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1.
  • Hovey, Daniel, et al. (författare)
  • Antisocial behavior and polymorphisms in the oxytocin receptor gene: findings in two independent samples.
  • 2016
  • Ingår i: Molecular psychiatry. - Stockholm : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • The quantitative genetic contribution to antisocial behavior is well established, but few, if any, genetic variants are established as risk factors. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may modulate interpersonal aggression. We here investigated whether single-nucleotide polymorphisms (SNPs) in the OXT receptor gene (OXTR) are associated with the expression of antisocial behavior. A discovery sample, including both sexes, was drawn from the Child and Adolescent Twin Study in Sweden (CATSS; n=2372), and a sample from the Twin Study of Child and Adolescent Development (TCHAD; n=1232) was used for replication. Eight SNPs in OXTR, selected on previous associations with social and antisocial behavior, were genotyped in the participants of CATSS. Significant polymorphisms were subsequently genotyped in TCHAD for replication. Participants completed self-assessment questionnaires-Life History of Aggression (LHA; available only in CATSS), and Self-Reported Delinquency (SRD; available in both samples)-designed to capture antisocial behavior as continuous traits. In the discovery sample, the rs7632287 AA genotype was associated with higher frequency of antisocial behavior in boys, and this was then replicated in the second sample. In particular, overt aggression (directly targeting another individual) was strongly associated with this genotype in boys (P=6.2 × 10(-7) in the discovery sample). Meta-analysis of the results for antisocial behavior from both samples yielded P=2.5 × 10(-5). Furthermore, an association between rs4564970 and LHA (P=0.00013) survived correction in the discovery sample, but there was no association with the SRD in the replication sample. We conclude that the rs7632287 and rs4564970 polymorphisms in OXTR may independently influence antisocial behavior in adolescent boys. Further replication of our results will be crucial to understanding how aberrant social behavior arises, and would support the OXT receptor as one potential target in the treatment of aggressive antisocial behavior.Molecular Psychiatry advance online publication, 22 September 2015; doi:10.1038/mp.2015.144.
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2.
  • Walladbegi, Java, et al. (författare)
  • Innovative intraoral cooling device better tolerated and equally effective as ice cooling.
  • 2017
  • Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 80:5, s. 965-972
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Most of the patients who receive myeloablative therapy prior to stem cell transplantation develop oral mucositis (OM). This adverse reaction manifests as oral mucosal erythema and ulcerations and may require high doses of morphine for pain alleviation. OM may also interfere with food intake and result in weight loss, a need for parenteral nutrition, and impaired quality of life. To date, there have been very few studies of evidence-based interventions for the prevention of OM. Cryotherapy, using ice chips, has been shown to reduce in an efficient manner the severity and extent of OM, although clinical applications are still limited due to several shortcomings, such as adverse tooth sensations, problems with infectious organisms in the water, nausea, and uneven cooling of the oral mucosa. The present proof-of-concept study was conducted to compare the tolerability, temperature reduction, and cooling distribution profiles of an intra-oral cooling device and ice chips in healthy volunteers who did not receive myeloablative treatment, and therefore, did not experience the symptoms of OM.METHODS: Twenty healthy volunteers used the cooling device and ice chips for a maximum of 60 min each, using a cross-over design. The baseline and final temperatures were measured at eight intra-oral locations using an infra-red thermographic camera. The thermographic images were analysed using two digital software packages. A questionnaire was used to assess the tolerability levels of the two interventions.RESULTS: The intra-oral cooling device was significantly better tolerated than the ice-chips (p = 0.0118). The two interventions were equally effective regarding temperature reduction and cooling distribution.CONCLUSIONS: The intra-oral cooling device shows superior tolerability in healthy volunteers. Furthermore, this study shows that temperature reduction and cooling distribution are achieved equally well using either method.
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3.
  • Dåderman, Anna Maria, 1953-, et al. (författare)
  • Flunitrazepam (Rohypnol) abuse in combination with alcohol causes premeditated, grievous violence in male juvenile offenders
  • 1999
  • Ingår i: The journal of the American Academy of Psychiatry and the Law. - Bloomfield, CT, USA. - 1093-6793 .- 1943-3662. ; 27:1, s. 83-99
  • Tidskriftsartikel (refereegranskat)abstract
    • This study focuses on 19 juvenile offenders who were frequently intoxicated by flunitrazepam (FZ), almost exclusively under the brand name Rohypnol. Street names for Rohypnol tablets are Rophies, Ropies, Roofies, Ropes, Roches, Rochas, Rochas Dos, Rophs, Ropers, Ribs, R-25, Roach-2s, Trip and Fall, Remember All, Mind Erasers, Forget Pills, and the Date Rape Drug. An overdose of FZ gives an increased feeling of power and self-esteem, reduces fear and insecurity, and provides the belief that everything is possible. FZ is also associated with loss of episodic memory and with impulsive violence, particularly when combined with alcohol. The subjects were taken from a subpopulation of 47 male juvenile offenders from Swedish national correctional institutions. Background information for subjects was obtained by in-depth interviewing and personality inventories including the Zuckerman Sensation-Seeking Scales, the Eysenck Personality Questionnaire, and the Karolinska Scales of Personality. Data concerning previous criminal offenses was obtained from the Swedish National Police Board. Almost all of the FZ abusers had been previously sentenced for serious violent offenses. Our data suggest that FZ abused by psychiatrically vulnerable subjects (i.e., with high scores on boredom susceptibility and verbal aggression) poses a serious hazard both to the abusers as well as the community. Our results support the finding that FZ should be classified as a Schedule I drug (i.e., a drug similar to heavy narcotics).
