The prevalence of hemoglobin Tacoma in Finland detected by HbA1c capillary electrophoresis.

Previous studies have identified occasional cases of heterozygous Hb Tacoma in areas that have attracted Finnish immigrants, especially in Sweden and North America, but large studies of this slightly unstable beta variant have not been carried out. Here we determined the prevalence of hemoglobin variants across Finland. A total of 5059 samples from 11 different hospital districts were analyzed using HbA1c capillary electrophoresis and reviewed for atypical profiles (HbA1c, Capillarys 3 Tera, Sebia).

Promoting academic resilience through peer support in a new pre-registration nursing programme.

Nursing students can experience increased levels of stress while studying for their registration. It is acknowledged that higher education institutions should incorporate mechanisms to try to reduce these stress levels and build up resilience towards the difficult situations students may encounter during their studies. A bespoke method was created within a new part-time 4-year pre-registration nursing programme to support part-time junior (part 1) nursing students by implementing action learning sets within the programme.

Role of hyperpolarization-activated cyclic nucleotide-gated channel HCN2 in embryonic neural stem cell proliferation and differentiation.

Hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels) are involved in spontaneous activity in many electrically active cell types such as cardiomyocytes and neurons. In this study, the role of HCN channels in proliferation and migration of Nestin and Sox2 expressing embryonic neural progenitor cells (NPC) originating from the subventricular zone (SVZ) was examined. Immunostaining and PCR data showed that the HCN2 subtype was highly expressed in these cells.

APOE Genotypes, Lipid Profiles, and Associated Clinical Markers in a Finnish Population with Cardiovascular Disease Risk Factors.

Introduction: The APOE ε4 allele predisposes to high cholesterol and increases the risk for lifestyle-related diseases such as Alzheimer's disease and cardiovascular diseases (CVDs). The aim of this study was to analyse interrelationships of APOE genotypes with lipid metabolism and lifestyle factors in middle-aged Finns among whom the CVD risk factors are common.

Methods: Participants (n = 211) were analysed for APOE ε genotypes, physiological parameters, and health- and diet-related plasma markers.

The NUPHAC-EU Framework for Nurses' Role in Interprofessional Pharmaceutical Care: Cross-Sectional Evaluation in Europe.

Clear role descriptions promote the quality of interprofessional collaboration. Currently, it is unclear to what extent healthcare professionals consider pharmaceutical care (PC) activities to be nurses' responsibility in order to obtain best care quality. This study aimed to create and evaluate a framework describing potential nursing tasks in PC and to investigate nurses' level of responsibility.

Did we do everything we could have? Nurses' contributions to medicines optimization: A mixed-methods study.

Aim: To explore UK professionals' interpretations of medicines optimization and expansion of nurses' roles.

Design: This mixed-methods study sought professionals' views on nurses' involvement, competency and engagement in monitoring patients for adverse effects of medicines, monitoring adherence, prescribing and patient education.

Method: An online survey and interviews were undertaken with nurses, doctors and pharmacists in Wales and England, May 2018 to July 2019.

Acidic extracellular pH promotes accumulation of free cholesterol in human monocyte-derived macrophages via inhibition of ACAT1 activity.

Background And Aims: In focal areas of advanced human atherosclerotic lesions, the intimal fluid is acidic. An acidic medium impairs the ABCA1-mediated cholesterol efflux from macrophages, so tending to increase their content of free cholesterol, which is then available for esterification by the macrophage enzyme ACAT1. Here we investigated whether low extracellular pH would affect the activity of ACAT1.

Neurotransmitters and Endothelins Acting on Radial Glial G-Protein-Coupled Receptors Are, Through Proteolytic NRG/ErbB4 Activation, Able to Modify the Migratory Behavior of Neocortical Cells and Mediate Bipolar-to-Multipolar Transition.

Cell-cell communication plays a central role in the guidance of migrating neurons during the development of the cerebral cortex. Neuregulins (NRGs) are essential mediators for migration and maintenance of the radial glial scaffold. We show, in this study that soluble NRG reduces neuronal motility, causes transition of bipolar cells to multipolar ones, and induces neuronal mitosis.

Tannic acid inhibits electrogenic Na+/HCO3- co-transporter activity in embryonic neural stem cell-derived radial glial-like cells.

