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Sökning: WFRF:(Alonso P) > Örebro universitet

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1.
  • Venero, J. L., et al. (författare)
  • ARG1 expression in basal forebrain microglia modulates hippocampal innervation and cognition during postnatal development
  • 2023
  • Ingår i: Glia. - : John Wiley & Sons. - 0894-1491 .- 1098-1136. ; 71:Suppl. 1, s. E512-E512
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Diversity within microglia, the resident brain immune cells, is reported. Whether microglial subsets constitute different subtypes with intrinsic properties and unique functions has not been fully elucidated. Here, we describe a microglial subtype characterized by the expression of the enzyme Arginase-1, i.e.Arg1+microglia, which is found predominantly in the cholinergic neuron-rich forebrain region during early postnatal development. Arg1+microgliacontain cellular inclusions and exhibit a distinct molecular signature including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3and Mgl2. Arg1-knockout in microglia results in a deficient cholinergic innervation along with impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, impaired long-term potentiation and cognitive behavioural deficiencies in female mice. Our results expand on microglia diversity and provide insights into distinctive spatiotemporal functions exerted by microglial subtypes.
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  • Biström, M., et al. (författare)
  • Leptin levels are associated with multiple sclerosis risk
  • 2019
  • Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 904-904
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: One environmental factor that in the last decade repeatedly has been linked to increased risk of developing multiple sclerosis (MS) is overweight, including obesity, early in life. The incidence of both MS and overweight are increasing, making elucidation of this connection important. The adipokine leptin is strongly correlated to both body mass index and total fat mass and the peptide hormone insulin is associated with obesity and type 2 diabetes, making leptin and insulin suitable biomarkers to investigate the connection between overweight and MS.Objectives: To determine if leptin or insulin are risk factors for developing relapsing MS.Aims: To further the understanding of how overweight influence MS risk.Methods: In this case-control study, we compared concentrations of leptin and insulin in 649 individuals that later developed relapsing-remitting MS with 649 matched controls. Cases were matched for biobank, sex, date of sampling and age with decreasing priority. Only prospectively collected samples from individuals below the age of 40 were included in the study. Conditional logistic regression was performed on log10 transformed and z-scored values for the entire group, separately for men and women and divided into age groups.Results: A 1-unit leptin z-score increase was associated with increased risk of MS in individuals below 20 years of age (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1–1.9) and for all men (OR 1.4, 95% CI 1.0–2.0). In contrast, for women aged 30-39 years there was a lower risk of MS with increased leptin levels (OR 0.74, 95% CI 0.54–1.0) when adjusting for insulin levels. No statistically significant association was found between insulin levels and MS risk.Conclusions: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals. The age dependent relationship between leptin and MS risk in women - for whom leptin levels are several-fold higher than in men - suggests a possible role for leptin as being the link between MS risk and being overweight early in life.
