| 1. |
- Egerod, Kristoffer L, et al.
(författare)
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A Major Lineage of Enteroendocrine Cells Coexpress CCK, Secretin, GIP, GLP-1, PYY, and Neurotensin but Not Somatostatin.
- 2012
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170.
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Tidskriftsartikel (refereegranskat)abstract
- Enteroendocrine cells such as duodenal cholecystokinin (CCK cells) are generally thought to be confined to certain segments of the gastrointestinal (GI) tract and to store and release peptides derived from only a single peptide precursor. In the current study, however, transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the CCK promoter demonstrated a distribution pattern of CCK-eGFP positive cells that extended throughout the intestine. Quantitative PCR and liquid chromatography-mass spectrometry proteomic analyses of isolated, FACS-purified CCK-eGFP-positive cells demonstrated expression of not only CCK but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP), peptide YY (PYY), neurotensin, and secretin, but not somatostatin. Immunohistochemistry confirmed this expression pattern. The broad coexpression phenomenon was observed both in crypts and villi as demonstrated by immunohistochemistry and FACS analysis of separated cell populations. Single-cell quantitative PCR indicated that approximately half of the duodenal CCK-eGFP cells express one peptide precursor in addition to CCK, whereas an additional smaller fraction expresses two peptide precursors in addition to CCK. The coexpression pattern was further confirmed through a cell ablation study based on expression of the human diphtheria toxin receptor under the control of the proglucagon promoter, in which activation of the receptor resulted in a marked reduction not only in GLP-1 cells, but also PYY, neurotensin, GIP, CCK, and secretin cells, whereas somatostatin cells were spared. Key elements of the coexpression pattern were confirmed by immunohistochemical double staining in human small intestine. It is concluded that a lineage of mature enteroendocrine cells have the ability to coexpress members of a group of functionally related peptides: CCK, secretin, GIP, GLP-1, PYY, and neurotensin, suggesting a potential therapeutic target for the treatment and prevention of diabetes and obesity.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Brännström, Jonas, et al.
(författare)
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Acceptable noise level with Danish, Swedish, and non-semantic speech materials.
- 2012
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Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1708-8186 .- 1499-2027. ; 51, s. 146-156
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Acceptable noise level (ANL) has been established as a method to quantify the acceptance of background noise while listening to speech presented at the most comfortable level. The aim of the present study was to generate Danish, Swedish, and a non-semantic version of the ANL test and investigate normal-hearing Danish and Swedish subjects' performance on these tests. Design: ANL was measured using Danish and Swedish running speech with two different noises: Speech-weighted amplitude-modulated noise, and multitalker speech babble. ANL was also measured using the non-semantic international speech test signal (ISTS) as speech signal together with the speech-weighted amplitude-modulated noise. The latter condition was identical in both populations. Study sample: Forty Danish and 40 Swedish normal-hearing subjects. Results: In both populations ANL results were similar to previously reported results from American studies. Generally, significant differences were seen between test conditions using different types of noise within ears in each population. Significant differences were seen for ANL across populations, also when the non-semantic ISTS was used as speech signal. Conclusions: The present findings indicate that there are extrinsic factors, such as instructions, affecting the ANL results. Summario Objetivo: Se ha establecido el Nivel de Ruido Aceptable (ANL) como un método para cuantifi car la aceptación de ruido de fondo mientras se escucha lenguaje presentado al nivel más confortable. El objetivo de este estudio fue generar las versiones sueca, danesa y una no-semántica de la prueba ANL e investigar el desempeño de sujetos normoyentes daneses y suecos en estas pruebas. Diseño: Se midió el ANL utilizando un discurso continuo en danés y sueco con dos diferentes ruidos: ruido con amplitud modulada en el rango del lenguaje y balbuceo de varios hablantes. También se midió el ANL utilizando la prueba internacional no-semántica de señal de lenguaje (ISTS) como la señal lingüística junto con ruido con amplitud modulada en el rango del lenguaje. Esta última condición fue idéntica en ambas poblaciones. Muestra: Cuarenta sujetos daneses y 40 sujetos suecos normoyentes. Resultados: en ambas poblaciones los resultados de ANL fueron muy similares a los reportado previamente en estudios americanos. Generalmente, se vieron diferencias signifi cativas para el ANL entre poblaciones, también cuando el ISTS no semántico fue utilizado como señal lingüística. Conclusiones: Estos hallazgos indican que hay factores extrínsecos tales como las instrucciones, que afectan los resultados de ANL.
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| 7. |
- Brännström, Jonas, et al.
(författare)
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Prediction of IOI-HA Scores Using Speech Reception Thresholds and Speech Discrimination Scores in Quiet.
