Overcoming the Pitfalls of Cytochrome P450 Immobilization Through the Use of Fusogenic Liposomes

This work describes a new nanotechnology-based immobilization strategy for cytochrome P450s (CYPs), the major class of drug metabolizing enzymes. Immobilization of CYPs on solid supports provides a significant leap forward compared with soluble enzyme assays by enabling the implementation of through-flow microreactors for, for example, determination of time-dependent inhibition. Immobilization of the complex CYP membrane-protein system is however particularly challenging as the preservation of the authentic enzyme kinetic parameters requires the full complexity of the lipid environment. The developed strategy is based on the spontaneous fusion of biotinylated fusogenic liposomes with lipid bilayers to facilitate the gentle biotinylation of human liver microsomes that incorporate all main natural CYP isoforms. The same process is also feasible for the biotinylation of recombinant CYPs expressed in insect cells, same as any membrane-bound enzymes in principle. As a result, CYPs could be immobilized on streptavidin-functionalized surfaces, both those of commercial magnetic beads and customized microfluidic arrays, so that the enzyme kinetic parameters remain unchanged, unlike in previously reported immobilization approaches that often suffer from restricted substrate diffusion to the enzyme's active site and steric hindrances. The specificity and robustness of the functionalization method of customized microfluidic CYP assays are also carefully examined.Peer reviewe

Beyond On-Hold Messages: Conversational Time-Buying in Task-Oriented Dialogue

Lopez Gambino MS, Zarrieß S, Schlangen D. Beyond On-Hold Messages: Conversational Time-Buying in Task-Oriented Dialogue. In: Jokinen K, Stede M, DeVault D, Louis A, eds. 18th Annual Meeting of the Special Interest Group on Discourse and Dialogue. Proceedings of the conference. 2017: 241-246

Risk factors for suicidal behaviour in individuals on disability pension due to common mental disorders - a nationwide register-based prospective cohort study in Sweden.

BACKGROUND: Common mental disorders (CMD) have become one of the leading causes for disability pension (DP). Studies on predictors of adverse health outcome following DP are sparse. This study aimed to examine the association of different socio-demographic factors and health care consumption with subsequent suicidal behaviour among individuals on DP due to CMD. METHOD: This is a population-based prospective cohort study based on register data. All individuals aged 18-64 years, living in Sweden on 31-Dec-2004 who in 2005 were on DP due to CMD (N = 46 745) were followed regarding suicide attempt and suicide (2006-10). Univariate and multivariate hazard ratios (HR) and 95% confidence intervals (CI) for suicidal behaviour were estimated by Cox regression. RESULTS: During the five-year follow-up, 1 046 (2.2%) and 210 (0.4%) individuals attempted and committed suicide, respectively. Multivariate analyses showed that young age (18-24 years) and low education predicted suicide attempt, while living alone was associated with both higher suicide attempt and suicide (range of HRs 1.23 to 1.68). Combined prescription of antidepressants with anxiolytics during 2005 and inpatient care due to mental diagnoses or suicide attempt (2001-05) were strongly associated with suicide attempt and suicide (range of HRs 1.3 to 4.9), while inpatient care due to somatic diagnoses and specialized outpatient care due to mental diagnoses during 2001-05 only predicted suicide attempt (HR 1.45; 95% CI: 1.3-1.7; HR 1.30; 95% CI: 1.1-1.7). CONCLUSIONS: Along with socio-demographic factors, it is very important to consider type of previous healthcare use and medication history when designing further research or intervention aiming at individuals on DP due to CMD. Further research is warranted to investigate both characteristics of disability pension due to CMD, like duration, diagnoses and grade as well as mechanisms to subsequent suicidal behavior, taking potential gender differences into consideration

Sosiaalinen ja kulttuurinen kestävyys luonnonvarojen hallinnassa : Socially and Culturally Sustainable Natural Resource Governance (SOCCA)

Socially and Culturally Sustainable Natural Resource Governance (SOCCA) -hanke kokoaa yhteen, esittelee ja kehittää edelleen Luonnonvarakeskuksen (Luke) tutkimusta ja asiantuntemusta luonnonvarojen hallinnan sosiaalisista ja kulttuurisista näkökulmista. Tämän raportin taustalla on SOCCA-hankkeessa toteutettu kirjallisuuskatsaus (2020, kts. liite 1), jossa tarkasteltiin Luken tutkimusta koskien luonnonvarojen sosiaalista ja kulttuurista kestävyyttä, sekä vuosina 2020 ja 2021 toteutetut työpajat, joissa Luken tutkijat ovat muodostaneet yhteistä ymmärrystä tästä aihepiiristä. Julkaisun toimittajat kiittävät lämpimästi kaikkia työpajoihin osallistuneita Luken tutkijoita.202

