| 1. |
- Korek, Michal J., et al.
(författare)
-
Traffic-related air pollution exposure and incidence of stroke in four cohorts from Stockholm
- 2015
-
Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Springer Science and Business Media LLC. - 1559-0631 .- 1559-064X. ; 25:5, s. 517-523
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the risk of stroke related to long-term ambient air pollution exposure, in particular the role of various exposure time windows, using four cohorts from Stockholm County, Sweden. In total, 22,587 individuals were recruited from 1992 to 2004 and followed until 2011. Yearly air pollution levels resulting from local road traffic emissions were assessed at participant residences using dispersion models for particulate matter (PM10) and nitrogen oxides (NOX). Cohort-specific hazard ratios were estimated for time-weighted air pollution exposure during different time windows and the incidence of stroke, adjusted for common risk factors, and then meta-analysed. Overall, 868 subjects suffered a non-fatal or fatal stroke during 238,731 person-years of follow-up. An increment of 20 mu g/m(3) in estimated annual mean of road-traffic related NOX exposure at recruitment was associated with a hazard ratio of 1.16 (95% Cl 0.83-1.61), with evidence of heterogeneity between the cohorts. For PM10, an increment of 10 mu g/m(3) corresponded to a hazard ratio of 1.14(95% Cl 0.68-1.90). Time-window analyses did not reveal any clear induction-latency pattern. In conclusion, we found suggestive evidence of an association between long-term exposure to NOX and PM10 from local traffic and stroke at comparatively low levels of air pollution.
|
|
| 2. |
- Aqvist, Johan, et al.
(författare)
-
Bridging the gap between ribosome structure and biochemistry by mechanistic computations
- 2012
-
Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 22:6, s. 815-823
-
Tidskriftsartikel (refereegranskat)abstract
- The wealth of structural and biochemical data now available for protein synthesis on the ribosome presents major new challenges for computational biochemistry. Apart from technical difficulties in modeling ribosome systems, the complexity of the overall translation cycle with a multitude of different kinetic steps presents a formidable problem for computational efforts where we have only seen the beginning. However, a range of methodologies including molecular dynamics simulations, free energy calculations, molecular docking and quantum chemical approaches have already been put to work with promising results. In particular, the combined efforts of structural biology, biochemistry, kinetics and computational modeling can lead towards a quantitative structure-based description of translation.
|
|
| 3. |
- DHaens, Geert, et al.
(författare)
-
Neuroimmune Modulation Through Vagus Nerve Stimulation Reduces Inflammatory Activity in Crohns Disease Patients: A Prospective Open-label Study
- 2023
-
Ingår i: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 17:12, s. 1897-1909
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aims Crohns disease [CD] is a debilitating, inflammatory condition affecting the gastrointestinal tract. There is no cure and sustained clinical and endoscopic remission is achieved by fewer than half of patients with current therapies. The immunoregulatory function of the vagus nerve, the inflammatory reflex, has been established in patients with rheumatoid arthritis and biologic-naive CD. The aim of this study was to explore the safety and efficacy of vagus nerve stimulation in patients with treatment-refractory CD, in a 16-week, open-label, multicentre, clinical trial.Methods A vagus nerve stimulator was implanted in 17 biologic drug-refractory patients with moderately to severely active CD. One patient exited the study pre-treatment, and 16 patients were treated with vagus nerve stimulation [4/16 receiving concomitant biologics] during 16 weeks of induction and 24 months of maintenance treatment. Endpoints included clinical improvement, patient-reported outcomes, objective measures of inflammation [endoscopic/molecular], and safety.Results There was a statistically significant and clinically meaningful decrease in CD Activity Index at Week 16 [mean +/- SD: -86.2 +/- 92.8, p = 0.003], a significant decrease in faecal calprotectin [-2923 +/- 4104, p = 0.015], a decrease in mucosal inflammation in 11/15 patients with paired endoscopies [-2.1 +/- 1.7, p = 0.23], and a decrease in serum tumour necrosis factor and interferon-gamma [46-52%]. Two quality-of-life indices improved in 7/11 patients treated without biologics. There was one study-related severe adverse event: a postoperative infection requiring device explantation.Conclusions Neuroimmune modulation via vagus nerve stimulation was generally safe and well tolerated, with a clinically meaningful reduction in clinical disease activity associated with endoscopic improvement, reduced levels of faecal calprotectin and serum cytokines, and improved quality of life. Graphical Abstract
|
|
| 4. |
- Hagstrom, Emil, et al.
