| 1. |
- Alföldi, Peter, et al.
(författare)
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Comorbid insomnia in patients with chronic pain : a study based on the Swedish quality registry for pain rehabilitation (SQRP)
- 2014
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Ingår i: Disability and Rehabilitation. - : Informa Healthcare. - 0963-8288 .- 1464-5165. ; 36:20, s. 1661-1669
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study investigates the prevalence of insomnia and its relationship to other symptoms and health aspects in patients with chronic pain. Methods: Patients with chronic pain conditions (n = 845) referred to a multidisciplinary pain centre completed surveys provided by the Swedish quality registry for pain rehabilitation (SQRP). The SQRP collects data on socio-demographics, health status, symptoms of pain, mood and insomnia and life satisfaction. Results: The majority of patients (65.3%) had clinical insomnia according to the insomnia severity index (ISI). Insomnia correlated significantly but weakly with pain, depression, anxiety and coping; the strongest multivariate correlations were found with depression and anxiety followed by pain interference and pain severity. Pain intensity, depression and anxiety correlated stronger than ISI with respect to the two investigated aspects of health. Conclusions: The prevalence of insomnia is high in patients with chronic pain conditions, but the level of importance in relation to other symptoms for health aspects is low, and the associations with other important symptoms are relatively weak. One way to increase the effects of multimodal rehabilitation programs may be to provide interventions directed specifically at insomnia rather than focusing only on interventions that address pain, depression and anxiety. Implications for Rehabilitation The prevalence of insomnia is high in patients with complex chronic pain conditions. Relatively low correlations existed between insomnia and pain intensity, depression, anxiety and other psychological aspects. Pain intensity, anxiety and depression were more important for perceived health aspects than insomnia. One way to increase the effects of multimodal rehabilitation programs may be to also include interventions directed directly to insomnia.
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| 2. |
- Alföldi, Peter, 1959-, et al.
(författare)
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SPREADING OF PAIN AND INSOMNIA IN PATIENTS WITH CHRONIC PAIN: RESULTS FROM A NATIONAL QUALITY REGISTRY (SQRP)
- 2017
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Ingår i: Journal of Rehabilitation Medicine. - : FOUNDATION REHABILITATION INFORMATION. - 1650-1977 .- 1651-2081. ; 49:1, s. 63-70
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore how demographics, pain, psychosocial factors and insomnia relate to the spread of chronic pain. Methods: The study included 708 patients (68% women; median age 46 years; interquartile range 3557 years) with chronic pain who were referred to a multidisciplinary pain centre. Spreading of pain was assessed using a questionnaire covering 36 anatomically predefined pain regions. Data were collected on demographics, pain symptoms, psychological distress, and insomnia (Insomnia Severity Index). Four sub-categories of chronic pain were established: chronic local pain, chronic regional pain medium, chronic regional pain heavy, and chronic widespread pain. Results: The median number of pain regions was 10 (interquartile range 6-18). Prevalence of chronic pain was as follows: chronic local pain 9%, chronic regional pain medium 21%, chronic regional pain heavy 39%, and chronic widespread pain 31%. In the regression models, being a woman and persistent pain duration had the strongest associations with spreading of pain, but anxiety, pain interference, and insomnia were also important factors. Conclusion: Spreading of chronic pain can only partly be explained by the simultaneous levels of insomnia. Female sex, pain duration, pain interference and anxiety appear to have more significant relationships with the spread of pain. Targeting these factors may lead to improvements in treatment and prevention strategies.
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| 3. |
- Blom, Kerstin, et al.