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  • Fink, K., et al. (författare)
  • CLADCOMS - CLADribine tablets long-term Control Of MS - a post-marketing investigator driven study
  • 2022
  • Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:Suppl. 3, s. 847-848
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Cladribine  is  a  deoxyadenosine  analogue  prodrug  that selectively  induces  immune  reconstitution  by  targeting  B-  and  T-lymphocytes. Cladribine  tablets  (CladT)  are  administered  in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). Post-marketing surveillance is important for evaluation  of  long-term  safety  and  effectiveness  in  a  real-world setting. CLADCOMS (CLADribine tablets long-term Control Of MS) is a post-marketing investigator driven study. Here we report one year follow-up data on the first 100 patients included in the study in April 2021.Objective: 1) To  investigate for how long a full dose treatment with Cladribine 10 mg tablets (3.5 mg/kg over two years) offers freedom of disease activity in relapsing MS patients.2) To collect complete data on safety and effectiveness with the help of the Swedish Neuroregistry to enable future assessment on effectiveness and safety in comparison with other in Sweden commonly used disease modifying treatments.Methods: CLADCOMS  includes  patients  with  relapsing  MS  from  the  eight academic  clinics  starting  Cladribine  treatment  after  23rd  of  March  2018. Data  is  collected  in  the  Swedish  Neuroregistry  using  highly  structured  yearly follow-up  routines.   Descriptive   data   on   relapses,   MRI   activity,   Patient   Reported   Outcome   Measures   and   Serious   Adverse   events   (SAEs)  from the  first  100  patient  included  in  the  study  are  obtained from the registry.Results: Up  to  April  2022  1XX  patients  were  included  in  the  study. In April 2021 the first 100 patient entered the study. 40% of patients included were treatment naïve, 29% switched from natalizumab and 13% from rituximab. By April 2022, 5 patients experienced a relapse during the treatment initiation and showed MRT activity with contrast enhancing (CEL)lesions more than six months after initiation of treatment, of which 2 patients showed CEL more than six months after the second treatment course year two. 20% of the patients showed new lesions on the first MRI performed up to 18 months after treatment initiation. Two patients reported SEAs. Analysis of CD19   and   CD27-   B-cells   counts   over   time   will   be   performed.Conclusions: Cladribine treatment demonstrates clinical stability in patients treated ⩾ 12 months. However, continued follow-up is needed to assess the effectiveness and safety of treatment with Cladribine over a longer time to investigate time to disease reactivation after the second treatment course year two has been administered.
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6.
  • Jons, D., et al. (författare)
  • Increase in Epstein Barr virus serologies precedes neuroaxonal damage in pre-symptomatic multiple sclerosis
  • 2022
  • Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:Suppl. 3, s. 86-87
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Epstein-Barr virus (EBV) infection may be a pre-condition  for  the development  of  multiple  sclerosis  (MS).  EBV  antibodies, predominantly anti-EBNA1, develop in the presymp-tomatic phase of virtually all MS patients. Using material from a serum repository, studies in advance of MS onset indicated that EBV  seropositivity  preceded  the  first  expression  of  incipient  axonal lesions, serum Neurofilament Light (sNFL) .Objectives: To  determine  the  onset  and  individual  order  of  appearance  of EBV  seroreactivity  and  the  serum  neuroaxonal  injury marker neurofilament light (sNfL) in a wide age spectrum of presymptomatic MS patients.Aims: To  characterize  the  presymptomatic  appearance  of  anti-bodies against an intranuclear (EBNA1) and a surface EBV anti-gen (gp350) and sNfL.Methods:  A nested  case-control  study  in  669  pre-symptomati-cally acquired blood samples from persons who later received an MS diagnosis, and from 1:1 matched control persons. Serum lev-els of EBNA1, VCA and gp350 IgG antibodies and sNFL (n=519) were   measured   in   individual   presymptomatic   samples   and   expressed  as delta  scores  with  matched  controls  in  relation  to  time until MS onset.Results: Serum levels expressed as delta scores for anti EBV and NfL IgG showed an incipient increase for anti EBNA1 and gp350 from  15-20  years  before  MS debut.  Significant  (p=0.001  and  p=0.002) from 10-15 years, with consistent delta-scores succes-sively closer to MS onset. These findings contrasted to the level of sNfL which increasingly diverged from matched controls from 5-10 years before the onset of MS. None of the individual sam-ples  negative  for  both EBNA1 and  VCA  IgG  antibodies  in  the  pre-MS group (n = 36) showed any elevation of the sNfL level.Conclusions: In  a  pre-MS  material,  the  seroreactivity  against  EBNA1  was followed  by  VCA  and  gp350,  before  increased  sNFL appeared, indicating incipient axonal injury. Together with its biological characteristics this temporal order confirms the role of EBV as a trigger of MS.
