194 research outputs found

    Lactate-Induced Glucose Output Is Unchanged by Metformin at a Therapeutic Concentration - A Mass Spectrometry Imaging Study of the Perfused Rat Liver

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    Metformin is the first line drug for type 2 diabetes but its molecular mechanisms remain unclear. Here, we have studied the acute effect of a therapeutically relevant intrahepatic concentration of metformin on glucose production from lactate. We selected the perfused rat liver as experimental system since it enables the complete control of drug dosage. We used MALDI (matrix-assisted laser desorption/ionization) mass spectrometry imaging to estimate the concentration of metformin in the livers and we measured the concentration of glucose in the effluent medium under basal conditions and following lactate addition. MALDI mass spectra of thin-sections of freeze-clamped rat liver perfused with metformin showed a peak at 130.16 m/z which was unambiguously assigned to metformin. The mass spectrometric detection limit was at a tissue concentration of about 250 nM, and uptake of metformin from the perfusion medium to the liver occurred with a K-m of 0.44 mM. Metformin was evenly distributed in the liver irrespective of its concentration in the perfusion medium and the duration of a perfusion. At a parenchymal concentration of 30 mu M, metformin did not induce any significant suppression of the basal or lactate-induced glucose release from the liver. These results show that matrix-assisted laser desorption/ionization mass spectrometry imaging can be applied to estimate the tissue concentration and distribution of metformin in a therapeutically relevant micromolar concentration range. Our findings challenge the view that metformin causes an inhibition of glucose release from the liver by an acute inhibition of mitochondrial glycerol 3-phosphate dehydrogenase (EC 1.1.5.3).Peer reviewe

    Häusliche Gewalt bei Frauen einer Kriseninterventionspopulation - Formen der Gewalt und Risikofaktoren

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    Hintergrund und Fragestellung: Häusliche Gewalt ist häufig und kann zu ernsthaften physischen und psychischen Problemen führen. Wir haben deshalb Häufigkeit, Formen und Risikofaktoren häuslicher Gewalt bei Patientinnen einer psychiatrischen Kriseninterventionsstation untersucht. Methoden: 115 Frauen konnten mit dem „Screening Partnergewalt“ (SPG) und „Index of Spouse Abuse“ (ISA) befragt werden. Ergebnisse: Die Lebenszeitprävalenz bez. Partnergewalt lag bei 70%. Von den 74 der Befragten, die aktuell in einer Partnerschaft lebten, waren 28 (38%) in den letzten 12 Monaten vor Eintritt von Gewalt betroffen. Frauen mit Gewalterfahrung hatten eine signifikant schlechtere Schul- und Berufsausbildung. Schlussfolgerungen: Die Befragung von Patientin- nen im Bereich Krisenintervention und Psychiatrie nach häuslicher Gewalt sollte zum Standard einer „good clinical practice“ gehören. Background and Hypotheses: Domestic violence is common and can lead to severe physical and psychological problems. Thus, we have investigated the frequency of occurrence, forms and risk factors of domestic violence against female patients on a crisis intervention ward.Methods: 115 women were screened with the "screening spouse violence" (SPG) and the "index of spouse abuse" (ISA).Results: The life time prevalence concerning spouse violence was 70 %. Out of 74 women who were currently living in a relationship 28 (38%) were victims of violence in the last 12 months prior to their admission. Women who experienced violence had a significantly lower level of education.Conclusion: Screening for domestic violence in female patients in the field of crisis intervention and psychiatry should become a standard of "good clinical practice"

    Effects of similar intakes of marine n-3 fatty acids from enriched food products and fish oil on cardiovascular risk markers in healthy human subjects