(författare)
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Internet-vs. group-delivered cognitive behavior therapy for insomnia : A randomized controlled non-inferiority trial
- 2015
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Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 70, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare guided Internet-delivered to group-delivered cognitive behavioral therapy (CBT) for insomnia. We conducted an 8-week randomized controlled non-inferiority trial with 6-months follow-up. Participants were forty-eight adults with insomnia, recruited via media. Interventions were guided Internet-delivered CBT (ICBT) and group-delivered CBT (GCBT) for insomnia. Primary outcome measure was the Insomnia Severity Index (ISI), secondary outcome measures were sleep diary data, depressive symptoms, response- and remission rates. Both treatment groups showed significant improvements and large effect sizes for ISI (Within Cohen's d: ICBT post = 1.8, 6-months follow-up = 2.1; GCBT post = 2.1, 6-months follow-up = 2.2). Confidence interval of the difference between groups posttreatment and at FU6 indicated non-inferiority of ICBT compared to GCBT. At post-treatment, two thirds of patients in both groups were considered responders (ISI-reduction > 7p). Using diagnostic criteria, 63% (ICBT) and 75% (GCBT) were in remission. Sleep diary data showed moderate to large effect sizes. We conclude that both guided Internet-CBT and group-CBT in this study were efficacious with regard to insomnia severity, sleep parameters and depressive symptoms. The results are in line with previous research, and strengthen the evidence for guided Internet-CBT for insomnia. Trial registration: The study protocol was approved by, and registered with, the regional ethics review board in Linkoping, Sweden, registration number 2010/385-31. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 4. |
- Bolin, Sara, 1988-, et al.
(författare)
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Dormant SOX9-positive cells behind MYC-driven medulloblastoma recurrence
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Tidskriftsartikel (refereegranskat)abstract
- Tumor recurrence is a slow biological process involving therapy resistance, immune escape, and metastasis and is the leading cause of death in medulloblastoma, the most frequent malignant pediatric brain tumor. By studying paired primary-recurrent patient samples and patient-derived xenografts we identified a significant accumulation of SOX9-positive cells in relapses and metastases. They exist as rare, quiescent cells in Group 3 and Group 4 patients that constitute two-thirds of medulloblastoma. To follow relapse at the single-cell level we developed an inducible dual Tet model of MYC-driven MB, where MYC can be directed from treatment-sensitive bulk cells to resistant, dormant SOX9-positive cells by doxycycline. SOX9 promoted immune es-cape, DNA repair suppression and was essential for recurrence. Tumor cell dormancy was non-hierarchical, migratory, and depended on MYC suppression by SOX9 to promote relapse. By using computational modeling and treatment we further showed how doxorubicin and MGMT inhibitors are specifically targeting relapsing cells.
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| 5. |
- Borgenvik, Anna, 1987-, et al.
(författare)
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Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma
- 2022
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 82:24, s. 4586-4603
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Tidskriftsartikel (refereegranskat)abstract
- Relapse is the leading cause of death in patients with medulloblas-toma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, whereas MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse.Significance: SOX9 facilitates therapy escape and recurrence in medulloblastoma via temporal inhibition of MYC/MYCN genes, revealing a strategy to specifically target SOX9-positive cells to prevent tumor relapse.
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| 6. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 7. |
- Dahlberg, Tobias, et al.
(författare)
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3D printed water-soluble scaffolds for rapid production of PDMS micro-fluidic flow chambers
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- We report a novel method for fabrication of three-dimensional (3D) biocompatible micro-fluidic flow chambers in polydimethylsiloxane (PDMS) by 3D-printing water-soluble polyvinyl alcohol (PVA) filaments as master scaffolds. The scaffolds are first embedded in the PDMS and later residue-free dissolved in water leaving an inscription of the scaffolds in the hardened PDMS. We demonstrate the strength of our method using a regular, cheap 3D printer, and evaluate the inscription process and the channels micro-fluidic properties using image analysis and digital holographic microscopy. Furthermore, we provide a protocol that allows for direct printing on coverslips and we show that flow chambers with a channel cross section down to 40 x 300 μm can be realized within 60 min. These flow channels are perfectly transparent, biocompatible and can be used for microscopic applications without further treatment. Our proposed protocols facilitate an easy, fast and adaptable production of micro-fluidic channel designs that are cost-effective, do not require specialized training and can be used for a variety of cell and bacterial assays. To help readers reproduce our micro-fluidic devices, we provide: full preparation protocols, 3D-printing CAD files for channel scaffolds and our custom-made molding device, 3D printer build-plate leveling instructions, and G-code.
