| 1. |
|
|
| 2. |
- Boraxbekk, Carl-Johan, 1980-, et al.
(author)
-
Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task
- 2015
-
In: Obesity Facts. - : S. Karger AG. - 1662-4025 .- 1662-4033. ; 8:4, s. 261-272
-
Journal article (peer-reviewed)abstract
- Objective: It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods: 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results: Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions: Diet induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. (C) 2015 S. Karger GmbH, Freiburg
|
|
| 3. |
- Brekkan, Ari, et al.
(author)
-
Sensitivity of Pegfilgrastim Pharmacokinetic and Pharmacodynamic Parameters to Product Differences in Similarity Studies
- 2019
-
In: AAPS Journal. - : Springer. - 1550-7416. ; 21:85
-
Journal article (peer-reviewed)abstract
- In this work, a previously developed pegfilgrastim (PG) population pharmacokinetic-pharmacodynamic (PKPD) model was used to evaluate potential factors of importance in the assessment of PG PK and PD similarity. Absolute neutrophil count (ANC) was the modelled PD variable. A two-way cross-over study was simulated where a reference PG and a potentially biosimilar test product were administered to healthy volunteers. Differences in delivered dose amounts or potency between the products were simulated. A different baseline absolute neutrophil count (ANC) was also considered. Additionally, the power to conclude PK or PD similarity based on areas under the PG concentration-time curve (AUC) and ANC-time curve (AUEC) were calculated. Delivered dose differences between the products led to a greater than dose proportional differences in AUC but not in AUEC, respectively. A 10% dose difference from a 6 mg dose resulted in 51% and 7% differences in AUC and AUEC, respectively. These differences were more pronounced with low baseline ANC. Potency differences up to 50% were not associated with large differences in either AUCs or AUECs. The power to conclude PK similarity was affected by the simulated dose difference; with a 4% dose difference from 6 mg the power was approximately 29% with 250 subjects. The power to conclude PD similarity was high for all delivered dose differences and sample sizes.
|
|
| 4. |
- Jäderling, Fredrik, et al.
(author)
-
Preoperative staging using magnetic resonance imaging and risk of positive surgical margins after prostate-cancer surgery
- 2019
-
In: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 22:3, s. 391-398
-
Journal article (peer-reviewed)abstract
- Background: It is unclear whether preoperative staging using Magnetic Resonance Imaging (MRI) reduces the risk of positive margins in prostate cancer. We aimed to assess the effect on surgical margins and degree of nerve sparing of a pelvic MRI presented at a preoperative MRI conference. Methods: Single institution, observational cohort study including 1037 men that underwent robot assisted radical prostatectomy between October 2013 and June 2015. Of these, 557 underwent a preoperative MRI combined with a preoperative MRI conference and 410 did not. With whole-mount prostate specimen histopathology as gold standard we assessed the ability of MRI in finding the index tumor and the sensitivity and specificity for extra prostatic extension. We calculated relative risks for positive surgical margins and non-nerve sparing procedure, adjusting for preoperative risk factors using stabilized inverse-probability weighting. Results: MRI detected the index tumor in 80% of the cases. Non-organ confined disease (pT3) at histology was present in the MRI and the non-MRI group in 42% and 24%, respectively. Rate of positive surgical margins comparing the MRI and non-MRI groups was 26.7% and 33.7%, respectively, relative risk 0.79 [95% CI 0.65-0.96], weighted relative risk (wRR) 0.69 [95% CI 0.55-0.86]. The wRR of extensive positive surgical margins was 0.45 [95% CI 0.31-0.67]. Undergoing MRI was also associated with an increased risk of being operated with a non-nerve sparing technique (wRR, 1.84 [95% CI 1.11-3.03]). Conclusions: Our study suggests that preoperative prostate MRI in combination with a preoperative MRI conference affects the degree of nerve-sparing surgery and reduces positive surgical margins.
|
|
| 5. |
- Mc Ewen, Birgitta, et al.
(author)
-
Female and male teachers’ pro-environmental behaviour, conceptions and attitudes towards nature and the environment do not differ : Ecofeminism put to the test
- 2015
-
In: Asia-Pacific Forum on Science Learning and Teaching. - Hong Kong : Hong Kong Institute of education. - 1609-4913. ; 16:1, s. 1-25
-
Journal article (peer-reviewed)abstract
- Abstract Teachers' pro-environmental behaviour, conceptions and attitudes towards nature and the environment were investigated using 47 questions from the BIOHEAD-Citizen questionnaire. The sample included 1,109 pre-and in-service teachers from Sweden and France. Analyses showed only few significant differences between female and male teachers. Forty-one questions were further analysed in terms of ecofeminism. Ecofeminism claims that women and men's conceptions and attitudes towards nature and the ...
|
|
| 6. |
- Mc Ewen, Birgitta, et al.
(author)
-
Female and male teachers’ pro-environmental behaviour, conceptions and attitudes towards nature and the environment do not differ : Ecofeminism put to the test
- 2015
-
In: Asia-Pacific Forum on Science Learning and Teaching. - Hong Kong : Hong Kong Institute of education. - 1609-4913. ; 16:1, s. 1-25
-
Journal article (peer-reviewed)abstract
- Teachers’ pro-environmental behaviour, conceptions and attitudes towards nature and the environment were investigated using 47 questions from the BIOHEAD-Citizen questionnaire. The sample included 1,109 pre- and in-service teachers from Sweden and France. Analyses showed only few significant differences between female and male teachers. Forty-one questions were further analysed in terms of ecofeminism. Ecofeminism claims that women and men’s conceptions and attitudes towards nature and the environment differ, in the sense that women show higher awareness of environmental issues than men. Our study finds quite poor support for this claim and therefore challenges ecofeminism. This may have implications for environmental education and the perspectives of sustainable development at schools, as our results indicate that there is no reason to fear that male teachers are less engaged with environmental education than female teachers.
|
|
| 7. |
- Nazir, Madiha, et al.
