomeric materials

Migrant minors in detention: Practical needs and the limits set by the European Convention

State officials report practical needs to put migrant minors in detention, and the European Convention on Human Rights sets legal limits on this practice. This article defines the scope of circumstances under which migrating minors may be detained by analyzing The European Court of Human Rights case law, using judgments in which the detention of migrant minors has been alleged a violation of Articles 3, 5.1, or 8. It also explores states’ needs for detaining such children, using data from 19 interviews with Swedish police officers, and compares these views with the case law. Police interviewees primarily describe two needs to detain children: to make deportations of children smooth and dignified, and to prevent minors from committing crimes. The investigation finds that migrant minor detentions are rarely permissible according to the Convention—especially under Article 3—and that the permissible scope is too small to meet the expressed practical needs. The actors involved in the issue of detaining migrant minors might have different perspectives on the issue, but they must not lose sight of the fact that these children are categorized as some of the most vulnerable in society and that their rights must be protected

Entreprenörens motivation

Gasellföretagen skapar många nya arbetstillfällen i Sverige. Under åren 2004 till 2007 stod gasellföretagen för drygt 10 procent av ökningen av Sveriges BNP. För att framgångsrika företag ska skapas och växa krävs individer som tar initiativet att starta och driva dessa. Tidigare forskning har fokuserat på vad som driver entreprenörer i uppstartsskedet, men lika viktigt är det att förstå vad det är som driver entreprenören i senare skeden. Vi har därför valt att se hur motivationen förändras över tiden hos den grundande entreprenören i gasellföretag. Den kvalitativa studien bygger på nio intervjuer med företagsgrundare av gaseller som delat med sig av sina berättelser och erfarenheter. Vi presenterar i vår studie vad som utmärker samt motiverar dem i deras arbete

Collagen Type I Improves the Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm

Human embryonic stem cells have the ability to generate all cell types in the body and can potentially provide an unlimited source of cells for cell replacement therapy to treat degenerative diseases such as diabetes. Current differentiation protocols of human embryonic stem cells towards insulin producing beta cells focus on soluble molecules whereas the impact of cell-matrix interactions has been mainly unattended. In this study almost 500 different extracellular matrix protein combinations were screened to systemically identify extracellular matrix proteins that influence differentiation of human embryonic stem cells to the definitive endoderm lineage. The percentage of definitive endoderm cells after differentiation on collagen I and fibronectin was >85% and 65%, respectively. The cells on collagen I substrates displayed different morphology and gene expression during differentiation as assessed by time lapse studies compared to cells on the other tested substrates. Global gene expression analysis showed that cells differentiated on collagen I were largely similar to cells on fibronectin after completed differentiation. Collectively, the data suggest that collagen I induces a more rapid and consistent differentiation of stem cells to definitive endoderm. The results shed light on the importance of extracellular matrix proteins for differentiation and also points to a cost effective and easy method to improve differentiation

Environmental benefits of circular food systems: The case of upcycled protein recovered using genome edited potato

Although essential in the human diet, large quantities of available protein are currently lost or under-utilized within the food system, including protein rich side streams from conventional potato starch production. By using the genome editing technique CRISPR-Cas9, conventional starch potato cultivars can be upgraded to facilitate high-value recovery of potato protein fit for human consumption. In turn, this could support the nessecary transition towards more circular food systems. The aim of this study was to assess what environmental benefits could be gained by shifting from conventional protein recovery practice to a novel approach using genome edited potato. Our results, using consequential life cycle assessment, showed that the novel protein recovery scenario provided substantial environmental savings for every ton potato starch produced, with a reduction in global warming impact, terrestrial acidification, land use and ecosystem damage of −720 kgCO2eq, −13 kgSO2eq, −760 m2a crop eq, and −1.1 × 10−5 species.yr respectively. The potential environmental benefits of using genome edited potato were maintained even when simulating reduced tuber yield, increased production inputs, and substitution of various protein sources. Although currently limited by EU legislation and technical maturity, high-value protein recovery from food side streams holds a promising potential to support sustainable production and circularity within the food system

Controlling fluid flow to improve cell seeding uniformity

Standard methods for seeding monolayer cell cultures in a multiwell plate or dish do not uniformly distribute cells on the surface. With traditional methods, users find aggregation around the circumference, in the centre, or a combination of the two. This variation is introduced due to the macro scale flow of the cell seeding suspension, and movement of the dish before cells can settle and attach to the surface. Reproducibility between labs, users, and experiments is hampered by this variability in cell seeding. We present a simple method for uniform and user-independent the cell seeding using an easily produced uniform cell seeder (UCS) device. This allows precise control of cell density in a reproducible manner. By containing the cell seeding suspension in a defined volume above the culture surface with the UCS, fluctuations in cell density are minimised. Seeding accuracy, as defined by the actual cell density versus the target seeding density is improved dramatically across users with various levels of expertise. We go on to demonstrate the impact of local variation in cell density on the lineage commitment of human embryonic stem cells (hESCs) towards pancreatic endoderm (PE). Variations in the differentiation profile of cells across a culture well closely mirror variations in cell density introduced by seeding method–with the UCS correcting variations in differentiation efficiency. The UCS device provides a simple and reproducible method for uniform seeding across multiple culture systems

Single-Cell Gene Expression Analysis of a Human ESC Model of Pancreatic Endocrine Development Reveals Different Paths to β-Cell Differentiation

The production of insulin-producing β cells from human embryonic stem cells (hESCs) in vitro represents a promising strategy for a cell-based therapy for type 1 diabetes mellitus. To explore the cellular heterogeneity and temporal progression of endocrine progenitors and their progeny, we performed single-cell qPCR on more than 500 cells across several stages of in vitro differentiation of hESCs and compared them with human islets. We reveal distinct subpopulations along the endocrine differentiation path and an early lineage bifurcation toward either polyhormonal cells or β-like cells. We uncover several similarities and differences with mouse development and reveal that cells can take multiple paths to the same differentiation state, a principle that could be relevant to other systems. Notably, activation of the key β-cell transcription factor NKX6.1 can be initiated before or after endocrine commitment. The single-cell temporal resolution we provide can be used to improve the production of functional β cells