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| 8. |
- Dahlberg, Tobias, 1990-
(författare)
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KNOW YOUR ENEMY : Characterizing Pathogenic Biomaterials Using Laser Tweezers
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diseases caused by pathogenic agents such as bacteria and viruses result in devastating costs on personal and societal levels. However, it is not just the emergence of new diseases that is problematic. Antibiotic resistance among bacteria makes uncomplicated infections difficult and lethal. Resilient disease-causing spores spread in hospitals, the food industry, and water supplies requiring effective detection and disinfection methods. Further, we face complex neurological diseases where no effective treatment or diagnostic methods exist. Thus, we must increase our fundamental understanding of these diseases to develop effective diagnostic, detection, disinfection, and treatment methods.Classically, the methods used for detecting and studying the underlying mechanics of pathogenic agents work on a large scale, measuring the average macroscopic behavior and properties of these pathogens. However, just as with humans, the average behavior is not always representative of individual behavior. Therefore, it is also essential to investigate the characteristics of these pathogens on a single cell or particle level. This thesis develops and applies optical techniques to characterize pathogenic biomaterial on a single cell or particle level. At the heart of all these studies is our Optical Tweezers (OT) instrument. OT are a tool that allows us to reach into the microscopic world and interact with it. Finally, by combining OT with other experimental techniques, we can chemically characterize biomaterials and develop assays that mimic different biological settings. Using these tools, we investigate bacterial adhesion, disinfection, and detection of pathogenic spores and proteins.Hopefully, the insights of these studies can lessen the burden on society caused by diseases by helping others develop effective treatment, diagnostic, detection, and disinfection methods in the future.
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| 9. |
- Dragioti, Elena, Ph.D., et al.
(författare)
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Could PANSS be a useful tool in the determining of the stages of schizophrenia? A clinically operational approach
- 2017
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Ingår i: Journal of Psychiatric Research. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0022-3956 .- 1879-1379. ; 86, s. 66-72
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Tidskriftsartikel (refereegranskat)abstract
- Staging in schizophrenia might be an important approach for the better treatment and rehabilitation of patients. The purpose of this study was to empirically devise a staging approach in a sample of stabilized patients with schizophrenia. One hundred and seventy patients aged amp;gt;= 18 years (mean = 40.7, SD = 11.6) diagnosed by DSM-5 criteria were evaluated with the Positive and Negative Syndrome Scale (PANSS). Principal components analysis (PCA) with varimax rotation was used. The model was examined in the total sample and separately across a hypothesized stage of illness based on three age groups and between the two sexes. The PCA revealed a six factor structure for the total sample: 1) Negative, 2) Positive, 3) Depression and anxiety, 4) Excitement and Hostility, 5) Neurocognition and 6) Disorganization. The separate PCAs by stage of illness and sex revealed different patterns and quality of symptomatology. The Negative and Positive factors were stable across all examined groups. The models corresponding to different stages differed mainly in terms of neurocognition and disorganization and their interplay. Catatonic features appear more prominent in males while in females neurocognition takes two forms; one with disorganization and one with stereotype thinking with delusions. This study suggests that the three arbitrary defined stages of illness (on the basis of age) seem to reflect a progress from a preserved insight and more coherent mental functioning to disorganization and eventually neurocognitive impairment. Sexes differ in terms of the relationship of psychotic features with neurocognition. These results might have significant research and clinical implications. (C) 2016 Elsevier Ltd. All rights reserved.
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| 10. |
- Fountoulakis, Konstantinos N., et al.
(författare)
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Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia : an international multicenter study
- 2022
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Ingår i: CNS Spectrums. - : CAMBRIDGE UNIV PRESS. - 1092-8529 .- 2165-6509. ; 27:6, s. 716-723
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. Methods Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 +/- 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. Results There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. Discussion Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.