Self-renewing neural stem cells and progenitor cells are cell populations that generate radial glial cells and neurons through asymmetric division. Regulation of intracellular pH in stem cells with high metabolic activity is critical for both cell signaling and proliferation. We have recently found that a S0859-inhibitable electrogenic Na/HCO3 co-transporter (NBCe1, Slc4a4), is the primary pHi regulatory mechanism in stem cell-derived radial glial-like cells.

A Long-Term Follow-Up Study on Disclosing Genetic Risk Information (APOE) to Promote Healthy Lifestyles in Finland.

Aim: This observational follow-up study was designed to assess the long-term behavioural and clinical effects of receiving personal genetic risk information. The information disclosed was the carrier status of the apolipoprotein E (APOE)alleles, which differentially contribute to the genetic risk for cardiovascular disease (CVD) and Alzheimer's disease.

Methods: This study forms a continuum with a previous 1-year intervention (2010-2011) monitoring the effects of disclosing the carrier status of the APOE ε4risk allele.

Regulation of intracellular pH by electrogenic Na+/HCO3- co-transporters in embryonic neural stem cell-derived radial glia-like cells.

A stroke causes a hypoxic brain microenvironment that alters neural cell metabolism resulting in cell membrane hyperpolarization and intracellular acidosis. We studied how intracellular pH (pH) is regulated in differentiated mouse neural progenitor cells during hyperpolarizing conditions, induced by prompt reduction of the extracellular K concentration. We found that the radial glia-like population in differentiating embryonic neural progenitor cells, but not neuronal cells, was rapidly acidified under these conditions.

Evidence for Inhibition of Topoisomerase 1A by Gold(III) Macrocycles and Chelates Targeting Mycobacterium tuberculosis and Mycobacterium abscessus.

and the fast-growing species are two important human pathogens causing persistent pulmonary infections that are difficult to cure and require long treatment times. The emergence of drug-resistant strains and the high level of intrinsic resistance of call for novel drug scaffolds that effectively target both pathogens. In this study, we evaluated the activity of bis(pyrrolide-imine) gold(III) macrocycles and chelates, originally designed as DNA intercalators capable of targeting human topoisomerase types I and II (Topo1 and Topo2), against and We identified a total of 5 noncytotoxic compounds active against both mycobacterial pathogens under replicating conditions.

Endocannabinoid Signaling in Embryonic Neuronal Motility and Cell-Cell Contact - Role of mGluR5 and TRPC3 Channels.

Cell-cell communication plays a central role in the guidance of migrating neuronal precursor cells during the development of the cerebral cortex. Endocannabinoids (eCBs) have previously been shown to be one of the central factors regulating neuronal migration. In this study the effects of eCBs on different parameters, expected to affect embryonic cortical neuronal motility have been analyzed in neurosphere-derived neuroblasts using time-lapse microscopy.

Regulation of radial glial process growth by glutamate via mGluR5/TRPC3 and neuregulin/ErbB4.

Radial glial cells play an essential role through their function as guides for neuronal migration during development. Disruption of metabotropic glutamate receptor 5 (mGluR5) function retards the growth of radial glial processes in vitro. Neuregulins (NRG) are activated by proteolytic cleavage and regulate (radial) glial maintenance via ErbB3/ErbB4 receptors.

Pronociceptive effects induced by cutaneous application of a transient receptor potential ankyrin 1 (TRPA1) channel agonist methylglyoxal in diabetic animals: comparison with tunicamycin-induced endoplastic reticulum stress.

Methylglyoxal (MG) is a reactive carbonyl compound generated in diabetes mellitus. MG is an established transient receptor potential ankyrin 1 (TRPA1) channel agonist that contributes to TRPA1-mediated diabetic pain hypersensitivity. Here we studied whether exposure to diabetes and thereby to elevated endogenous MG modulates hypersensitivity induced by intradermal MG.

Calpain Activity Is Essential for ATP-Driven Unconventional Vesicle-Mediated Protein Secretion and Inflammasome Activation in Human Macrophages.

Extracellular ATP is an endogenous danger signal that is known to activate inflammatory responses in innate immune cells, including macrophages. Activated macrophages start to secrete proteins to induce an immune response, as well as to recruit other immune cells to the site of infection and tissue damage. In this study, we characterized the secretome (i.