(author)
-
Targeting tumor cells based on Phosphodiesterase 3A expression
- 2017
-
In: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 361:2, s. 308-315
-
Journal article (peer-reviewed)abstract
- We and others have previously reported a correlation between high phosphodiesterase 3 A (PDE3A) expression and selective sensitivity to phosphodiesterase (PDE) inhibitors. This indicates that PDE3A could serve both as a drug target and a biomarker of sensitivity to PDE3 inhibition. In this report, we explored publicly available mRNA gene expression data to identify cell lines with different PDE3A expression. Cell lines with high PDE3A expression showed marked in vitro sensitivity to PDE inhibitors zardaverine and quazinone, when compared with those having low PDE3A expression. Immunofluorescence and immunohistochemical stainings were in agreement with PDE3A mRNA expression, providing suitable alternatives for biomarker analysis of clinical tissue specimens. Moreover, we here demonstrate that tumor cells from patients with ovarian carcinoma show great variability in PDE3A protein expression and that level of PDE3A expression is correlated with sensitivity to PDE inhibition. Finally, we demonstrate that PDE3A is highly expressed in subsets of patient tumor cell samples from different solid cancer diagnoses and expressed at exceptional levels in gastrointestinal stromal tumor (GIST) specimens. Importantly, vulnerability to PDE3 inhibitors has recently been associated with co-expression of PDE3A and Schlafen family member 12 (SLFN12). We here demonstrate that high expression of PDE3A in clinical specimens, at least on the mRNA level, seems to be frequently associated with high SLFIV12 expression. In conclusion, PDE3A seems to be both a promising biomarker and drug target for individualized drug treatment of various cancers.
|
|
| 8. |
- Niebecker, Ronald, et al.
(author)
-
Population pharmacokinetics of edoxaban in patients with symptomatic deep-vein thrombosis and/or pulmonary embolism-the Hokusai-VTE phase 3 study
- 2015
-
In: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 80:6, s. 1374-1387
-
Journal article (peer-reviewed)abstract
- AIMS: This study characterized the population pharmacokinetics of edoxaban in patients with symptomatic deep-vein thrombosis and/or pulmonary embolism in the Hokusai-VTE phase 3 study. The impact of the protocol-specified 50% dose reductions applied to patients with body weight ≤ 60 kg, creatinine clearance (CLcr ) of 30 to 50 ml min(-1) or concomitant P-glycoprotein inhibitor on edoxaban exposure was assessed using simulations.METHODS: The sparse data from Hokusai-VTE, 9531 concentrations collected from 3707 patients, were pooled with data from 13 phase 1 studies. In the analysis, the covariate relationships used for dose reductions were estimated and differences between healthy subjects and patients as well as additional covariate effects of age, race and gender were explored based on statistical and clinical significance.RESULTS: A linear two-compartment model with first order absorption preceded by a lag time best described the data. Allometrically scaled body weight was included on disposition parameters. Apparent clearance was parameterized as non-renal and renal. The latter increased non-linearly with increasing CLcr . Compared with healthy volunteers, inter-compartmental clearance and the CLcr covariate effect were different in patients (+64.6% and +274%). Asian patients had a 22.6% increased apparent central volume of distribution. The effect of co-administration of P-glycoprotein inhibitors seen in phase 1 could not be confirmed in the phase 3 data. Model-based simulations revealed lower exposure in dose-reduced compared with non-dose-reduced patients.CONCLUSIONS: The adopted dose-reduction strategy resulted in reduced exposure compared with non-dose-reduced, thereby overcompensating for covariate effects. The clinical impact of these differences on safety and efficacy remains to be evaluated.
|
|
| 9. |
- Nyberg, Christoffer, et al.
(author)
-
The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage
- 2016
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
-
Journal article (peer-reviewed)abstract
- IntroductionIn patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH), a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems.MethodsA porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, catecholamines and chromogranin-A were performed.ResultsPlasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased.ConclusionsThe endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult.
|
|
| 10. |
- Nyberg, Joakim, 1978-, et al.
(author)
-
Edoxaban Exposure-Response Analysis and Clinical Utility Index Assessment in Patients With Symptomatic Deep-Vein Thrombosis or Pulmonary Embolism
- 2016
-
In: CPT. - : Wiley. - 2163-8306. ; 5:4, s. 222-232
-
Journal article (peer-reviewed)abstract
- Edoxaban exposure-response relationships from the phase III study evaluating edoxaban for prevention and treatment of venous thromboembolism (VTE) in patients with acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) were assessed by parametric time-to-event analysis. Statistical significant exposure-response relationships were recurrent VTE with hazard ratio (HR) based on average edoxaban concentration at steady state (C-av) (HRCav) 50.98 (i.e., change in the HR with every 1 ng/mL increase of C-av); the composite of recurrent DVT and nonfatal PE with HRC(av)50.99; and the composite of recurrent DVT, nonfatal PE, and all-cause mortality HRC(av)50.98, and all death using maximal edoxaban concentration (C-max) with HR (C-max) 50.99. No statistical significant exposure-response relationships were found for clinically relevant bleeding or major adverse cardiovascular event. Results support the recommendation of once-daily edoxaban 60 mg, and a reduced 30 mg dose in patients with moderate renal impairment, body weight <= 60 kg, or use of P-glycoprotein inhibitors verapamil or quinidine.
|
|