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| 11. |
- Fountoulakis, K.N., et al.
(författare)
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Modeling psychological function in patients with schizophrenia with the PANSS : An international multi-center study
- 2021
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Ingår i: CNS Spectrums. - : Cambridge University Press. - 1092-8529 .- 2165-6509. ; 26:3, s. 290-298
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Tidskriftsartikel (refereegranskat)abstract
- Background.The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.Methods.Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.Results.The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.Conclusions.The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.
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| 12. |
- Fountoulakis, Konstantinos N., et al.
(författare)
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Staging of Schizophrenia With the Use of PANSS : An International Multi-Center Study
- 2019
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Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press. - 1461-1457 .- 1469-5111. ; 22:11, s. 681-697
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionA specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method.MethodsTwenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed.ResultsExploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients.DiscussionThis study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.
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| 13. |
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| 14. |
- Malyshev, Dmitry, et al.
(författare)
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Laser induced degradation of bacterial spores during micro-Raman spectroscopy
- 2022
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Ingår i: Spectrochimica Acta Part A - Molecular and Biomolecular Spectroscopy. - : Elsevier. - 1386-1425 .- 1873-3557. ; 265
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Tidskriftsartikel (refereegranskat)abstract
- Micro-Raman spectroscopy combined with optical tweezers is a powerful method to analyze how the biochemical composition and molecular structures of individual biological objects change with time. In this work we investigate laser induced effects in the trapped object. Bacillus thuringiensis spores, which are robust organisms known for their resilience to light, heat, and chemicals are used for this study. We trap spores and monitor the Raman peak from CaDPA (calcium dipicolinic acid), which is a chemical protecting the spore core. We see a correlation between the amount of laser power used in the trap and the release of CaDPA from the spore. At a laser power of 5 mW, the CaDPA from spores in water suspension remain intact over the 90 min experiment, however, at higher laser powers an induced effect could be observed. SEM images of laser exposed spores (after loss of CaDPA Raman peak was confirmed) show a notable alteration of the spores' structure. Our Raman data indicates that the median dose exposure to lose the CaDPA peak was ∼60 J at 808 nm. For decontaminated/deactivated spores, i.e., treated in sodium hypochlorite or peracetic acid solutions, the sensitivity on laser power is even more pronounced and different behavior could be observed on spores treated by the two chemicals. Importantly, the observed effect is most likely photochemical since the increase of the spore temperature is in the order of 0.1 K as suggested by our numerical multiphysics model. Our results show that care must be taken when using micro-Raman spectroscopy on biological objects since photoinduced effects may substantially affect the results.
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| 15. |
- Malyshev, Dmitry, et al.
(författare)
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Mode of action of Disinfection chemicals on the bacterial spore structure and their Raman spectra
- 2021
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 93:6, s. 3146-3153
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Tidskriftsartikel (refereegranskat)abstract
- Contamination of toxic spore-forming bacteria is problematic since spores can survive a plethora of disinfection chemicals and it is hard to rapidly detect if the disinfection chemical has inactivated the spores. Thus, robust decontamination strategies and reliable detection methods to identify dead from viable spores are critical. In this work, we investigate the chemical changes of Bacillus thuringiensis spores treated with sporicidal agents such as chlorine dioxide, peracetic acid, and sodium hypochlorite using laser tweezers Raman spectroscopy. We also image treated spores using SEM and TEM to verify if we can correlate structural changes in the spores with changes to their Raman spectra. We found that over 30 min, chlorine dioxide did not change the Raman spectrum or the spore structure, peracetic acid showed a time-dependent decrease in the characteristic DNA/DPA peaks and ∼20% of the spores were degraded and collapsed, and spores treated with sodium hypochlorite showed an abrupt drop in DNA and DPA peaks within 20 min and some structural damage to the exosporium. Structural changes appeared in spores after 10 min, compared to the inactivation time of the spores, which is less than a minute. We conclude that vibrational spectroscopy provides powerful means to detect changes in spores but it might be problematic to identify if spores are live or dead after a decontamination procedure.