Transient receptor potential channels and their role in modulating radial glial-neuronal interaction: a signaling pathway involving mGluR5.

The guidance of developing neurons to the right position in the central nervous system is of central importance in brain development. Canonical transient receptor potential (TRPC) channels are thought to mediate turning responses of growth cones to guidance cues through fine control of calcium transients. Proliferating and 1- to 5-day-differentiated neural progenitor cells (NPCs) showed expression of Trpc1 and Trpc3 mRNA, while Trpc4-7 was not clearly detected.

Serum soluble urokinase plasminogen activator receptor in alcoholics: relation to liver disease severity, fibrogenesis, and alcohol use.

Background And Aim: Heavy alcohol consumption may lead to development of liver disease and the need for non-invasive parameters for detecting those at risk is widely acknowledged.

Methods: We measured serum soluble urokinase-type plasminogen activator receptor (suPAR) levels from 63 patients with alcoholic liver disease (ALD), 57 heavy drinkers without apparent liver disease, and 39 controls who were either moderate drinkers or abstainers.

Results: The highest serum suPAR concentrations were detected in patients with ALD (P < 0.

Gold(III) macrocycles: nucleotide-specific unconventional catalytic inhibitors of human topoisomerase I.

Topoisomerase IB (Top1) is a key eukaryotic nuclear enzyme that regulates the topology of DNA during replication and gene transcription. Anticancer drugs that block Top1 are either well-characterized interfacial poisons or lesser-known catalytic inhibitor compounds. Here we describe a new class of cytotoxic redox-stable cationic Au(3+) macrocycles which, through hierarchical cluster analysis of cytotoxicity data for the lead compound, 3, were identified as either poisons or inhibitors of Top1.

The role of glutamate and its receptors in the proliferation, migration, differentiation and survival of neural progenitor cells.

The mammalian central nervous system derives from multipotent neural progenitor cells (NPCs) of the developing brain. During development the progenitor cells have enormous potential. They proliferate actively and differentiate into all the three main cell types, i.

Enhanced early expression of membrane receptors with the Rous sarcoma virus promoter in baculovirus-infected insect cells.

The effect of the Rous sarcoma virus (RSV) long terminal repeat enhancer/promoter on expression levels of complementary DNAs (cDNAs) encoding seven transmembrane receptors was studied using the baculovirus expression vector system. Expression of the human α(2B)-adrenoceptor (AR) cDNA under the control of the polyhedrin (POL) promoter produced up to 7.6 pmol/mg protein at 28 H post infection (p.

Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3 inflammasome.

Background: Local acidosis has been demonstrated in ischemic tissues and at inflammatory sites.

Results: Acidic extracellular pH triggers NLRP3 inflammasome activation and interleukin-1β secretion in human macrophages.

Conclusion: Acidic pH represents a novel danger signal alerting the innate immunity.

(1R*,2S*)-N,N'-Bis[(E)-1H-pyrrol-2-yl-methyl-idene]cyclo-hexane-1,2-diamine monohydrate.

The title compound, C16H20N4·H2O, was synthesized from cis-1,2-diamino-cyclo-hexane (a racemic mixture of the (1R,2S) and (1S,2R) enanti-omers). The compound crystallized with two mol-ecules (A and B) in the asymmetric unit with a single water solvent mol-ecule per Schiff base mol-ecule. Mol-ecules A and B have similar conformations as illustrated by the least-squares-fit with an r.

An X-ray crystallographic and density functional theory study of (3Z)-4-(5-ethylsulfonyl-2-hydroxyanilino)pent-3-en-2-one and (3Z)-4-(5-tert-butyl-2-hydroxyanilino)pent-3-en-2-one.

The Schiff base enaminones (3Z)-4-(5-ethylsulfonyl-2-hydroxyanilino)pent-3-en-2-one, C13H17NO4S, (I), and (3Z)-4-(5-tert-butyl-2-hydroxyanilino)pent-3-en-2-one, C15H21NO2, (II), were studied by X-ray crystallography and density functional theory (DFT). Although the keto tautomer of these compounds is dominant, the O=C-C=C-N bond lengths are consistent with some electron delocalization and partial enol character. Both (I) and (II) are nonplanar, with the amino-phenol group canted relative to the rest of the molecule; the twist about the N(enamine)-C(aryl) bond leads to dihedral angles of 40.