- 2014
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Ingår i: Journal of the American Academy of Audiology. - : Georg Thieme Verlag KG. - 2157-3107 .- 1050-0545. ; 25:2, s. 154-163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Outcome measures can be used to improve the quality of the rehabilitation by identifying and understanding which variables influence the outcome. This information can be used to improve outcomes for clients. In clinical practice, pure-tone audiometry, speech reception thresholds (SRTs), and speech discrimination scores (SDSs) in quiet or in noise are common assessments made prior to hearing aid (HA) fittings. It is not known whether SRT and SDS in quiet relate to HA outcome measured with the International Outcome Inventory for Hearing Aids (IOI-HA). Purpose: The aim of the present study was to investigate the relationship between pure-tone average (PTA), SRT, and SDS in quiet and IOI-HA in both first-time and experienced HA users. Research Design: SRT and SDS were measured in a sample of HA users who also responded to the IOI-HA. Study Sample: Fifty-eight Danish-speaking adult HA users. Data Collection and Analysis: The psychometric properties were evaluated and compared to previous studies using the IOI-HA. The associations and differences between the outcome scores and a number of descriptive variables (age, gender, fitted monaurally/binaurally with HA, first-time/experienced HA users, years of HA use, time since last HA fitting, best ear PTA, best ear SRT, or best ear SDS) were examined. A multiple forward stepwise regression analysis was conducted using scores on the separate IOI-HA items, the global score, and scores on the introspection and interaction subscales as dependent variables to examine whether the descriptive variables could predict these outcome measures. Results: Scores on single IOI-HA items, the global score, and scores on the introspection (items 1, 2, 4, and 7) and interaction (items 3, 5, and 6) subscales closely resemble those previously reported. Multiple regression analysis showed that the best ear SDS predicts about 18-19% of the outcome on items 3 and 5 separately, and about 16% on the interaction subscale (sum of items 3, 5, and 6) Conclusions: The best ears SDS explains some of the variance displayed in the IOI-HA global score and the interaction subscale. The relation between SDS and IOI-HA suggests that a poor unaided SDS might in itself be a limiting factor for the HA rehabilitation efficacy and hence the IOI-HA outcome. The clinician could use this information to align the user's HA expectations to what is within possible reach.
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| 8. |
- Brännström, Jonas, et al.
(författare)
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Should the acceptable noise level be considered to be an acceptable noise range?
- 2013
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Ingår i: The Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 1520-8524 .- 0001-4966. ; 134:5
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Tidskriftsartikel (refereegranskat)abstract
- The acceptable noise level (ANL) test is used to quantify the amount of competing background noise (BNL) that a listener is willing to accept when listening to speech at the most comfortable level (MCL). ANL is calculated by subtracting the BNL from the MCL. Most studies show large intersubject ANL variability and a few also demonstrate large intrasubject variability. Very few predictor variables for ANL have been identified and it has been proposed that the ANL depends on an inherent characteristic of the listener. However, some of the variability seems to depend on poor precision of the ANL test. After removing the effect of poor precision, some variability still remains. One possible explanation for these findings may be that the ANL is not a single level but a range of levels. Using recent data, this presentation examines the notion of an acceptable noise range.
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| 9. |
- Brännström, Jonas, et al.
(författare)
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The acceptable noise level and the pure-tone audiogram
- 2017
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Ingår i: American Journal of Audiology. - 1059-0889. ; 26:1, s. 80-87
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The vast majority of previous studies suggest that there is no relationship between the acceptable noise level (ANL) and pure-tone hearing thresholds reported as the average pure-tone hearing thresholds (pure-tone average). This study aims to explore (a) the relationship between hearing thresholds at individual frequencies and the ANL and (b) a measure of the slope of the audiogram and ANL. Method: Sixty-three Danish adult hearing aid users participated. Assessments were pure-tone audiogram and 3 different versions of the ANL test made monaurally at 2 different sessions. Results: The findings show that low-frequency hearing thresholds and the slope of the audiogram are significantly related to all versions of the ANL. Conclusion: It is possible that previous studies have failed to discover a relationship between ANL and hearing thresholds due to the use of the broad 4-frequency pure-tone average. This has implications for our understanding of the ANL test.
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| 10. |
- Brännström, Jonas, et al.
(författare)
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The acceptable noise level: The effect of repeated measurements.
- 2014
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Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1708-8186 .- 1499-2027. ; 53:1, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study explores if increasing number of repetitions might improve the precision of the acceptable noise level (ANL) test. Design: We measured twelve ANL repetitions, i.e. four complete ANL tests (4 × 3 repetitions), at one session using diotic presentation and a non-semantic ANL version. Study sample: Thirty-two normal-hearing adults. Results: Small order and fatigue effects were seen. We used the coefficient of repeatability (CR) to assess the repeatability; CRs ranged between 3.9 and 7.6 dB for the four ANL tests. Using the twelve ANL repetitions we removed the variability of the ANL across subjects by normalizing the data to the individual mean ANL for the twelve repetitions. The mean normalized ANL across the subjects rapidly approached the ANL normalized to the individual mean for the 12 repetitions (0 dB), and after three repetitions the SD seemed to be stable at about 3 dB. Conclusions: The findings suggest that both order and fatigue affect the ANL. The findings also suggest that it may be more accurate to speak of an acceptable noise range than ANL. These findings have large implications for how we understand acceptable noise and it would explain a large part of the variability seen among normal-hearing and perhaps hearing-impaired subjects.
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| 11. |
- Brännström, Jonas, et al.
(författare)
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The effect of repeated measurements and working memory on the most comfortable level in the ANL test.