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| 16. |
- Nilsson, Daniel, et al.
(författare)
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Patient-specific brain arteries molded as a flexible phantom model using 3D printed water-soluble resin
- 2022
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Visualizing medical images from patients as physical 3D models (phantom models) have many roles in the medical field, from education to preclinical preparation and clinical research. However, current phantom models are generally generic, expensive, and time-consuming to fabricate. Thus, there is a need for a cost- and time-efficient pipeline from medical imaging to patient-specific phantom models. In this work, we present a method for creating complex 3D sacrificial molds using an off-the-shelf water-soluble resin and a low-cost desktop 3D printer. This enables us to recreate parts of the cerebral arterial tree as a full-scale phantom model (10×6×410×6×4 cm) in transparent silicone rubber (polydimethylsiloxane, PDMS) from computed tomography angiography images (CTA). We analyzed the model with magnetic resonance imaging (MRI) and compared it with the patient data. The results show good agreement and smooth surfaces for the arteries. We also evaluate our method by looking at its capability to reproduce 1 mm channels and sharp corners. We found that round shapes are well reproduced, whereas sharp features show some divergence. Our method can fabricate a patient-specific phantom model with less than 2 h of total labor time and at a low fabrication cost.
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| 17. |
- Stangner, Tim, et al.
(författare)
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Cooke-Triplet-Tweezers : More compact, robust and efficient optical tweezers
- 2018
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Ingår i: Optics Letters. - 0146-9592 .- 1539-4794. ; 43:9, s. 1990-1993
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Tidskriftsartikel (refereegranskat)abstract
- We present a versatile three-lens optical design to improve the overall compactness, efficiency, and robustness for optical tweezers based applications. The design, inspired by the Cooke–Triplet configuration, allows for continuous beam magnifications of 2–10× , and axial as well as lateral focal shifts can be realized without switching lenses or introducing optical aberrations. We quantify the beam quality and trapping stiffness and compare the Cooke–Triplet design with the commonly used double Kepler design through simulations and direct experiments. Optical trapping of 1 and 2 μm beads shows that the Cooke–Triplet possesses an equally strong optical trap stiffness compared to the double Kepler lens design but reduces its lens system length by a factor of 2.6. Finally, we demonstrate how a Twyman–Green interferometer integrated in the Cooke–Triplet optical tweezers setup provides a fast and simple method to characterize the wavefront aberrations in the lens system and how it can help in aligning the optical components perfectly.
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| 18. |
- Stangner, Tim, et al.
(författare)
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Step-by-step guide to reduce spatial coherence of laser light using a rotating ground glass diffuser
- 2017
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Ingår i: Applied Optics. - : Optical Society of America. - 1559-128X .- 2155-3165. ; 56:19, s. 5427-5435
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Tidskriftsartikel (refereegranskat)abstract
- Wide field-of-view imaging of fast processes in a microscope requires high light intensities motivating the use of lasers as light sources. However, due to their long spatial coherence length, lasers are inappropriate for such applications, as they produce coherent noise and parasitic reflections, such as speckle, degrading image quality. Therefore, we provide a step-by-step guide for constructing a speckle-free and high-contrast laser illumination setup using a rotating ground glass diffuser driven by a stepper motor. The setup is easy to build, cheap, and allows a significant light throughput of 48%, which is 40% higher in comparison to a single lens collector commonly used in reported setups. This is achieved by using only one objective to collect the scattered light from the ground glass diffuser. We validate our setup in terms of image quality, speckle contrast, motor-induced vibrations, and light throughput. To highlight the latter, we record Brownian motion of micro-particles using a 100x oil immersion objective and a high-speed camera operating at 2000 Hz with a laser output power of only 22 mW. Moreover, by reducing the objective magnification to 50x, sampling rates up to 10,000 Hz are realized. To help readers with basic or advanced optics knowledge realize this setup, we provide a full component list, 3D-printing CAD files, setup protocol, and the code for running the stepper motor.