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4.
  • Jenkins, Samantha, 1967-, et al. (författare)
  • Spanning QTAIM topology phase diagrams of water isomers W4, W5 and W6
  • 2011
  • Ingår i: Physical Chemistry, Chemical Physics - PCCP. - 1463-9076 .- 1463-9084. ; 13:24, s. 11644-11656
  • Tidskriftsartikel (refereegranskat)abstract
    • Structural and chemical properties of the small water clusters W-4, W-5 and W-6 are investigated with the theory of atoms and molecules (QTAIM). For the W-4, W-5 and W-6 clusters, nine, fourteen and twenty-seven conformers, respectively, have been analyzed. For the W-4, W-5 and W-6 clusters one, two and three of these structures, respectively, have not been reported before. We then proceed to extend the W-4, W-5 and W-6 water cluster topology space using QTAIM; the Poincare-Hopf topological sum rules are applied to create rules to identify the spanning set of conformer topologies, this includes finding three, ten and eight new distinct topologies that satisfy the Poincare-Hopf relation for W-4, W-5 and W-6 respectively. The topological stability of degenerate solutions to the Poincare-Hopf relation is compared by evaluating the proximity to rupturing of critical points of the gradient vector field of the charge density. We introduce a QTAIM topology space to replace the inconsistent use of Euclidean geometry to determine whether a cluster is 1-, 2- or 3-D. We show from the topology of the charge density that the conformers of the W-4, W-5 clusters are more energetically stable in less compact, planar forms, conversely the conformers of W-6 are more energetically stable with compact 3-D topologies. Quantifying the degree of covalent character in the hydrogen bonding for the W-4, W-5 and W-6 clusters independently verifies this finding. Differences in simple rules for the number of hydrogen bonds obeying the Bernal-Fowler ice rules between W-4, W-5 and W-6 reflect the transition from 2-D to 3-D structures being more energetically stable. In addition, we identify a new class of O-O bonding interactions that are up to 48% longer than the inter-nuclear separation and appear to be failed hydrogen bonds.
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5.
  • Lind, Simon, et al. (författare)
  • Functional selective FPR1 signaling in favor of an activation of the neutrophil superoxide generating NOX2 complex
  • 2020
  • Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 109:6, s. 1105-1120
  • Tidskriftsartikel (refereegranskat)abstract
    • The formyl peptide receptors FPR1 and FPR2 are abundantly expressed by neutrophils, in which they regulate proinflammatory tissue recruitment of inflammatory cells, the production of reactive oxygen species (ROS), and resolution of inflammatory reactions. The unique dual functionality of the FPRs makes them attractive targets to develop FPR-based therapeutics as novel anti-inflammatory treatments. The small compound RE-04-001 has earlier been identified as an inducer of ROS in differentiated HL60 cells but the precise target and the mechanism of action of the compound was has until now not been elucidated. In this study, we reveal that RE-04-001 specifically targets and activates FPR1, and the concentrations needed to activate the neutrophil NADPH-oxidase was very low (EC50 ∼1 nM). RE-04-001 was also found to be a neutrophil chemoattractant, but when compared to the prototype FPR1 agonist N-formyl-Met-Leu-Phe (fMLF), the concentrations required were comparably high, suggesting that signaling downstream of the RE-04-001-activated-FPR1 is functionally selective. In addition, the RE-04-001-induced response was strongly biased toward the PLC-PIP2 -Ca2+ pathway and ERK1/2 activation but away from β-arrestin recruitment. Compared to the peptide agonist fMLF, RE-04-001 is more resistant to inactivation by the MPO-H2 O2 -halide system. In summary, this study describes RE-04-001 as a novel small molecule agonist specific for FPR1, which displays a biased signaling profile that leads to a functional selective activating of human neutrophils. RE-04-001 is, therefore, a useful tool, not only for further mechanistic studies of the regulatory role of FPR1 in inflammation in vitro and in vivo, but also for developing FPR1-specific drug therapeutics.
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6.