- 2014
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Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1708-8186 .- 1499-2027. ; 53:11, s. 787-795
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the effect of a large number of repetitions on the most comfortable level (MCL) when doing the acceptable noise level (ANL) test, and explore if MCL variability is related to central cognitive processes. Design: Twelve MCL repetitions were measured within the ANL test using interleaved methodology during one session using a non-semantic version. Phonological (PWM) and visuospatial working memory (VSWM) was measured. Study sample: Thirty-two normal-hearing adults. Results: Repeated measures ANOVA, intraclass correlations, and the coefficient of repeatability (CR) were used to assess the repeatability. Repeated measures ANOVA and CR indicated poor agreement between the two first repetitions. After excluding the first repetition, analyses showed that the MCL in the ANL test is reliable. A negative association was found between PWM and MCL variability indicating that subjects with higher PWM show less variability. Conclusions: The findings suggest that, after excluding the first repetition, the MCL in the ANL test is reliable. A single repetition of the MCL in the ANL test should be avoided. If an interleaved methodology is used, a single ANL repetition should be added prior to the actual testing. The findings also suggest that MCL variability is associated to PWM but not VSWM.
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| 12. |
- Christensen, Diana Hedevang, et al.
(författare)
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Type 2 diabetes classification : a data-driven cluster study of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort
- 2022
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction A Swedish data-driven cluster study identified four distinct type 2 diabetes (T2D) clusters, based on age at diagnosis, body mass index (BMI), hemoglobin A1c (HbA1c) level, and homeostatic model assessment 2 (HOMA2) estimates of insulin resistance and beta-cell function. A Danish study proposed three T2D phenotypes (insulinopenic, hyperinsulinemic, and classical) based on HOMA2 measures only. We examined these two new T2D classifications using the Danish Centre for Strategic Research in Type 2 Diabetes cohort. Research design and methods In 3529 individuals, we first performed a k-means cluster analysis with a forced k-value of four to replicate the Swedish clusters: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild age-related (MARD), and mild obesity-related (MOD) diabetes. Next, we did an analysis open to alternative k-values (ie, data determined the optimal number of clusters). Finally, we compared the data-driven clusters with the three Danish phenotypes. Results Compared with the Swedish findings, the replicated Danish SIDD cluster included patients with lower mean HbA1c (86 mmol/mol vs 101 mmol/mol), and the Danish MOD cluster patients were less obese (mean BMI 32 kg/m 2 vs 36 kg/m 2). Our data-driven alternative k-value analysis suggested the optimal number of T2D clusters in our data to be three, rather than four. When comparing the four replicated Swedish clusters with the three proposed Danish phenotypes, 81%, 79%, and 69% of the SIDD, MOD, and MARD patients, respectively, fitted the classical T2D phenotype, whereas 70% of SIRD patients fitted the hyperinsulinemic phenotype. Among the three alternative data-driven clusters, 60% of patients in the most insulin-resistant cluster constituted 76% of patients with a hyperinsulinemic phenotype. Conclusion Different HOMA2-based approaches did not classify patients with T2D in a consistent manner. The T2D classes characterized by high insulin resistance/hyperinsulinemia appeared most distinct.
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| 13. |
- Hadad, Ronza, 1984-, et al.
(författare)
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A Chlamydia trachomatis 23S rRNA G1523A variant escaping detection in the Aptima Combo 2 assay (Hologic) was widespread across Denmark in July-September 2019
- 2020
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell Publishing Inc.. - 0903-4641 .- 1600-0463. ; 128:6, s. 440-444
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis infection is the most common bacterial sexually transmitted infection globally, and nucleic acid amplification tests (NAATs) are recommended for highly sensitive and specific diagnosis. In early 2019, the Finnish new variant of Chlamydia trachomatis (FI-nvCT) was identified. The FI-nvCT has a C1515T mutation in the 23S rRNA gene, making it escaping detection in the Aptima Combo 2 (AC2; Hologic) NAAT, and the FI-nvCT has been subsequently reported in Sweden and Norway. In the present study, we investigated the presence of the FI-nvCT and other AC2 diagnostic-escape CT mutants in July-September 2019 in Denmark. The FI-nvCT was present but rare in Denmark. However, another AC2 diagnostic-escape CT mutant (with a 23S rRNA G1523A mutation) was found to be widespread across Denmark, accounting for 95% (76/80) of AC2 diagnostic-escape nvCT samples from five Danish CT-diagnostic laboratories. This nvCT-G1523A has previously only been detected in one single sample in the United Kingdom and Norway, respectively. It is vital to monitor the continued stability of the NAAT targets in local, national and international settings and monitor as well as appropriately analyse incidence, unexplained shifts in diagnostics rates, and/or annual collections of samples diagnosed as negative/equivocal using NAATs with different target(s). Furthermore, diagnostic CT NAATs with dual target sequences are crucial and fortunately, an updated Hologic AC2 assay including one additional target sequence is in advanced development.
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| 14. |
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| 15. |
- Hjorth Larsen, Ask, et al.