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| 19. |
- Tobias, Joshua, 1969, et al.
(författare)
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Construction of non-toxic Escherichia coli and Vibrio cholerae strains expressing high and immunogenic levels of enterotoxigenic E. coli colonization factor I fimbriae.
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 26:6, s. 743-52
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Tidskriftsartikel (refereegranskat)abstract
- To express high quantities of colonization factor antigen I (CFA/I) derived from enterotoxigenic Escherichia coli (ETEC) for use in ETEC vaccines, the entire CFA/I operon consisting of four genes (cfa-A, -B, -C, -E) was cloned into plasmid expression vectors that could be maintained either with or without antibiotic selection. Expression from the powerful tac promoter was under the control of the lacIq repressor present on the plasmids. Fimbriae were expressed on the surface of both a non-toxigenic E. coli K12 strain and a non-toxigenic strain of Vibrio cholerae following induction with isopropyl-beta-D-thiogalactopyranoside (IPTG). It was found that the recombinant E. coli strains expressed up to 16-fold higher levels of CFA/I fimbriae compared to a reference strain which had previously been shown to be among the highest natural producers of the CFA/I fimbriae among tested wild type ETEC strains. Oral immunization with formalin-killed recombinant E. coli bacteria over-expressing CFA/I induced significantly higher serum IgA and IgG+M antibodies responses compared to the reference strain. Oral immunization with formalin-killed recombinant V. cholerae bacteria also induce strong CFA/I-specific serum IgA and IgG+M responses. We conclude that our constructs may be useful as candidate strains in an oral killed CF-ETEC vaccine.
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| 20. |
- von Mentzer, Astrid, 1983, et al.
(författare)
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Identification and characterization of the novel colonization factor CS30 based on whole genome sequencing in enterotoxigenic Escherichia coli (ETEC)
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The ability to colonize the small intestine is essential for enterotoxigenic Escherichia coli (ETEC) to cause diarrhea. Although 22 antigenically different colonization factors (CFs) have been identified and characterized in ETEC at least 30% of clinical ETEC isolates lack known CFs. Ninety-four whole genome sequenced "CF negative" isolates were searched for novel CFs using a reverse genetics approach followed by phenotypic analyses. We identified a novel CF, CS30, encoded by a set of seven genes, csmA-G, related to the human CF operon CS18 and the porcine CF operon 987P (F6). CS30 was shown to be thermo-regulated, expressed at 37 degrees C, but not at 20 degrees C, by SDS-page and mass spectrometry analyses as well as electron microscopy imaging. Bacteria expressing CS30 were also shown to bind to differentiated human intestinal Caco-2 cells. The genes encoding CS30 were located on a plasmid (E873p3) together with the genes encoding LT and STp. PCR screening of ETEC isolates revealed that 8.6% (n = 13) of "CF negative" (n = 152) and 19.4% (n = 13) of " CF negative" LT + STp (n = 67) expressing isolates analyzed harbored CS30. Hence, we conclude that CS30 is common among " CF negative" LT + STp isolates and is associated with ETEC that cause diarrhea. RAHAM JM, 1985, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES
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| 21. |
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| 22. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 23. |
- Wiklund, Tobias, et al.
