| 1. |
- Bach, Anders, et al.
(författare)
-
A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage
- 2012
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:9, s. 3317-3322
-
Tidskriftsartikel (refereegranskat)abstract
- Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lacking. Here we report the design and synthesis of a novel dimeric inhibitor, Tat-NPEG4(IETDV)(2) (Tat-N-dimer), which binds the tandem PDZ1-2 domain of PSD-95 with an unprecedented high affinity of 4.6 nM, and displays extensive protease-resistance as evaluated in vitro by stability-measurements in human blood plasma. X-ray crystallography, NMR, and small-angle X-ray scattering (SAXS) deduced a true bivalent interaction between dimeric inhibitor and PDZ1-2, and also provided a dynamic model of the conformational changes of PDZ1-2 induced by the dimeric inhibitor. A single intravenous injection of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke.
|
|
| 2. |
- Bjorkenstam, Charlotte, et al.
(författare)
-
An Association between Initiation of Selective Serotonin Reuptake Inhibitors and Suicide - A Nationwide Register-Based Case-Crossover Study
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9, s. e73973-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment with selective serotonin reuptake inhibitors (SSRI) is one of the most common treatments for depression. It is however not clear whether or not there is an increased short-term suicide risk during initiation with SSRI. Methods: A register-based nationwide case-crossover study including 5,866 suicides, 1,698 women and 4,168 men, from the Death Register 2007-2010 in Sweden. SSRI initiation was defined as a dispensed prescription of SSRI within 28 days prior to the date of suicide with no previous dispensed prescription of SSRI within 4 months prior that prescription. The control period took place one year earlier. Odds ratio (OR) was estimated using conditional logistic regression. Result: During the 28 day period prior to suicide 48 women and 138 men were exposed to SSRI initiation (while not being exposed in the control period) and 22 women and 43 men were exposed in the control period (while not being exposed in the case period). The OR for suicide after initiation with SSRI was 2.7 (95% CI: 1.6-44) for women, and 4.3 (95% CI: 3.0-6.1) for men. The highest OR was found 8-11 days after initiation with SSRI 9.7 (95% CI: 3.0-31.7) for women and men combined. Conclusion: The main limitation in this study is confounding by indication, but the descriptive question is however not confounded by indication. Together with plausible biological mechanisms and previous clinical and epidemiological observations our findings, linking initiation of SSRI to increased short-term suicide risk, deserve further attention specifically in the clinical setting.
|
|
| 3. |
- Helgadóttir, Björg, et al.
(författare)
-
Patterns in health-related behaviours and fall injuries among older people : a population-based study in Stockholm County, Sweden.
- 2015
-
Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 44:4, s. 604-10
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: we identified clusters of older people with similar health-related behaviours and assessed the association between those clusters and the risk of injurious fall.METHODS: we linked self-reported and register-based data on the over-65s from the Stockholm public health cohort (N = 20,212). Groups of people with similar health-related behaviours were identified by cluster analysis using four measures of physical activity, two of smoking and alcohol habits and two individual attributes (age and type of housing). The association between clusters and falls leading to hospitalisation (422 cases) was studied using a nested case-control design. Odds ratios (ORs), crude and adjusted for health status, were compiled by cluster using the one with the most 'protective' health behaviour profile as the reference.RESULTS: five clusters were identified revealing a variety of combinations of health-related behaviours, all linked to specific age groups and types of housing and with a tendency towards higher levels of physical activity among the younger ones. The risk of injurious falls differed across clusters, and for three out of four, it was significantly higher than in the comparison cluster. Adjusting for health status only partially reduced the ORs for those clusters and this was observed both in men and women.CONCLUSION: health-related behaviours aggregate in different manners among older people. Some health-related profiles are associated with an excess risk of falls leading to hospitalisation. Although this is partly a reflection of age differences across clusters, health status alone cannot fully explain the association.
|
|
| 4. |
- Hultin, Hanna, et al.
(författare)
-
Lack of Adjustment Latitude at Work as a Trigger of Taking Sick Leave : A Swedish Case-Crossover Study
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:4
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesResearch has shown that individuals reporting a low level of adjustment latitude, defined as having few possibilities to temporarily adjust work demands to illness, have a higher risk of sick leave. To what extent lack of adjustment latitude influences the individual when making the decision to take sick leave is unknown. We hypothesize that ill individuals are more likely to take sick leave on days when they experience a lack of adjustment latitude at work than on days with access to adjustment latitude.MethodsA case-crossover design was applied to 546 sick-leave spells, extracted from a cohort of 1 430 employees at six Swedish workplaces, with a 3–12 month follow-up of all new sick-leave spells. Exposure to lack of adjustment latitude on the first sick-leave day was compared with exposure during several types of control periods sampled from the previous two months for the same individual.ResultsOnly 35% of the respondents reported variations in access to adjustment latitude, and 19% reported a constant lack of adjustment latitude during the two weeks prior to the sick-leave spell. Among those that did report variation, the risk of sick leave was lower on days with lack of adjustment latitude, than on days with access (Odds Ratio 0.36, 95% Confidence Interval 0.25–0.52).ConclusionsThis is the first study to show the influence of adjustment latitude on the decision to take sick leave. Among those with variations in exposure, lack of adjustment latitude was a deterrent of sick leave, which is contrary to the à priori hypothesis. These results indicate that adjustment latitude may not only capture long-lasting effects of a flexible working environment, but also temporary possibilities to adjust work to being absent. Further studies are needed to disentangle the causal mechanisms of adjustment latitude on sick-leave.
|
|
| 5. |
- Hultin, Hanna, et al.