(författare)
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The atomic simulation environment-a Python library for working with atoms
- 2017
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Ingår i: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 0953-8984 .- 1361-648X. ; 29:27
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Forskningsöversikt (refereegranskat)abstract
- The atomic simulation environment (ASE) is a software package written in the Python programming language with the aim of setting up, steering, and analyzing atomistic simulations. In ASE, tasks are fully scripted in Python. The powerful syntax of Python combined with the NumPy array library make it possible to perform very complex simulation tasks. For example, a sequence of calculations may be performed with the use of a simple 'for-loop' construction. Calculations of energy, forces, stresses and other quantities are performed through interfaces to many external electronic structure codes or force fields using a uniform interface. On top of this calculator interface, ASE provides modules for performing many standard simulation tasks such as structure optimization, molecular dynamics, handling of constraints and performing nudged elastic band calculations.
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| 16. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 17. |
- Kadi, Fawzi, et al.
(författare)
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The behaviour of satellite cells in response to exercise : what have we learned from human studies?
- 2005
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Ingår i: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 451:2, s. 319-327
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the complex role played by satellite cells in the adaptive response to exercise in human skeletal muscle has just begun. The development of reliable markers for the identification of satellite cell status (quiescence/activation/proliferation) is an important step towards the understanding of satellite cell behaviour in exercised human muscles. It is hypothesised currently that exercise in humans can induce (1) the activation of satellite cells without proliferation, (2) proliferation and withdrawal from differentiation, (3) proliferation and differentiation to provide myonuclei and (4) proliferation and differentiation to generate new muscle fibres or to repair segmental fibre injuries. In humans, the satellite cell pool can increase as early as 4 days following a single bout of exercise and is maintained at higher level following several weeks of training. Cessation of training is associated with a gradual reduction of the previously enhanced satellite cell pool. In the elderly, training counteracts the normal decline in satellite cell number seen with ageing. When the transcriptional activity of existing myonuclei reaches its maximum, daughter cells generated by satellite cell proliferation are involved in protein synthesis by enhancing the number of nuclear domains. Clearly, delineating the events and the mechanisms behind the activation of satellite cells both under physiological and pathological conditions in human skeletal muscles remains an important challenge.
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| 18. |
- Kellner, Martin, 1978-, et al.
(författare)
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Environmentally relevant concentrations of citalopram partially inhibit feeding in the three-spine stickleback (Gasterosteus aculeatus)
- 2015
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Ingår i: Aquatic Toxicology. - : Elsevier. - 0166-445X .- 1879-1514. ; 158, s. 165-170
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Tidskriftsartikel (refereegranskat)abstract
- Selective Serotonin Re-uptake Inhibitors (SSRI) are mood-altering, psychotropic drugs commonly used in the treatment of depression and other psychological illnesses. Many of them are poorly degraded in sewage treatment plants and enter the environment unaltered. In laboratory studies, they have been demonstrated to affect a wide range of behaviours in aquatic organisms. In this study we investigated the effect of a three-week exposure to 0.15 and 1.5 μg/l of the SSRI citalopram dissolved in the ambient water on the feeding behaviour in three-spine stickleback (Gasterosteus aculeatus). Feeding, measured as the number of attacks performed on a piece of frozen bloodworms during a 10-min period, was reduced by 30–40% in fish exposed to both 0.15 and 1.5 μg/l citalopram. The effects of the environmentally relevant concentration 0.15 μg/l on feeding, an important fitness characteristic, suggests that the ecological significance of environmental SSRI exposure may be pronounced.
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| 19. |
- Kristensen, Frederik Pagh Bredahl, et al.
(författare)
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The Prevalence of Polyneuropathy in Type 2 Diabetes Subgroups Based on HOMA2 Indices of b-Cell Function and Insulin Sensitivity
- 2023
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Ingår i: Diabetes Care. - 0149-5992. ; 46:8, s. 1546-1555
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of b-cell function and insulin sensitivity. RESEARCH DESIGN AND METHODS We estimated b-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM. Patients were categorized into subgroups of hyperinsulinemic (high HOMA2-B, low HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and insulinopenic (low HOMA2-B, high HOMA2-S) T2DM. After a median follow-up of 3 years, patients filled the Michigan Neuropathy Screening Instrument questionnaire (MNSIq) to identify DPN (score ‡ 4). We used Poisson regression to calculate adjusted prevalence ratios (PRs) for DPN, and spline models to examine the association with HOMA2-B and HOMA2-S. RESULTS A total of 3,397 (77%) patients filled in the MNSIq. The prevalence of DPN was 23% among hyperinsulinemic, 16% among classical, and 14% among insulinopenic pa-tients. After adjusting for demographics, diabetes duration and therapy, lifestyle behaviors, and metabolic syndrome components (waist circumference, triglycer-ides, HDL cholesterol, hypertension, and HbA1c), the PR of DPN was 1.35 (95% CI 1.15–1.57) for the hyperinsulinemic compared with the classical patients. In spline analyses, we observed a linear relation of higher DPN prevalence with increasing HOMA2-B, independent of both metabolic syndrome components and HOMA2-S. CONCLUSIONS Hyperinsulinemia marked by high HOMA2-B is likely an important risk factor for DPN beyond metabolic syndrome components and insulin resistance. This should be considered when developing interventions to prevent DPN.
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| 20. |
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| 21. |
- Lillethorup, Thea Pinholt, et al.