  • Uvnäs-Moberg, Kerstin, et al. (författare)
  • Maternal plasma levels of oxytocin during physiological childbirth : a systematic review with implications for uterine contractions and central actions of oxytocin
  • 2019
  • Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Oxytocin is a key hormone in childbirth, and synthetic oxytocin is widely administered to induce or speed labour. Due to lack of synthetized knowledge, we conducted a systematic review of maternal plasma levels of oxytocin during physiological childbirth, and in response to infusions of synthetic oxytocin, if reported in the included studies.METHODS: An a priori protocol was designed and a systematic search was conducted in PubMed, CINAHL, and PsycINFO in October 2015. Search hits were screened on title and abstract after duplicates were removed (n = 4039), 69 articles were examined in full-text and 20 papers met inclusion criteria. As the articles differed in design and methodology used for analysis of oxytocin levels, a narrative synthesis was created and the material was categorised according to effects.RESULTS: Basal levels of oxytocin increased 3-4-fold during pregnancy. Pulses of oxytocin occurred with increasing frequency, duration, and amplitude, from late pregnancy through labour, reaching a maximum of 3 pulses/10 min towards the end of labour. There was a maximal 3- to 4-fold rise in oxytocin at birth. Oxytocin pulses also occurred in the third stage of labour associated with placental expulsion. Oxytocin peaks during labour did not correlate in time with individual uterine contractions, suggesting additional mechanisms in the control of contractions. Oxytocin levels were also raised in the cerebrospinal fluid during labour, indicating that oxytocin is released into the brain, as well as into the circulation. Oxytocin released into the brain induces beneficial adaptive effects during birth and postpartum. Oxytocin levels following infusion of synthetic oxytocin up to 10 mU/min were similar to oxytocin levels in physiological labour. Oxytocin levels doubled in response to doubling of the rate of infusion of synthetic oxytocin.CONCLUSIONS: Plasma oxytocin levels increase gradually during pregnancy, and during the first and second stages of labour, with increasing size and frequency of pulses of oxytocin. A large pulse of oxytocin occurs with birth. Oxytocin in the circulation stimulates uterine contractions and oxytocin released within the brain influences maternal physiology and behaviour during birth. Oxytocin given as an infusion does not cross into the mother's brain because of the blood brain barrier and does not influence brain function in the same way as oxytocin during normal labour does.
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7.
  • Bjalkefur, K., et al. (författare)
  • Self-rated health over the first five years after stroke
  • 2020
  • Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Self-rated health (SRH) focuses on the patient's own perception, and represents an important patient-reported outcome. The aim was to investigate SRH one to 5 years after stroke, follow the development over time and search for factors associated with SRH. Methods Consecutive stroke patients admitted to Stroke Units at the Skaraborg Hospital, Sweden were included 2007-2009 (n = 2190). Patient-reported outcomes were collected annually over 5 years using a postal questionnaire. SRH was assessed by the question about general health from SF-36. Factors associated with SRH were investigated by multiple logistic regression analysis. Results Response-rate was > 90% at all time points. Overall, 40.2, 41.9, 40.7, 45.0 and 46.3% of the patients reported good SRH, 1 to 5 years after stroke. Performance in activities of daily living (ADL) was strongly associated with good SRH; 49.8 and 14.7% after 1 year in independent and dependent survivors respectively, p < 0.001. In independent survivors 1 year after stroke, good SRH was positively associated with female sex (OR = 2.0; p = < 0,001), physical activity (OR = 2.14; p = < 0,001), car driving (OR = 2.25; p = < 0,001), and negatively associated with age (OR = 0.99; p = < 0,001), pain (OR = 0.49; p = < 0,001), depression (OR = 0.30; p = < 0,001), and self-perceived unmet care needs (OR = 0.39; p = < 0,001). In dependent survivors, depression (OR = 0.23; p = < 0,001) and age (OR = 0.96; p = < 0,05), were negatively associated with good SRH 1 year after stroke. Similar patterns were observed throughout the follow-up. Conclusion The proportion stroke survivors reporting their health as good is slightly increasing over time. After stroke, SRH is associated with pain, depression, ability to perform activities and self-perceived unmet care needs, indicating that efforts to support stroke survivors in the chronic phase after stroke should concentrate on targeting these factors.
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8.
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9.
  • Dåderman, Anna Maria, 1953-, et al. (författare)
  • Different Personality Patterns in Non-Socialized (Juvenile Delinquents) and Socialized (Air Force Pilot Recruits) Sensation Seekers
  • 2001
  • Ingår i: European Journal of Personality. - : SAGE Publications. - 0890-2070 .- 1099-0984. ; 15, s. 239-252
  • Tidskriftsartikel (refereegranskat)abstract
    • Young delinquents are known to be sensation seekers. Not all sensation seekers become delinquents: many engage in socially accepted activities, such as mountaineering or parachute jumping. The present study compares 47 juvenile delinquents (mean age 17 years) with 18 Swedish air force pilot recruits (mean age 23 years) and 19 conscripts (mean age 18 years) as a control group. Sensation-seeking behaviour, impulsiveness, and psychiatric/psychological vulnerability were measured by the Zuckerman Sensation-Seeking Scales (SSS), the Karolinska Scales of Personality, and the Eysenck Personality Questionnaire. Two separate multivariate analyses of variance were performed, followed up by stepdown analyses to identify those personality scale scores that contributed uniquely. In order to clarify the relationships, the pooled within-group correlations among scales were computed. Juvenile delinquents and pilot recruits were both high in sensation seeking, but on different subscales. Delinquents were high in impulsiveness, somatic anxiety, and extraversion–sociability, and low in socialization, suggesting psychiatric/psychological vulnerability. The findings may have implications for the treatment of juvenile delinquents. Copyright © 2001 John Wiley & Sons, Ltd
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10.
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