(författare)
-
Low Workload as a Trigger of Sick Leave Results From a Swedish Case-Crossover Study
- 2012
-
Ingår i: Journal of Occupational and Environmental Medicine. - : Lippincott, Williams and Wilkins. - 1076-2752 .- 1536-5948. ; 54:2, s. 202-209
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate if exposure to an unusually low workload when ill can trigger taking sick leave. Methods: A case-crossover design was applied to 546 sick-leave spells obtained from a cohort of 1430 employees within six Swedish workplaces. New sick-leave spells were reported from the workplaces during 3 to 12 months follow-up. Exposure was assessed in structured participant interviews at sick leave. Case and control periods from the same individual were sampled according to the matched-pair and usual-frequency approaches. Results are presented as odds ratios with surrounding 95% confidence intervals. Results: The odds ratio of sick leave on a day with an unusually low workload was 2.57 (confidence interval, 1.07-6.16). Conclusions: Becoming ill on a day with a lower workload than usual can trigger the decision to take sick leave.
|
|
| 6. |
- Jaghult, Susanna, et al.
(författare)
-
Stress as a trigger for relapses in IBD : A case-crossover study
- 2013
-
Ingår i: Gastroenterology Research. - : Elmer Press, Inc.. - 1918-2805 .- 1918-2813. ; 6:1, s. 10-16
-
Tidskriftsartikel (refereegranskat)abstract
- Background: It is important to identify factors that influence the risk of relapses in inflammatory bowel disease. Few studies have been conducted and with limited methodology. This prospective case-crossover study, aims to examine whether perceived stress has a short-term acute effect, namely whether it acts as a trigger, on the risk of relapse in inflammatory bowel disease.Methods: Sixty patients with inflammatory bowel disease and in remission were included. The case-crossover design was employed, which is an epidemiological design developed to study triggers for acute events and diseases. To collect information regarding symptoms and potential trigger factors, such as perceived stress, a structured diary was constructed. The participants were instructed to fill in the diary daily during six months. Fifty patients completed the study.Results: The analysis showed an effect for high level of perceived stress. Being exposed to “quite a lot” of stress, yield an increase in risk for relapse during the forthcoming day (OR = 4.8, 95% CI 1.09 - 21.10). No statistically increased risk for lower levels of perceived stress was found, although elevated effect estimates were found for “some” stress.Conclusion: This study supports earlier findings regarding perceived stress as an important factor in triggering relapses in IBD. However, this is the first case-crossover study performed to explore the trigger risk of stress in this population. Further investigations with larger patient samples are needed to confirm the findings.
|
|
| 7. |
- Laflamme, Lucie, et al.
(författare)
-
Type, Number or Both? : A Population-Based Matched Case-Control Study on the Risk of Fall Injuries among Older People and Number of Medications beyond Fall-Inducing Drugs
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives Drug use is a modifiable risk factor for fall-related injuries in older people. Whereas the injurious effect of polypharmacy is established, that of low numbers of medications has not been fully ascertained. Neither do we know whether it is the number per se or the type of medications that actually matters. We assessed this question for fall injuries leading to hospitalization. Design National register-based, population-based, matched case-control study. Setting Community dwellers aged 65+ years living in Sweden between March 2006 and December 2009. Methods Cases (n = 64,399) were identified in the national inpatient register and four controls per case were randomly matched by gender, date of birth and residential area. The association between number of prescribed medications, assessed through linkage with the Swedish prescribed drug register, and the risk of injurious falls was estimated with odds ratios with 95% confidence intervals using conditional logistic regression, adjusted for demographic and health status. Results The number of medications was associated with an increased risk of fall injury in a dose-response fashion, even after adjustment for marital status, comorbidity and number of fall-risk-inducing drugs (FRIDs). Using ten or more medications was associated with an almost two-fold higher risk (adjusted OR: 1.76, 95% CI: 1.66 to 1.88). When stratified by use (or not) of at least one FRID, the association weakened slightly among both non-users (adjusted OR: 1.50, 95% CI: 1.34 to 1.67) and users (adjusted OR: 1.67, 95% CI: 1.58 to 1.77). Conclusion In older people, not only large but also small numbers of medications may affect the risk for them to sustain injurious falls. Although the mechanisms lying behind this are complex, the finding challenges the prevention strategies targeting either specific types of medications (FRIDs) or high numbers of them.
|
|
| 8. |
|
|