(författare)
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In vivo quantification of glial activation in minipigs overexpressing human α-synuclein
- 2018
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Ingår i: Synapse. - : Wiley. - 0887-4476. ; 72:12
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson’s disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha-synuclein (α-syn). The pathology of Parkinson’s disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergic response to overexpression of α-syn. We used positron emission tomography (PET) and the 18 kDa translocator protein radioligand, [11C](R)PK11195, to image brain microglial activation and (+)-α-[11C]dihydrotetrabenazine ([11C]DTBZ), to measure vesicular monoamine transporter 2 (VMAT2) availability in Göttingen minipigs following injection with recombinant adeno-associated virus (rAAV) vectors expressing either mutant A53T α-syn or green fluorescent protein (GFP) into the SN (4 rAAV-α-syn, 4 rAAV-GFP, 5 non-injected control minipigs). We performed motor symptom assessment and immunohistochemical examination of tyrosine hydroxylase (TH) and transgene expression. Expression of GFP and α-syn was observed at the SN injection site and in the striatum. We observed no motor symptoms or changes in striatal [11C]DTBZ binding potential in vivo or striatal or SN TH staining in vitro between the groups. The mean [11C](R)PK11195 total volume of distribution was significantly higher in the basal ganglia and cortical areas of the α-syn group than the control animals. We conclude that mutant α-syn expression in the SN resulted in microglial activation in multiple sub- and cortical regions, while it did not affect TH stains or VMAT2 availability. Our data suggest that microglial activation constitutes an early response to accumulation of α-syn in the absence of dopamine neuron degeneration.
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| 22. |
- Modvig, Signe, et al.
(författare)
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High CD34 surface expression in BCP-ALL predicts poor induction therapy response and is associated with altered expression of genes related to cell migration and adhesion
- 2022
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 16:10, s. 2015-2030
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Tidskriftsartikel (refereegranskat)abstract
- Minimal residual disease (MRD) constitutes the most important prognostic factor in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Flow cytometry is widely used in MRD assessment, yet little is known regarding the effect of different immunophenotypic subsets on outcome. In this study of 200 BCP-ALL patients, we found that a CD34-positive, CD38 dim-positive, nTdT dim-positive immunophenotype on the leukemic blasts was associated with poor induction therapy response and predicted an MRD level at the end of induction therapy (EOI) of ≥ 0.001. CD34 expression was strongly and positively associated with EOI MRD, whereas CD34-negative patients had a low relapse risk. Further, CD34 expression increased from diagnosis to relapse. CD34 is a stemness-associated cell-surface molecule, possibly involved in cell adhesion/migration or survival. Accordingly, genes associated with stemness were overrepresented among the most upregulated genes in CD34-positive leukemias, and protein–protein interaction networks showed an overrepresentation of genes associated with cell migration, cell adhesion, and negative regulation of apoptosis. The present work is the first to demonstrate a CD34-negative immunophenotype as a good prognostic factor in ALL, whereas high CD34 expression is associated with poor therapy response and an altered gene expression profile reminiscent of migrating cancer stem-like cells.
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| 23. |
- Nielsen, Sebastian V, et al.
(författare)
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The psychoactive drug Escitalopram affects swimming behaviour and increases boldness in zebrafish (Danio rerio)
- 2018
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Ingår i: Ecotoxicology. - : Kluwer Academic Publishers. - 0963-9292 .- 1573-3017. ; 27:4, s. 485-497
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Tidskriftsartikel (refereegranskat)abstract
- Selective serotonin re-uptake inhibitors are pharmaceuticals used to treat a range of psychological disorders. They are frequently found in surface waters in populated areas. In recent years, they have been shown to affect the behaviour of various aquatic organisms in a way that can have ecological effects. In this study, we exposed zebrafish of both sexes to nominally 0.00, 0.15 and 1.50 µg L−1 Escitalopram in flow-through tanks for three weeks. Subsequently, ten swimming behaviour parameters were quantified using high-resolution video tracking. There were noticeable gender differences in the behaviour responses to Escitalopram. Female fish exposed to 1.50 µg L−1 Escitalopram had a lower maximum swimming velocity, stopped less often and exhibited increased boldness (reduced thigmotaxis) compared to controls. Male fish exposed to 1.50 µg L−1 had a lower maximum swimming velocity compared to control fish. At the end of exposures, both length and weight of the females exposed to 1.50 µg L−1 Escitalopram were significantly less than the group of control fish. In addition, males exposed to 1.50 µg L−1 Escitalopram were significantly shorter than control fish. The behaviour, weight and body length of the fish exposed to nominally 0.15 µg L−1 was not significantly different from control fish in either sex. The results of this study demonstrate that Escitalopram can affect subtle but ecologically important aspects of fish behaviour and lends further credibility to the assumption that Escitalopram is an environmentally active pharmaceutical.
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| 24. |
- Olsen, Steen, et al.