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  • Lopez-Alonso, Ana, et al. (författare)
  • Individual Platelet Adhesion Assay: Measuring Platelet Function and Antiplatelet Therapies in Whole Blood via Digital Quantification of Cell Adhesion
  • 2013
  • Ingår i: Analytical Chemistry. - : American Chemical Society. - 0003-2700 .- 1520-6882. ; 85:13, s. 6497-6504
  • Tidskriftsartikel (refereegranskat)abstract
    • Widespread monitoring of platelet function and the effect of antiplatelet drugs will improve outcomes in cardiovascular patients, but platelet function testing is not routine in clinical practice. We report a rapid, accurate methodology to quantify platelet-protein interactions: a microarray of contact-printed 6-mu m fibrinogen dots on a transparent substrate binds platelets from whole blood, one platelet per dot. The fractional occupancy of an array of fibrinogen dots after a predefined incubation time quantitatively assays platelet adhesion to the protein matrix. We demonstrate this technique by measurement of platelet adhesion to fibrinogen as a means to quantify the effect of the P2Y(12) and alpha IIb beta 3 receptor inhibitors cangrelor and abciximab, respectively, both in vitro-by incubating the drug with a freshly drawn blood sample-and in blood from patients treated with antiplatelet agents. The effects of single- and dual-antiplatelet therapy are also assessed. Results from this platelet-binding assay are well correlated with standard techniques including flow cytometry and light transmission aggregometry. This assay technology, readily integrated with microfluidic platforms, is generally applicable to the assay of cell-protein interactions and promises more effective, rapid assay of drug effects in cardiovascular disease patients.
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  • Maastrup, Ragnhild, et al. (författare)
  • Compliance with the Baby-friendly Hospital Initiative for Neonatal Wards (Neo-BFHI) : A cross-sectional study in 36 countries
  • 2019
  • Ingår i: Maternal and Child Nutrition. - : Blackwell Science Ltd.. - 1740-8695 .- 1740-8709. ; 15:2
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2012, the Baby-friendly Hospital Initiative for Neonatal Wards (Neo-BFHI) began providing recommendations to improve breastfeeding support for preterm and ill infants. This cross-sectional survey aimed to measure compliance on a global level with the Neo-BFHI’s expanded Ten steps to Successful Breastfeeding and three Guiding Principles in neonatal wards. In 2017 the Neo-BFHI Self-Assessment questionnaire was used in 15 languages to collect data from neonatal wards of all levels of care. Answers were summarized into compliance scores ranging from 0 to 100 at the ward, country and international levels. A total of 917 neonatal wards from 36 low, middle and high-income countries from all continents participated. The median international overall score was 77, and median country overall scores ranged from 52 to 91. Guiding Principle 1 (respect for mothers), Step 5 (breastfeeding initiation and support), and Step 6 (human milk use) had the highest scores, 100, 88, and 88, respectively. Steps 3 (antenatal information) and 7 (rooming-in) had the lowest scores, 63 and 67, respectively. High-income countries had significantly higher scores for Guiding principle 2 (family-centered care), Step 4 (skin-to-skin contact) and Step 5. Neonatal wards in hospitals ever-designated Baby-friendly had significantly higher scores than those never designated. Sixty percent of managers stated they would like to obtain Neo-BFHI designation. Currently, Neo-BFHI recommendations are partly implemented in many countries. The high number of participating wards indicates international readiness to expand Baby-friendly standards to neonatal settings. Hospitals and governments should increase their efforts to better support breastfeeding in neonatal wards.
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10.
  • Wittchen, H U, et al. (författare)
  • The size and burden of mental disorders and other disorders of the brain in Europe 2010.
  • 2011
  • Ingår i: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. - : Elsevier BV. - 1873-7862 .- 0924-977X. ; 21:9, s. 655-79
  • Tidskriftsartikel (refereegranskat)abstract
    • To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range of disorders than previously covered are needed for basic, clinical and public health research and policy decisions and to inform about the estimated number of persons affected in the EU.
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