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    There is convincing evidence that consumption of fish and fish oil rich in long-chain (LC) n-3 PUFA (n-3 LCPUFA), EPA (20 : 5n-3) and DHA (22 : 6n-3) reduce the risk of CHD. The aim of the present study was to investigate whether n-3 LCPUFA-enriched food products provide similar beneficial effects as fish oil with regard to incorporation into plasma lipids and effects on cardiovascular risk markers. A parallel 7-week intervention trial was performed where 159 healthy men and women were randomised to consume either 34 g fish pâté (n 44), 500 ml fruit juice (n 38) or three capsules of concentrated fish oil (n 40), all contributing to a daily intake of approximately 1 g EPA and DHA. A fourth group did not receive any supplementation or food product and served as controls (n 37). Plasma fatty acid composition, serum lipids, and markers of inflammation and oxidative stress were measured. Compared with the control group, plasma n-3 LCPUFA and EPA:arachidonic acid ratio increased equally in all intervention groups. However, no significant changes in blood lipids and markers of inflammation and oxidative stress were observed. In conclusion, enriched fish pâté and fruit juice represent suitable delivery systems for n-3 LCPUFA. However, although the dose given is known to reduce the risk of CVD, no significant changes were observed on cardiovascular risk markers in this healthy populatio

    Emotional demands at work and risk of long-term sickness absence in 1·5 million employees in Denmark : a prospective cohort study on effect modifiers

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    Publisher Copyright: © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under CC BY-NC-ND 4.0 licenseBackground: High emotional demands at work can affect employees’ health and there is a need to understand whether such an association might be modified by other working conditions. We aimed to examine emotional demands at work as a risk factor for long-term sickness absence and analyse whether influence, possibilities for development, role conflicts, and physical demands at work might modify this risk. Methods: We did a nationwide, population-based, prospective cohort study in Denmark and included employed individuals who were residing in Denmark in 2000, aged 30–59 years, who had complete data on age, sex, and migration background, with information on emotional demands and possible effect modifiers from job exposure matrices, and covariates and outcome (sickness absence) from population registers. Individuals with long-term sickness absence (≥6 weeks of consecutive sickness absence) between Jan 1, 1998, and Dec 31, 2000, and self-employed individuals were excluded. We assessed long-term sickness absence during a 10-year period from Jan 1, 2001, to Dec 31, 2010. Using Cox regression, we estimated hazard ratios (HRs) and 95% CIs and tested interaction as departure from additivity, estimating relative excess risk due to interaction (RERI). Multivariable adjusted models included sex, age, cohabitation, migration background, and income. Findings: 1 521 352 employed individuals were included and contributed data between Jan 1, 2000, and Dec 31, 2010. During 11 919 021 person-years (mean follow-up 7·8 years), we identified 480 685 new cases of long-term sickness absence. High emotional demands were associated with increased risk of long-term sickness absence compared with low emotional demands, after adjusting for age, sex, cohabitation, migration background, income, and the four possible effect modifiers (adjusted HR 1·55 [95% CI 1·53–1·56]). The association between high emotional demands and risk of long-term sickness absence was stronger in a synergistic way when individuals were also exposed to low possibilities for development (RERI 0·35 [95% CI 0·22–0·47]; 28·9 additional cases per 1000 person-years) and high role conflicts (0·13 [0·11–0·15]; 22·0 additional cases per 1000 person-years). No synergy was observed for influence and physical demands at work. Interpretation: People in occupations with high emotional demands were at increased risk of long-term sickness absence. Our findings on synergistic interactions suggest that, in emotionally demanding occupations, increasing possibilities for development and reducing work-related role conflicts might reduce long-term sickness absence. Further interventional studies are needed to confirm or refute this hypothesis. Funding: Danish Work Environment Research Fund, NordForsk.Peer reviewe

    Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5-90 years

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    The recent development of assays that accurately quantify neurofilament light, a neuronal cytoskeleton protein, in plasma has generated a vast literature supporting that it is a sensitive, dynamic, and robust biomarker of neuroaxonal damage. As a result, efforts are now made to introduce plasma neurofilament light into clinical routine practice, making it an easily accessible complement to its cerebrospinal fluid counterpart. An increasing literature supports the use of plasma neurofilament light in differentiating neurodegenerative diseases from their non-neurodegenerative mimics and suggests it is a valuable biomarker for the evaluation of the effect of putative disease-modifying treatments (e.g. in multiple sclerosis). More contexts of use will likely emerge over the coming years. However, to assist clinical interpretation of laboratory test values, it is crucial to establish normal reference intervals. In this study, we sought to derive reliable cut-offs by pooling quantified plasma neurofilament light in neurologically healthy participants (5-90 years) from eight cohorts. A strong relationship between age and plasma neurofilament light prompted us to define the following age-partitioned reference limits (upper 95th percentile in each age category): 5-17 years = 7 pg/mL; 18-50 years = 10 pg/mL; 51-60 years = 15 pg/mL; 61-70 years = 20 pg/mL; 70 + years = 35 pg/mL. The established reference limits across the lifespan will aid the introduction of plasma neurofilament light into clinical routine, and thereby contribute to diagnostics and disease-monitoring in neurological practice

    Work stress and loss of years lived without chronic disease : an 18-year follow-up of 1.5 million employees in Denmark

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    We aimed to examine the association between exposure to work stress and chronic disease incidence and loss of chronic disease-free life years in the Danish workforce. The study population included 1,592,491 employees, aged 30-59 in 2000 and without prevalent chronic diseases. We assessed work stress as the combination of job strain and effort-reward imbalance using job exposure matrices. We used Cox regressions to estimate risk of incident hospital-diagnoses or death of chronic diseases (i.e., type 2 diabetes, coronary heart disease, stroke, cancer, asthma, chronic obstructive pulmonary disease, heart failure, and dementia) during 18 years of follow-up and calculated corresponding chronic disease-free life expectancy from age 30 to age 75. Individuals working in occupations with high prevalence of work stress had a higher risk of incident chronic disease compared to those in occupations with low prevalence of work stress (women: HR 1.04 (95% CI 1.02-1.05), men: HR 1.12 (95% CI 1.11-1.14)). The corresponding loss in chronic disease-free life expectancy was 0.25 (95% CI - 0.10 to 0.60) and 0.84 (95% CI 0.56-1.11) years in women and men, respectively. Additional adjustment for health behaviours attenuated these associations among men. We conclude that men working in high-stress occupations have a small loss of years lived without chronic disease compared to men working in low-stress occupations. This finding appeared to be partially attributable to harmful health behaviours. In women, high work stress indicated a very small and statistically non-significant loss of years lived without chronic disease.Peer reviewe

    Persistent and changing job strain and risk of coronary heart disease. A population-based cohort study of 1.6 million employees in Denmark

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    Objectives This study aimed to examine the association between job strain and incident coronary heart disease (CHD) in Denmark, while accounting for changes of job strain. Methods We included all employees residing in Denmark in 2000, aged 30-59 years with no prevalent CHD (N=1660 150). We determined exposure to job strain from 1996-2009 using a job exposure matrix (JEM) with annual updates. Follow-up for incident CHD was from 2001-2010 via linkage to health records. We used Cox regression to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between job strain and incident CHD. Results During 16.1 million person-years, we identified 24 159 incident CHD cases (15.0 per 10 000 person-years). After adjustment for covariates, job strain in 2000 predicted onset of CHD during a mean follow-up of 9.71 years (HR 1.10, 95% CI 1.07-1.13). When analyzing changes in job strain from one year to the next and CHD in the subsequent year, persistent job strain (HR 1.07, 95% CI 1.03-1.10), onset of job strain (HR 1.20, 95% CI 1.12-1.29) and removal of strain (HR 1.20, 95% CI 1.12-1.28) were associated with higher CHD incidence compared to persistent no job strain. Associations were similar among men and women. Conclusions Job strain is associated with a higher risk of incident CHD in Denmark. As we used a JEM, we can rule out reporting bias. However, under- or overestimation of associations is possible due to non-differential misclassification of job strain and residual confounding by socioeconomic position.Peer reviewe
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