(författare)
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Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training
- 2006
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Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 573:Pt 2, s. 525-534
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the influence of creatine and protein supplementation on satellite cell frequency and number of myonuclei in human skeletal muscle during 16 weeks of heavy-resistance training. In a double-blinded design 32 healthy, male subjects (19-26 years) were assigned to strength training (STR) while receiving a timed intake of creatine (STR-CRE) (n=9), protein (STR-PRO) (n=8) or placebo (STR-CON) (n=8), or serving as a non-training control group (CON) (n=7). Supplementation was given daily (STR-CRE: 6-24 g creatine monohydrate, STR-PRO: 20 g protein, STR-CON: placebo). Furthermore, timed protein/placebo intake were administered at all training sessions. Muscle biopsies were obtained at week 0, 4, 8 (week 8 not CON) and 16 of resistance training (3 days per week). Satellite cells were identified by immunohistochemistry. Muscle mean fibre (MFA) area was determined after histochemical analysis. All training regimes were found to increase the proportion of satellite cells, but significantly greater enhancements were observed with creatine supplementation at week 4 (compared to STR-CON) and at week 8 (compared to STR-PRO and STR-CON) (P<0.01-0.05). At week 16, satellite cell number was no longer elevated in STR-CRE, while it remained elevated in STR-PRO and STR-CON. Furthermore, creatine supplementation resulted in an increased number of myonuclei per fibre and increases of 14-17% in MFA at week 4, 8 and 16 (P<0.01). In contrast, STR-PRO showed increase in MFA only in the later (16 week, +8%) and STR-CON only in the early (week 4, +14%) phases of training, respectively (P<0.05). In STR-CRE a positive relationship was found between the percentage increases in MFA and myonuclei from baseline to week 16, respectively (r=0.67, P<0.05). No changes were observed in the control group (CON). In conclusion, the present study demonstrates for the first time that creatine supplementation in combination with strength training amplifies the training-induced increase in satellite cell number and myonuclei concentration in human skeletal muscle fibres, thereby allowing an enhanced muscle fibre growth in response to strength training.
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| 25. |
- Olsen, Steen Ostergaard, et al.
(författare)
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Acceptable noise level (ANL) with Danish and non-semantic speech materials in adult hearing-aid users
- 2012
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Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1708-8186 .- 1499-2027. ; 51:9, s. 678-688
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The acceptable noise level (ANL) test is used for quantification of the amount of background noise subjects accept when listening to speech. This study investigates Danish hearing-aid users' ANL performance using Danish and non-semantic speech signals, the repeatability of ANL, and the association between ANL and outcome of the international outcome inventory for hearing aids (IOI-HA). Design: ANL was measured in three conditions in both ears at two test sessions. Subjects completed the IOI-HA and the ANL questionnaire. Study sample: Sixty-three Danish hearing-aid users; fifty-seven subjects were full time users and 6 were part time/non users of hearing aids according to the ANL questionnaire. Results: ANLs were similar to results with American English speech material. The coefficient of repeatability (CR) was 6.5-8.8 dB. IOI-HA scores were not associated to ANL. Conclusions: Danish and non-semantic ANL versions yield results similar to the American English version. The magnitude of the CR indicates that ANL with Danish and non-semantic speech materials is not suitable for prediction of individual patterns of future hearing-aid use or evaluation of individual benefit from hearing-aid features. The ANL with Danish and non-semantic speech materials is not related to IOI-HA outcome.
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| 26. |
- Olsen, Steen Ostergaard, et al.
(författare)
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Acceptable noise level: Repeatability with Danish and non-semantic speech materials for adults with normal hearing
- 2012
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Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1708-8186 .- 1499-2027. ; 51:7, s. 557-563
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The acceptable noise level (ANL) is used to quantify the amount of background noise that subjects can accept while listening to speech, and is suggested for prediction of individual hearing-aid use. The aim of this study was to assess the repeatability of the ANL measured in normal-hearing subjects using running Danish and non-semantic speech materials as stimuli and modulated speech-spectrum and multi-talker babble noises as competing stimuli. Design: ANL was measured in both ears at two test sessions separated by a period ranging from 12 to 77 days. At each session the measurements at the first and the second ear were separated in time by 15-30 minutes. Bland-Altman plots and calculation of the coefficient of repeatability (CR) were used to estimate the repeatability. Study sample: Thirty nine normal-hearing subjects. Results: The ANL CR was 6.0-8.9 dB for repeated tests separated by about 15-30 minutes and 7.2-10.2 dB for repeated tests separated by 12 days or more. Conclusions: The ANL test has poor repeatability when assessed with Danish and non-semantic speech materials on normal-hearing subjects. The same CR among hearing-impaired subjects would imply too poor repeatability to predict individual patterns of future hearing-aid use.
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| 27. |
- Olsen, Steen Ostergaard, et al.
(författare)
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Does the acceptable noise level (ANL) predict hearing-aid use?
- 2014
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Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1708-8186 .- 1499-2027. ; 53:1, s. 2-10
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: It has been suggested that individuals have an inherent acceptance of noise in the presence of speech, and that different acceptance of noise results in different hearing-aid (HA) use. The acceptable noise level (ANL) has been proposed for measurement of this property. It has been claimed that the ANL magnitude can predict hearing-aid use patterns. Many papers have been published reporting on different aspects of ANL, but none have challenged the predictive power of ANL. The purpose of this study was to discuss whether ANL can predict HA use and how more reliable ANL results can be obtained. Design: Relevant literature regarding the ANL was found on Medline, Embase, and Google Scholar. Additional information was found as references in the included papers and through personal contacts, for instance when attending audiology conferences. Study sample: Forty-five papers published in peer reviewed journals as well as a number of papers from trade journals, posters and oral presentations from audiology conventions. Conclusions: An inherent acceptance of noise in the presence of speech may exist, but no method for precise measurement of ANL is available. The ANL model for prediction of HA use has yet to be proven valid.