(författare)
-
IMPACT OF BODY WEIGHT AT AGE 20 AND WEIGHT GAIN DURING ADULTHOOD ON MIDLIFE CORONARY ARTERY CALCIUM IN 15,000 MEN AND WOMEN : AN INTERIM ANALYSIS OF THE SWEDISH CARDIOPULMONARY BIOIMAGE STUDY
- 2019
-
Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 73:9, s. 1692-1692
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundElevated body weight in adolescence is strongly associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, or to weight gain with subsequent high adult weight is not known. Using data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), we investigated the association between weight at age 20, weight gain to midlife and coronary artery calcium score (CACS) at midlife.MethodsIn the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on CACS at midlife, self-reported body weight at age 20 and weight at examination in SCAPIS were recorded.ResultsCACS in midlife was significantly higher with increasing weight at age 20 (p<0.001 for both sexes), and then increased with weight gain until midlife at all levels of body weight at age 20 after adjusting for age, height, smoking, alcohol intake, education level, exercise levels and LDL cholesterol. However, the association with weight gain was only significant in men (p = 0.047), not in women (p=0.474). No significant interaction was seen between weight at age 20 and midlife weight with CACS. The effect of weight at age 20 on CACS was significantly more marked in men than in women, as was the effect of weight gain (p<0.001 for both interactions).ConclusionWeight at age 20 and weight gain to midlife were both related to CACS, but much more markedly so in men than in women, indicating a generally larger effect of both early adult weight and further weight gain until midlife on CACS in men, compared to women.
|
|
| 5. |
- Karami, Azadeh, et al.
(författare)
-
Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease
- 2015
-
Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:11, s. 1316-1328
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF). The purpose of this study was to see if EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT, and acetylcholinesterase. Method: Encapsulated cell implants releasing NGF (EC-NGF) were surgically implanted bilaterally in the basal forebrain of six AD patients for 12 months and cholinergic markers in CSF were analyzed. Results: Activities of both enzymes were altered after 12 months. In particular, the activity of soluble ChAT showed high correlation with cognition, CSF tau and amyloid-beta, in vivo cerebral glucose utilization and nicotinic binding sites, and morphometric and volumetric magnetic resonance imaging measures. Discussion: A clear pattern of association is demonstrated showing a proof-of-principle effect on CSF cholinergic markers, suggestive of a beneficial EC-NGF implant therapy.
|
|
| 6. |
- Korek, Michal, et al.
(författare)
-
Can dispersion modeling of air pollution be improved by land-use regression? An example from Stockholm, Sweden
- 2017
-
Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Springer Science and Business Media LLC. - 1559-0631 .- 1559-064X. ; 27:6, s. 575-581
-
Tidskriftsartikel (refereegranskat)abstract
- Both dispersion modeling (DM) and land-use regression modeling (LUR) are often used for assessment of long-term air pollution exposure in epidemiological studies, but seldom in combination. We developed a hybrid DM-LUR model using 93 biweekly observations of NOx at 31 sites in greater Stockholm (Sweden). The DM was based on spatially resolved topographic, physiographic and emission data, and hourly meteorological data from a diagnostic wind model. Other data were from land use, meteorology and routine monitoring of NOx. We built a linear regression model for NOx, using a stepwise forward selection of covariates. The resulting model predicted observed NOx (R-2 = 0.89) better than the DM without covariates (R-2 = 0.68, P-interaction < 0.001) and with minimal apparent bias. The model included (in descending order of importance) DM, traffic intensity on the nearest street, population (number of inhabitants) within 100 m radius, global radiation (direct sunlight plus diffuse or scattered light) and urban contribution to NOx levels (routine urban NOx, less routine rural NOx). Our results indicate that there is a potential for improving estimates of air pollutant concentrations based on DM, by incorporating further spatial characteristics of the immediate surroundings, possibly accounting for imperfections in the emission data.
|
|
| 7. |
- Lind, Goran, et al.