(författare)
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Insomnia is a risk factor for spreading of chronic pain : A Swedish longitudinal population study (SwePain)
- 2020
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Ingår i: European Journal of Pain. - : John Wiley & Sons. - 1090-3801 .- 1532-2149. ; 24:7, s. 1348-1356
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent evidence suggests that insomnia negatively influences the occurrence of generalized pain. This study examined whether insomnia is a risk factor for the transition from local pain to generalized pain (i.e., spreading of pain).METHODS: This longitudinal study, with a follow-up of 24 months, included 959 participants (mean age: 55.8 years; SD: 13.9) with local or regional pain at baseline. Participants were grouped by insomnia symptoms as measured by the Insomnia Severity Index. Spreading of pain was measured by body manikins based on the spatial distribution of pain on the body. We defined two outcome categories; one with relatively localized pain (i.e., local pain and moderate regional pain ), and one with relatively generalized pain (i.e., substantial regional pain and widespread pain). Baseline age, sex, education, depressive symptoms, anxiety symptoms, catastrophizing, pain intensity, and spread of pain were also included in the Generalized Linear Model analysis.RESULTS: The unadjusted model showed that the risk of spreading of pain increased with an increase in insomnia symptoms (no insomnia: 55.4%; subthreshold insomnia: 25.4% moderate insomnia: 16.5% and severe insomnia: 2.7%). The risk increased in a dose-dependent manner; moderate insomnia risk ratio (RR) 2.34 (95% confidence interval [CI]: 1.34 - 4.09) and severe insomnia RR 4.13 (95% CI: 1.56 - 10.92). The results were maintained in the fully adjusted model although moderate regional pain was the strongest predictor RR 6.95 (95% CI: 3.11-15.54).CONCLUSION: Our findings show a strong prospective relationship between insomnia symptoms and the transition from relatively localized to generalized pain.
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| 24. |
- Wiklund, Tobias, 1986-
(författare)
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Insomnia Symptoms in Chronic Pain : Clinical presentation, risk and treatment
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In recent years, chronic and recurrent pain have gained interest as distinct conditions interacting both with peripheral and central parts of the nervous system as well as with the immune system. The risk of getting affected by abnormal pain modulation i.e., chronic pain is not equally distributed in the population and the search for risk factors is therefore of interest. One potential risk factor for chronic pain is insomnia symptoms i.e., difficulties falling asleep or maintaining sleep. In turn, insomnia symptoms are overrepresented in persons with chronic pain. Common current pain treatments lead to limited improvement of insomnia symptoms calling for treatments specifically directed to improve sleep. The overall aim of this thesis is therefore to investigate the distribution of insomnia severity in patients seeking specialized care for chronic pain, to investigate the role of insomnia severity as a risk factor for spreading of pre-existing pain, and to evaluate potential treatments for insomnia symptoms comorbid to chronic pain.Study I highlighted the high prevalence rates of insomnia symptoms in patients with chronic pain conditions. Roughly, insomnia was six times more common in our sample compared to the general population. We also showed that there were weak connections between insomnia symptoms and other variables (primarily psychological symptoms and pain intensity). In Study II physical exercise was more efficacious than Acceptance and Commitment Therapy-based stress management and the active control group in reducing insomnia symptoms and pain intensity short term. Improvements in physical exercise were largely maintained after twelve months but pain intensity had then also declined in the control group. No improvements in the Acceptance and Commitment Therapy-based stress management remain significant when an intention to treat principles were applied. In Study III, a dose-dependent increase in risk for spreading of pain was confirmed in subjects reporting moderate and severe insomnia symptoms. Though, there was no increase in the risk of pain spreading in subjects reporting sub-threshold insomnia symptoms (according to Insomnia Severity Index). In Study IV patients in the Internet-delivered Cognitive Behavioural Therapy for insomnia group, showed a more rapid improvement in insomnia symptoms than patients in the internet-delivered applied relaxation. The effect of Cognitive Behavioural Therapy for insomnia had declined slightly after six months and the Applied Relaxation group had continued to improve, leading to a comparable outcome on the Insomnia Severity Index at six-month follow-up.In conclusion, insomnia symptoms are common in patients seeking specialized pain care. High levels of insomnia symptoms increase the risk of spreading of pre-existing pain and this in a dose-dependent manner. Physical exercise has significant, but not clinically meaningful effects on pain intensity and insomnia symptoms. Internet-delivered Cognitive Behavioral Therapy for insomnia leads to a more rapid reduction of insomnia symptoms compared to applied relaxation, although long-term effects are uncertain
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| 25. |
- Wiklund, Tobias, et al.