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| 28. |
- Olsen, Steen Ostergaard, et al.
(författare)
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Intertester Reliability of the Acceptable Noise Level
- 2013
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Ingår i: Journal of the American Academy of Audiology. - : Georg Thieme Verlag KG. - 2157-3107 .- 1050-0545. ; 24:3, s. 241-243
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 29. |
- Ostergaard Olsen, Steen
(författare)
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Simulated real-ear measurements of benefit from digital feedback suppression
- 2008
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Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1708-8186 .- 1499-2027. ; 47:2, s. 51-58
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Tidskriftsartikel (refereegranskat)abstract
- Digital feedback suppression (DFS) enables users of hearing instruments (HI) to benefit from amplification levels that normally would provoke whistling or poor sound quality. A standardized test for the measurement of DFS benefit is not available. This paper proposes and evaluates an objective method for assessment of extra feedback-free amplification (headroom) provided by a given DFS. It is shown that the whistle-free loop gain can be calculated from data obtained with simulated real-car measurements with the modified pressure method. Test-retest trials were carried out to assess the reliability of the proposed method. Also, a method was developed for defining an appropriate gain level at which the proposed measurement should be carried out, It is concluded that the proposed method needs to be modified to provide useful information.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Thomassen, Sisse Anette, et al.
(författare)
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Cerebral blood flow measured by positron emission tomography during normothermic cardiopulmonary bypass : an experimental porcine study
- 2018
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Ingår i: Perfusion. - : SAGE Publications. - 0267-6591 .- 1477-111X. ; 33:5, s. 346-353
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mean arterial blood pressure (MAP) and/or pump flow during normothermic cardiopulmonary bypass (CPB) are the most important factors of cerebral perfusion. The aim of this study was to explore the influence of CPB blood flow on cerebral blood flow (CBF) measured by dynamic positron emission tomography (PET) using O-15-labelled water with no pharmacological interventions to maintain the MAP.Methods: Eight pigs (69-71 kg) were connected to normothermic CPB. After 60 minutes (min) with a CPB pump flow of 60 mL/kg/min, the pigs were changed to either 35 mL/kg/min or 47.5 mL/kg/min for 60 min and, thereafter, all the pigs returned to 60 mL/kg/min for another 60 min. The MAP was measured continuously and the CBF was measured by positron emission tomography (PET) during spontaneous circulation and at each CPB pump flow after 30 min of steady state.Results: Two pigs were excluded due to complications. CBF increased from spontaneous circulation to a CPB pump flow of 60 mL/kg/min. A reduction in CPB pump flow to 47.5 mL/kg/min (n=3) resulted in only minor changes in CBF while a reduction to 35 mL/kg/min (n=3) caused a pronounced change (correlation coefficient (R-2) 0.56). A return of CPB pump flow to 60 mL/kg/min was followed by an increase in CBF, except in the one pig with the lowest CBF during low flow (R-2=0.44). CBF and MAP were not correlated (R-2=0.20).Conclusion: In this experimental porcine study, a relationship was observed between pump flow and CBF under normothermic low-flow CPB. The effect of low pump flow on MAP showed substantial variations, with no correlation between CBF and MAP.
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| 35. |
- Thomassen, Sisse Anette, et al.
(författare)
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Muscle Tissue Saturation Compared With Muscle Tissue Perfusion During Low Blood Flows : An Experimental Study.
- 2017
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770 .- 1532-8422. ; 31:6, s. 2065-2071
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether changes in muscle tissue perfusion measured with positron emission tomography would be reflected by parallel changes in muscle tissue oxygen saturation (StO2) measured using near-infrared spectroscopy during high and low blood flow levels achieved using cardiopulmonary bypass (CPB) in an animal model.DESIGN: A prospective, randomized study.SETTING: Research laboratory, single institution.PARTICIPANTS: Eight pigs (69-71 kg).INTERVENTIONS: In anesthetized pigs, normothermic CPB was established with a blood flow of 60 mL/kg/min for 1 hour. Thereafter, a low blood flow of either 47.5 or 35 mL/kg/min was applied for 1 hour followed by a blood flow of 60 mL/kg/min for an additional hour. Regional StO2 was measured continuously by placing a near-infrared spectroscopy electrode on the skin above the gracilis muscle of the noncannulated back leg. Muscle tissue perfusion was measured using positron emission tomography with (15)O-labeled water during spontaneous circulation and the different CPB blood flows. Systemic oxygen consumption was estimated by measurement of venous saturation and lactate levels.MEASUREMENTS AND MAIN RESULTS: The results showed profound systemic ischemia during low CPB blood flow. StO2 remained high until muscle tissue perfusion decreased to about 50%, after which StO2 paralleled the linear decrease in muscle tissue perfusion.CONCLUSION: In an experimental CPB animal model, StO2 was stable until muscle tissue perfusion was reduced by about 50%, and at lower blood flow levels, there was almost a linear relationship between StO2 and muscle tissue perfusion.
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| 36. |
- Tritsaris, Katerina, et al.