Disability pension due to common mental disorders and subsequent suicidal behaviour : a population-based prospective cohort study

Objective: Adverse health outcomes, including suicide, in individuals on disability pension (DP) due to mental diagnoses have been reported. However, scientific knowledge on possible risk factors for suicidal behaviour (suicide attempt and suicide) in this group, such as age, gender, underlying DP diagnoses, comorbidity and DP duration and grade, is surprisingly sparse. This study aimed to investigate associations of different measures (main and secondary diagnoses, duration and grade) of DP due to common mental disorders (CMD) with subsequent suicidal behaviour, considering gender and age differences. Design: Population-based prospective cohort study based on Swedish nationwide registers. Methods: A cohort of 46 515 individuals aged 19-64 years on DP due to CMD throughout 2005 was followed-up for 5 years. In relation to different measures of DP, univariate and multivariate HRs and 95% CIs for suicidal behaviour were estimated by Cox regression. All analyses were stratified by gender and age. Results: During 2006-2010, 1036 (2.2%) individuals attempted and 207 (0.5%) completed suicide. Multivariate analyses showed that a main DP diagnosis of 'stress-related mental disorders' was associated with a lower risk of subsequent suicidal behaviour than 'depressive disorders' (HR range 0.4-0.7). Substance abuse or personality disorders as a secondary DP diagnosis predicted suicide attempt in all subgroups (HR range 1.4-2.3) and suicide in women and younger individuals (HR range 2.6-3.3). Full-time DP was associated with a higher risk of suicide attempt compared with part-time DP in women and both age groups (HR range 1.4-1.7). Conclusions: Depressive disorders as the main DP diagnosis and substance abuse or personality disorders as the secondary DP diagnosis were risk markers for subsequent suicidal behaviour in individuals on DP due to CMD. Particular attention should be paid to younger individuals on DP due to anxiety disorders because of the higher suicide risk

Trajectories of antidepressant medication use in individuals before and after being granted disability pension due to common mental disorders : a nationwide register-based study

Background: Early retirement caused by disability pension (DP) due to common mental disorders (CMDs) is frequent in European countries. Inadequate treatment, e.g., suboptimal antidepressant (AD) medication before DP can be crucial in such DP. This explorative study aimed to disentangle trajectories of AD based on defined daily dose (DDD) before and after granted DP, and to characterize the trajectories by socio-demographics and medical factors. Methods: All 4642 individuals in Sweden aged 19–64 with incident DP due to CMD in 2009–2010 were included. Trajectories of annual DDDs of AD were analysed over a 6-year period by a group-based trajectory method. Associations between socio-demographic or medical factors and different trajectories were estimated by chi2-test and multinomial logistic regression. Results: Five trajectories of ADs were identified. Three groups, comprising 34%, 34%, and 21% of the cohort, had constant AD levels before and after DP with mean annual DDDs of 29, 234, and 580, respectively. Two groups, each including 6% of the cohort, had increasing levels of DDDs, levelling off at around 1150 and 785 DDDs after DP. Particularly age, outpatient care due to mental diagnoses and DP diagnoses were significantly associated with different trajectories (p < 0.05). All the groups had a larger proportion of older individuals (> 50%, 45–64 years), except for the ‘increasing low’ group, where younger individuals were in majority (> 60%, 18–44 years), who more frequently exited labour market due to ‘anxiety disorders’, with lower education and more specialised healthcare before DP than the other groups. Conclusion: The heterogeneity among the five trajectory groups was partly explained by age, the severity of the mental disorder and the DP diagnoses. DDDs of ADs, though on different levels, varied marginally before and after granted DP in the majority. Moreover, AD levels were very low in one third of the individuals. Early identification and focus on the ‘increasing low’ group might be important in order to identify individuals at risk for further increase in annual DDDs of ADs even after granted DP, and might also contribute in prevention of DP. Further detailed research regarding different groups is warranted

Univariate hazard ratios for suicide attempt and suicide (2006–10), 46 745 women and men, aged 18–64 years and living in Sweden on 31-Dec-2004, and on disability pension in 2005 due to common mental disorders.

1<p>Type of living area: Big cities: Stockholm, Gothenburg and Malmo; Medium-sized cities: cities with more than 90 000 inhabitants within 30 km distance from the centre of the city; small cities/villages;</p>2<p>Single means living without partner and includes divorces, separated or widowed</p

Proportion of suicide attempt, Life table estimates, 1-survival; during follow-up according to medication and sex.

<p>Proportion of suicide attempt, Life table estimates, 1-survival; during follow-up according to medication and sex.</p