(författare)
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Internet-Delivered Cognitive Behavioral Therapy for Insomnia Comorbid With Chronic Pain : Randomized Controlled Trial
- 2022
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc. - 1438-8871. ; 24:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with chronic pain often experience insomnia symptoms. Pain initiates, maintains, and exacerbates insomnia symptoms, and vice versa, indicating a complex situation with an additional burden for these patients. Hence, the evaluation of insomnia-related interventions for patients with chronic pain is important. Objective: This randomized controlled trial examined the effectiveness of internet-based cognitive behavioral therapy for insomnia (ICBT-i) for reducing insomnia severity and other sleep- and pain-related parameters in patients with chronic pain. Participants were recruited from the Swedish Quality Registry for Pain Rehabilitation. Methods: We included 54 patients (mean age 49.3, SD 12.3 years) who were randomly assigned to the ICBT-i condition and 24 to an active control condition (applied relaxation). Both treatment conditions were delivered via the internet. The Insomnia Severity Index (ISI), a sleep diary, and a battery of anxiety, depression, and pain-related parameter measurements were assessed at baseline, after treatment, and at a 6-month follow-up (only ISI, anxiety, depression, and pain-related parameters). For the ISI and sleep diary, we also recorded weekly measurements during the 5-week treatment. Negative effects were also monitored and reported. Results: Results showed a significant immediate interaction effect (time by treatment) on the ISI and other sleep parameters, namely, sleep efficiency, sleep onset latency, early morning awakenings, and wake time after sleep onset. Participants in the applied relaxation group reported no significant immediate improvements, but both groups exhibited a time effect for anxiety and depression at the 6-month follow-up. No significant improvements on pain-related parameters were found. At the 6-month follow-up, both the ICBT-i and applied relaxation groups had similar sleep parameters. For both treatment arms, increased stress was the most frequently reported negative effect. Conclusions: In patients with chronic pain, brief ICBT-i leads to a more rapid decline in insomnia symptoms than does applied relaxation. As these results are unique, further research is needed to investigate the effect of ICBT-i on a larger sample size of people with chronic pain. Using both treatments might lead to an even better outcome in patients with comorbid insomnia and chronic pain.
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| 26. |
- Wiklund, Tobias, et al.
(författare)
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Is sleep disturbance in patients with chronic pain affected by physical exercise or ACT-based stress management? : A randomized controlled study
- 2018
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central. - 1471-2474. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Most people suffering chronic pain are plagued by sleeping difficulties. Cognitive behaviour therapy has produced promising results for insomnia comorbid with chronic pain, but the access to such treatment is often limited. Over the last ten years, interventions aiming to increase cognitive flexibility and physical activity have been assumed to be effective treatments for a variety of conditions, including insomnia and chronic pain. If proven effective, these treatments could constitute the first steps in a stepped care model for chronic pain and insomnia.METHODS: Two hundred ninety-nine chronic pain subjects were randomized to Exercise, ACT-based stress management (ACT-bsm), or an active control group. Two hundred thirty-two participants (78%) received their allocated intervention at least to some extent. These participants were evaluated using mixed model analyses for changes in sleep (Insomnia Severity Index, ISI), pain intensity, depression, and anxiety immediately after treatment, six months and twelve months after treatment.RESULTS: The mixed model analyses revealed that Exercise had a positive effect on insomnia compared with the control group and the effect remained after 12 months. No clear effect (i.e., both for completers and for completers together with treatment non-completers) upon ISI was found for the ACT-bsm. Pain intensity decreased significantly both in the exercise group and in the control group. For the two psychological variables (i.e., symptoms of anxiety and depression) were found significant improvements over time but no group differences. The treatment effects for ISI and pain intensity did not reach clinical significance per definitions presented in other relevant studies.CONCLUSIONS: Beneficial significant effects on insomnia was confirmed in the exercise condition. However, these changes were probably not clinically important. For pain intensity a general decrease was found in the Exercise condition and in the control condition, while no change occurred in ACT-bsm. No group differences were found for the two psychological variables.
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