(författare)
-
Therapeutic value of spinal cord stimulation in irritable bowel syndrome : a randomized crossover pilot study
- 2015
-
Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 308:10, s. R887-R894
-
Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is characterized by abdominal pain and changed bowel habits. Spinal cord stimulation (SCS) has been used for treatment of chronic pain syndromes. Animal studies have shown SCS to reduce the reaction to colonic balloon distension, known to be increased in IBS patients. To elucidate the potential for SCS as treatment for IBS, a pilot study was performed. Ten IBS patients (age 26-56 yr) were recruited. A SCS system with a four-polar electrode was implanted at the T5-T8 level. After a 2-wk run-in, a randomized, crossover design SCS during 6 wk was compared with no stimulation, with an ensuing stimulation period for 12 wk; total study period 28 wk. Patients recorded pain level, pain attacks, diarrheas, and global quality of life in a diary. At end of the study patients could choose to retain their SCS system or have it removed. Nine patients completed the whole trial. During stimulation periods the median pain scores were significantly reduced from visual analogue scale (VAS) 7 (4-8) to 3 (2.5-7) and to 4 (2-6) during early and late stimulation periods, respectively (P < 0.03-0.04). Pain attacks were numerically reduced. A few patients reported reduced number of diarrheas. After study termination, six patients chose to retain their SCS system. To conclude, SCS is a minimally invasive treatment option for pain in IBS. With SCS the pain level was reduced though with merely a trend for number of attacks and diarrheas. The efficacy of SCS in IBS pain indicates a possible usefulness in other painful bowel disorders.
|
|
| 8. |
- Lind, Thomas, et al.
(författare)
-
Excessive dietary intake of vitamin A reduces skull bone thickness in mice
- 2017
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- Calvarial thinning and skull bone defects have been reported in infants with hypervitaminosis A. These findings have also been described in humans, mice and zebrafish with loss-of-function mutations in the enzyme CYP26B1 that degrades retinoic acid (RA), the active metabolite of vitamin A, indicating that these effects are indeed caused by too high levels of vitamin A and that evolutionary conserved mechanisms are involved. To explore these mechanisms, we have fed young mice excessive doses of vitamin A for one week and then analyzed the skull bones using micro computed tomography, histomorphometry, histology and immunohistochemistry. In addition, we have examined the effect of RA on gene expression in osteoblasts in vitro. Compared to a standard diet, a high dietary intake of vitamin A resulted in a rapid and significant reduction in calvarial bone density and suture diastasis. The bone formation rate was almost halved. There was also increased staining of tartrate resistant acid phosphatase in osteocytes and an increased perilacunar matrix area, indicating osteocytic osteolysis. Consistent with this, RA induced genes associated with bone degradation in osteoblasts in vitro. Moreover, and in contrast to other known bone resorption stimulators, vitamin A induced osteoclastic bone resorption on the endocranial surfaces.
|
|
| 9. |
- Linderoth, Bengt, et al.
(författare)
-
Bjorn Meyerson 1933-2019 OBITUARY
- 2020
-
Ingår i: Neuromodulation. - : John Wiley & Sons. - 1094-7159 .- 1525-1403. ; 23:1, s. 1-2
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 10. |
- Paul-Visse, Gesine, et al.
(författare)
-
Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson's disease patients
- 2015
-
Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 125:3, s. 1339-1346
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 mu g rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD.
|
|