(författare)
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IL-20 is an arteriogenic cytokine that remodels collateral networks and improves functions of ischemic hind limbs
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:39, s. 15364-15369
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Tidskriftsartikel (refereegranskat)abstract
- Successful therapeutic angiogenesis for the treatment of ischemic disorders relies on selection of optimal proangiogenic or arteriogenic agents that are able to promote establishment of functional collateral networks. Here, we show that IL-20, a pleiotropic inflammatory cytokine, displays an imperative effect on vascular remodeling. Stimulation of both large and microvascular endothelial cells with IL-20 leads to activation of receptor-dependent multiple intracellular signaling components, including increased phosphorylation levels of JAK2/STAT5, Erk1/2, and Akt; activation of small GTP-binding proteins Rac and Rho; and intracellular release of calcium. Surprisingly, IL-20 significantly promotes endothelial cell tube formation without affecting their proliferation and motility. These findings suggest that the vascular function of IL-20 involves endothelial cell organization, vessel maturation, and remodeling. Consistent with this notion, delivery of IL-20 to the ischemic muscle tissue significantly improves arteriogenesis and blood perfusion in a rat hind-limb model. Our findings provide mechanistic insights on vascular functions of IL-20 and define therapeutic implication of this cytokine for the treatment of ischemic disorders.
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| 37. |
- Trobos, Margarita, 1980, et al.
(författare)
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Characterization of sulphonamide-resistant Escherichia coli using comparison of sul2 gene sequences and multilocus sequence typing.
- 2009
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Ingår i: Microbiology (Reading, England). - : Microbiology Society. - 1350-0872 .- 1465-2080. ; 155:Pt 3, s. 831-836
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Tidskriftsartikel (refereegranskat)abstract
- The sul2 gene encodes sulphonamide resistance (Sul(R)) and is commonly found in Escherichia coli from different hosts. We typed E. coli isolates by multilocus sequence typing (MLST) and compared the results to sequence variation of sul2, in order to investigate the relation to host origin of pathogenic and commensal E. coli strains and to investigate whether transfer of sul2 into different genomic lineages has happened multiple times. Sixty-eight E. coli isolated in Denmark and Norway from different hosts and years were MLST typed and sul2 PCR products were sequenced and compared. PFGE was performed in a subset of isolates. All isolates were divided into 45 different sequence types (STs), with clonal complexes CC10, CC23, CC168, CC350 and CC69 being the most frequent. The sul2 gene from the majority of E. coli strains had only two point mutations, at positions 159 and 197, leading to a synonymous and a non-synonymous change, respectively. Five strains had extra single mutations. All poultry, poultry meat, and Danish human blood isolates had the same sul2 ST and some of these strains clustered under the same MLST STs, indicating that they shared habitats. Most PFGE profiles clustered according to source, but some included different sources. Sul(R) E. coli from different animals, food, human faeces and infections did not cluster according to their origin, suggesting that these habitats share E. coli and sul2 gene types. However, while pig isolates on one occasion clustered with urinary tract infection isolates, poultry isolates seemed more related to isolates from bloodstream infections in humans. Presence of mainly two types of the sul2 gene in both human and animal isolates, irrespective of date and geography, and the presence of both types in the same clonal lineages, suggest horizontal transfer of sul2.
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| 38. |
- Vongsangnak, Wanwipa, 1982, et al.
(författare)
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Improved annotation through genome-scale metabolic modeling of Aspergillus oryzae
- 2008
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Ingår i: BMC Genomics. ; 9:245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Since ancient times the filamentous fungus Aspergillus oryzae has been used in the fermenation industry for the production of fermented sauces and the production of industrial enzymes. Recently, the genome sequence of A. oryzae with 12,074 annotated genes was released but the number of hypothetical proteins accounted for more than 50% of the annotated genes. Considering the industrial importance of this fungus, it is therefore valuable to improve the annotation and further integrate genomic information with biochemical and physiological information available for this microorganism and other related fungi. Here we proposed the gene prediction by construction of an A. oryzae Expressed Sequence Tag (EST) library, sequencing and assembly. We enhanced the function assignment by our developed annotation strategy. The resulting better annotation was used to reconstruct the metabolic network leading to a genome scale metabolic model of A. oryzae.Results: Our assembled EST sequences we identified 1,046 newly predicted genes in the A. oryzae genome. Furthermore, it was possible to assign putative protein functions to 398 of the newly predicted genes. Noteworthy, our annotation strategy resulted in assignment of new putative functions to 1,469 hypothetical proteins already present in the A. oryzae genome database. Using the substantially improved annotated genome we reconstructed the metabolic network of A. oryzae. This network contains 729 enzymes, 1,314 enzyme-encoding genes, 1,073 metabolites and 1,846 (1,053 unique) biochemical reactions. The metabolic reactions are compartmentalized into the cytosol, the mitochondria, the peroxisome and the extracellular space. Transport steps between the compartments and the extracellular space represent 281 reactions, of which 161 are unique. The metabolic model was validated and shown to correctly describe the phenotypic behavior of A. oryzae grown on different carbon sources. Conclusion: A much enhanced annotation of the A. oryzae genome was performed and a genome-scale metabolic model of A. oryzae was reconstructed. The model accurately predicted the growth and biomass yield on different carbon sources. The model serves as an important resource for gaining further insight into understanding of A. oryzae physiology.
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